rn item ect meee fa patil LG ial a cn 22101828475 RESPIRATORY TUBERCULOSIS CHEST EXAMINATION: The Correlation of Physical and X-ray Findings in Diseases of the Lung By KeeR. Trai, v..G,, SD, ERCP Tied Edition. tog Illustrations. 12s. 6d. TUBERCULOSIS AND CHEST DISEASE FOR NURSES By G.S. Erwin, M.D. 39 Illustrations. 10s. 6d. THE ACUTE INFECTIOUS FEVERS By Ax JORAD .G. BL ra et te ee Charts and 24 Plates. 18s. DISEASES OF INFANCY AND CHILDHOOD By WILFRID SHELDON, M.D., F.R.C.P. Fifth Edition. 18 Plates and 143 Text-figures. 30s. PROGRESS IN CLINICAL MEDICINE A symposium by various authors Edited by RayMonpD DaALEy, M.D., M.R.C.P., and A GJ MILiEr, M.D. MLUR.C2.,. DiPIMots Plates and 22 Text-figures. 21s. CHILD HEALTH AND DEVELOPMENT By various authors. Edited by RicHarp W. B. ELLs, O.B.E., M.D., F.R.C.P. 49 Illustrations. 18s. SYNOPSIS OF HYGIENE (Jameson and Parkinson) By G.°S. Parkinson, €C.B.E:; D.5.0., M-K.C.S., D.P.H. Assisted by KATHLEEN SHAw, M.B.E. Ninth Edition. 28s. THE PRACTICE OF INDUSTRIAL MEDICINE With an account of the Hazards of Coal Mining By T. A. Ltoyp Daviss, M.D., M.R.C.P. 15s. J. & A, Churchill Ltd, IN RESPIRATORY TUBERCULOSIS By FREDERICK HEAF M.A., M.D., F.R.C.P. Senior Medical Officer, London County Council; Hon. Medical Director, British Legion Village, Preston Halli, Kent; Consulting Physician, Papworth Village Settlement AND N. LLOYD RUSBY M.A., D.M., F.R.C.P. Assistant Physician, The London Hospital; Physician, The London Chest Hospital; Consulting Physician to the British Legion Sanatorium, Preston Hall, and the National Sana- torium, Benenden FOURTH EDITION WELLCOME LIBRARY ivst E-dition : . J 1929 econd ,, (Burrell) « 11934 hivrd _,, ; T1037 Fourth _,, : ‘ . 1948 This book is copyright. It may not be repro- duced by -any means, in whole or in part, without permission. Application with regard to copyright should be addressed to the Publishers WELLCOME INSTITUTE LIBRARY Printed in England SPOTTISWOODE, BALLANTYNE & Co. LTD. London & Colchester PREFACE TO THE FOURTH EDITION Tue tuberculosis world sustained a serious loss in the death of Dr. L. S. T. Burrell ten years ago. He was the author of the first three editions of this book, and we have been stimulated to revise it now by the notable advances in the subject which have taken place since his death. In taking what he admitted to be a broad-minded view of “* recent advances ”’ Dr. Burrell presented to the Practitioner and Senior Student a book predominantly clinical in character. We have allowed ourselves a similar latitude and have felt that the subject of Respiratory Tuberculosis could best be presented as a consecutive narrative with the new developments engrafted upon a background of the ideas and conceptions previously held. It is our firm con- viction that the most outstanding single development which has taken place in the management of tuberculosis during the last decade has been the realisation of the important part which the environment and social circumstances of the patient play in the successful control of the disease, both from the point of view of the individual and the public health. By the inclusion of chapters dealing with this particular aspect of the disease this edition differs from its predecessors. In presenting the subject as a review of modern work we are conscious that the work of some authors, in this and other countries, has not been included. Limitation of space has rendered this omission necessary. Our policy has been to make this review largely objective and to refrain from stating our own views dog- matically. Nevertheless, from time to time we have thought fit to pass Judgement upon certain methods of management and treatment and so place them in proper perspective. The task has been greatly simplified by the help which we have received from many quarters. In particular we wish to thank Dr. S. Roodhouse Gloyne, Dr. J. L. Livingstone, Mr. T. Holmes Sellors, and Dr. Norman F. Smith for their kindness in reading the proofs of certain chapters. Their advice and criticism was most welcome to us. Also, we express our thanks to Miss M. JI. Kibble, physio- therapist at the London Chest Hospital, for her help ; to Miss A. M. vi PREFACE Jones for checking the bibliography ; to Mr. T. Wade, of the Staff of the library of the Royal Society of Medicine, for assistance in compiling the index ; and to Mr. A. Hart of Preston Hall for clerical assistance. Our indebtedness to those of our colleagues who have loaned us illustrations is acknowledged in the text. Finally, we cannot allow this occasion to pass without expressing our appre- ciation of the kindness and courtesy which we have always received from Mr. J. Rivers and Mr. A. S. Knightley of J. & A. Churchill Ltd. who have shown much patience with us and who have met our wishes whenever possible. FREDERICK HEAr. Luoyp Russy. London, July, 1948. CONTENTS Introduction. Incidence and Mortality Resistance and Infection Prevention Diagnosis Radiology Certain Complications and Associated Conditions General Treatment and Chemotherapy The Artificial Pneumothorax . Collapse Therapy—Surgical Procedures I Collapse Therapy—Surgical Procedures IT Rehabilitation Prognosis Classification and Types of Tuberculosis . Public Health Services . Index . 102 135 165 185 212 229 250 264 283 INTRODUCTION INCIDENCE AND MORTALITY Tue prevention and treatment of tuberculosis is an undertaking that demands for its achievement a wide knowledge of general, social and environmental medicine. Because the task has to be shared by the clinician and the public health officer, and because tuberculosis of the lungs is a chronic, infectious, lethal and wide- spread disease, it was natural that it should have become by slow stages during the course of the last fifty years a national concern and one which already lies largely under the aegis of the State. It is hoped in the pages which follow to show how this problem is being faced to-day and to trace the recent developments and trends of thought which have marked the last few years ; advances which have made it possible not only to control the local lesion more effectively, but also to adjust satisfactorily the life, work and social circumstances of those affected. Tuberculosis attacks the youth of the nation, sapping its vital energy at a time when it is most needed, and leaving a host of invalids to remain a financial burden on the State giving little hope of economic return. The fight against tuberculosis is not merely the treatment of the disease, it involves the prevention of its spread from one imdividual to another and also the effort to reinstate its victims to the privileges of the healthy. These difficult tasks are as yet not completed; the cure of the disease evades us, the ubiquity of the bacillus defies control, the curious selectiveness of the infection presents problems to which we cannot at present give any satis- factory answer and the employment of the phthisical remains a fear and an anxiety to industry. The epidemiology of tuberculosis is a complex subject, and although hygiene and social conditions play a most important part in preventing the disease, the gradual decline in the mortality rate which has taken place in the majority of civilised communities cannot be completely explained by improvement in social and sanitary conditions. We are still without accurate knowledge of the protective influence of a primary infection in infancy, neither H. & R. TUBERC. 1 are we sure of the mechanism of genetic resistance which seems to be present in races in which the disease has been endemic for many generations. Some authorities regard tuberculosis as an endemic disease with epidemic waves ; the last one, having reached its peak about seventy years ago, is now declining. Zimmerli (1) thinks this contention is supported by conditions in Egypt where the same rapid abatement of consumption has occurred even in districts which he says are as unhealthy and as picturesque as they were a hundred years ago. Apart from the war years, there has been an almost universal decline in the mortality of tuberculosis throughout the world. Even between 1911 and 1927, when tuberculosis schemes were for the most part in their infancy, the percentage decline in a number of countries is shown in the following table :— United States. a. 6 40 Hires : 2. eee Seotland . 4 Sweden ; ae ok Germany . a oat Norway. yao Netherlands ; ay 4k Belgium —. ee SF Northern Ireland . 40 Italy . ' 2 ees Switzerland Bi France : a ed. England and Wales . 34 Japan ~ "SLG Australia . 5 tee ted Spain : , New Zealand : : 33 (Figures calculated from International Health Year Book, 1928, quoted in Journ. of the States & Soc. Inquiry Soc. of Ireland, Dublin, (19380). The steady decrease in the mortality figures has been twice disturbed by the outbreak of world war. Heaf (2) has shown that in the World War of 1914-18 the rise was directly proportional to the degree in which the respective countries were involved in the international conflict. At the end of the war there was a rapid return to the normal rate of fall as the countries were relieved of food restrictions and overcame the depressing conditions of overcrowding and the strain of overwork. During the 1989-45 World War the rise in both notifications and deaths showed some interesting and rather unusual features. The deaths increased during the first two years and then remained stationary for a year, eventually showing a slight decrease in the fourth year. Notifications have steadily risen, partly due to the persistent search for new cases and the introduction of mass radio- New cases Rate per 100,000 Deaths Rate per 100,000 1939 46,206 111-4 25,623 61-8 1940 46,572 112-2 28,144 67-9 1941 50,964 122-9 28,670 69-2 1942 52,619 126-9 25,549 61-6 1943 54,342 131-1 25,649 61-9 1944 54,313 131-0 24,163 58°5 1945 52,110 122-2 23,955 56-2 1946 51,289 119-9* 22,838 53°3* * Provisional. SCOTLAND New cases Rate per 100,000 Deaths Rate per 100,000 1989* (09% 141°8 3,026 70-4 1940 7,722 153:1 4,003 79°3 1941 8,294 161-7 4,175 81-4 1942 9,048 175-9 3,998 Te 1943 10,088 195-6 3,959 76-8 1944 9,641 185:°8 3,936 75-9 1945 9,658 187-3 3,803 73°7 1946 9,713 189-2 3,984 Tie * Estimated mid-year population. EIRE New cases Rate per 100,000 Deaths Rate per 100,000 1939 5,604 | 191-0 3,304 112:°6 1940 A V72 | 161:°3 3,685 124-6 1941 5,168 U2 3,711 124-0 1942 5,631 190-0 4,347 146 uf 1943 5,674 192:°6 4,306 146-1 1944 Mey are 194-5 3,839 130-4 1945 5,971 200-2 3,694 123:°8 1946 5,953 199-6 3,390 113-6 U.S.A. | New cases Rate per 100,000 Deaths Rate per 100,000 | 19389 101,740 41 'D 61,606 47-1 1940 | 100,772 76°4 40,428 45°8 1941 101,714 79-4 59,251 44°5 1942 ) 117,157 87-6 57,690 43°+1 1943 118,042 88-1 57,005 42-6 1944 124,749 94-1 54,731 41:3 1945 | 117,400 | 89-0 52,916 40-1 It will be seen that the deaths reached a maximum in 1941 when there were 28,670 deaths in England and Wales from all forms of tuberculosis and 4,175 in Scotland. In the year 1916, the mid year of the 1914-19 war, there were 53,858 deaths from tubercu- losis in England and Wales. After 1941 there is a steady decline in the number of deaths in both pulmonary and non-pulmonary forms, the death rates for England and Wales being as follows :— STANDARDISED DEATH RATES FROM TUBERCULOSIS PER MILLION (3) (ENGLAND AND WALES) RESPIRATORY OTHER FORMS ALL FORMS Year ose , = : ae Males | Females | Persons; Males | Females Persons| Males | Females | Persons 1931 756 588 667 201 | 173 186 957 T61 853 1937 577 488 | 508 | 145 124 |- 185 | 722 572 643 1938 534 402 | 463 136 119 | 128 | 670 | 521 | 591 1939* | 539 396 | 468 | 182 | 109 | 120 | 671 505 583 1940* | 648 | 440 588 4 147.1. 124 | 185.) 795 564 673 1941* | 712 4A5 571 181 | 147 164 | 893 | 59% 735 1942* | 644 897 | 524 | 165 126 144 | 829 523 688 1943* | 724 391 549 | 157 123 | 189 | 881 514. 688 1944* | 702 373 528 | 145 | 112 | 129 | 847 485 657 | | * Non-civilian males are excluded from the deaths and population after September 8, 1939, and non-civilian females after mid-1941, MENINGEAL TUBERCULOSIS i) In 1940 a serious increase from meningeal tuberculosis occurred and reached its maximum in the first half of 1941, when the excess of deaths over the expected deaths was 557 ; this-fell to 347 by the. first half of 1942. There is little doubt that the increased over- crowding, shelter life and inadequate ventilation coupled with an increased number of ambulant infectious persons amongst the population was the main cause for this increase particularly among children under five. The total number of deaths from tuberculosis of the meninges and the nervous system in England and Wales from 1938-1944 by sex and age are given in the following table : TUBERCULOSIS OF MENINGES AND NERVOUS SYSTEM (4), 1938 1939 1940 1941 1942 1943 1944 Males 0-14 Civilians 655 623 660 872 716 665 656 15—44 Civilian 1AZF 2TH S82 155 132 To 110 Non-Civilian — 5 30 Page 40 33 56 45 Civilian 92* 87* 99 93 92 82 Gz Non-Civilian — — 5 18 13 9 24. 45 + Civilian 29* 32% 31 30 30 40 24 Non-Civilian — — — — — — — ALL A 4 ae Os 868 957 1,195 | 1,028 960 942 LL ae es ET 8 1 Dea a Ne eT? ROWE ae PML Be rene; Females | 0-14 Total 652 561 630 820 643 631 587 15-44 ,, 131 155 199 229 208 237 192 45 a 71 UP | 5 94 99 92 90 45 + rs 19 28 | 25 PAG 22, 28 30 ALL 873 816 | 929 | 1,170 972 988 899 TOTALS 1,791 | 1,684 | 1,886 | 2,365 | 1,995 | 1,948 | 1,841 | { were : T.B. Meningitis | Ronen toad Percentage ot Year =_s under a eee s 0-4 5-9 10-14 all anders") oF 15 19388 57 24 18 99 147 67 19389 45 16 7 / 68 102 67 1940 40 ibs 14 69 106 65 1941 64 24. 22 1107 j& pAnl54 71 1942 39 12 7 58 | 84 69 1943 37 33 7 eae 08 =) a le7D 1944 38 14 15 67 | 89 75 AGES 5-14 | Year | | Pulmonary Non-pulmonary Pulmonary Non-pulmonary | 1938 30 (0-12) 88 (0-35) 25 (0:05) | 59 (0-11) 1939 15 (0-08) 64 (0-34) 16 (0:04) | 88 (0-09) 194.0 22 (0-19) 64 (0-57) 24 (0-18) | 42 (0-28) 1941 41 (0-65) 92 (1:45) | 25 (0-22) 62 (0-55) 1942 22 (0-16) 56 (0-41) 17 (0-07) 28 (0-12) 1943 24 (0-14) 51 (0-30) 23 (0-08) 47 (0-16) | 1944, 14 (0:08) 58 (0°31) 10 (0-03) 36 (0-12) life. death rate for pulmonary tuberculosis increased by 72 per cent. for the same period and the non-pulmonary rate by 67 per cent. These increases are much greater than for England and Wales as a whole and the increase in incidence affected children much more than adults, particularly in the non-pulmonary type. The increase in © this type has occurred almost equally for all the principal sites except in abdominal tuberculosis. The precentage increases in the death rates for each site over the period 1938-41 are : All bones and joints. . 184 Abdomen ‘ : : . 141 Peripheral glands : ; i 2D Meninges . i ; ck ae Other sites ; : ‘ . 269 In 1942 the tuberculosis mortality was considerably lower than in 1941, but the incidence of new cases among adults continued to increase, but at a smaller rate. The authors regard the chief factors influencing the incidence of tuberculosis unfavourably to have been changes in the age and sex distribution of the population as a result of evacuation and of recruitment to the forces, the strain and overcrowding resulting from bombing, fatigue and lack of rest and restrictions of diet. Beneficial factors were increased employ- ment and increased financial resources for those formerly on the verge of poverty. In Glasgow up to 1941 Laidlaw (6) found the increased incidence . of tuberculosis involved the age groups 15—45 in males and 15-35 in females. The rate of increase slowed down considerably after 1941 in young adults, but in the under 15 age groups of both sexes as well as the over 45 group in males it still remained high. The increase in .the under 15 ages is considered to be due to an increased proportion of home contacts, and that in the older age groups to overwork and long hours. This is borne out by the fact that there is little increase among the commercial and professional classes, among whom less than 20 per cent. exceeded the, recommended maximum hours of work, whereas 67 per cent. of the workers of heavy industries were working in excess of normal hours. It is among these latter workers that the main increase in the incidence occurred. Generally speaking, employment has a definite influence on the mortality rates. Apart from the well-known risk associated with occupations inyolving contact with siliceous dusts there is a high mortality rate in those trades where working environment is un- hygienic or where there are low wages and irregular living. Bar- tenders, newspaper vendors, actors and waiters are examples of the type of occupation in which the incidence of tuberculosis is high because of the conditions under which work is done, whilst nurses and medical students in a general hospital appear to run risks because of contact with infectious cases, very often undiag- nosed, and therefore more dangerous than in a tuberculosis hospital or sanatorium where proper preventive precautions are taken, as a result of which the incidence of tuberculosis among the staff is low. Social status has also a considerable influence on the mortality rate. From the Registrar General’s figures for 1931-2 it is signifi- cant to note that the standard mortality rate per 100,000 for his Group 1 (professional classes—males between 20 and 65) is 61, and for Group V (unskilled workers) is 125. This wide difference is mainly due to conditions of living and employment. An interesting and somewhat surprising point, revealed on consideration of the Registrar General’s return for this period, is that in all the social groups the maximum death rate for males occurs at the age of 45. If, however, the mortality figures are taken with regard to conditions and type of occupation the peak is found to shift to 55 in the dusty industries (Heaf (7) ). Tuberculosis as a National Problem Not infrequently a figure is quoted which is said to represent the total number of tuberculous persons in the country. This is not definitely known, although an approximation may be made from the evidence of case finding surveys which have been made in the past and also from the results of mass radiography examinations. One of the earliest attempts to determine the case incidence of tuberculosis within a limited area was made by Armstrong (8) at Framlingham in U.S.A. in 1916. Examining a community of 16,000 persons, a morbidity rate of 2 per cent. in the general popu- lation was found ; this figure, when compared with the mortality rate, indicated that there were about ten active cases and nine arrested cases for every death. Recent publications on mass radiography surveys show that from 2-0 to 4-0 adult persons per 1,000 examined are in need of immediate sanatorium treatment for active tuberculosis and that another 8:0 to 9:0 per 1,000 show lesions of clinical significance and a total of 15 to 22 per 1,000 show changes in the lungs due to inactive tuberculosis. Stocks (9) has reviewed the problem and from the rate of persons dying after notification estimates that there were upward of 770,000 DEATH RATES FROM RESPIRATORY TUBERCULOSIS PER MILLION LIVING (Including non-civilians and based on the estimated ‘total populations at risk). Complete years Annual rates Mean annual 1931-1935 1939 1945 Males : | 0- : F F 85 54 65 beget } f 42 . 15 19 10- 4 : ‘ 64 31 38 15— : : : 489 368 266 20-— : ; . 967 682 5T4 25- , F , 966 723 632 35— : : ; 1,135 859 725 A5— : ; ; 1,369 1,158 1,024 55-— . ‘ , 1,175 1,171 1,149 65 and over . ; 610 559 642 All ages (crude) ; 768 638 588 Females : | | O- : : ‘i 74 | 38 69 | [le Oe et eet! 43 20 27 10— 4 A ey 143 86 68 Bo: |) iy 842 601 512 20-— ; : ot 1,144 955 865 25- iN 914 707 657 35- r 2 mae 64.4 469 419 45— r F ‘ ATA Bo2 288 | Dor ibe die res 6 ld sali 392 300 229 | 65 and over . = 265 | 209 188 | All ages (crude) «4 543 | 410 359 Compiled from figures given by Percy Stocks in the Monthly Bulletin of the Ministry of Health (February 1946). persons living in 1938 who had at some time been notified as suffering from tuberculosis. Most of these persons who had had active tuberculosis were now either healed or quiescent. A further calculation leads him to the conclusion that at any given moment in 1938 there were from 80,000 to 100,000 persons with notified clinically active tuberculosis, and about 10,000 unnotified active cases in England and Wales, i.e., 24 per 10,000 ‘clinically active cases, and 160 per 10,000 at some time of notifiable standard, but now inactive. Stock’s figure for the total number of persons with tuberculous lesions both healed and active approximates closely with that so far indicated by mass radiography surveys which is approximately 200 per 10,000 or a total of about 800,000, but his figure for active cases would seem to be rather low both from radio- graphic surveys and case. finding methods based on tracing in- fectious cases from observations on the changes of the Mantoux reaction in children. But whichever way one approaches the problem the conclusion is reached that there is a considerable number of unknown persons suffering from active tuberculosis amongst the population of this country. The full significance of tuberculosis as a matter of national im- portance can only be appreciated by analysing the mortality figures into age groups. The death rates in 1938 from tuberculosis by age is given in the tables on pages 9-10. NON-RESPIRATORY TUBERCULOSIS STATISTICS COMPILED FROM DALEY AND BENJAMIN (1943) FOR THE YEAR 1938 (5) England and Wales London ee cs Age Group Total Deaths New Cases Deaths Males Females No. Rate per 1000 No. | Rate per 100 2 ; = = oe ee | = O-— 4 649 569 142 0°57 88 0-35 | 5-14 355 B47 253 0:47 59 | O-11 15-19 252 228 } } as 20-24 177 148 | fie tase nfogualy ota nena 25-44 A865 *) 5008 AA ae 45-64 258 | 216 |} | ) 65 + 84 90 40 21 The important features of these tables are the high figures for the 15 to 25 age groups for both males and females but particularly females. These are the years of life when the economic value of the individual to the nation is being established and in the case of females the rate remains high during almost the whole of the child bearing period. It will be noted that the rise in deaths takes place earlier in females, but in males the rate is approximately three times higher than in females for the 45-65 age groups. Deaths from non-respiratory tuberculosis are greatest during the early years of life, falling off rapidly after the age of 5; the majority of deaths up to 5 years being due to meningitis. | If notification figures are compared for the last seven years according to age groups, the rise will be seen to be greater in males than in females, and to be more pronounced in the higher age groups. This has important economic and domestic repercussions as it is the bread-winner of the family that is being increasingly affected by the disease. The general trend of the disease in adults is towards an increasing susceptibility in young women and elderly men. COMPARISON OF NOTIFICATIONS ACCORDING TO AGE-GROUPS (10) 1938 and 1944 (ENGLAND AND WALES) PULMONARY TUBERCULOSIS | Year 0-14 15-24 25-44 45 + Total | . : | Males: 1938 557 4,637 8,443 6,665 21,302 1944 1,639 5,872 9,762 7,697 24,970 + 82 + 1,235 + 1,319 | + 1,082 | Females : 1938 1,494. 5,730 6,806 2,544 16,577 1944 1,504 7,489 7,417 2,414 18,824 =i) + 1,756 + 611 — 130 s NON-PULMONARY TUBERCULOSIS Year 0-14 15-24 | 25—44 | 45 + Total Males: | | 19388 3,749 1,282 1,007 | 473 6,511 1944. 2,817 988 889 | 380 5,074. — - ~| a — 932 — 294 11s) 7 Pee o5 Females : 1938 3,104 1,408 1,311 476 6,299 1944 2,574 1,245 1,169 | 457 5,445 ry 500) — 163 = 143 ap eae ke The Decline in Tuberculosis Mortality Apart from war years tuberculosis mortality rates have shown a steady decline for the last sixty years. During the same period there has been a similar but not necessarily a corresponding decline in the general mortality rates from all causes, but it is difficult and probably not possible to prove statistically that the mortality from tuberculosis is decreasing more rapidly than that from all causes. We have to rely on generalisations in determining the causes of the decline although the rise during the changed environment of war periods does help to fix certain conditions as influential factors. There is little doubt that the rise in the general standard of living, improved personal hygiene, better housing and working conditions, higher nutritional standards particularly for the poorer classes, all play their part in preventing death from tuberculosis. How far our tuberculosis services assist in this direction cannot be measured with certainty, although evidence has been brought forward to show the result of neglecting to provide efficient anti- tuberculosis measures. Lissant Cox (13) has stressed another factor which is frequently overlooked, that is the supervision of homes by the tuberculosis officer and nurse. A cleaner milk supply has no doubt reduced the number of cases, particularly in children. This is seen in the returns from the City of Toronto where abdominal tuberculosis has been practically eliminated in the City since all the milk has been systematically pasteurised. In the London area for similar reasons the death rate of abdominal tuberculosis per 1,000,000 in children under 5 has fallen from 136 in 1921 to 6 in 1944. Although there has been a remarkable decline in the death rate from tuberculosis during the last fifty years, the rate of decline has been slower in young adults than other age groups—in fact, in young females there has been a slight rise in mortality at ages 15-25 in recent years, and this un- favourable change is most marked in urban areas. The figures have been reviewed by A. Bradford Hill (14) and he is unable to find much statistical support for the usual explanations that a “ much lower level of infection in early life has led to a decline of im- munisation in childhood ” or “‘ that the strain and stress of com- petitive wage earning with the associated changes in their social life’ are the two main factors responsible for the increased death . rates in these age groups. Hill stresses more the importance of internal migration and the consequent distribution of young adults in different parts of the country. He shows that the excess mor- tality at the young adult ages in the rural areas has completely disappeared. Another cause which he thinks has a strong bearing on the problem is unfavourable housing standards, and considers it frequently associated with young adult phthisis. There is, however, one observation which has been frequently made and has not yet been satisfactorily answered. At no period in the steadily declining mortality curve can we point to a marked decline due to the introduction of any special form of treatment, but it should be noted that whilst the annual rate of decline in mortality from tuberculosis during the 60-year period 1851-1910 was less than 1 per cent., it was nearly 2 per cent for the period 1911-46, during which time the tuberculosis services were being established and developed. The gradual increased segregation of the infectious case may have far-reaching effects in preventing new cases arising, but it is possible that the greatest factor of all in the combat against tuberculosis is the increase of genetic resistance. Bovine Tuberculosis Although the majority of cases of respiratory tuberculosis are due to the human type of tubercule bacillus, the prevalence of bovine infection is becoming increasingly recognised as typing of . the bacillus is practised more frequently. The frequency with which this type of bacillus attacks various sites at different ages is indicated by the work of Griffith which is summarised in the following tables : ENGLAND Percentage of cases infected with the bovine type of bacillus Variety of Tuberculosis No. of Cases Under 5 5-15 | All Ages Cervical gland. 126 90-9 53:4 | 50-0 Lupus : : 191 58-4 44+ 4 48 +7 Scrofulodermia . 60 53°3 43°38 36-6 Meningeal . : 265 28-1 24°5 24°6 Bone and Joint. 558 29-5 19-1 19-5 Genito Urinary . 23 — — | 17-4 | SCOTLAND Percentage of cases infected with the No. vf bovine type of bacillus Variety of Tuberculosis Cases Under 4 5-15 All Ages = = SS = =, = = = |e = Cervical gland. 93 | 65-0 62:3 51-6 _ Lupus : d 13 100-0 | 71-4 69-2 | Meningeal . ; 208 | 84-4 14-0 29-6 | Bone and Joint. 218 46-2 28-9 29°8 Genito Urinary . 42 | —- — 31-0 | It will be noted that the figures are generally higher in Scotland than in England. This is also marked in pulmonary tuberculosis in which the figures are 1 per cent. for Wales, 1-6 per cent. for England, and 7 per cent. for Scotland. Savage estimated that in 1927 there were 310 deaths from respiratory and 1,635 from non-respiratory forms of tuberculosis in England and Wales and Gloyne (24), using the same method of calculation estimates that there were 219 respira- tory, and 976 non-respiratory, calculated deaths in 1938 due to bovine infection. If the calculations are based on notifications instead of death statistics, the results for 1938 are :— 37,879 respiratory disease notifications 378 calculated due to bovine bacillus notifications 50,689 Total notifications bovine bacillus ——— 2,324 calculated due to bovine bacillus Following Sir W. Savage’s estimate that 1 per cent. of the respira- tory, and 23 per cent. of the non-respiratory cases of tuberculosis each year are of the bovine origin and applying those figures to the tables of the Registrar-General, it is possible to give an approximate BOVINE ORIGIN Galeneen | Moar Bey. Non-respira- t otal ae ene of eaths tory Deaths Dovine Cabin Respiratory | Non-respiratory 2 1920 32,791 9,754 328 2,249 2,577 1930 29,414 6,336 294 1,457 1,751 1940 23,660 4,484 236 1,030 1,266 In children respiratory tuberculosis of bovine origin is a rare condition as is shown by the investigations of Blacklock (15) in 160 children under 13 years. The human type of bacillus was isolated in 160 (96-4 per cent.) and the bovine in only 6 (3-6 per cent.) of cases. : Type Years Years Years Years Total 0-1 1-2 2-3 3-6 6-18 Human ; 58 31 21 24 26 160 Bovine : 1 2 2 1 — 6 The recent work of Sigurdsson (16) in Denmark on 566 cases of pulmonary tuberculosis or pleurisy in which the bacillus had been typed showed that 40-6 per cent. of the 165 cases which came from rural areas were infected with the bovine type of tubercle bacillus, whilst only 3-6 per cent. of the 362 cases coming from urban areas were due to that type of infection. The investigation showed that 94 per cent. of the patients who had a bovine infection had been in contact with tuberculous cattle within the past two years. The incidence of bovine tuberculosis in man is closely connected with the extent of tuberculosis in cattle. In England and Wales there are no accurate data relating to the incidence of tuberculosis in cattle. The Cattle Diseases Committee of the Economic Advisory Council reported in 1934 that about 40 per cent. of the total dairy stock in Great Britain might be considered to be infected. This figure was accepted by the National Veterinary Medical Associa- tion which stated that 0-5 per cent. of cows yield infected milk (Pool (17) ). J. N. Ritchie considers that the figure 40 per cent. is too high and, from tuberculin surveys and the autopsies on animals slaugh- tered under the Tuberculosis Order, he considers that 20 per cent. as the approximate incidence of the reactors in ‘England and a probable 30 to 35 per cent. infection among cows, although the distribution throughout the country varies considerably. In other countries similar investigations have revealed the com- paratively high percentage of cases of pulmonary tuberculosis due to bovine infection. Bruno Lange (18) in Berlin found 9 cases in 148 adults with pulmonary tuberculosis ; 69 of these adults had been engaged in cow milking; P. Mourier (19) during 1933-6 among 161 unselected patients found the bovine bacillus in 20-5 per cent., most of the patients being farm workers. Charlotte Ruys (20) isolated 13 cases of bovine tuberculosis from 204 adult patients and 16 cases from 188 children in Holland. These figures are for pulmonary cases: if all forms of tuberculosis are included they will all become very much higher, so much so that A. S. Griffith stated in 1938 that ‘‘ bovine tuberculosis is a serious menace which must be fought with utmost vigour.” Not infrequently it is believed that pulmonary disease due to bovine infection runs a comparatively benign course. This is strongly denied by Griffith and other workers who claim that the bovine bacillus is as virulent as the human type in man, and that there is no clinical evidence to support the idea that lesions due to bovine infection run a slowly progressive mild course. In the series of 44 cases of bovine pulmonary tuberculosis described by Griffith and Smith (21) enlargement of lymphatic glands preceded the development of ulcerative pulmonary lesions in 12 patients. The extent of the pulmonary disease varied from slight affection of one apex to widespread bilateral disease with cavities at the apices in 29 cases, Krom symptoms, physical signs and radiologically it is not possible to distinguish between bovine and human forms of pul- monary tuberculosis. Munro (22) found the bovine strain of bacillus in 58 persons suffering from pulmonary tuberculosis and following them up carefully came to the conclusion that the bovine bacillus was more virulent to man than the human strain. The incidence of bovine tuberculosis in England and Wales is not known definitely, mainly because there is no reliable clinical test for differentiating between human and bovine type infections in man. The detection of the bovine type is a relatively slow and laborious bacteriological investigation, but sufficient work has been done by Griffith and Smith (23), and Blacklock (15), to show that there is a higher percentage of bovine type infection in Scotland than in England. The work has been reviewed by Gloyne (24), who states that “in England, taking all ages into consideration, about half the eases of cervical gland tuberculosis and lupus, about one quarter of the meningeal, and rather more than one sixth of the bone and joint and genito-urinary cases are due to the bovine bacillus.”’ References (1) ZIMMERLI, E. (1936) Brit. J. Tuberc. 30, 62. (2) Hear, F. R. G. (1941) Brit. J. Tuberc. 35, 127. (3). Rep. med. Offr. Minist. Hith. Lond. On the state of the public health during six years of war. H.M. Stationery Office (1946) 268. (4) Ibid. 269. (5) Datrey, W. A. and BENJamIn, B. (1942) Brit. med, J. 2, 417. (6) LarpLaw, S. and MACFARLANE, D. (1942) Brit. med. J. 2, 63. (7) Hear, F. R. G. (1946) Brit. med. J. 2, 975. (8) ArmMsTRONG, D. B. (1921) Amer. Rev. Tuberc. 4, 908. (9) Srocks, P. (1944) Practitioner, 153, 1. (10) (1947) Mon. Bull. Minist. Hlth. Lond. 6, 24. (13) Cox, G. L. (1932) Publ. Hlth., Lond. 45, 205. (14) Hix, A. B. (1936) Lancet, 1, 219. (15) Biacxiock, J. W. S. (1947) Brit. med. J. 1, 707. (16) British Medical Journal. Editorial (1947) 1, 726. (17) Poot, W. A. (1945) Proc. R. Soc. Med. 39, 77. (18) Lance, B. (1987) Lancet, 2, 1204 (Extract). (19) Mourier, P. (1937) Brit. med. J. 1, 21 (Extract). (20) Ruys, C. (1987) Brit. med. J. 1, 1216. (21) Grirrirnu, A. S. and Smiru, J. (1935) Lancet, 2, 1339. (22) Munro, W. T. (1940) Edinb. med. J. 47, 110. (23) GrirFitH, A. S. and Smiru, J. (1988) Lancet, 1, 739. (24) GLOYNE, S. R. (1942) Proc. R. Soc. Med. 35, 171. CHAPTER IT RESISTANCE AND INFECTION DuRING recent years a great deal of work has been done to deter- mine the reaction of the body to infection by the tubercle bacillus and the reason for the changes that have been observed. Although much new light has been thrown on the pathogenesis of tuberculosis, and some useful information has been revealed, the work has shown that there is still a wide field to be explored and many important problems yet to be solved. Two factors still impede progress, one is the adherence to conclusions which have been accepted on insuffi- cient and sometimes complete absence of satisfactory evidence and the other is the confusion that has arisen due to the lack of definition of terms and the consequent variation in meanings attached to them by different individuals. Definitions. In dealing with the problem of tuberculous infec- tion it is thought better to use the word ‘“ resistance ’’ rather than “immunity,” for the latter word implies that the individual develops complete protection from infection, either for life, or for a considerable period of time. As there is no evidence that such a state can be established, but some proof that partial protection from the disease is present in the body to a varying degree, both before and after infection by the tubercle bacillus, it is less confusing to refer to that power which effects this protection as the resistance of the body to infection by the tubercle bacillus. This property of resisting tuberculous infection is possessed by all humans to a varying degree, otherwise the result of invasion of the body by the tubercle bacillus would be rapidly fatal in every instance. As it is genetic to the human species we refer to it as native or natural resistance and it has been clearly defined by Ustvedt (1) as the “‘ power to withstand the attack of the tubercle bacillus which the organism possesses apart from the effects of the infection itself.” There is another type of resistance to tuberculous infection which only develops as a result of the reaction of the tissues to the infection. This is a specific increase in the resisting power of the body against the infecting agent which is acquired as a result of the invasion of _ the body by the organism. It has a direct relationship to the magni- tude of the infection and the virulence of the organism and is a change in the tissues that is dependent on the nature and composition of the organism. It is, therefore, referred to as “ acquired resist- ance’ and plays a major part in determining the development of the lesion which results from the infection. Native Resistance. It is well known that certain animals do not succumb to an experimental inoculation as readily as others. The guinea-pig is particularly susceptible to both the human and bovine type of bacillus, the rabbit is less affected by the human than the bovine bacillus, the goat is more resistant than the rabbit, and the kangaroo relatively unharmed by comparatively large doses of the human bacillus. Furthermore, individual members of the same species show some difference in their reactions to the same dose, and in experimental work certain organs of the body appear to develop lesions more frequently than others. This may be due to the organ being more readily attacked and that the bacillus _ can lodge more easily in the tissues, but the relative infrequency with ~ which the muscular and nervous system show tuberculous lesions may be due to a special resistance which these tissues possess against the infection. In the human species native resistance varies according to race, age, nurture, and the presence of other infections. | The Influence of Race. Depending upon the degree to which tuberculosis has been indigenous in a community in the past, it is possible to recognise four broad groups of mankind in relation to their reaction to the disease. First, the pure virgin soil which has never been infected: this is now extremely rare and is practically confined to certain tribes of Central Africa. Secondly, the cross-bred tribes in Mexico and of American Indians. Thirdly, those of a past civilisation, such as Chinese and other Asiatic peoples, who had the disease years ago and in whom it is now reappearing owing to industrialisation. Fourthly, the white races of Europe and North America. The work of Lyle Cummins (2) and others has shown that in certain races infection by the tubercle bacillus causes a rapidly spreading acute generalised disease, particularly if members of the race are removed from their native environment. The negro in North America, although he has now lived under similar conditions to the white population for two or three generations, still shows a higher mortality rate than the white and also develops a less fibrotic type of lesion. Observations made on tuberculosis occurring among native races show that if they had had no previous contact with the infec- ‘tion they were exceedingly susceptible and tended to develop a severe and generalised form of the disease when they became infeeted. ‘This susceptibility to the disease is increased if the ex- posure to infection is at the same time accompanied by a sudden change in occupation, food, housing, and mode of life. Lyle Cummins (2) maintains that, under their own natural or tribal con- ditions, tuberculosis is on the whole fairly well tolerated by native races and might even assume a more or less chronic type of disease which is amenable to treatment. The American negro has always been more susceptible than the American white man and also de- velops much more frequently an exudative type of disease. This may be due to lack of native or acquired immunity, or environ- mental conditions, but the fact that the pathological findings in white and negro patients dying from the disease are markedly different indicates that there is a true genotypic difference between the two races. A similar, though less pronounced lack of resistance is found in persons coming from the west of Ireland. Oswald (17) has recently contributed a study of the disease among African Native troops in the Middle East which illustrates the acute form of the disease (pneumonic phthisis, glandular enlargement, serous effusion, and miliary spread) which prevailed among them under the conditions of military service during the last war. On the other hand the Chinese and the Jews seem to possess the faculty of developing fibrous and calcified lesions so that those suffering from pulmonary tuberculosis present very chronic disease with dense masses of fibrosis and calcareous deposits. In a careful study made by Goldmann and Wolff (8) of the mortality experienced by Jews in Berlin during two periods of years 1924-26 and 1932-84 the standardised death rate from tuberculosis for the Jews was less than half the corresponding rate for the non-Jews. Age. If figures showing in age groups the incidence of tuber- culosis among the estimated infected population are studied it will be noted that approximately one in every ten infected infants under the age of one develops active tuberculosis, this figure drops to about 4 per 1,000 by the age of two and to 4 per 10,000 by the age of twelve. From this low figure the incidence steadily rises in both males and females to the age of thirty when it falls steadily in females but keeps at about 1-5 per 1,000 males until the age of fifty-five when there is another rise. When considering the relation of age and resistance it is neces- sary to be careful to restrict our remarks to native resistance, for, as an individual grows older, it is more and more probable that acquired resistance will be conferred by the development of the primary complex from contact with the infection. The lack of resistance, both native and acquired, at various ages can be seen from a table which has been extracted from the statistics given by Rich (4) showing the mortality from tuberculosis at different age periods in the general population in the United States and in the estimated infected portion of the population. The figures demon- strate clearly the vulnerability of persons in the different age groups particularly in the first year of life. ‘ | from Tuberculosis iafocted - persons of each age period | | | 0-1 | 496 0:5 | 4,920 1-4 | 1,047 10 123 - 5-9 | 469 ae 18 10-14 | T15 35 19 15-19 | 3,375 A5 . 61 20-24 | 5,752 55 90 25-29 | 6,243 65 87 30-34 5,775 75 "5 35-39 5,448 85 67 40-44 | 5,438 90 69 45-49 5,222 95 66 50-54 5,058 95 73 55-59 4,409 95 | 79 60-64 | 3,641 95 81 65-69 | 2,975 95 | 82 70-74 2,179 95 89 pat | 2,057 | 95 82 | The estimation of the percentage infected has been calculated from recent tuberculin surveys in the United States and is only an approximate figure. In England and Wales sufficient information has not been collected to make such an estimate, but in all probability the number of persons infected in any age group is higher than in the United States. This figure is dependent on several factors among which should be mentioned increased contact with the infection, environment, physiological changes and greater strain of life. All these factors operate at certain periods of life but native resistance is of great significance with regard to the vulnerability of the infant under one year. The ability to overcome tuberculous infection depends on the power of the body to develop acquired resistance. The frequency with which an infected infant develops tuberculosis indicates that either native resistance or the mechanism to produce acquired resistance must be very poor. By the time the child reaches the age of ten, resistance to the disease has become well developed and is generally maintained to a certain degree throughout life. Although fluctuations may occur due to the influence of conditions under which the person lives and of other infections which may change the power of the body to resist invasion by the tubercule bacillus. Frequency of exposure to infection will be further discussed under the section dealing with exogenous and endogenous infection ; here it must be emphasised that once the primary infection has been overcome danger of exogenous infection becomes less, provided that the number of bacilli at any one time is not greater than can be con- trolled by the acquired resistance that has been developed. ‘This is not likely in the ordinary course of events, although it is conceivable that under certain circumstances frequent infection at short intervals could break down the resistance and cause progressively active disease. The rather surprisingly low incidence of tuberculosis in the consort of married tuberculous persons and also in those employed in sanatoria supports the contention that in those age groups the danger from even repeated exogenous infection is not high. On the other hand, as the majority of tuberculous infants become infected by in- halation the accident of exogenous infection must not be ignored. The work of Lloyd and Maepherson’(5) on child contacts shows that in children under five, nurtured in a tuberculous environment, the number of positive reactors to tuberculin was five times greater than in children from non-tuberculous households. Furthermore, there was a contact history in 40 per cent. of 1,000 persons suffering from pulmonary tuberculous between the ages of fifteen to twenty- five and four out of five of the contact cases developed the disease within five years of the exposure to the last known contact with infection. A number of reasons may be given for this, among others, that tuberculous households are often of poor standard and the economic status of the home is often low, and although the main difference between the tuberculous household and any other is that in the former there is usually a constant source of tubercle bacilli which can infect and superinfect all who reside in it, yet the develop- ment of active disease will depend on the individual’s resistance. The rise in incidence during adolescence is due in part to the physiological changes of the body which take place at that time and also the increase in general activity of life under less sheltered condi- tions. It is the age when most persons come into contact with the _ stresses and strains of life for the first time and the many calls on the energy of the individual may reduce the power of resistance. Hypersensitivity. When a normal animal is inoculated with a small number of live virulent tubercle bacilli a small inflammatory area occurs at the site of injection. This disappears in a few days and the tissues return to normal. The lymph nodes draining the infected area become enlarged and inflamed and eventually show signs of necrosis. If the dose of bacilli has not been large, some degree of enlargement of the lymph node persists and a proliferation of fibrous tissue occurs which eventually becomes dense and deposits of calcium become scattered through the lymphatic tissues. Micro- scopically there is a multiplication of bacilli first at the site of entry, with aggregation of leucocytes. This disappears and the infecting organisms pass on to the nearest lymph node where considerable increase in the number of bacilli takes place accompanied by en- largement of the gland and a round-celled infiltration of the lymph node and the surrounding tissues. There follows an increase in the mononuclear and the polymorphonuclear cells. Both these cells take on the work of destroying the bacilli by phagocytosis but the main destruction of the organisms appears to be effected by the mononuclear cells. A struggle then takes place between the white cells and proliferating bacilli, in the course of which some organisms escape and cause a temporary bacillaemia. Some of the blood- borne bacilli set up foci in other parts of the body, or they may be completely destroyed; if the polymorphonuclear cells and the monocytes gain supremacy over the bacilli fibrous tissue cells will surround the tubercules which have formed. These tubercles are the result of an increase in the endothelial cells and the development of giant-cell systems. Necrosis takes place in the centre of the tubercles and a number may coalesce to form a large necrotic area which may discharge its contents, containing live and dead tubercle bacilli along with dead and partially destroyed phagocytes, into an air passage or a blood vessel and thereby form metastases which may lodge and form fresh foci of infection in other parts of the body. On the other hand the tubercles may be completely surrounded by fibrous tissue which becomes denser, and deposits of caletum mark the final healing of the lesion. It is, however, possible that all tubercle bacilli are destroyed in the lymph node. Feldman and Helmholz (6) have investigated the persistence of live tubercle bacilli in these apparently healed lymph nodes by removing them and injecting the material into guinea-pigs. ‘They found that in only five instances out of twenty-nine did the infected animals develop tuberculous lesions, which indicates that in the majority of instances the bacilli are completely destroyed in the lymph nodes of the primary infec- tion. The small reaction at the site of infection and the enlarged ‘lymph node comprise the primary complex and constitute the morbid process which results in a body protected by native resistance to primary infection by tubercle bacilli. In addition to these pathological changes the body acquires the ability to protect itself against further invasions of the tubercle bacilli by an intense inflammatory reaction to the bacillus at the site of invasion, along with the power to suppress the multi- plication of the organism both at the point of entry and at other sites to which it may be conveyed in the body. This development of hypersensitivity towards the tubercle bacilli as a result of the primary infection is one of the most important factors in the mech- anism of defence against the spread of the disease. Another is the development of acquired resistance. Although these two factors often run parallel they are not necessarily dependent on each other. It is possible to have a very high degree of sensitivity and a low resistance to the infection. The exact relationship between these two important characteristics of the infected animal is not known but the whole future of a tuberculous infection depends on the presence and degree of these two acquired properties. It is becoming in- creasingly realised that hypersensitivity and resistance can exist independently of each other, although it is only recently that proof of this has been forthcoming from the biological laboratory. Attempts to establish the relationship have been made by ob- serving the tissue responses to various isolated portions of the bacillus and the power of such components to produce active im- munisation. Raffel (7) has shown that the protein and wax of the human tubercle bacillus regularly induce reactivity to old tuberculin in guinea pigs and although the work is not complete “ sufficient of the criteria have been satisfied to indicate that the hypersensitivity is the same as that consequent to the presence of whole tubercle bacilli in the tissues.” From his latest report it would appear that guinea pigs which have been rendered hypersensitive by means of isolated bacterial constituents do not develop resistance to in- fection with the tubercle bacillus. If resistance can be developed without hypersensitivity a new light will be thrown on the relation of the individual to the infection. From the work of Seibert (8) it appears that it is the protein content of the tubercle bacillus that is mainly responsible for exciting hypersensitiveness, but which cells are responsible for its development is not known. So far it has not been possible to _ transfer hypersensitivity from one animal to another by injection of blood or serum which would seem to indicate that it is not due to a specific antigen circulating in the body fluids. Variation in hypersensitivity frequently occurs if the tuberculous disease is complicated by rubella, or whooping cough, when it be- comes suppressed and may disappear altogether, a similar pheno- menon being noted during the terminal stages of tuberculosis. It is also possible for hypersensitivity to disappear if the tuberculous lesion has been healed for many years, or if the primary infection was slight and healed without causing any macroscopic changes in the lymph nodes. Experimentally hypersensitivity can be depressed and eventually eliminated by frequent small doses of tuberculin leaving a certain degree of acquired resistance. It may be that a similar process of desensitising occurs in those patients, occasionally seen in mental hospitals, who present large healed calcified lesions and a negative skin reaction to high concentrations of tuber- culin. Hypersensitivity can cause a local inflammatory reaction around a previously quiescent lesion if superinfection occurs, but this reaction is generally transitory, and is rarely seen around the primary focus. Acquired Resistance. The primary infection endows a body with hypersensitivity and modifies the manner with which it deals with subsequent infections. The reaction of the tissues to post- primary tuberculous infection has been frequently described and need not be repeated here, although there are certain features which must be stressed in order to appreciate the course of a super- or re-infection lesion. ‘The term super-infection is used to denote a post-primary invasion of the body by tubercle bacilli whilst the lesion caused by the previous infection is still unhealed. By re- infection is understood infection by tubercle bacilli after the primary lesion has completely healed. The previously infected body will — react to subsequent contact with tubercle bacilli by : (a) Prohibiting the growth of the bacillus at the portal of entry and at such other sites to which it may be carried ; (b) causing’ inflammation, phagocytosis, necrosis of tissues, and tubercle formation at the site of infection ; (c) preventing the main reaction from reaching the lymph nodes which will show no appreciable enlargement in contrast to their reaction in the case of the primary infection ; and (d) by causing proliferation of fibrous tissue around the lesion which will show alternate healing and progression and a tendency to metastasise by haematogenous and bronchogenic spread. The ability to create a barrier to the progress of the bacilli at the site of entry, and the attempt to heal the local lesion without in- volvement of the neighbouring lymph nodes, can be ascribed to resistance acquired as a result of the primary infection. The de- velopment of this resistance takes place soon after the primary complex has been established; any extension, therefore, of the infection either by haematogenous or bronchogenic, or direct spread from the primary complex, even if it occurs shortly after the primary infection, will cause lesions to develop of a reinfection type, as determined by the hypersensitive tissues and the presence of acquired resistance. For this reason it is very rare to find more than one primary focus. Two primary foci of different ages could only occur if resistance and hypersensitivity disappeared at some period following the complete healing of the primary complex. As this is unlikely, almost all lesions developing after the formation of the primary complex will be of the reinfection type. A true progressive primary lesion can occur if hypersensitivity and acquired resistance are absent or develop very slowly, and may be seen when the infecting bacilli are numerous and the body has not developed its mechanism for the production of antibodies; a state that is met with in very young infants. In such cases the whole lesion is rapidly progressive and little or no attempt is made to inhibit the multiplication of the bacilli or arrest the progress of the pathological changes in the tissues. In the majority of lesions that appear to show progressive activity following the primary infection hypersensitivity has developed and some acquired resist- ance is present, but of such low power that the disease progresses rapidly, with acute inflammation, necrosis, and tubercle formation, characteristic of the re-infection type. Although progressive primary complexes are not uncommon in children, they only occasionally occur in adults, but cases have been recorded by Koester (9) in» which the infection has assumed a malignant form rapidly causing the death of the patient from generalised tuberculosis. In these cases there is usually no calcification of the lymph glands which remain soft and. caseous, with cavitation developing in the primary focus. Terplan (10) records an apparently primary progressive phthisic form of pulmonary tuberculosis in a senile person aged ninety, in which no remnants of a primary complex could be found and no calcified scars discovered in any part of the lungs. The fate of a primary infection depends on the virulence and size of the dose, age of the host, environment, and conditions of life after infection and the presence of any native resistance to the infection, strengthened by acquired resistance which develops as a result of the infection. If we consider the four variables : (1) Number of bacilli, (3) degree of acquired resistance, (2) degree of native resistance, (4) hypersensitivity, it is possible to give an indication of the development of the lesion under certain circumstances. Generally speaking, one of five possibilities may occur, these have been outlined as episodes that may occur when infection takes place ; there are other combinations of the variables, but those described illustrate the main principles of the pathogenesis of tuberculosis. It will be seen that the future of any tuberculous infection depends mainly on the number of bacilli invading the body and the power of the body to suppress the multiplication of the bacilli in the tissues, or in other words the ability of the tissues to develop acquired resistance. 4 Episode I, Native resistance low or absent, the body without hypersensitivity and the number of bacilli large. At the site of infection slight inflammatory process will occur. Rapid transfer of the tubercle bacilli will take place to the nearest lymph node. This will enlarge, and the bacilli will multiply and eventually escape into the blood stream. Hypersensitivity of the tissue usually develops, but as the native resistance is low, the acquired resistance, if any will be poor, so that there will be little inhibition to the multi- plication of bacilli wherever they may lodge in the body. Inflam- mation, necrosis and tubercle formation will occur at these sites and a state of acute miliary generalised tuberculosis will develop. If the number of invading bacilli is small, the progress of the disease will depend on the rapidity with which acquired resistance is developed. If this is rapid, then the growth of the bacilli will be inhibited and a more chronic type of miliary spread will occur with enlargement of the lymph nodes and a localisation of the bacilli to certain organs and hence a more limited distribution of the tubercles. Episode II. Native resistance high, hypersensitivity absent, and the dose moderate or small. | There will be slight inflammation at the site of infection with round-celled infiltration, and formation of fibroblasts. Bacilli will travel to the nearest lymph nodes where some enlargement will take place and considerable phagocytosis of the invading bacilli by polymorphonuclear and mononuclear cells will begin. Suppression of the growth of bacilli will be vigorous with the formation of giant cells and fibroblasts. Some necrosis and tubercle formation may occur, but eventually the invading bacilli will be shut off by fibrosis and calcification. Hypersensitivity will have developed, and with it a high degree of acquired resistance. A healed primary complex will result. Calcification and complete healing with sterilisation of the lesion, both at the site of infection and in the lymphatics connected with it, may result eventually with desensitisation of the body, but acquired and native resistance are still maintained so that if re- infection occurs hypersensitivity will soon be established. Some- times there are, however, some live tubercle bacilli left in the lymph node although the primary focus may be completely sterile. These live bacilli may escape and cause endogenous reinfection with tubercles wherever they may lodge in the tissues, but such lesions are usually well controlled and form isolated tuberculous foci within a limited area. The course of the lesion at the site of infection is interesting in that when hypersensitivity develops, if live bacilli are still present and active the lesion will take on the characteristics of tubercle formation with necrosis and inflammation and will heal by fibrosis and calcifica- tion which will show in the X-ray film. If the infecting dose is very small and complete sterilisation occurs locally at the site of infection before hypersensitivity has developed the lesion will heal rapidly and may be so small that eventually it is completely absorbed and no trace can be seen on the X-ray film or at autopsy. But if the invasion of bacilli is large, some will escape into the blood stream and form isolated foci in the lungs which owing to the high native and acquired resistance will heal by fibrosis and form fibrous. scars usually at the extreme apices of the lungs and may be seen in skiagrams as Simons foci. Some viable bacilli may remain enclosed in these foci and remain as potential sources for future endogenous infection if the level of the resistance is lowered. Episode III. Infection in a body with high native resistance, acquired resistance and hypersensitivity. This will be a post- primary infection and may be endogenous or exogenous. If the number of bacilli is small there will be a fairly intense localised inflammatory reaction, where the bacilli are caught up in the lung tissues, which will pass on to tubercle formation, necrosis and giant- cell formation. Some perifocal localised pneumonia may occur and a well-defined area will be seen in the X-ray film. This will soon resolve and healing will take place by fibrosis and an Assmann’s focus may become evident. This may heal completely or by har- bouring live bacilli form an area from which metastasis may occur in other parts of the lung if resistance is lowered. If further infection takes place, due to liberation of bacilli from the rupture of an infected lymphatic node, other discrete areas of tuberculous inflammation will occur which may progress if resistance has been lowered and eventually develop into progressive disease with extensive infiltra- tion of the tissues showing localised pneumonic patches with tubercle formation. Further extension of necrosis, and coalescing of the tubercles, will cause cavitation to develop and typical fibrocaseous ulcerative tuberculosis will be the result. Episode IV. Infection in a body with moderate to low oe resistance and hypersensitivity. The bacilli may be disseminated in the lung tissues by haemato- genous or bronchogenic infection and at each point where they settle they will continue to multiply for a time. Acquired resistance will increase but not before considerable necrosis and inflammation occur. Considerable areas will be involved depending largely on the magnitude of the infection. If a large number of bacilli have been liberated from a caseous lymph node an extensive ulcerative process will develop with cavity formation. If the number of bacilli is very large, complete consolidation of a lobe by exudative pneumonia may occur in which bacilli will multiply and by bron- chogenic spread will form fresh foci of tuberculous inflammation in other lobes. Episode V. Repeated small infections in a body with completely healed primary lesion, with high-grade native and acquired resist- ance and with hypersensitivity low or absent. Although hypersensitivity is low or absent it would soon be restored by repeated small infections. If acquired resistance is depressed by the repeated infections, small necrotic foci will appear at points to which the bacilli are carried either by the blood stream or the air passages. As resistance is high, the multiplication of the bacilli will be suppressed. Healing at each focus will take place by fibrosis and eventually some calcium will be deposited in the majority of the localised tubercles. There will not be much peri- focal pneumonia owing to the low degree of hypersensitivity so that a picture of chronic miliary tuberculosis will be seen in the X-ray either confined to a limited area or generalised through both lungs depending on the number of bacilli liberated or invading the body. ‘The general changes that take place in circumstances of controlled and uncontrolled infection have been diagrammatically represented in figure 1. It has not been possible to demonstrate the many developments which occur as a result of varying degrees of native and acquired resistance, but the simple diagrams present the main principles which govern the changes that take place when tubercle bacilli invade the body. With these considerations in mind it is possible to envisage the clinico-pathological states which characterise the initial tuberculous infection in children and young adults. Dorothy Price (11) has depicted the fate of the primary complex as follows :— Healing. By fibrosis and calcification (visible and invisible to X-rays) (i) Immediate. (ii) Delayed, Non-healing. She recognises several forms : (i) Caseous pneumonia—although death from toxaemia not uncommonly results the prognosis is not universally unfavourable and some children recover. Cavitation in the primary focus may occur and bronchogenic spread from the cavity to healthy parts of the lung is a danger. (ii) Involvement of mediastinal glands. (iii) Haemic spread from mediastinal glands via the thoracic duct. . (iv) Haemic spread from the primary focus to a gland. (v) Rupture of a caseous gland into a bronchus, giving rise to an aspiration caseous pneumonia. Richards (12) has made an important contribution to the subject. He followed up 445 children admitted to the wards of the Highwood Hospital, London County Council, 387 of them suffering from primary pulmonary tuberculosis and the remaining 58 from pleural effusion. The complications of the primary infection which he encounted were as follows :— Atelectasis. This proved to be more common in the younger than the older children ; he found it in 50 out of 239 children under 5 years of age (or 20:5 per cent.). Tuberculous caseous pneumonia. ‘This occurred in 2-5 per cent. of total admissions and 8 out of the 11 cases recorded died. ‘The younger the child the more lethal was this form of the disease. Lung spread from primary focus. 'This was observed in 6-25 per cent. of total admissions. Pleural effusion. Pleural effusion occurred in 15 per cent. of all admissions. Miliary tuberculosis. Noted in 1-8 per cent. of the whole series. The author quotes Fish (13) as observing that the position of the affected glands is important. These examples in which the high paratracheal glands were affected were especially liable to haemic spread. Other complications. Other complications seen include: menin- gitis, infection of the abdominal glands, enteritis, ischio-rectal abscess, tuberculosis of cervical glands, bone and joint implication, phlyctenula conjunctivitis, and erythema nodosum. There were 16 deaths in the series and Richards analysed these according to age groups. Three children under 1 year died, one with miliary tuberculosis, and 2 with meningitis. Seven died between the ages of 1 and 2 years, all from caseous pneumonia. Three died between 2 and 5 years, the causes being caseous pneumonia, acute miliary tuberculosis and meningitis. Two children died between 6 and 9 years, in both instances from meningitis. One child over the age of 10 years died from miliary tuberculosis following an effusion. Finally Richards concludes that in the child under 6 years primary pulmonary tuberculosis takes a longer time to become arrested than in older children. The Pulmonary Lymphatics and Infection. From the site of infection the bacillus finds its way into the lymph vessels. The distribution of this system in the lungs becomes of primary import- ance in the study of the development of the disease. The observa- tions of Snow Miller (14) indicate that the flow of lymph in the bronchial and arterial lymphatics is towards the interior of the lung; but that beyond the alveolar ducts no lymphatics are found and no lymphatics are present in the walls of the atria or sacculi alveolares. ‘There appears to be a narrow zone just below the pleura which averages between 2 and 3 millimetres in depth, in which the lymphatics situated in the septa, arising from the pleura and mark- ing out the secondary lobules, are provided with valves which open outward, i.e. towards the pleura. The only communication between the superficial (pleural) lymphatics and the deep (pulmonary) lymphatics takes place at the medial border of this zone, but the presence in the pulmonary lymphatics of valves which point towards the pleura prevents the flow in the pleural lymphatics from entering the lung. The pleural lymphatics eventually unite to form main trunks which together with the lymphatics coming from the interior of the lung along the pulmonary veins enter the tracheo- bronchial lymph nodes. From these details we are able to understand the connection between primary infection and pleural involvement which may lead to pleural effusion. If aerogenous infection reaches the terminal alveoli beyond the alveolar ducts and lodges in that sub-pleural a Se Sloss) la nd 2 years, all from caseg OU ears, the causes bej Sis and meningitis, 9 years, in both instances from NY Caseoys s died from miliary tuberculosis 1 the child under 6 years primary er time to become arrested than and Infection. From the site ngs becomes of primary import- nt of the disease. The observa- that the flow of lymph in the is towards the interior of the ducts no lymphatics are found she walls of the atria or sacculi arrow zone just below the pleura llimetres in depth, in which the ising from the pleura and mark- rovided with valves which open 1e only communication betwee! os and the deep (pulmonary) al border of this zone, but the 2s of valves which point towards leural lymphatics from entering n eventually unite to form 7 - lymphatics coming oe e tracheo onary veins enter th y lea 5 the termina -pleura s—N x é trolled doses ¢ bacilli ent or lar uncon of tubercl Invasion by ae | eae Boe Re freq Natural resistance will Gf f with A cted bod no sensitivity to tuberculin (S) Yfe natural resistance (NV) Unin small by natural measuved b of TR clion or dose infe infe Te, ction of B.C.G. gp ad ihe Bie! eae | Invasion CONTROLLED ee Se P > ] ’ 7 7 ) g : : ts , J i , J zone from which the lymphatics drain towards the pleura, then, if hypersensitivity has developed, an acute serous reaction of the pleura may be expected when the bacilli carried by the lymphatics outward to the pleura reach the sensitive membrane. Eventually the infection will be carried along the pleural lymphatics to the main trunks which unite with the internal pulmonary lymphatics and the infection will then be carried to the tracheobronchial lymph glands. It is possible, therefore, for pleural effusion to be a mani- festation of a primary infection. It also may occur as a post- primary infection from haematogenous or bronchogenic spread to the terminal alveoli when tubercules will form in the subpleural tissues and cause pleural involvement either by direct extension or through the pleural lymphatics. Epituberculosis. The term “epituberculosis”’ has caused much confusion, owing to the various pathological states to which it has been loosely applied. Radiographically it is seen as a dense fan-shaped shadow that “ flares ”’ out from the hilum. It is unilateral and often clears in a comparatively short time leaving a little haziness or in some cases no trace of its presence at all. In children it often occurs without any major constitutional disturbance, but in adults the reaction is usually more severe. Three explanations have been given to account for the lesion : That it is an atelectasis produced by pressure of enlarged lymph nodes on a bronchus. . That it is a resolving tuberculous pneumonia caused by the rupture of a lymph node into a bronchus producing a localised lobular pneumonia by the aspiration of a limited number of tubercle bacilli in the lung of an individual with high-level acquired resistance. That it is a perifocal pneumonia caused by the reaction of hypersensitive lung tissue to a reinfection by tubercle bacilli. Rich claims that tubercle bacilli can be recovered from such lesions and also that experimentally the introduction of heat-killed bacilli into the bronchus of a hypersensitive animal produces lesions that appear to be similar to those classified as epituberculosis. He also states that a small number of live bacilli can produce a similar result. Burton Wood (15) in his observations on the condition favoured the atelectatic theory, and the work of Richards at High- wood Hospital, Brentwood, indicates that when obstruction of the H. & R. TUBERC. 2, bronchi is relieved by cauterisation of granulations the atelectatic condition of the lung disappears in certain instances. There is very little evidence that the condition is due to a perifocal pneumonia and it is probable that both the first and second causes operate. Endogenous and Exogenous Infection. It must be under- stood that by primary infection is understood the first contact of the tissues with the bacillus. Post-primary infection is any subsequent infection. ‘This may be exogenous, in which case it is a fresh infection from without, usually by inhalation or ingestion; or it may be endogenous, in which no fresh invasion occurs from outside the body but infection comes from the reactivation and breakdown of a focus already in the body, in both cases a re-infection type of lesion will develop. The general process of primary infection has been carefully observed and the development of a primary complex consisting of the lesion at the site of invasion and the subsequent changes in the nearest lymph node or gland are well known and have been — accurately described, but there is still considerable controversy over the development of the post-primary lesion either by exogenous or endogenous infection. R. C. Wingfield suggested that ‘‘exogenous infection causes endo- genous exacerbation ”’ and this may be true in the case of the re- activation of old apparently healed post-primary lesions. Pagel (16) feels that in those cases where bronchogenic tuberculosis ensues within a short period of late primary infection, with the formation of haematogenous foci at the extreme apex of the lung (Simon Foci) and the development of post-primary caseous changes in the infra- clavicular region (Assmann foci), are strong circumstantial evidence that these manifestations are affiliated to the primary focus, and are due to haematogenous dissemination from it. He thinks that endogenous reinfection does occur from comparatively fresh primary foci, particularly in the young adult. Most observers agree that it is exceptional to find more than one primary focus in the lungs, and that the majority of such foci heal completely in children but sometimes leave a reservoir of infectious material in the lymphatic glands draining the site of the infection. These residues of the primary infection may become re-activated and the rupture of an infected lymphatic node or gland into the bronchial system will cause a bronchogenic spread of endogenous origin. Pagel’s experiments show that in animals re-infection by intravenous or intracheal injections usually cause massive localised infections in animals previously infected by an avirulent strain of tubercle bacilli, whereas, the same dose of virulent organisms in a normal animal produces invariably generalised miliary tuberculosis. There is definite proof that tuberculous lesions can be. caused by both exogenous and endogenous infection. When a lesion occurs in an internal organ as a complication of pulmonary tuberculosis it must be the result of endogenous infection, the spread of the disease having occurred through the blood stream. There is, there- fore, no reason why metastasis should not also occur in a similar manner in the lungs. On the other hand, the primary infection is always exogenous and therefore if such a means of access to the body occurs once, it can occur again, although on the second occa- sion it may cause only a minor lesion unless the number of bacilli is very large and frequent infection takes place. From animal experiments it is doubtful whether tubercle bacilli can penetrate the mucous membrane of the bronchi but must reach the alveoli in order to gain access to the lungs. It is improbable that large quantities of bacilli can reach the alveoli by inhalation so that exogenous infection is less likely in adults than in young children. In young children the air passages can admit particles of fine dust to the alveoli more easily than in adults so that exogenous infection is more probable. It is also well known that a tuberculous bacillaemia takes place in both with primary and post-primary lesions. It is, therefore, more probable that endogenous infection is responsible for reactivation of the disease than exogenous infection. Although reactivation of the lymph node element of the primary complex may cause haematogenous or bronchogenic spread of the infection by erosion into a blood vessel or a bronchus, it is not easy to explain why the lymph node becomes reactivated except that there may be a fall in the level of the resistance to the disease through environmental causes or other infections. On re-infection some perifocal activity may occur around old lesions due to the hypersensitivity of the tissues, but such a reaction does not produce tubercules and usually is only of a temporary nature. The whole problem of endogenous and exogenous infection still requires much investigation : useful though these terms have been it may be now that Gloyne (18) is right when he says: ‘* Conclusions must be tentative, but one thing seems clear : the terms endogenous and exogenous have served their purpose and should disappear.” References (1) UstveptT, H. J. (1942) Pulmonary tuberculosis. London. (2) Cummins, S. L. (1946)-Empire and colonial tuberculosis. London. (3) GoLDMANN, F. and Wo trr, G. (1937) Lancet, 1, 1295 (Extract). (4) Ricu, A. R. (1946) The pathogenesis of tuberculosis. 2nd Ed.  Lllinois, p. 217. (5) Luoyp, W. E. and Macpuerson, A. M. C. (1936) Brit. med. J. 2, 1131. (6) FELDMAN, W. H. and Hetmuorz, H. F. (1945) Amer. J. Dis. Child. 70, 201. (7) RAFFEL, S. (1946) Amer. Rev. Tuberc. 54, 564. (8) SEIBERT, F. B. (1941) Amer. Rev. Tuberc. 44, 1. (9) Koester, F. (1940) Z. Tuberk. 84, 147. (10) TERPLAN, K. (1945) Amer. Rev. Tuberc. 52, 155. (11) Price, E. D. S. (1942) Tuberculosis in childhood. Bristol. (12) Ricwarps, W. F. (1944) Tubercle, 25, 60. (13) Fisu, R. H. (1937) Arch. Dis. Childh. 12, 1. (14) MriLuER, S. (1937) The Lung. Illinois, p. 110. (15) Woop, W. B. (19389) Tubercle, 20, 205. (16) Pace, W. (1939) Brit. med. J. 2, 791. (17) Oswatp, N. C. (1946) Thorax, 1, 100. (18) GLoynE, S. R. (1946) Brit. J. Tuberc. 40, 938. CHAPTER III PREVENTION THE two main principles of prevention are the destruction of the infecting power of the organism and increasing the resistance in the host. The first implies finding and rendering the bacillus innocuous, or reducing the possibility of contact with it. It is known that the main vehicles of transmission of the bacillus in human infection are sputum and milk. There is also a considerable amount of information on. the viability of the organism and the conditions under which it cannot exist outside the body. Yet in spite of the possession of this knowledge the prevention of the spread of the infection still remains a difficult problem. This is mainly due to the ubiquity of the germ and the difficulty of collecting and destroy- ing the infectious material. The perversity of human nature also mitigates the success of many of our efforts and in all preventive work the systematic education of the public in methods of self- protection is of paramount importance in order that full benefit from investigation and research may be reaped. A primary move in prevention is to search for the tubercle bacillus and in all patients with symptoms of chronic respiratory disease a thorough examina- tion should be made of the sputum for the tubercle bacillus. In suspected cases it is not sufficient to be content with a negative on the examination of a smear preparation, but further search should be made by concentration methods and finally by culture or animal inoculation. The Joint Tuberculosis Council published in 1936 a memorandum which gives details of the various methods of demonstrating tubercle bacilli in sputum by the microscope with an account of sources of error which may lead to an incorrect report (1). These are mainly due to insufficient cleansing of glassware, the use of tap water which often contains acid-fast saprophytes, and thirdly the contamination of the oil immersion lens by bacilli which become dislodged from a positive slide. The memorandum concludes that a definite diagnosis should not be made on the finding of a single bacillus, or even of a single clump of bacilli. Search for the bacillus must be made in urine, faeces, stomach contents and material collected by means of the laryngeal swab. This latter method is simple and produces a high percentage of positive results in active cases. The technique of Nassau (2) is given in detail on page 76. Although not directly concerned with the search for the bacillus recent work on the morphology, culture and life history of the organism assists in the development of means to combat infection. A wide field of investigation has been opened up in photomicro- graphy by use of the ultra violet and electron microscopes and work is proceeding at the Medical Research Council’s Laboratories on the tubercle bacillus, using these instruments. The exact signifi- cance of the various structures seen in the photomicrograph of tubercle bacilli is not known, but certain features appear so frequently that they may be taken as having a bearing on the life history of the organism. ‘The electron microscope is as yet only being used by a limited number of pathologists and its use in tuber- culosis has not been investigated, but those who are interested are referred to the description of the apparatus by Donovan (38). Brieger and Honor Fell (4) have studied the development of the avian bacillus in centrifuged embryo extract in large hanging drop preparations. ‘They have determined four stages in the life cycle of the organism. First a stage of elongation is followed by one in which the elongated rods divide into branch-like structures. In the third phase these break into short rods and finally the development of mycelial forms completes the cycle. Hunter (10) also found complex branching forms of tubercle bacilli in sputum by direct smear examination, thus confirming that the organism belongs to the Streptotricheae or higher bacteria. Of more importance from the prevention and treatment side is the resistance which the bacillus exhibits to various chemothera- peutic agents both in vitro and in vivo. From a summary by Gardiner Middlebrook (5) on the experi- mental work done in this direction with the sulphonamide group of compounds it would seem evident that the agent must be able to penetrate the peripheral structure of the bacterial cell in order to reach the susceptible nucleus. This power of penetration depends on the presence of a chemical structure similar to para-amino- benzoic acid, with additional links that are easily dissociated into particular groups which have the power of attacking the cell nucleus ; this must be susceptible to the continued action of these groups. The continued action is stressed because there is evidence from experiments in vivo that the tubercle bacillus has the power to develop an increasing resistance to sulphonamide preparations so that the hope of being able to eliminate the bacillus from the host with such substances cannot be sustained. As Middlebrook points out, the future may lie in the employment of two or more anti- bacterial agents in our attack on the disease, but at present although research is proceeding along the right lines, much more knowledge is required of the many variable factors which enter into these bio- chemical reactions before our hopes can be achieved. (See also page 121.) The Habitation of the Bacillus. The tubercle bacillus may be found in any of the discharges or excreta of the person suffering from tuberculosis. It is, however, in the discharge from the pulmonary lesion in the form of sputum that the living germ usually escapes from the body and is transmitted to other persons. Many may leave the body through the faeces, but in civilised countries, with adequate sewage disposal systems, very little trans- mission of the infection occurs in this way. Pus from discharging sinuses and tuberculous ulcers occasionally contains tubercle bacilli but by no means as frequently as sputum, and such discharges are usually collected on dressings and burnt. We therefore may con- clude that the main habitat of the bacillus outside the body is sputum, saliva and nasal discharges from infected human beings, and milk from tuberculous cows. In 1945 a report was published by the Committee of the London Sector Pathologists (6) on the demonstration of tubercle bacilli in infected material. The report covers the collection of material and the various methods of examination giving details of the technique in each case. The Sputum Problem. There were 71,997 persons in England and Wales on the dispensary registers in 1938 who had at some time coughed up sputum containing tubercle bacilli which, if not properly collected and killed, could infect other individuals and cause active tuberculosis. In the control of this infectious material lies one of the major public health problems of tuberculosis. In an institution the routine collection of sputum and its proper disposal is a simpler matter than in the home, although in many places very crude and unsatisfactory practices are in operation. Excellent steam sputum sterilisers are made by a number of firms : in one type the mugs and flasks are collected on special trays, lids and stoppers are removed, and all are placed in wire trays for sterilisation. These are put on shelves which can be rotated within a disinfecting chamber under high pressure steam and afterwards washed by jets of hot water ; the whole operation taking place with the minimum amount.of handling of the mugs and flasks by the operator. When the utensils come out of the chamber they are both sterilised and washed ; the disinfecting chamber can be washed out and the sterile contents flushed down a closed drain through an outlet pipe. It must be emphasised that any article which comes into contact with sputum or saliva may carry the infection. Attention, therefore, must be given to sterilising cutlery, crockery, handkerchiefs, and such refuse as cigarette ends and apple cores must be collected and burnt. The disposal of infectious material in the home is not so simple, but is of equal importance. Whether the sputum is collected in mugs and boiled or absorbed by paper or linen handkerchiefs and burnt, the method must be thorough and the danger of allowing drops of infectious material to scatter must be prevented, particularly if children are in the home. ‘The National Association for the Pre- vention of Tuberculosis issues pamphlets which contain clear and simple instructions on the problem of collecting and destroying infectous material in tuberculous households. Danger can only be evaded by the education and active co-operation of all concerned. Work has been proceeding on the viability of the tubercle bacillus under certain conditions and from these experiments it has been found that a pure culture of tubercle bacilli on clothing is killed by dry cleaning by the Stoddard solvent cleaning method. Other means of sterilising articles are given as follows :— Ordinary woollens Dry heat at 250° F. for 30 minutes. Mattresses . . Cotton materials . Ordinary laundering. Toys filled with kapok or cotton Dry heat at 300 to 400° IF’. for 30 minutes. Cotton goods not colour fast . Dry heat at 300 to 400° F. for 20 minutes. Unclean bottles . 3 per cent. alkali solution of which not less than 60 per cent. is sodium hydroxide, for 10 minutes at 130°. 99 99 99 Formaldehyde vapour for sterilisation (7) is falling more and more into disfavour as it only accomplishes surface disinfection. MILK | A A report by Roodhouse Gloyne and others to the Joint Tuber- culosis Council on the disinfection of books used by tuberculous persons concludes that the probability of living tubercle bacilli being deposited on books read by consumptive patients is high, and in the ease of children the risk is probably real, but the chance of their causing infection of an adult is very small. Dry heat appears to be the only form of active sterilisation applicable to books at economic costs. It is, therefore, recommended that cheap books and much soiled books should be destroyed (and not sent for salvage) and that other books known to have been exposed to infection should be set aside for a period of one month or more before being used, as the experiments of Kenwood and Dove (8) indicate that at most a minute proportion of bacilli in sputum remain alive after one month — in the dry state. Milk. There is no subject upon which the medical profession are more unanimous than that of the necessity for the production and supply of clean safe milk throughout the whole country. It is stated, on the evidence of the tuberculin test and post mortem examination, that 40 per cent. of the milk cows of England and Wales are tuberculous. The incidence of infection increases with the age of the cow and about 0-2 per cent. of cows have clinically recognisable tuberculosis of the udder. As tuberculous cows secrete tubercle bacilli either continuously or intermittently in the milk, the faeces, and discharges from the lungs, it is easy to understand how the infection is transmitted from one cow to another even though they may be in open fields. An average of 6-7 per cent. up to 20 per cent. of samples of raw market milk are infected with virulent bovine bacilli and about 2,000 deaths occur every year, mainly in children, from tuberculosis of bovine origin. Griffith (9) from 1930 onwards typed the bacillus in a large number of cases of tuberculosis and his results are summarised in the tables on page 42, which show the significance of bovine infection, particularly in tuberculosis of the lymphatic and central nervous system. The work was followed up by Munro (11) in Scotland, and by Cutbill and Lynn in England (12). The latter found that the number of cases of pulmonary tuberculosis due to bovine type bacilli among 2,101 cases in a sanatorium, was 2:28 per cent., and of these in 33 per cent. infection occurred most probably from milk. Evidence of infection by direct contact with cattle was strongly suggested in 21 per cent. of the cases. / TABLES SHOWING THE INCIDENCE OF BOVINE TUBERCULOSIS ACCORDING TO SITE AT AGE (Griffith) ENGLAND. ALL AGES 0-4 YEARS | 5-15 YEARS Variety of ee => L — | Tuberculosis No. of % No. of | % No. of % Cases Bovine Cases Bovine Cases Bovine Wien Mh) Ne Rte bie bo SE Ta Cervical Glands . : 116 | 45°7 | 21 | 85:7 | 54 48-1 Lupus : ; oh CTT: 48-6 Th) 674384 87 47-1 Meningeal . Pale 68 ee B0e 1 23 | 84-8 | 29 | 31-0 Bone and Joint . . | 520 | 18-0 88 | 27-3 | 3851 | 18-5 Genito-Urinary . ; ee a Aten 3. | 33-3 Necropsies . : : 188 | 22-3* 101 | 29-77} 55 14:37 Pulmonary : . | 492 0:8 Rant aa a Miscellaneous ; 23 8-7 3 | 33°38 | 11 9-1 * Including 4 cases where human bacilli were also present. + Including 1 case where human bacilli were also present. SCOTLAND. ALL AGES 0-4 YEARS 5-15 YEARS Variety of b=. eae <er Tuberculosis No. of Hh No. of % No. of ov Oases Bovine Cases | Bovine Cases Bovine Cervical Glands . : 144 | 73°6 53 84-9 rok 74-6 Lupus : : 13 | 53-8 8 | 100-0} 5 | 60-0 Meningeal . ; . 15 13-3 12 16-7 3 — Bone and Joint . : 196 42-8 86 60-5 65 38°5 Genito-Urinary . , 22 | 91 |; — — 5 | 40-0 Necropsies . é oa eke PL a 201 33°37) 46 32-0 Pulmonary . ; 548 3°8* | — fnke BPE LE none — Miscellaneous. oa 9 | Gash 1 | 100-0 | 8 | 75-0 * Including 1 case where human bacilli were also present. t+ Including 2 cases where human bacilli were also present. The work of Blacklock (18) indicates that rural inhabitants are more liable to bovine infection in Scotland than those in urban MILK AB areas. The percentage for cerebral tuberculosis of bovine origin was found to be three times higher in rural than in urban cases and ‘in tuberculous méningitis 8 per cent. were infected with bovine strains in the large burghs and cities of Scotland as against 15-9 per cent. in the rural areas and counties.” From England similar evidence comes from the deaths due to abdominal tuberculosis under 5 which is nearly always the result of bovine infection. DEATH-RATES FROM ABDOMINAL TUBERCULOSIS PER MILLION CHILDREN UNDER 5 YEARS OF AGE LIVING IN EACH AREA. 1921 1930 1938 1944 London Adminis- trative County . 136 (51) 24 (8) 12 (3) 6 (1) Combined County Boroughs . . | 487 (490) 157 (166) 63 (57) 35 (32) Combined Urban Districts . . | 866 (390) 134 (189) 77 (66) 42 (42) Combined Rural Districts . . | 252 (176) 92 (57) 63 (31) 60 (37) These death rates summarised by Letham (14) give a good indica- tion of the prevalence of bovine disease in different areas; the difference between urban and rural districts is strikingly demon- strated and is directly connected with the degree of pasteurisation of the milk supply of the respective area. The need for action to prevent infection by the bovine bacillus through milk is obvious, but the effort to obtain a safe milk supply free from the virulent tubercle bacilli has not yet been successful. This is all the more surprising in that the immediate remedy is to pasteurise all milk which may be infected. Pasteurisation may be carried out by two methods. The positive holder method, which has received the recognition of the legislature by being defined in the Milk Order, 1923, as “ retained at a tem- perature of not less than 145° and not more than 150° F’. for at least half an hour and be immediately cooled to a temperature of not more than 55° F. The other method by heating the milk to a high temperature for a short time (H.T.S.T.) demands that the milk is kept at not less than 162° F. for at least 15 seconds and then cooled to a temperature of not more than 55° F. To be effective both methods require to be carefully and accurately carried out. Milk that is efficiently pasteurised is negative to the phospha- tase test of Kay and Neave (15). ‘This test depends on the fact that the tubercle bacillus is destroyed more quickly than the enzyme phosphatase. Pasteurised milk, therefore, that is found free of phosphatase may be for all practical purposes considered free from pathogenic organisms. Since 1936 milk has been graded as follows : Tuberculin Tested, to which the word “‘ certified’ is added if bottled on the farm, and the word ‘“ Pasteurised ” if subjected to the requisite heat treatment. Accredited and if bottled on the farm, ‘‘ Accredited Farm Bottled.” Pasteurised. These terms are intended to simplify those of the Milk (Special Designations) Order of 1923 when the grades were: Certified ; Grade “‘ A” Tuberculin Tested ; Grade ‘“‘ A”; Pasteurised ; but as Wilson points out in his recent book: The Pasteurisation of Milk, ** Accredited ” milk may be just as heavily infected with tubercle bacilli as ungraded milk ; and the Tuberculin Tested milk may be just as heavily infected with Br. abortus as ungraded milk. The naming and renaming of the various grades of milk can never eliminate the necessity for efficient pasteurisation so long as cattle produce infected milk. It must not, however, be forgotten that contamination of milk may occur after efficient pasteurisation, and the sterilised product must be handled in such a way as to prevent this occurring. Persons suffering from tuberculosis must be rigidly excluded from handling milk at any time and an efficient method used for the cleaning and sterilising of all bottles and apparatus connected with the collecting and distribution of milk. The Milk and Dairies Order, 1926-88, and the Milk (Special Designation) Regulations have taken these considerations into account and must be executed and enforced by local authorities. The subject is so important in the prevention of tuberculosis that the principal regulations are quoted. Registration.—No person may carry on the trade of cowkeeper or dairyman or use any farm or other premises as a dairy unless he and the premises are registered with the local authority. <A local authority may, in the case of persons applying to be registered, or registered as retail purveyors of milk, refuse to register, or cancel the registration if they are satisfied that the public health is, or is likely to be, endangered by any act or default of the person concerned. A person aggrieved by any such decision may appeal to a court of summary jurisdiction. Conditions and Methods of Production. 'The Milk and Dairies Order, 1926, contains a series of provisions with regard to cleanliness and methods of production, etc. For example, certain requirements are laid down for the lighting, ventilation and cleansing of cowsheds and buildings used for keeping milk, and for methods of milking. Requirements are also laid down for cooling and for preventing the contamination of milk, and for the cleansing of all churns, vessels or other utensils with which milk may be brought into contact. [* Conveyance, Distribution, etc. Special provisions are laid down with regard to cleanliness and avoidance of contamination of milk in connection with premises used for the sale of milk and in connection with its conveyance and distribution. Infected Milk. A supply of milk may be temporarily stopped if the Medical Officer of Health has evidence that infectious disease has been caused by it, or that the milk has been infected with such disease. It is further an offence to sell for human consumption or use in the manufacture of products for sale for human consumption the milk of a cow which has given tuberculous milk or is suffering from certain specified animal diseases. Milk (Special Designations) Regulations. These regulations establish three grades of milk for which the special designations are tuberculin tested, accredited, and pasteurised. It is unlawful to sell milk under these desig- nations except in accordance with a licence. Licences are granted, for dealers, bottlers and pasteurising establishments, by borough, urban and rural dis- trict councils. An appeal lies to the Minister against the refusal, suspension or revocation of a licence by a local authority. Tuberculin tested milk is the milk of cows which pass a tuberculin test and a periodical clinical veterinary examination. The milk must also comply with a prescribed test for cleanli- ness and keeping quality. Accredited milk is the milk of cows which pass a periodical clinical veterinary examination, and is subject to the same cleanli- ness test as is tuberculin-tested milk. Pasteurised milk is milk which is treated in accordance with one of two prescribed processes and it must also comply with a bacteriologicial test. Prevention of Contact with the Bacillus. Heat, sunlight, or chemical action are the chief methods for the destruction of the bacillus in sputum and pasteurisation or boiling in the case of infected milk. These methods are comparatively simple and quite effective provided the infected material can be collected and con- trolled. This is not usually possible when the carrier of the infecting focus is a peripatetic and careless human being. However thorough our educational methods may be there will always be times when the most conscientious of patients will make mistakes and may do a great deal of harm in a moment of distraction, particularly if living under crowded and unhygienic conditions. Schemes, therefore, have to be devised whereby the healthy may be separated from the focus of infection. This can be done either by removing the open case of tuberculosis from the healthy or vice versa. The patient may be accommodated in a segregation bed at an economic- ally maintained home or at an industrial colony. This separation from home life has its disadvantages and can be partially overcome by establishing “‘ night sanatoria”’ as has been done in the U.S.S.R. Such institutions provide sleeping accommodation for positive cases who have unsuitable home conditions, or no home at all, and, therefore, remain a continuous burden on the accommodation of the tuberculosis schemes. Similar arrangements in this. country would avoid the necessity for some chronic cases having to find lodgings or to resort to common lodging houses and also in other circumstances, the reception of an open case in a crowded household where there are young children. One advantage of the scheme is that it does not entirely separate the tuberculous person from his family but only removes him during the hours when contact infec- tion is most likely to occur. The removal of healthy persons from the source of infection at present chiefly applies to children. Most local authorities have boarding-out schemes for this purpose, the aim being to arrange for the care of all infants of infectious tuberculous mothers. Ifno healthy relative can be found to look after the child then it is most desirable that other fit persons are found so that the child can be nurtured in a tuberculous-free environment. In the London area the Invalid Children’s Aid Association is most helpful in this respect and, during 1937, 253 children were boarded out under the London County Council’s boarding-out scheme. This arrange- ment enables children of tuberculous mothers to receive care and attention whilst the parent is undergoing residential treatment. When the child becomes of school age it may be admitted to a residential school which provides for its education and, if necessary, open air conditions with medical and nursing attention if the child is debilitated or shows signs of tuberculous infection. In this way children can be protected from the continuous exposure to infection which prevails in most tuberculous households. Of course the CASE-FINDING METHODS AT success of boarding-out schemes depends on locating the sources of infection and that is closely related to our methods of case finding. In fact the prevention of spread of infection is directly related to our knowledge of the incidence and location of the existing sources of infection. : Case-finding Methods. These fall into four categories : (a) Examination of contacts of known cases of tuberculosis. (b) Serial tuberculin testing of children, followed by tracing the source of infection when there is a conversion of a negative to a positive reaction. (c) Mass radiographic surveys. (d) Other radiographic surveys. A contact may be defined as a person who has been living, working or otherwise intimately associating with a person who has notifiable tuberculosis. The duration and intimacy of the association must be recent enough to make it reasonable to suppose that any tuber- culous lesion in the contact is connected with the known focus of infection in the person with whom association has been established. The term frequently is taken to refer only to children, but it cannot be too strongly emphasised that the principal object of contact examination should be to find the source of infection, which not infre- quently is some elderly relation or other members of the household. Lissant Cox said in 1935: ‘‘ Find, isolate, educate and treat the adult positive case ”’ and thus safeguard the child. Where there is a case of tuberculosis all the members of the household should be examined to discover the source of infection. Absence of physical signs does not exclude the possibility of pulmonary tuberculosis. A Mantoux skin test should be made in children and young adults and an X-ray examination in every case except those who fail to react to the tuberculin test. Examining 1,000 “‘ white ” families Opie (16) found that : “* about 75 per cent. of children, under 5 years, contacts of sputum positive cases (Group A), were tuberculin positive as compared with 30 per cent. among contacts to sputum negative patients (Group B). The last figure was only slightly greater, and remained so until early adult life, than in non-contact (Group C). X-ray lesions were dis- covered in 37 per cent. of Group A children (0 to 4 years) but in only 1-2 per cent. of Group B and this difference held good through- out childhood and adolescence.” Similar results were obtained by Lloyd and Dow (17) who found that for an average English working class population more than twice as many exposed children die of tuberculosis within the first year of life as compared with the unexposed, the figures being 1-3 per cent. and 0-58 per cent. and that the percentage death rate within the first five years of life for children who have lived from birth in contact with a parent with positive sputum is 2-6 per cent. a Further important findings by Opie-as regards the after histories of contacts, according to the age at which contact took place, may be tabulated as follows : — ho Number of years between contact and development of tuberculosis Age at which contact took Percentage of those living place developing tuberculosis With ‘‘ Positive” | Sputum cases : 0-9 . : ; 10 | 12-14 years 10-14 . é ‘ 20 | 10-14 years After 15 years “A 10 | 10-14 years With ‘‘ Negative” | Sputum cases’: | | 0-9 ° ‘ , 2 12-14 years After 15 years | £6 10-14 years Previous work by Braeuning and Neumann quoted by Kayne (18) shows that the tuberculosis mortality in contacts varied according to the age at which contact took place. Tuberculosis Mortality Age when contact 7 began with sputum si grew of Positive cases ; Within 1 2 At end of five eer eS is years of contact per cent. per cent. O-l year . =o, 246 6-1 8-1 1—5 years ‘ 569 1-4 1-4 6-10 years . 618 0-49 1-4 11-15 years : 617 nil 1-0 In the home the examination of contacts of a known case of tuberculosis is an efficacious measure of prevention of the spread of the disease. This is of particular importance in the children of tuberculous households. Kayne (19) after a detailed investigation of the incidence and the role of human contagion. in home contacts came to the conclusion that the younger the infant the more likely is it to be infected, and the younger when infected the graver is the prognosis. Separating an infant in contact with a tuberculous parent before infection has occurred prevents the development of tuberculous disease, but there is no evidence to show whether the separation of an older child with a positive tuberculin test has any effect in preventing the development of tuberculous disease. Banks (20) advocates the examination of the whole family when a child is discovered to be suffering from any form of tuberculosis. In this way the source of infection may be found, although in a recent survey by Pointon Dick and Brian Thompson (21) of 3,168 persons (2,025 adults and 1,143 children) were examined and 186 persons were found to have significant lesions. They found that among contacts the percentage of cases of previously undiagnosed tubercu- losis requiring treatment, is five times that found among the general population by mass radiography. With regard to the examination of contacts, the Medical Research Council (22), recommends that young adults (15-80) should be radiographed at three-monthly intervals and kept under observation for at least two years after contact is broken, but that re-examination of contacts over 30 may be dispensed with if the pressure of work is great. Pointon Dick and Thompson found that the age group 0-4 years produced the highest proportion of cases. Examination of contacts is difficult and often heart-breaking work owing to the reluctance of parents and other members of the family to come up for examination and, in the report of the Joint Tuber- culosis Council (23) on the subject, it is strongly emphasised that efforts should be made to secure the co-operation of the general medical practitioner and the school medical officer in the search for suspects, and that use should be made of all opportunities for ex- plaining to the general public the object and benefits of contact examination. A valuable contribution to case finding methods has been made by Toussaint and Pritchard (24) who arranged with the general practitioners of the Boroughs of Bermondsey and Southwark to ! refer for immediate X-ray examination any patient complaining of minor chest symptoms. The patients attended the X-ray Depart- ment without prior clinical examination, and no mention was made of tuberculosis. The total number X-rayed under the scheme was 2,433 of whom 1,122 presented some type of abnormality. Of these 80 were found to be suffering from active tuberculosis, that is 3:23 per cent. of the total number examined. Similar surveys have been done in other countries, particularly in Detroit, with a corresponding discovery of a comparatively large number of cases of active tuberculosis, and it would seem to be a very profitable practice in all out-patient departments of our general hospitals to examine all patients with minor chest symptoms radiographically as a routine. The results would not only be valuable as from the preventive aspect, but also would provide material for the study and treatment of early lesions. Prevention of Infection by increasing Resistance of the Host. Immunisation. There are three methods described by Petroff (25) (26). Injecting Living Virulent Tubercle Bacilli. He found ten living virulent bacilli could produce tuberculosis in a guinea-pig. The bacilli were counted by Barber’s method, and he tried to produce immunity in guinea-pigs by giving gradually increasing numbers of bacilli at weekly intervals, as follows : one, three, five, eight, twelve and soon. He found that this method gave fairly good immunity, but it was necessary to keep up the injections, and there was a great risk of causing the disease if the resistance of the animal fell so that the proceeding was considered too dangerous to employ on human beings. By using Avirulent Tubercle Bacilli. Many attempts have been made to protect by using attenuated bacilli. The most successful preparation has been that derived from the Bacillus Calmette Guérin, and known as B.C.G. This consists of bovine tubercle bacilli, attenuated by 280 passages in thirteen years on potato glycerine and bile. By using Killed Bacilli. Petroff thinks that an increased state of resistance can be produced by injecting dead tubercle bacilli and, although the immunity is more partial than when living bacilli are used, it is free from danger. It is generally admitted that the use of virulent tubercle bacilli is too risky and that tuberculin or dead bacilli, when injected, do not give an adequate protection. The attempt to produce im- munity by using attenuated bacilli is therefore receiving most attention at the present time and a great deal of work has been done with B.C.G. Irvine (27) has made a valuable summary of the work and modern views concerning B.C.G. He concludes that it has not been proved to have caused pro- gressive tuberculosis in man and that a certain increase of immunity is produced in man by B.C.G. vaccination. He thinks it should be given to children in tuberculous families, but it is not possible to say as yet whether it gives enough protection to warrant the re- organisation of our present scheme for dealing with tuberculosis. Since 1934 in many European countries and in U.S.A. thousands of children and adults have received B.C.G. From these vaccina- tions, and particularly the work of Heimbeck (28) on nurses in Norway, the general conclusions are : That B.C.G., properly prepared and correctly administered, is a harmless substance. That it can confer a certain degree of protection against the development of active tuberculosis, The preparation of B.C.G. demands the utmost care, otherwise disasters due to contamination or return of virulence of the bacillus will occur and cause tragic results. From the experience gained in other countries it appears that in order to produce B.C.G. with safety it is necessary to reserve one laboratory solely for the preparation of the vaccine and that no other work whatsoever should be done in that establishment, which should be either a separate building or completely shut off from other departments. To prevent contamination, great care must be taken to employ healthy staff and attention to detail is essential in all technical procedures. The strain of the bacillus must not be varied and records must be kept of the virulence tests of each batch of the vaccine issued. As Tytler (29) says, “‘ the presence of virulent tubercle bacilli must be excluded by the most rigidly systematic discipline in preparation.” _ This condition must be remembered when planning for the pro- duction of the vaccine and can be most easily met by arranging for the vaccine for the country to be prepared at one centre thereby avoiding the increased risks involved by the use of a number of laboratories. Various methods have been employed in administering the vaccine. Calmette used the oral method giving three doses of 100 mg. on fourth, sixth and eighth, or fifth, seventh, and ninth days of life. Weill Hallé and Turpin gave the vaccine sub- cutaneously using 0:01 or 0:02 mg. doses. Wallgren introduced the intradermal technique in 1933, and in Scandinavia this method is the one most frequently used. Complications there have fallen from 3-0 per cent. in 1944 to 0-3 per cent. in 1947, mainly due to the vaccination being done truly intradermally and to a more constant standard of vaccine. NRosenthal’s multiple puncture method is rarely used for three reasons, (a) the dose of vaccine given cannot be accurately measured, (b) the time and degree of sensitivity produced is not considered as being so certain as in the intradermal method, (c) the instrument is difficult to clean and sterilise. If ulceration develops after B.C.G., it usually responds to treatment by scraping and ultra-violet light. One case in Sweden in which an area of ulceration of 5 cm. diameter developed after vaccination healed quite satisfactorily under this treatment. It is important that all recipients of the vaccine should be ascertained to be definitely non- reactors to the Mantoux test using 1 mg. of tuberculin. Therefore, except for newborn infants they must be tuberculin tested before receiving B.C.G. It follows also that when a person is known to be a non-reactor he should be segregated from all possible sources of tuberculosis infection until such time as he becomes tuberculin sensitive as a result of the B.C.G. inoculation. The technique usually adopted in persons who do not react to tuberculin skin tests is to give 0:05 or 0-1 mg. of the vaccine intracutaneously. In six weeks they are re-tested and should have developed sensitivity to tuberculo-protein. During this period when sensitivity is developing, the possibility of reinfection should be avoided. The vaccination is repeated after six weeks if the tuberculin skin reaction has failed to become positive. It is not unusual for the vaccine to produce some local induration at the site of injection and sometimes abscess and open ulceration may develop, but Rosenthal (80) claims that this can be considerably reduced by adopting the multiple needle puncture technique, which has also been used with advantage by Weill Hallé for vaccination of infants, Négre and Brebey (81) using guinea-pigs claim that inoculation by cutaneous scarification is superior to Rosenthal’s method and that allergy develops in from 6 to 12 days and that there was very little decrease in immunity after a period of three years. Trius and Pusik (32) have done a considerable amount of work on the pathological changes produced by vaccination with B.C.G. With the “ Paris”’ strain a chronic lymphadenitis was produced in vaccinated infants. The glands showed endothelial proliferation which appeared to be benign. The cellular reaction began one week after vaccination and reached a maximum in three to four months, retrogressing over a period of two years. In a few instances caseation occurred with limited tubercle formation. Acid-fast bacilli were recovered from some of the glands and also by gastric lavage investigations. Recent work in U.S.S.R. confirms the protective power of the vaccine against primary infection. Klebanoff (83) has inves- tigated the efficiency of mass anti-tuberculosis vaccination by the Calmette method in a series of 56,951 vaccinated infants having 17,469 other infants as controls. His reports are tabulated as follows : Deaths per 100,000 from Age tuberculosis vaccinated Unvaccinated 0-6 months 4+ 4, 5-7 7-12 months 8-3 17-0 Ist year 12-3 21-8 2nd year . 10-4 20°8 —— He found that of the 2,800 vaccinated infants exposed to contact infections 15 died in the first year showing that there is still a considerable danger of contact infection in spite of vaccination. A memorandum prepared by Tytler (29) for the Joint Tuber- culosis Council gives a comprehensive survey of the results of work with B.C.G. up to 1946. The conclusions which he arrives at with regard to the efficacy of immunisation by B.C.G. are that : (a) Oral administration is unsatisfactory but that even from this method of administration in new-born infants a lower mor- tality from tuberculosis during childhood years can be de- monstrated when compared with unvaccinated infants from the same communities. (b) More precise conclusions can be obtained from better con- trolled series on parental injections. (c) The data collected over a number of years and from a large series of observations show that in pupil-nurses the risk of developing tuberculosis is greater in non-reactors than in reactors to tuberculin tests. (d) That among original non-reactors to tuberculin who have been vaccinated with B.C.G. and been converted to reactors the risk of developing the disease is reduced to a level approaching that of the reactor group. There is some divergence of opinion on the duration of the im- munity produced by B.C.G. vaccination. The individual usually becomes sensitive to tuberculin in from four to eight weeks. More rapid conversion is obtained by intracutaneous injection than by the oral or subcutaneous technique although the most rapid develop- ment of allergy occurred by using the “ scarification ”’ method. The highest percentage of reactors is claimed by some observers by using the multiple puncture instrument of Rosenthal but this is denied by others. With regard to the duration of the sensitivity produced, it is fairly certain that it lasts from two to three years whilst others claim that it is present for six to ten years. The literature on the subject is scanty and the whole question needs thorough investigation. One of the most difficult tasks connected with the investigation of the results of vaccination by B.C.G. is to establish adequate con- trols. Levine and Sackett (84) in a careful study of 2,084 vacci- nated children of tuberculous families from New York City and 1,073 controls are of the opinion that the efficacy of B.C.G. must be judged by its ability to reduce the tuberculosis mortality of children vaccinated in their homes in the midst of a tuberculous environment, and that as such the routine vaccination with B.C.G. is less ad- vantageous than removal of the tuberculous subject from the home. A similar study has been carried out by Olbrechts Tyteca, L., and Olbrechts, E. (35) in Belgium who found that there is only a slight difference in the mortality figures in favour of the B.C.G. vaccinated children. Ferguson (86) has carried out an important investigation on the use of B.C.G. in the prevention of tuberculosis among nurses. He compares his series of vaccinated nurses with non-vaccinated tuberculin-negative nurses living under similar conditions and doing comparable work. Among 203 vaccinated nurses, 5 developed manifest tuberculosis (2-46 per cent.) ; among 113 non-vaccinated negative nurses, 18 developed manifest tuberculosis (15-9 per cent.) ; among 293 nurses positive to tuberculin, 11 developed manifest tuberculosis or 3-75 percent. The difference in percentages between vaccinated and non-vaccinated negative nurses is 13:44 per cent. which is 5-5 times its own probable error and therefore of statistical significance. He found the use of B.C.G. safe, and concludes that although it is not a completely effective prophylactic, its protection is very considerable but not absolute. Furthermore he found that . the lesions of manifest tuberculosis that developed among the vaccinated were less severe and extensive than those in the non- vaccinated negatives. | The work of Aronson and Palmer (37) has an important bearing on the value of B.C.G. as the study was made among 3,700 North American Indians, aged 1-20 years, of whom 1,457 served as controls. Annual tuberculin tests and X-ray examinations were done for 6 years. In terms of death per 1,000 person-years the death rates of unvaccinated and vaccinated were 7:2 and 3:8 respectively. The figures are significant in view of the care which was taken to obtain satisfactory controls. From the long experience of P. and H. Cantonnet Blanch (38) it is concluded that the administration of B.C.G. by mouth is unsatis- factory. ‘They are very emphatic that close observation and follow- up of all vaccinated cases is necessary in order to protect from re- infection. They recommend that all allergic children living in a tuberculous environment should be vaccinated intradermally and that subsequent annual tests should be made to ensure that the acquired allergy is maintained, but too much reliance must not be placed on the immunity produced by B.C.G. vaccination and the child must be protected from subsequent re-infection. They are of the opinion that separation from a tuberculous environment without vaccination is better than vaccination without separation. The marked decrease in the incidence of pulmonary tuberculosis in the island of Bornholm in the 15-30 age group, since the use of B.C.G., speaks very favourably for the use of the vaccine as a pre- ventive measure. In Bornholm a systematic effort by Olsen (39) has been made since 1940 to ensure that the whole population was tuberculin sensitive. All non-reactors were offered vaccination and the response has been so good that 98 per cent. of the entire population are now known to be Mantoux positive. For the period 1935-40 the number of new cases between the ages of 15-80 was ISLAND OF BORNHOLM I. Age grouping of 184 notifications 1936-40 when B.C.G. was used only for individuals with tuberculosis milieu. 2,394 persons had been vaccinated by 1940. II. Age grouping of 82 notifications 1941-46 when B.C.G. was used for all negative reactors in school children, conscripts, and new-born infants, 10,337 persons had been vaccinated by 1945, i.e., 23 per cent. of the whole population. 70. During that period B.C.G. was only used for non-reactors with a tuberculous milieu ; during 1941-46 all non-reactors were offered VOLE BACILLUS 5 B.C.G. and by 1945, 23 per cent. of the population had been vac- cinated and 98 per cent. were Mantoux positive. During this period the total number of new cases in the 15-30 age group fell to 27. It is difficult not to give B.C.G. due credit for this marked | fall in the incidence of tuberculosis which is demonstrated clearly in the diagrams on page 56. Heaf (40) has pointed out that one of the great administrative difficulties in the use of B.C.G. is the provision of adequate segrega- tion during pre- and post-vaccination periods in order to protect those being inoculated from being infected from other sources. | Confirmation of this is seen in the work of Dorothy Price (41) at St. Ultan’s Hospital, Dublin, where she has vaccinated 68 children. Four out of thirty-five (11 per cent.) highly exposed infants developed tuberculosis whilst awaiting vaccination at the same hospital. Sheila O’Donovan (42) has investigated the blood changes after B.C.G. vaccination. She found an increase in lympho- eytes during the first week after vaccination followed by an in- crease in the mononuclears at the time of Mantoux conversion. The conflicting opinions that are being published in the plethora of articles on B.C.G. are probably due to difference in methods of preparation, administration, and standard of controls. Although the consensus of opinion is generally in favour of the use of B.C.G. it is important that we become fully acquainted with the strain of bacillus used for the vaccine and that both the preparation and administration are strictly controlled, being always in the hands of experts. That there are practical difficulties in the extended administration of the vaccine in this country has recently been emphasised by Wilson (43), who doubts whether its efficacy has yet been convincingly proved. He also points out that the introduction _of B.C.G. may have an undesirable influence on the readiness with which parents will allow their children to be immunised against diphtheria thereby reducing the number who might benefit from an inoculation the value of which has been generally accepted. Most persons, however, are of the opinion that the time has come for a controlled trial to be made of the vaccine in this country although due regard must be taken of the criticisms of those who are not wholly in favour of its use. Vaccination with the Vole Bacillus. Another method of pro- ducing active immunity against the tubercle bacillus is by use of ‘the vole bacillus. This organism, which may be regarded as allied to the tubercle bacillus causes a disease in voles which partly resembles tuberculosis and partly rat leprosy. It is highly patho- genic to these animals and is responsible for their deaths in con- siderable numbers, but is relatively avirulent for guinea-pigs and rabbits. Wells and Brook (44) made preliminary investigation on the possibility of producing immunity against tuberculosis in animals by inoculations with living vole bacilli and further work was done by Griffith and Dalling (45). From these experiments in which four weekly doses totalling 2 mg. of pure culture of vole bacilli were given to guinea-pigs and five months later half these animals were given 0-000001 mg. of virulent bovine bacilli. Experiments of a similar character were made with calves. Im all cases it was found that the controls de- veloped extensive glandular tuberculosis whereas the vaccinated animals exhibited no tubercles or only a few scattered foci in the mesenteric glands. Although further investigations will have to be carried out before definite conclusions can be made, it is probable that the vole bacillus will be an effective immunising agent against tuberculosis. Wells has summarised the situation in his report to the Medical Research Council (46) in which he states that tuberculin allergy following vaccination with the vole bacillus is greater and occurs earlier than that following B.C.G. vaccination. In the early stages of virulent infection in guinea pigs, vaccination with the vole bacillus leads to a greater degree of resistance to the disease than does B.C.G., but in the later stages the degree of resistance is approximately equal. The vole bacillus produces a resistance to subsequent infec- tion with virulent tubercle bacilli in animals but the degree of resist- ance in cattle or man has not yet been determined. A point of importance in all this work is that the vole bacillus possesses naturally a suitable virulence for vaccination and that this virulence ean be maintained indefinitely by passage. It must be noted, however, that severe sequele have been observed in calves, rabbits and guinea-pigs inoculated with strain G.564 of the vole acid-fast bacillus and Young (47) concludes that no strain of the acid-fast bacillus should be used as a living vaccine in the man before exhaustive tests have been made to determine the highest virulence which it is capable of attaining. Prevention of Infection. That a low standard of living and conditions of overcrowding, poor ventilation, dampness, dirt and lack of sunshine favour the development of tuberculosis has been well known since the work of Sir Robert Philip in Edinburgh and the Tyneside enquiry by Bradbury (48), which left no doubt the close connection between poverty and the incidence of tuber- eulosis. In a civilised community much canbe done by Public Health Authorities to remove these predisposing causes of disease, and in all anti-tuberculosis work the dispensary is the centre for organisation and control of preventive work. Through its activities foci of infection are discovered, domestic conditions investigated and relief given where privations exist. The guidance of a family in matters of hygiene when the disease is diagnosed, and the care of the patient after return from sanatorium treatment are important functions of the dispensary staff, which includes tuberculosis nurses and health visitors. The respective importance of each of the predisposing factors which have been mentioned above is not known, but much ean be learnt from the vital statistics of the country under the circum- stances of war when unfavourable conditions are more prevalent, and from the study of the relatively closed community of an indus- trial village settlement which is comprised of a considerable number of tuberculosis households living under good conditions and regular medical supervision. From the figures which have been quoted previously the rise in the mortality from tuberculosis which occurs during war periods can be seen, and the returns for children, in particular those relative to deaths from meningitis under three years of age, are a rough indication of the amount of infection that is present amongst the general population. Infection in Tuberculosis Village Settlements. The unique facilities offered at Village Settlements for observing and following up the children of tuberculous parents have been used at Papworth and Preston Hall and, as a result of these investigations, it appears that the incidence of tuberculosis amongst the healthy population at these centres is negligible. In 1933 Noel Bardswell (49) was impressed by the facts that at both these colonies there were : (a) a large aggregation of infected persons ; (b) evidence that some 78 to 80 per cent. of the younger inhabi- tants gave a positive tuberculin reaction. (c) None of the children born in the villages showed any sign of clinical tuberculosis. (d) At neither Papworth nor Preston Hall had there been a case of tuberculous meningitis in a child. More recent work by McDougall, Heaf, Cox and Powell (50), in- vestigating 204 families with a total dependant population of 996 has confirmed these observations. The families under review had been resident in the colony from two to eighteen years and in that period there had been only two deaths from tuberculosis amongst dependants of settlers, only three wives had been diagnosed as tuberculous and one son of a settler who had lived in the village for a period of three years had died of tuberculosis since leaving the community but there had not been a single death amongst the children of the village. From these practical demonstrations it may be concluded that the extremely low morbidity and mortality rates amongst the village settlement populations is mainly due to the environmental conditions. Bardswell summed up the situation very tersely by saying: “* Trans- late Sanatorium Village Settlement principles into everyday life for the community as a whole and we should have little to fear from tuberculosis infection.” Brieger (51) has made careful observations over a period of 25 years on the case histories and clinical details of all the families resident in the village settlement of Papworth. From 1918 to 19388 199 ex-patients’ families have lived in the village with the families of some 30 members of the staff. There were 137 families with children, of these 97 remained for less than 10 years and 40 for more than 10 years. The head of the family in 120 of the families was tuberculous. 108 children were born in the village and the radiological survey of this group was as follows : 51 per cent. nothing abnormal, 43 per cent. calcified foci, 46 per cent. primary lung lesion, 1-9 per cent. transient perifocal reaction. No child of the 25 children born of families in which there was a case with positive sputum developed clinical tuberculosis : 16 were normal, 2 showed a primary complex, 5 calcified foci, 1 transient perifocal reaction and 1 residual primary infection. ‘The average age of the village-born children in 1988, of this last group of children, was 5 years, those of the sputum negative families 6 years, and those of the staff 9 years. In the 260 children not born in the village but admitted to the settlement there were 151 from sputum positive families: 24-5 per cent. of these showed normal chests, 5-9 per cent. Gohn foci, 42-4 per cent. calcified foci, 16-6 per cent. residium of primary infection, 2 per cent. transient perifocal reaction, 2-7 per cent. childhood tuberculosis and 5-8 per cent. adult phthisis. These observations demonstrate clearly that the village settlement has, in addition to its economic and curative value, a most important function as a measure for the prevention of the development of tuberculosis among children born in tuberculous households. TABLE COMPARING THE INCIDENCE OF LESIONS IN THE VARIOUS GROUPS OF ADMITTED CHILDREN AND IN THE GROUP OF CHILDREN BORN IN THE VILLAGE (ALL FAMILIES INCLUDED) (51) CHILDREN ADMITTED IN FAMILIES OF Village-born Children Sputum Positive | (all families) Cas Type of Lesion Sputum-Negative | Healthy Staff and Surgical Cases No clin. or rad..| evidence . —.._|- «18 (40-9 %) | 25 (82-5 %) | 87 (24-5 %) | 55 (51 %) Ghon foci . i Med ey 6 Clie Sap la O, (eo 9) |. 6 (aa 5) Calcified foci . | 16 (50 %) 43 (55-8 %) | 64 (42-4 %) | 40 (37 %) Residuum of pri- | : mary infection . | 0 2. (26%) | 25:'(16-6 %) | 5 (4°6%) Transient _—peri- | focal reaction .| 1 (8%) 0 oz 2) 2 (1-9 %) Childhood tuber- | culosis . .1 O 1 (1-3%)| 4 (2-7%)| 0 Adult phthisis 0 0 YASS). Oo TOTAL . eal 32 7 151 108 The continued fall in the mortality figures of tuberculosis has led some persons to venture to suggest that the disease will eventually disappear. Such optimism must not allow us to slacken in the enforcement of preventive measures, for the eradication of the disease depends on at least two important factors. First, that the general standard of living conditions and the environment of the population does not deteriorate, and secondly, the adequate control of the carrier of the infection. Maxwell (52) has stressed the im- portance of the symptomless carrier as a cause of the development of the disease in children and young adults. There must be a con- siderable number of foci of infection scattered through the com- munity if over 90 per cent. become infected by the age of 30, and so long as these foci remain unknown and uncontrolled, new cases will arise in those individuals whose resistance to the infection is low and particularly if they are non-reactors to tuberculin. Mass radio- graphy has demonstrated the prevalence of the symptomless positive case in our midst. Assuming that there are only 2 per 1,000 popula- tion, a figure that is below that given by the majority of surveys, and taking the adult population as being 30,000,000, it means that there are 60,000 undetected positive cases among the population in addi- tion to the known ones on the tuberculosis register. So long as this vast source of infection remains unchecked new cases will continue to develop and cause disablement. It is, however, insufficient merely to discover sources of infection without taking action. Means must be adopted whereby such persons are rendered harmless by treatment and education. Case finding, treatment and after-care, all play their part in prevention, but the most important principle in the campaign against tuberculosis is the maintenance of a high resistance, either natural or acquired, and in this environment, mode of living, and nutrition are still the most influential factors. References (1) Joint TUBERCULOSIS CoUNCIL. Rep. 1936. (2) Nassau, E. (1940-41) Proc. R. Soc. Med. 34, 397. (3) Donovan, G. E. (1943-44) Proc. R. Soc. Med. 37, 708. (4) Briecer, E. and Fe.x, H. B. (1945) J. Hyg. 44, 158. (5) MippLEBROOK, G. (1945) Amer. Rev. Tuberc. 51, 244. (6) (No author) Extr. (1945) Mon. Bull. Minist. Hlth. 4, 202. (7) (No author) Extr. (1945) J. Amer. med. Ass. 128, No. 3. (8) Kenwoop, H. and Dove, HE. L. (1915) Lancet, 2, 66. (9) GrirrirH, A. S. (1937) Tubercle, 18, 529. (10) HunTER, R. A. (1941) Tubercle, 22, 257 (11) GrirrirH, A. S. and Munro, W. T. (1935) Brit. med. J. 2, 147. (12) Cursii1, L. J. and Lynn, A. (1944) Brit. med. J. 1, 283. (13) Buackiock, J. W. S. (1947) Brit. med. J. 1, 707. (14) Leruam, W. A. (1946) Mon, Bull. Minist. Hlth. 5, 80. (15) Kay, H. D. and Nrave, F. K. (1935) Lancet, 1, 1516. (16) Orrr, E. L. Quoted in Brit. Med. J. 1936, 1, 25. (17) Dow, D. and Luoyp, W. E. (1931) Brit. med. J. 2, 183. (18) Kayne, G. G. (1935) Brit. med. J. 1, 692. (19) ibid., p. 692. (20) Banks, G. S. (1987) Edinb. med. J. 44, 153. (21) Dick, W. P. and Tuompson, B. C. (1946) Lancet, 2, 791. (22) MepicaL RESEARCH CouNCcIL. Spec. Rep. Ser. No. 246 (1942) London. (23) Joint TUBERCULOSIS CoUNCIL. Rep. 1936, p. 7. (24) Toussaint, C. H. C. and Prircuarp, E. K. (1944) Post Grad. med. J. 20, 143. | (25) PEerrorr, S. A. (1927) J. Amer. med. Ass. 89, 285. (26) Brown, L., Heisr, F. H. and Perrorr, A. S. (1914) J. med. Res. 30, A475. (27) Irvine, K. N. (1984) B.C.G. vaccine. London. (28) HemmBECKE, J. (1936) Tubercle, 18, 97. (29) TyTLeR, W. H. (1945) Memorandum on B.C.G. London. (30) ROSENTHAL, S. R. (1939) Amer. Rev. Tuberc. 39, 128. (31) NEGrE, L. and Bresey, J..(1944) Ann. Inst. Pasteur, 70, 186. abstr. : Bull. Hyg. 1945, 20, 540. (32) Trrus, M. V. and KurBanova, A. A. (1944) Probl. Tuberk. No. 5, p. 35. abstr. : Bull. Hyg. 1945, 20, 395. Pus, V. I. (1944) Probl. Tuberk. No. 5, p. 25.  abstr.: Bull. Hyg. 1945, 20, 394. (33) KLEBANOFF, M. A. (1944) Probl. Tuberk. No. 5, p. 48-49. (34) Levine, M. I. and Sackett, M. F. (1946) Amer. Rev. Tuberc. 53, 517. (35) OLBREcHTS-TyTECA, L. and OLBRECcHTS, E. (1946) Rev. belge Tuberc. 37, 69. (36) FERGUSON, R. G. (1946) Canad. J. publ. Hlth. 37, 435. (37) Aronson, J. D. and PALMER, C. E. (1946) Publ. Hlth. Rep. Wash. 61, 802. (38) CANTONNET Buancu, P. and H. and LiecvuTIER, H. (1945) Rev, Tuberc. Uruguay, 13,1. abstr.; Bull. Hyg. 1946, 21, 654. (39) OusEN, C. N. (1941) Tuberculosen paa Bornholm. Ronne. (40) Hear, F. R. G. (1947) Mon. Bull. Minist. Hlth. 6, 184. (41) Price, D. (1947) Irish J. med. Sci., p. 711. (42) O’Donovan, S. (1947) Irish J. med. Sct. p. 717. (43) Witson, G. S. (1947) Brit. med. J. 2, 855. (44) WELLS, A. Q. and Brook, W. S. (1940) Brit. J. exp. Path. 21, 104. (45) GrirriTH, A. S. and Da.uine, T. (1940) J. Hyg. (Camb.) 40, 673. abstr. Editorial (1941) Brit. med. J. 1, 717. (46) WELLS, A. Q. (1946) Med. Res. Counc. Spec. Rep. Ser. No. 259. (47) Youne, J. A. and Paterson, J. S. (1947) Lancet, 1, 707. (48) BrapBury, F. C. S. (1983) Tyneside Enquiry, N.A.P.T. London. (49) BARDSWELL, N. Trans. 19th Ann. Conf. N.A.P.T. 1938. (50) Cox, G. L., Hear, F. R. G., McDouGatt, J. B. and PowE 1, D. A. (1942) Infection and environment in tuberculosis. Maidstone. (51) Briecer, E. M. (1944) Papworth families. London. (52) MaxweELL, J. (1941) Brit. med. J. 1, 665. CHAPTER IV DIAGNOSIS Ir has been appreciated for some time that pulmonary tuber- culosis presents radiographic abnormalities before clinical features appear, and that the surest way of recognising the disease early is by means of an X-ray examination of the chest at the time of, if not before, the first suspicious indication. This has been practised in the examination of ‘‘ contact” cases. It is only comparatively recently, however, that this method of case-finding has been ex- tended to apparently healthy sections of the population in a search for the disease in this symptomless ‘‘ radiographic” phase. ‘The subject of Mass Radiography, as it has come to be called, its development and technique, what it can achieve, and the particular problems to which it has given rise, is discussed in Chapter V. It is sufficient at this point to say that it has proved one of the most important modern innovations in the campaign against tuberculosis, and by unmasking the ‘‘ minimal lesion”? in increasingly large numbers for observation and study it has opened up an altogether fresh line of research. It is important, therefore, to be “‘ X-ray minded ” in approaching the diagnosis of tuberculosis ; but it would be a mistake for the practitioner to imagine that his responsibility is now at an end. There are at least two reasons why he should be as watchful as ever and should train himself to suspect tuberculosis even if he has to enlist radiographic aid to diagnose it. First, it is not possible at the present time to X-ray the chests of the whole community at intervals, and this is what should be done if full benefit is to be derived from the scheme; secondly, experience has shown that a few cases, admittedly a very small proportion, do not apparently pass through this “ pre-clinical’? radiographic phase before causing symptoms and therefore the early recognition of these will continue to depend upon clinical judgment. The symptoms of pulmonary tuberculosis can be conveniently divided into those due to toxaemia (lack of energy, loss of weight, fever, night sweating, digestive disturbances, anaemia and amenor- rhoea), and those which are dependent upon the fact that the lung is the organ involved (cough, expectoration, haemoptysis, dyspnoea and pain in the chest). Not all of these require discussion but the more important will be mentioned. Night Sweating. This complaint is still regarded by the lay public as characteristic of tuberculosis. It occurs in cases of active disease if too many bedclothes are worn, or if the patient sleeps in a stuffy atmosphere, and the fact that it is seen now less commonly than it used to be can be largely attributed to an improved standard of nursing tuberculous patients in well-ventilated apartments or out-of-doors. Tuberculosis is not the only cause of night sweating: other con- ditions in which there is a sudden fall of body temperature such as pneumonia or lung abscess, can also produce it. Moreover, the drenching nocturnal sweats of phthisis should not be confused with excessive perspiration at night due to intractable coughing resulting from upper respiratory tract catarrh and bronchitis. Haemoptysis. Burton Wood used to teach that the tuberculous patient minimised his symptoms. This is particularly true of -haemoptysis. The tuberculous person will often dismiss as of little consequence a quantity of blood which most people would regard as alarming. In some unaccountable way he seems to have insight into the significance of the event, and, through fear of what it im- plies, has become the victim of a genuine process of self-deception. Haemoptysis can occur at any stage in the course of the disease and it has been variously estimated to be present in some degree in 25 to 80 per cent. of patients whose disease is allowed to pursue its natural course. A frank unheralded haemoptysis may be the presenting symptom, when it can be looked upon as a fortunate occurrence for it brings the patient at once under expert observation. But it is an extra- ordinary paradox that the spitting of blood, the one symptom above all others which arouses a suspicion of consumption in the mind of the layman, is still too frequently ignored or misdiagnosed without proper investigation. The belief that blood welling up into the mouth in fair quantity can arise from a “‘ ruptured vein in the back of the throat” is one of the most dangerous and damaging in clinical medicine. Keers and Rigden (1), in a recent textbook, state that they have yet to see an example in which this source of haemo- ptysis was proved. Most experienced physicians will agree that it is excessively rare. H. & R, TUBERC. 3 Dyspnoea. ‘This is not a common early symptom except as an expression of failure of general health, or as a result of secondary changes which interfere with functional efficiency such as fibrosis, partial atelectasis, and compensatory emphysema. Deflection and torsion of the heart, if present, is an additional cause of dyspnoea. Modes of Onset It will readily be seen that while some symptoms are more sug- gestive of tuberculosis than others, no one of them is pathognomonic of phthisis. Practical experience has shown, however, that the disease tends to adhere to certain fairly well-defined patterns in the early stages of its development and a recapitulation of these modes of onset may prove of assistance in early diagnosis. Slow and Insidious. This is a common way for the disease to start and is important, for it is the one which is likely to cause the longest delay in arriving at a diagnosis. An analysis of the symp- toms will show that they consist chiefly of lassitude and fatigue which may have been attributed to other causes, cough, of a type and frequency which are barely obtrusive, and a slow but con- sistent loss of weight and strength. These features may have been present for weeks, or even months, before the patient finally consults his doctor or a dramatic episode like an haemoptysis or chill leads to the diagnosis. On other occasions a tonic is prescribed and repeated, or a holiday recommended, in the belief that the patient is just “run down.” It is in this type of case that the precau- tionary X-ray picture is so valuable. Sudden. In contrast to the above, tuberculosis of the lungs sometimes throws out an early and unmistakable hint of its presence by the occurrence of two complications, haemoptysis and spon- taneous pneumothorax, both of which are sufficiently dramatic and frightening to lead to the enlistment of medical aid. Haemoptysis. The importance of this as an initial symptom and the necessity for a full investigation of anyone who exhibits it has already been discussed, and an X-ray of the chest and an examination of the sputum will in many such cases bring to light a tuberculous lesion which will respond favourably to treatment. It is, however, well known that in not all examples of sudden frank haemoptysis can the diagnosis be made so readily. Some will eventually prove to be due to a non-tuberculous condition such as dry bronchiectasis or, more rarely, carcinoma arising at an unusually early age; in others no apparent cause is found even after complete investigation. There is little doubt that this latter group includes examples of what Burton Wood termed the “ abortive haemorrhagic form ”’ of phthisis. That is to say the haemoptysis is the initial symptom of a very early tuberculous focus, a focus so immature as to give rise to no demonstrable toxaemia, so small as to escape radiological de- tection, and from which tubercle bacilli cannot be recovered in the scanty sputum or secretion submitted for the test. Such a focus may heal irrespective of whether the patient is treated or not and may continue permanently quiescent. There is no guarantee, how- ever, that healing will remain firm and in some of these patients this period of quiescence is terminated, it may be five or ten years later, by a gradual but progressive reactivation, and tuberculosis of the lungs becomes securely, and perhaps irretrievably, established before the diagnosis is finally made. There are two further points about this abortive haemorrhagic form which need to be remembered : first, it is not safe to pronounce the lung fields radiologically clear in the face of haemoptysis unless a left oblique view has been passed as normal, for an early focus may be concealed behind the heart shadow in the postero-anterior view; secondly, methods for detecting tubercle bacilli in secretions have improved considerably in the last few years and in consequence the number of patients labelled ** haemoptysis of undetermined origin ”’ can be expected to diminish. Tf all investigations of haemoptysis prove to be negative constant observation and repeated reviews are essential. Spontaneous Pneumothoraz. It has been convincingly shown that spontaneous pneumothorax occurring in the apparently healthy is less often due to active pulmonary tuberculosis than to other causes such as the rupture of emphysematous bullae or of tuberculous scar tissue vesicles. The suspicion of a tuberculous aetiology should be aroused if a history suggestive of phthisis during the preceding few months can be elicited, if fever persists for longer than a week or ten days, if fluid forms in the pneumothorax space, or if the blood sedimentation rate does not rapidly return to normal. All examples of spontaneous pneumothorax should have the sputum examined several times, and repeated X-rays taken of the chest to. study the lung fields during the process of re-expansion. Unexplained Fever. Pulmonary tuberculosis has sometimes been discovered from investigation set in train to elucidate a moderate but persistent evening rise of temperature. Influenzal. True influenza is a rare disease and _ practically confined to epidemics : the so-called “ influenzal chill ” on the other hand, is very common. Pulmonary tuberculosis with an explosive febrile onset without premonitory symptoms closely simulates an influenzal chill, and it is still debatable whether the illness was tuberculous from the beginning or whether it was an independent pulmonary infection lighting up a quiescent tuberculous focus. Whichever is the case it makes little difference from the practical point of view, for if an attack of “ influenza ”’ does not settle within ten days or a fortnight the diagnosis should be questioned. Bronchitis. The diagnosis of chronic bronchitis is frequently made in the middle-aged and elderly because of cough and sputum without other symptoms or conclusive physical signs. It is becom- ing increasingly apparent in recent years from routine investigation of many of these so-called “ bronchities,” carried out at tuberculosis clinics and elsewhere, that some of them are, in fact, open cases of tuberculosis ; while others exhibit both conditions, the one engrafted upon the other. Either of these varieties can be extremely dangerous in a family containing young children or susceptible adults, and the “chronic cough,” particularly if productive, should only be diagnosed as bronchitis by a process of exclusion. Pleurisy. Pleural pain is a frequent accompaniment of many respiratory diseases and tuberculosis is no exception. It is fair to say, however, that the adult form of phthisis rarely starts as a painful pleurisy, and that many workers are now of the opinion that tuberculosis of the pleura as an initial event is usually a post- primary manifestation related to the primary complex. The occurrence of pleurisy with a sterile, lymphocytic effusion in a young adult should be considered tuberculous unless there are good grounds for an alternative diagnosis. Dry pleurisy, especially if a friction rub is heard, may have to be similarly regarded on the assumption that it is but a milder, or earlier, manifestation of the wet form. Not every case of dry pleurisy can be so classified, how- ever, for Smart (2) has shown from a bronchographic study of a series of cases of idiopathic pleurisy with friction that some are examples of dry, and hitherto unsuspected, bronchiectasis. This cause can be justifiably entertained clinically if there have been several similar attacks previously. | Even if there is no direct evidence of a parenchymatous focus, tuberculous pleurisy should be looked upon as a possible precursor of phthisis and the immediate management and future surveillance of the case require care. Post-partum. It has been observed that pregnancy in a tuber- culous woman often has a beneficial effect upon the lung up to the time of delivery but thereafter the disease is hable to become in- creasingly active. What is possibly not so commonly appreciated is that the first few months after parturition is a favourable time for tuberculosis of the lungs to develop. A woman who does not pick up as quickly as she should after delivery, or who complains of symptoms of a general or respiratory character, should be investi- gated from the point of view of tuberculosis. Secondary Invasion. Finally, a pulmonary lesion may declare its presence through the medium of a distant organ of the body which is secondarily invaded. Thus, change in the voice and aphonia with signs of chronic laryngitis may, in rare cases, be the presenting symptom, especially in men between the ages of thirty and forty years. Similarly, fistula in ano should direct attention to the chest for it may be tuberculous and secondary to the lung, the organisms reaching the lower bowel in swallowed sputum. Predisposing, Factors Race. No race of mankind is immune from tuberculosis but differences in susceptibility have often been noticed. The Irish are unduly prone and display less resistance to the disease than the average English subject. The Jews, on the other hand, have ac- quired considerable resistance. Primary infection is acquired earlier and more universally in urban than in rural communities, and in the course of time through several generations an enhanced resistance to reinfection may follow. Sex. Morbidity statistics have shown that before the age of twenty-five years the disease is slightly more common in women than in men: after that age men are more commonly affected than women. In both sexes the incidence reaches a peak in the twenties in women and in the thirties in men and thereafter pro- gressively declines, more steeply in the case of women than in men. _A secondary rise in morbidity has been observed in late middle life, again affecting men more than women. Family History. Congenital tuberculosis is hardly ever seen ; on the rare occasions in which the foetus is infected through the placenta a stillbirth results or the child survives only a few days. The proved presence of the disease in one or more blood relations is a valuable point in diagnosis for it may imply not only propinquity to a source of bacilli but also the acquisition by inheritance of a constitutional proneness to the disease. Thus not only is the seed to hand but the soil well prepared. History of Contact. ‘This also is important but clearly differs from the family history in so far as it is solely concerned with the transmission of bacilli, whereas a bad family record remains to some extent suggestive even if the patient and his affected relatives have never met. Other things being equal a susceptible young adult is more likely to fall a victim to tuberculosis if he has lived intimately with an “ open ”’ case of phthisis. ‘The incidence of the disease in the husbands and wives of infected persons is higher than in the general population but how much higher:is hard to infer accurately. Paterson (3), from an analysis of 322 couples found the incidence higher in female consorts than in male, and greater below 30 years of age than above. Occupation and Mode of Life. Certain diseases such as the pneumonokonioses, contracted as a result of specific employment, predispose to the development of tuberculosis later, and in mining districts they account for a proportion of those suffering from tuberculosis in middle life. Hairdressing and bar-tending rank high in the list of dangerous occupations. Nurses and medical students may be exposed by the nature of their work to an increased risk of contracting phthisis. If the nature of some trades and occupations is specifically hazardous, the conditions under which the day’s work is carried out are equally important. Long hours of work, sometimes in semi-darkness or wholly in artificial light, with poor ventilation and insufficient rest, are patent contributory factors, and to them, combined with ‘* black-out ” and the “ shelter life,’ was largely attributed the increase in tuberculosis in Britain in 1941-42. Differential Diagnosis The differential diagnosis of pulmonary tuberculosis is a difficult subject to handle concisely and a detailed discussion of it is beyond the scope of this book. It is convenient to separate those conditions DIFFERENTIAL DIAGNOSIS 7a whose systemic symptoms resemble phthisis from those diseases of the respiratory tract which enter into the differential diagnosis. Systemic. There are a number of conditions appearing in young adults, such as Graves’ disease, diabetes mellitus and disorders of the blood-forming organs, in which lassitude, loss of weight and strength, and a failure of general health are prominent features. These enter into the differential diagnosis, as also do those diseases like infective endocarditis and lymphadenoma which may present with unex- plained fever. It is unnecessary to dwell longer in this field. An important group of clinical states which may be a source of confusion, and with which in the last few years the profession has become increasingly familiar, are the psychoneuroses. The term ‘‘ neurasthenia ”’ has often been employed to cover symptoms of a vague character in the absence of physical signs, and the temptation to regard an illness as “ functional” because no organic basis can be discovered is still prevalent. For instance, such complaints as listlessness and lack of energy, palpitations, left-sided chest pain, dyspepsia, and loss of weight, all of which can be reproduced by anxiety states or effort syndrome, may be, in fact, early indications of pulmonary tuberculosis, and a false diagnosis will lead to the loss of much valuable time. Such mistakes can be largely avoided if two important criteria for the confident diagnosis of a psycho-neurotic illness are borne in mind: first, the need to establish positive evidence of a psychopathy such as neurotic traits in the past per- sonal, or family history, or some environmental or occupational factor of significance, bearing a true relationship to the onset of the symptoms; and secondly, the realisation that a full physical examination, backed by relevant investigations, is indispensable in excluding organic disease before a psychiatric diagnosis can be entertained. Respiratory. Pulmonary tuberculosis can simulate most of the standard diseases of the respiratory tract and the differential diagnosis in this purely local sphere may occasionally be astonish- ingly difficult. It depends for success upon the careful evaluation of evidence furnished by the history, both personal and family, physical examination, and the result of special investigations of which the search for the tubercle bacillus is the most important. Without entering deeply into this subject the conditions which are most likely to cause difficulty are the various forms of pneumonia with slow or irregular resolution, the fleeting infiltration of Loeffler’s syndrome, suppurative lesions such as abscess and bronchiectasis, carcinoma of the bronchus, the pneumonokonioses, and, more rarely, chronic bronchitis and broncho-pulmonary catarrh. Fungus infections may resemble tuberculosis closely, and this is particularly true of coecidioidomycosis, a disease endemic in certain parts of California and Arizona, which, in addition to reproducing the clinical picture of phthisis in its primary and secondary stages with erythema nodosum, leads to X-ray changes with cavitation indistinguishable from those of tuberculosis. Diagnosis depends upon the recovery of the fungus, Coccidiodes tmmitis, and not tubercle bacilli from the sputum, and, in some cases, by a positive specific intradermal coccidiodin reaction. Some interest has recently been aroused, chiefly in the United States, by another fungus infection, histoplasmosis, due to the specific organism Histoplasma Capsulatum. ‘This disease in its flagrant form bears some resemblance to kala-azar, but it has been shown by means of a specific skin test with histoplasmin that infec- tion with the fungus can occur silently without producing symptoms. The practical importance of histoplasmosis lies in the fact that it is apparently responsible for caleareous deposits in the lung fields. Thus High and his associates (4) have reported 113 examples of disseminated pulmonary calcification of both miliary and multiple bilateral type culled from a survey of approximately 45,000 persons : they found that 96-3 per cent. of the cases reacted to histoplasmin, and only 10-2 per cent. to tuberculin. It is thus evident that, in the central region of the United States at least, calcification of this type is not synonymous with healed tuberculous infection. What part, if any, pneumomycotic infection plays in the production of pulmonary calcification in other parts of the world is not yet known. It is probably small. McWeeney e¢ al. (5) have carried out a survey into the histoplasmin sensitivity of 8320 Dublin children with negative results. The increasing use of radiography for the recognition of pulmonary tuberculosis in the symptomless preclinical stage has brought with it its own peculiar diagnostic problems. It is not uncommon for the clinician and radiologist to be faced with the differential diagnosis of a radiographic change in the absence of symptoms and with little prospect of much assistance from laboratory tests. The more diffuse and extensive shadows are generally amenable to further investigation along conventional lines, but a word will be devoted here to two types of radiographic appearance which may be a cause of perplexity, namely, diffuse miliary opacities and the solitary focus. Miliary Opacities. Acute miliary tuberculosis of the lungs is hardly likely to be long mistaken for any other condition ; chronic miliary disease, on the other hand, is in a different category for it is compatible with reasonably good health and ultimate recovery. The more commonly encountered causes of miliary shadows (not all of them necessarily symptomless) include silicosis, carcinomatosis, diffuse bronchopneumonia, sarcoidosis, and chronic passive venous congestion associated with cardiac failure, chiefly mitral stenosis (Anglin (6)). Lipiodol, retained in the alveoli from a former bronchographic study is a recognised source of error. Rarer causes of miliary radiographic shadows are patchy atelectasis, congenital cystic disease of the lung, lipoid pneumonia, fungus infection, and miliary amyloidosis. This subject will be found discussed by Hoyle and Vaizey (7) in their book Chronic Miliary Tuberculosis, and in an article by Austrian and Brown (8) in which over twenty conditions in which pul- monary miliary shadows have been seen are listed. The Solitary Focus. Pierson (9) defines the solitary lesion as a focus roughly spherical and of uniform density with sharply de- fined borders and measuring 1 to 5 centimetres in diameter. Tuber- culosis can be responsible for such a solitary lesion in three ways : (1) As the pulmonary component of the primary complex (Ghon’s focus) which is generally recognisable from the mediastinal glandular enlargement which accompanies it; (2) Assman’s infraclavicular focus before the stage of cavitation is reached ; and (3) the tubercu- loma consisting of a mass of tuberculous granulation tissue. Pierson doubts whether there is a great deal of difference between the essential pathology of the last two types, and in deciding between them account must be taken of the frequency with which areas of soft mottling surround Assman’s focus, of the tendency for the main lesion to cavitate, and of the fact that it is usually infraclavi- cular in situation. Among non-tuberculous conditions which may cause a similar X-ray appearance are lung abscess, lung cysts, including hydatid cyst, encapsulated interlobar empyema, and neoplasm which may be either primary in lung, benign or malignant, or secondary solitary deposits arising from other sites in the body such as kidney or testis. Special Investigations Whereas the existence of pulmonary tuberculosis can often be suspected on circumstantial and clinical grounds, the verification of the diagnosis and the assessment of the degree of activity requires the performance of special methods of investigation, an aspect of this subject which has recently been considerably amplified. Radiology. This now occupies so important a position in the diagnosis and management of intrathoracic disease as a whole and of pulmonary tuberculosis in particular that a separate chapter of this book has been devoted to its recent development and it will not be considered further here. (See Chapter V.) Recovery of the Tubercle Bacillus. Bacteriological proof of the disease is rightly regarded as the crucial test of a tuberculous aetiology, so long as certain innocuous organisms which have some- what similar staining properties to the tubercle bacillus are not con- fused with it. Examination of a smear of sputum stained by the Ziehl-Neelsen method is still universally practised and gives reason- ably accurate results so long as the portion of sputum to be tested is carefully chosen and the search is prolonged, and if necessary repeated. In an obvious case a -positive result can be quickly reached in this way ; it is when the bacilli are scanty that they may be missed and too much emphasis should not be placed upon even a series of negative results if other features of the case are suggestive of a tuberculous lesion. In order to reduce the number of negative findings to the minimum, and thus to gain finality in many doubtful cases, certain modifications of the original method have been devised and other tests employed. The “ concentration ’? method has been successfully used, the technique being to treat a sample of sputum with antiformin, centrifuge the mixture, and examine the deposit in the usual way. Nassau (10) has drawn attention to the disadvantages of existing methods of homogenisation and concentration of sputum, namely, the impairment of staining qualities and viability of bacilli. As an alternative he has tried out the method evolved by Jungmann, based upon the liquefaction of the sputum by hydrogen peroxide and sulphuric acid in the presence of a trace of iron. For the precise details of the technique Nassau’s original paper should be consulted. The author examined with the acid-peroxide-iron technique (A.P.I.) 650 specimens of sputum which had been pronounced T.B. negative on direct smear examination and found 13-6 per cent. positive on concentration compared with 32-3 per cent. on culture, results which bear favourable comparison with other concentration methods. A much more accurate method of demonstrating the presence of tubercle bacilli in sputum, discharges, or pleural fluid is by the guinea-pig inoculation test. Two pigs are used which are killed and examined after three weeks and six weeks respectively. The draw- back of this test is the length of time required to obtain the result. Until comparatively recently the tubercle bacillus was notoriously difficult to culture, and increased precision was given to laboratory tests by the introduction by Petragnani, in 1926, of the malachite green and egg medium. Upon this medium tubercle bacilli grow fairly readily, and the characteristic colonies become recognisable in a week or ten days, but may take three weeks. ' It is thus con- siderably cheaper and may be quicker than the guinea-pig inocu- lation test, but all pathologists do not yet agree that it is equally accurate. It is not always possible to obtain a sample of sputum to test. Young children almost invariably swallow their expectoration and many adults do the same, with the result that the secretion provided for the test consists of saliva and mucus from the upper respiratory tract. If this is the case a negative bacteriological finding is meaningless. This obstacle can sometimes be successfully overcome by examin- ing the gastric contents. A Ryle stomach tube is passed early in the morning before food is taken, the stomach washed out and the syphoned washings centrifuged and examined, first direct, and later by culture. This technique has been found particularly valuable in children, and it has often enabled an exact diagnosis to be made in cases which would otherwise have remained unproved. Cohen and Burton Wood (11) devised the “ laryngeal mirror test ” for adults. The tongue is held gently forwards and a laryn- geal mirror placed so that the vocal chords can be clearly seen, The patient is then asked to cough. The mirror is withdrawn and any sputum seen on the glass is transferred to a slide and examined in the usual way. Gastric lavage is the most convenient method of obtaining sputum from young children; the great drawback to its application to adults is that it cannot readily be employed on a large scale. Nassau (12), accepting the principle that the bacilli are present in many patients who have no spontaneous expectoration and that a more refined method of examination is required, has introduced the laryngeal swab culture technique for their detection, a method originally devised by veterinary surgeons for cattle. The swab consists of a piece of brass or chromium metal wire, 9 inches long and ;'g of an inch diameter, one end being flattened and spirally twisted around which the cotton wool is firmly wrapped. The wire is then bent at an angle. A large number of swabs are sterilised in a tin container and before use the swabs are dipped in sterile water. Two swabs are used on each patient, either with the help of a laryn- geal mirror under direct vision or after some practice without this guide. Each swab is passed down the larynx and the patient asked to cough. After the swabs are taken, the two wires are attached to a piece of paper bearing the patient’s name and other details. When received in the laboratory the wires are straightened with sterile forceps (sterilised by flaming after each swab) and the swab is placed for 5 minutes in a sterile test tube containing 10 per cent. sulphurie acid. It is then transferred to a second sterile test tube containing 2 per cent. sodium hydroxide for a further 8 minutes. Two tubes of media are inoculated with each swab, the surface is smeared with the swab which is at the same time rotated. A modification of Petragnani’s medium is used and cultures are in- cubated at 37° C. for 28 days. After 4 to 5 days the cultures are examined for saphrophytes or contamination and those which are contaminated are discarded. Cultures which are thought to be those of tubercle bacilli are filmed and their acid-fast nature verified by staining. In a subsequent article Munro-Ashman and Nassau (13) have de- monstrated the value of this method in the diagnosis of obscure radiological opacities, such as the solitary focus, and of the minimal lesions discovered by routine mass radiography, and also as a check upon the need for further treatment in those patients who have become “ sputum free ”’ following the induction of artificial pneumo- thorax or other procedures. There is no doubt that this method has proved a definite advance. Examination of the faeces is another method of recovering tubercle bacilli which have been swallowed. It is not so accurate, however, as gastric lavage and is a time-consuming test to carry out. The search for T.B. in smears of sputum and in other tissues has been made easier by the application of *‘ secondary ”’ fluorescence microscopy, an account of which has recently been furnished by Graham (14) and Lempert (15). The method depends upon the fact that certain chemical substances possess the power of absorbing ultra-violet rays and re-emitting rays of longer wavelength which are visible either to the naked eye or microscopically. Bacteria stained with such a chemical agent can be readily detected by the fluores- cence which they emit throughout the time that ultra-violet rays impinge upon them. In the case of tubercle bacilli the chemical agent or “ fluoro- chrome ”’ used is a solution of ,-auramine-phenol which is applied to an ordinary smear of sputum for 8-10 minutes at room temperature and then washed off, to be replaced with an acid-alcohol decolouriser twice for 2 minutes. The smear is washed and blotted dry and treated with a 0-1 per cent. solution of potassium permanganate as a counterstain for background. The smear is now ready for ex- amination on an ordinary microscope under illumination from a mercury vapour lamp as a source of the ultra-violet rays. The bacilli can be seen clearly under the § and ¢ objective : they show up as minute bright yellow needles against a dark red background. The advantages claimed for this method by Lempert are : Specificity. Tubercle bacilli alone among the many organisms which he tested resisted the acid-alcohol decolouriser. Speed. A positive or negative conclusion could be reached more rapidly with this method than with the ordinary Ziehl-Neelsen technique. | Accuracy. In a small investigation on 300 smears there was a slight increase in ‘the number of positives with the F—-M method when compared with similar smears examined by a practised staff using the routine Z—N technique. Clegg and Foster Carter (16) investigated the potentialities of the fluorescence method at the Aoinipeorw Hospital and found it as accurate, more sensitive, and more rapid than the Ziehl-Neelsen technique. They recommended it wherever large numbers of examinations are done. Tuberculin Test. The test commonly used for demonstrating sensitivity to tuberculin, for diagnostic purposes, is the intracu- taneous one of Mantoux in which Old Tuberculin is injected between the dermal layers ; it has now almost universally superseded the original scarification test of von Pirquet. O.'T. is prepared by heat concentration from a culture on synthetic medium and can be obtained from the manufacturers standardised against the Medical Research Council’s International Standard Tuberculin. It is made up in three strengths: 1 in 10,000, 1 in 1,000, and 1 in 100. The dose is 0-1 c.c. in each case. In the United States a purified protein derivative (P.P.D.) has been prepared by Long and Seibert (17) which is non-antigenic and which, therefore, does not sensitise nor lead to the formation of antibodies, but which is as highly potent and specific as the ordinary tuberculin containing antigenic substances. It is proving satis- factory for routine use. In this country the Ministry of Health, acting upon a report of the Standing Advisory Committee, has suggested (Circular 166/45) that the synthetic medium O.T. should be used for routine work to the exclusion of other tests in order to reach uniformity of diagnosis, treatment, and administrative action. The recommendations of this committee -contain much useful advice and information and some of their conclusions will be summarised. For the performance of the test the flexor surface of the forearm is used. After cleaning with spirit 0-1 ¢c.c. of O.T. solution is in- jected into the skin by a special all-glass 1 ¢.c. syringe graduated in tenths of a c.c. In adults the first injection usually consists of 0-1 c.c. of 1 in 10,000 dilution and the result is read at not less than 48 hours and preferably at 72 hours afterwards. A positive reaction is indicated by a palpable oedematous area which should measure not less than 5 mm. in diameter. Erythema alone does not constitute a positive test. IZfthe test with 1 in 10,000 is completely negative it is suggested that in the case of adults a second injection should be made with 1 in 100; in children, and in adults with a doubtful positive, 0-1 c¢.ce. of a dilution of 1 in 1,000 should next be used, progressing to the same quantity of 1 in 100 if this second injection is also negative or doubtful. An indeterminate reaction with 1 in 100 dilution should be recorded as negative. Repetition of the test in these dilu- tions, at once or after three months, will not of itself lead to a positive result in a non-tuberculous person. Freshly prepared solutions for each batch of tests must be used. Attempts which have been made to simplify and expedite the test by evolving a “‘ one-shot ” method are not viewed with favour in this report on the grounds that it is difficult to be certain that the selected strength and dosage employed will detect all the Mantoux positives and, at the same time, avoid severe local reactions in some of them. The importance of a standardised technique such as the above cannot be gainsaid if survey work up and down the country is to be fully correlated, and the suggestions made in this Ministry of Health pamphlet, even if they require subsequent modification, deserve careful consideration, particularly by those responsible for the health of nursing and domestic staff in tuberculosis institutions, for which groups of persons the recommendations are specifically designed. Other methods of tuberculin skin testing have been devised. Moro recommended rubbing into the skin an ointment containing equal parts of lanoline and O.T., redness appearing on the surface in positive reactions. Hamburger’s test consists of rubbing tuber- culin ointment over the sternum, a crop of papules in two to seven days indicating a positive result. The surface tests most recently introduced are the Vollmer patch (Lederle) and the tuberculin jelly (Allen and Hanbury). In the former O.T. is impregnated into the centre of an adhesive strip which is applied to the skin generally alongside the spine. After removal in 48 to 72 hours a slightly raised erythematous area is seen in a positive reaction. Tuberculin jelly is similar in principle and is believed to resist drying better than the Vollmer patch. The jelly is usually applied to an area of skin between the scapulae previously cleaned with acetone. A control is applied over a nearby area. The jelly and control are rubbed on the skin and covered with strapping. ‘The test is said to be equal to a 1:10,000 Mantoux. Both possess the advantage of dispensing with a needle prick which commends them for use in the case of young children. They are not as reliable, however, as the Mantoux test and negative results should be interpreted with caution ; nor can they be so readily placed on a quantitative basis as the intracuta- neous test and thus they do not lend themselves to standardisation. A comparison between the Mantoux reaction and the Vollmer patch and tuberculin jelly test has been made by Deane (18). Fifty children, known to be Mantoux-positive (1 in 1,000) were tested with Vollmer patch; 40 (80 per cent.) reacted positively. When patches 11 months old were used the number of positives was only 8 (16 per cent.). With tuberculin jelly the results were better. Forty Mantoux-positive children were used and the jelly was applied to the cleansed skin, covered with adhesive plaster for 48 hours, and the result read 48 hours later ; 35 (87 per cent.) reacted. With the object of improving the results still further Dean abraded the skin by rubbing it gently for 5 or 6 strokes with fine cabinet-makers’ sandpaper (No. 0) before applying the jelly. He found that all 40 children now reacted positively. The abrading should be only lightly done, insufficient to cause even an erythema, if severe re- actions are to be avoided. Preliminary “‘ sand papering ” thus seems to enhance the value of this simple and painless surface test. The tuberculin reaction becomes positive a few weeks after the primary infection and in most people remains positive for a long time thereafter. There is some evidence to suggest that in elderly subjects sensitivity diminishes and the response wanes. The reaction is temporarily lessened or suppressed in some of the acute exanthematata such as measles or scarlet fever due to the rash (Westwater (19)). In chicken-pox and diphtheria it is unaffected. A negative Mantoux may sometimes be found in the closing stages of advanced pulmonary tuberculosis, at a time when generalised spread of disease occurs, and in some examples of acute miliary tuberculosis. Hedvall (20) has summarised the causes for failure to react to tuberculin as follows : That the patient has never been infected. That the patient has been infected, but : (a) The infection has not “‘ caught on,” (6) The patient is in the incubation period, (c) The positive reaction has not been maintained— (1) owing to the intervention of tuberculous meningitis, miliary tuberculosis, tuberculous cachexia—and other forms of cachexia; also on account of the acute exanthemata (measles), and of whooping cough ; (2) rarely in cases of active tuberculosis ; (3) owing to complete biological healing. The diagnostic value of the tuberculin test, therefore, is neces- sarily limited. A positive response simply means that the initial infection has taken place but gives no guide as to whether this occurred in the remote or the near past. There is no evidence as yet that the promptness with which the reaction appears or its severity has any special clinical meaning. A positive finding in an adult does not necessarily mean that the person is suffering from tuber- culous disease, as ordinarily understood, or that any treatment is required, and the diagnosis of tuberculosis in such a case must rest HAEMOGRAM ‘oi upon other findings. Consequently tuberculin testing has ceased to be employed as a routine in the diagnosis of adult disease, and its use has become largely confined to the physical assessment, ‘before employment, of persons who will be exposed to infection. An exception is provided by Boeck’s Sarcoidosis (non-caseating tuberculosis); in this condition the tuberculin test supplies a valuable link in the chain of evidence in so far as the overwhelming majority of examples, in the early stages at least, exhibit a negative response. In the case of the child the test is of greater importance, and the younger the child the more important it becomes, as the chance of conversion already having taken place is less. The test is of more value in community case-finding than in indi- vidual diagnosis and this is its proper and acknowledged sphere. The routine use of the test in schools will often point to a focus of infection in a family or locality and by concentrating upon the adult members of this family or locality an undisclosed case of tuber- culosis may be discovered. This method was successfully used by Bardswell (21) in his survey of tuberculosis in the island of Cyprus. Sedimentation Test. Some recent work on blood sedimentation and its use in tuberculosis is described in Chapter XII. It is especially valuable as a check on progress and on the success of treatment. It cannot be relied upon for diagnosis. The majority of cases of active pulmonary tuberculosis show an increased blood sedimentation rate, but there are some early cases with no toxic symptoms and a fair condition of general health in which the B.S.R. isnormal. On the other hand, the rate is commonly raised in many other conditions, especially those accompanied by fever. Haemogram. Much work has been done in an attempt to cor- relate the clinical condition of the patient and his prognosis with changes in the blood picture. Arneth attached importance to the indentations or number of individual nuclei in the polymorphonuclear neutrophile leucocytes. He found in healthy individuals :— Mononuclear forms with round or indented nucleus 5 per cent. Forms with two nuclei, 35 per cent. Forms with three nuclei, 41 per cent. Forms with four nuclei, 17 per cent. In tuberculosis he found a predominance of the forms with one or with two nuclei. In one fatal case of pulmonary tuberculosis he found 46 per cent. with one and 49 per cent. with two nuclei. Cummins and Acland (22) discuss the value of this test: and the sedimentation test, and regard them of value as additional evidence. There are no grounds for changing this view. Von Bonsdorff’s modification of this method is to count the nuclei of 100 polymorphonuclear leucocytes. He takes the normal as 275 nuclei per 100 cells. When there are less than this it is called a shift to the left and the prognosis is bad, whereas a shift to the right indicates a good prognosis. | Houghton (23) has worked out an index the formula for which is V.B.—(P+M-+S — 2L), where V.B. is the Bonsdorff count, P the polymorphonuclear cells, M the monocytes, L the lymphocytes, and S the sedimentation rate. The index may vary from 0 to 300, and the higher the figure the better the prognosis. Medlar has worked out an index from the neutrophile-lymphocyte ratio modified by factors for the total leucocyte count and for the percentage of monocytes. These indices are based on the fact that an increase of monocytes and a decrease of lymphocytes indicate activity, and that lympho- cytes increase with healing, monocytes increase with tubercle formation, and polymorphonuclear leucocytes when there is breaking down of tissue and suppuration. Very much the same criticism can be applied to the haemogram as has been levelled against the blood sedimentation rate, namely, that it has practically no value in diagnosis but is of more use in judging prognosis if serial readings are used. Bacillaemia. Lowenstein (24) claims to have obtained cultures of tubercle bacilli from the blood not only of tuberculous patients but of patients suffering from rheumatism, disseminated sclerosis and other conditions not usually regarded as tuberculous, by the use of a special technique. His results have been confirmed by some workers, but others have failed to obtain tubercle bacilli from the blood even of definitely tuberculous patients although his technique has been strictly observed. This investigation is of no practical value in the diagnosis of adult phthisis. Wilson (25) conducted an investigation of tuberculous bacilleemia for the Medical Research Council and reached the definite conclusion that tubercle bacilli are not to be found in a variety of conditions such as nervous disease or rheumatism, but may occasionally be cultivated from the blood in the case of miliary or advanced pul- monary tuberculosis. Serial Observation. The introduction of routine chest radio- graphy of apparently healthy people has led to the discovery of X-ray shadows which in appearance and situation are almost certainly tuberculous. The patient may be free from all symptoms, and all tests to substantiate the diagnosis and to assess the degree of activity may be negative. In the absence of any indication to the contrary such shadows must be presumed to be tuberculous. But it is a mistake to assume too readily that such a lesion is inactive and to dismiss the patient with this assurance, because all tests are negative. An X-ray picture taken three or six months later may show that the opacity has increased in extent, or has softened in the centre, both of which are as much manifestations of activity as the appearance of symptoms or a rising blood sedimentation rate. Every example of such a lesion, unless completely calcified, should be reinvestigated at intervals of three or six months for at least one to two years and possibly at less frequent intervals for even longer. There is no pathognomonic symptom or sign of pulmonary tuber- culosis and it is desirable to emphasise yet again that the early recog- nition of the disease and the assessment of activity depends upon interpretation of the evidence derived from numerous sources, the the last of which, in certain circumstances, is the influence of the passage of time upon the nature and extent of the radiological lesion. References (1) KEErRs, R. Y. and RiegpeNn, B. G. (1945) Pulmonary Tuberculosis. Edinburgh. (2) Smart, J. (1942) Brit. med. J. 1, 604. (3) PATERSON, J. F. (1940) Amer. J. Hyg. 324, 67. (4) Hicu, R. H., Zwerwine, H. B. and Furcoiow, M. L. (1947) Publ. Hlth. Rep. Wash. 62, 20. (5) McWEENEY, E. J., Crowr, M., DUNLEVy, M. and Magan, M. (1946) J. med. Ass. Eire, 19, 162. (6) ANGLIN, A. F. W. (1988) Lancet, 2, 717. (7) Hoye, J. C. and Vaizey, J. M. (1987) Chronic Miliary Tuberculosis. London. (8) AusTRIAN, C. R. and Brown, W. H. (1942) Amer. Rev. Tuberc. 45, 751. (9) Pierson, P. H. (1942) Amer. Rev. Tuberc. 45, 75. (10) Nassau, E. (1942) Tubercle, 23, 179. (11) Conen, R. C. and Woop, B. W. (1936) Brit, med. J. 2, 65. (12) Nassau, E. (1940-41) Proc. R. Soc. Med. 34, 397. (138) Munro-AsHMAN, D. and Nassau, E. (1943) Tubercle, 24, 79. (14) Granam, C, F. (1942) J. Lab. Clin. Med. 27, 531. (15) Lempert, H. (1944) Lancet, 2, 818. (16) CLEGG, J. W. and Foster-Carter, A. F. (1946) Brit. J. Tuberc. 40, 98. (17) Lone, E. R., Aronson, J. D. and SEIBERT, F. (1934) Amer. Rev. Tuberc. 30, 733. (18) Drang, E. H. W. (1946) Lancet, 1, 162. (19) WestwaTer, J. S. (1935) Quart. J. Med. 28, 203. (20) HepvA.t, E. (1946) Acta med. scand. Supp. 170, p. 52. (21) BARDSWELL, N. D. (1938-389) Tubercle, 20, 97 and 165. (22) Cummins, S. L. and AcCLAND, C. M. (1927-28) Tubercle, 9, 1. (23) HoucuTon, L. E. (1931-82) Tubercle, 13, 385. (24) LOWENSTEIN, E. (1980) Miinch. med. Wschr. 77, 1662. (25) Witson, G. S. (1983) Med. Res. Counc. Spec. Rep. Ser. No. 182. CHAPTER V RADIOLOGY In recent years there has been a steady improvement in radio- graphic technique; this improvement is such that films which were considered of a high standard a few years ago are now regarded as being of poor quality. So much now depends on small variations in shape and density of minimal shadows seen in serial films that it is becoming increasingly recognised that a skiagram of the chest must conform to certain standards before a diagnosis can be made with any degree of certainty. The positioning, pene- tration, exposure, processing and illumination must be correct, and careful attention to these details is necessary in every case. Un- fortunately, films are too often presented for interpretation which exhibit a multitude of faults which could have been easily prevented by good technique. These faults can lead to errors in diagnosis ; it is therefore wiser to repeat the skiagram than to attempt to read a faulty film. Progressive improvements in apparatus have in- creased the simplicity of operation, but no X-ray plant can eliminate errors due to wrong positioning, dusty screens, incorrect penetration, bad developing, insufficient washing and damage due to transport or storage. These are factors to which the personal care and atten- tion of the radiographer must be continually directed. Technique Positioning. Chest skiagrams are usually taken, except in infants, in the upright position. The postero-anterior position being most frequently adopted, but valuable information can be obtained from antero-posterior, lateral and oblique positions, par- ticularly in cases with minima] lesions. Postero-anterior position. 'The person to be examined should stand with feet together in a relaxed position leaning slightly forward with the chest pressed evenly on both sides against the casette. The shoulders are pressed forwards and downwards and the hands placed below the waist line and above the buttocks de- pending on the length of the arms. The position in each case will vary with the physical characteristics of the individual but it must be always one that will separate the scapulae as much as possible. This is best done by pressing the elbows well against the stand and rotating the arms so that the dorsal surface of the hands rests on the buttocks, or the arms rotated medially and brought forward to the side of the stand. The chin should rest comfortably over the midline of the casette so that as large a surface of the chest makes contact evenly with the casette. The importance of even contact is stressed because in the majority of persons it is natural to press harder with the right side than the left, thereby causing an uneven density in skiagram which might be taken to indicate pleural thickening. Antero-posterior. This position is useful for examining apical lesions, and in this way a minimal lesion will in some cases be clearly brought into view when it is only imperfectly seen in a postero-anterior film. The subject stands with face towards the X-ray tube in a similar position to the postero-anterior position, leaning in relaxed position with the back against the casette but with the spine slightly flexed and the chin held upwards and for- wards. Lateral position. This may be either of the right or left side. The arms are folded above the head and the selected side placed against the casette. In the Medical Research Council’s Report (1) on mass miniature radiography of civilians, it is recommended “ that for upper, anterior lung lesions, the shoulders are pressed backwards ; the chest and chin are thrust forwards, and the exposure made on full inspiration with the tube centred in front of the shoulders.”’ It is most important that a true lateral skiagram is obtained so that careful checking of the position is needed before the exposure is made. ‘The same report gives details of the oblique position which is of value in separating the shadows of the heart and spine in the skiagraph. Right anterior oblique position. 'The chief points to attend to in positioning for this view are that the arms are folded above the head and the subject is rotated under the screen so that the right side is towards the observer until “the space between the anterior borders of the bodies of the vertebrae and the posterior border of the heart is at its widest, or until the minimum overlap is obtained.” The subject is then kept in that position and presses against the casette and the exposure made with the tube at 36 inches. “In the left anterior oblique position, the subject. is rotated until the aortic triangle is visible ; the posterior border of the heart usually overshadows the vertebral bodies. For an upper lesion the oblique view is taken with the arms lowered, the exact position being established by screening.” Chest skiagrams are usually taken on full inspiration, but it is important that the subject does not change his position in carrying out this instruction. A fourth position which is of value in determining middle lobe collapse is the lordotic position. The lordotic position. The positioning for this is described in the M.R.C. Special Report as follows :— ‘“* The subject, who is placed with the hands holding on to the sides of the stand, is asked to practise bending slowly backwards and forwards from the waist, in preparation for similar instructions to be given during the fluorescent screen examination. On screen- ing, it is possible to decide the best position to show the sharp tri- angular shadow of the lesion. The actual degree of dorsiflexion required will vary from subject to subject. A right lateral view completes the examination.” In children a considerable degree of patience is required to obtain the necessary relaxation for a good skiagram. Interpretation. Methods of interpretation of skiagrams vary con- siderably, and the value of written reports is reduced because there is no universal standard terminology or graphic representation of skiagraphic appearances in diagrammatic form. The Joint Tuber- culosis Council (2) issued in 1939 a valuable guide and made recom- mendations which, if more widely adopted, would remedy the present unsatisfactory situation. The Report recommends that in the inter- pretation of skiagrams the terms “‘ lobe ”’ and * base ” be abandoned and substituted by i zone. -- Thee zones.” are recognised : The upper zone is that area above a straight line running through the lower borders of the anterior ends of the second ribs. The middle zone is that area bounded by the above line and one running through the lower borders of the anterior ends of the fourth ribs. The lower zone is the remainder of the lung below the middle zone. The apex may be defined as that portion of lungs seen above the level of the clavicle when the skiagram has been taken in the postero-anterior erect position. The report also recommends the following symbols for use in diagrams : Homogeneous opacity. WY Dense mottling (more shadow than air). ee ¢s Discrete mottling. ee Cavity without fluid level. wo Cavity with fluid level. Signifying displacement, e.g., mediastinum, trachea, inter- lobar fissures, etc. ° Calcification. Miniature Radiography In order to obtain skiagrams of a large number of persons in a short period of time a technique has been developed whereby the image on the fluorescent screen is photographed on to sensitive film thereby producing a miniature negative which gives a permanent skiagraphic representation of the individual’s chest. The size of the miniature varies according to the apparatus used and may be 35 < 35 mm., 70 x 70mm, or 4 X Sinches. It will be appreciated that the term miniature radiography is a misnomer and that a more correct description of the process should be miniature fluorography. For this indirect method of producing skiagrams on the 35 mm. film special apparatus is needed the fundamentals of which may be briefly summarised as follows :— High Tension Unit—output from 100 to 400 mA with maximum kVp of 100 and 91 respectively with screening device at 3 mA and 88 kVp. The set operates on 50 cycles current supply on voltages between 140 and 250 single phase and needs a cable that can carry 100 amps. Tube—rotating anode tube with dual focus of 1 mm. and 2 mm. square. Fluorescent screen—16 16 inches with a radiographic grid. Camera Unit—electrically or hand controlled camera fixed to light tunnel. Aperture f/1-5 and focal length of 2 inches and capable of holding 50 to 100 feet of 35 mm. film. The skiagrams are taken at an anode film distance of 36 inches and an exposure of 12 to 48 milliampere seconds or (0:06 to 0:24 seconds at 200 mA) there being a special arrangement for recording the number and date of the film which eliminates the possibility of film-subject errors. The apparatus weighs approximately 18 cwt. and is transportable but requires a special power generating van to provide complete mobility. Such a generator must have an output of 20 kVA. Full details of the apparatus may be found in the M.R.C. Special Report, No. 251. A recent improvement has been devised whereby the exposure time is regulated by the degree of illumination of the fluorescent screen as measured by a photo-electric cell. This device eliminates the necessity of chest measurement and the calculation of the exposure time in each case. It should be a considerable help in obtaining comparable films in all cases and no doubt will be a standard fitting to all sets in the future, both for fluorography and radiography. Mass Miniature Radiography. The idea of making radiographic ‘examination of large sections of the population to discover and detect pulmonary tuberculosis has been in the minds of many people ever since Roentgen discovered X-rays, but the first suc- cessful effort at screen photography on a large scale was made by De Abreu in Brazil in 1936. This was by photographing the image on the fluorescent screen and the majority of persons associate this method with the term “ mass radiography ”; there are, however, four possible ways of carrying out a radiographic survey of a group of people :— | (i) By means of a full-sized celluloid film. . This is costly and slow, but gives the greatest accuracy. (ii) By means of the paper film. This is also slow and less accurate but considerably less expensive. (il) By fluoroscopy. This method is easy and cheap but it is not very accurate and provides no permanent record. It also involves certain risks to the operator. (iv) By photographing the image on the fluorescent screen and thereby obtaining a miniature skiagram. This method is rapid, relatively inexpensive and reasonably accurate. All four methods have been used but the main developments have taken place along the line of producing miniature skiagrams on 35 < 85 mm, 70 * 70 mm, or 4 X 5 inch films. The 85 x 35 mm. unit is the one which is used mainly in this country and has the advantage of speed, economy and general ease of manipulation. In Scandinavia, the 70 x 70 mm. film is finding greater favour where it is claimed that the larger size is interpreted with greater accuracy, is less fatiguing to read and reduces the number of large size films in that a decision can often be made by inspection of the miniature alone. The 4 x 5 inch miniature has been used mostly in America. The apparatus is more costly, immobile, and the process much slower than when using the 85 mm. film. To obtain satisfactory results a 500 mA unit is necessary which involves a high power main circuit. The method has not been used to any extent in this country. Which ever method is used it must be realised that mass radiography has limitations. These have been summarised by Jessel (8) under these headings : (1) A skiagram can only illustrate such condition as is present at the time of examination ; a negative finding is no guarantee that tuberculosis will not become manifest at a later date. Periodic re-examination of cases where the first skiagrams show no abnormality is necessary. (2) The interpretation of shadows seen in a skiagram is often a matter of difficulty, particularly with regard to activity of the disease. (3) X-ray examination by itself is often insufficient to establish a diagnosis. The most it can frequently offer is an appear- ance consistent with one or more diseases. It is helpful to remember these limitations when interpreting miniature skiagrams. Results of Surveys Reviewing the results of mass radiography it is convenient to refer firstly to the findings in the Services. In these surveys it is found that an average of 0-4 per cent. of the men examined showed active pulmonary tuberculosis. Important observations in the Services have been published by Cooper (4) who found 0-49 per cent. active cases among 22,000 members of the second Australian Imperial Force, and Dudley (5) who found an incidence of 0-45 per cent. active tuberculosis in trained men and 0-82 per cent. in new entrants of the Royal Navy. A second survey of 100,000 Australian troops by Galbraith (6) produced an incidence of 0:56 per cent. active tuberculosis and 0:47 per cent. quiescent disease. A survey by Brooks (7) of 166,598 men from the Royal Navy showed an incidence of 0-33 per cent. active tuberculosis, and in the R.A.F. Trail (8) demonstrated active disease in 0:27 per cent., and arrested tuber- culosis in 0:33 per cent. in a survey of 19,969 personnel. Temple Clive (10) examined 30,000 W.A.A.F. recruits and found 0-33 per cent. with active tuberculosis and a total of 1-75 per cent. with tuberculous lesions. More recently the results of mass radiography published by Trail (9) on 250,027 personnel of the Royal Air Force— 190,076 were males and 59,951 females—mostly between the ages of 17 and 30 revealed : Active tuberculosis in 0°28 per cent. males, 0°36 per cent. females, Inactive is » 0°49 2 Vo ODS A an and the sputum was positive in 0°07 per cent. males and 0°08 per cent. females of the total examined. These statistics show the value of mass radiography in a selected community all of whom presumably had had a medical examination and been passed fit for service. In civilians Hall (11) in a survey of 1,595 women factory-workers found 4 cases of tuberculosis and 17 who required further investi- gation. A survey of 11,342 Viennese women born in 1923 found 1-21 per cent. (41 infectious and 96 non-infectious) cases of active pulmonary tuberculosis. In London the Mass Radiography Unit under the direction of Stuart Robertson during 1944 in a survey of 45,682 persons found 1°4 per cent. radiologically inactive lesions, 0°73 per cent. were considered as probably tuberculous, and 0:24 per cent. of the total examined were advised to have sanatorium treatment. In Bir- mingham during the same year 13,692 people were examined and of these 1,401 presented some form of abnormality in the chest skiagram : 168 (1-2 per cent. of the total examined) were referred for detailed investigation and of these 50 (0-36 per cent. of the total) were found to be suffering from active tuberculosis (12). An inves- tigation by Pointon Dick (13) on factory groups in Middlesex in which he examined 34,227 persons and found evidence of pulmonary tuberculosis, either healed or active, in 1,435 cases, 484 of which showed significant lesions, 88 of whom (0-3 per cent. of the total) required treatment. He estimated that at the time of the survey there were some 3,000 undiagnosed cases of pulmonary tuberculosis in the county of Middlesex in need of treatment and that half of these cases were without symptoms. The percentage of active cases of tuberculosis found by mass radiography varies according to the age, sex, occupation, social standing and selection of the group examined. This is seen in the report of Edwards (14) on the examination of 162,000 adolescents and adult persons in New York in which the percentage of chronic pulmonary tuberculosis varied from 0-3 per cent. to 16-0 per cent., the highest figure being in transient and homeless men and the lowest in college students. A similar variation is shown in a collection of statistics from various countries by Banszky (28) in which the active cases discovered varied from 0:24 per cent. in Holland to 17-9 per cent. in China. In the work done on patients in the London County Council mental hospitals approximately 4 per cent. of the male and 2-5 per cent. of the female patients have been found to have active or probably active tuberculous lesions. Trenchard (15) analysed 200 consecutive cases of active pul- monary tuberculosis discovered as a result of mass radiography of Royal Air Force personnel] and found a positive sputum in 61 cases. The lesions varied from Assmann’s focus (12 cases), true apical tuberculosis (10 cases) ; and 178 cases of the fibrocaseous type. In 184 cases there were physical signs in the chest but in no case had the patient considered any symptoms that he may have had sufficient grounds for troubling his medical officer. There was an acknowledged family history of tuberculosis in 33 cases and 37 ad- mitted contact with persons suffering from pulmonary tuberculosis. The scheme to examine by radiography a large proportion of the population is slowly developing. Up to June 1946, there were 19 units operating among civilians and 1,111,000 persons had been examined by that date, of whom 4,200 were diagnosed as suffering from active tuberculosis. (Ref. Med. Officer, Dec. 1946.) It is im- portant, however, that our case finding methods do not advance too far ahead of our facilities for accurate diagnosis, assessment, and treatment, as the effective value of mass surveys is determined by the availability of such facilities to classify the lesions found in the survey. When there is co-ordination between all the anti-tuber- culosis services, the value of radiographic surveys becomes very definite. This has been demonstrated in Sweden by Nelson (16) who, in his fluorographic survey of 44,072 personnel of the Swedish Navy (1941-42), found 1,209 (2-74 per cent.) with suspicious markings. These were further divided into the following categories :— Doubtful pathological changes (9-0 per cent.) ; calcified lesions (30-0 per cent.) ; lesions of intermediate activity (59-3 per cent.), and those with cavitation (1-7 per cent.). By following up these cases he found that the risk of death for the fluorographically suspect cases is double the normal mortality for corresponding age groups, whereas the mortality for the open cases discovered by the survey appears to be four times less than the average of open cases. ; The need for following up the suspect cases has been clearly demonstrated by Brooks (17), who, in a survey of 1,826 minimal lesions the stability of which was uncertain, discovered in ratings of the Royal Navy, found that 191 of these lesions showed signs of activity during the two-year period of observation ; the majority breaking down in the first year. The figures of Brooks are parti- cularly interesting because they throw light on the significance of the *“‘minimal”’ lesion discovered by mass radiography. Of 479,373 apparently healthy male personnel of the Royal Navy 7-27 per cent. had radiological signs of adult type pulmonary tuberculosis, and in 47-9 per cent. of these the lesion was minimal. Of 23,344 female personnel 9-01 per cent. had similar evidence of tuberculosis, and of these the lesion was minimal in 55-4 per cent. The minimal lesions were investigated in 2,911 sailors and 16 per cent. showed active infection, 63 per cent. appeared to be inactivé but the stability of the lesion was in doubt, and in 21 per cent. the disease was arrested. Brooks concludes that “‘ the findings indicate that a diagnosis of apparently inactive minimal tuberculosis in males under 50 should imply out-patient supervision, together with regular in-patient re- examination during the next two years.’ For patients under 30 this observation should probably last longer. Supervision should be combined with appropriate modification in the patient’s mode of life. Opportunities for “ industrial convalescence’? may be needed. These are ideal precepts but serve to show the respon- sibility and liabilities which mass radiography schemes impose upon those organising them. The infectivity of cases showing lesions discovered by mass radiography has been investigated by Bigger (18) who found one positive case among four that had been diagnosed as “‘ pulmonary infiltration considered to be non-tuberculous” and two positive cases among five cases diagnosed as “‘ healed pulmonary tuberculosis, no evidence of activity.” In all cases culture of both sputum and gastric juice was found to be practicable, valuable, and an early diagnostic method. Webster (19) has investigated, bacterio- logically, 1,548 persons, mostly from the Australian Military Forces, who were found to have abnormal chest shadows. Tubercle bacilli were discovered in 364 of these individuals and 189 of these positive cases said at the time of the examination that they felt quite well and fit. The work also shows that care must be exercised in diagnosing individuals non-tuberculous, or inactive tuberculosis, until the fullest investigations have been carried out. Also the importance of ensuring that the degree of search for evidence of activity is of the same standard throughout when series of mass radiography observations are being compared. It will, however, be impossible to ‘carry out serial examination on all the population as it would require a vast staff with a number of units continually operating. The best that can be done is to examine as large a number of groups as possible and pay particular attention by serial examinations to susceptible age groups and industries where there is a known risk of tuberculosis. In this way the most profitable results will be obtained from the available facilities. Classification of the Types of Lesion likely to be found with Suggestions as to Procedure Classification of the abnormals is difficult, for the significance of shadows which simulate tuberculosis cannot be determined in all instances except by a period of observation. Further research is needed on the pathogenesis of tuberculosis before a satisfactory classi- fication can be made, although, as Edwards (20) has pointed out, the effectiveness and value of mass surveys is determined by the availability of facilities to classify promptly and properly the sig- nificance of lesions found in the survey. It must be remembered that a final diagnosis cannot be reached by inspection of the miniature film alone and an abnormality found in this way spells the need for a full clinical and radiological examina- tion and nothing more. It is after such an examination has been conducted that a tentative diagnosis can be made and appropriate steps taken. The types of lesion commonly encountered in any mass radiographic survey can be conveniently listed on the basis of recent experience as follows :— Early Active Disease with or without Cavitation. The presence of cavitation in the majority of instances implies activity and necessitates appropriate treatment. In those cases in which cavitation is absent activity is inferred either from the existence of suggestive symptoms extracted from the patient by direct questioning, or else is obvious as a result of the clinical investigation which follows and which will be briefly outlined under the heading of ‘‘ Minimal Lesions.” For this type of case also, necessary treatment in an institution, possibly with collapse therapy, must be arranged. | | Calcified Foci. So long as these foci are the only abnormalities seen and are unaccompanied by softer shadows they can be ignored and no further action need be taken. Calcified Primary Complex. Under this title is included both the peripheral and the glandular components. It can be disregarded. Minimal Lesions. This is the most important group of all for it will probably contain the majority of the abnormalities discovered. Moreover, the satisfactory management of these individuals presents a difficult problem. A definition of a minimal lesion is bound to possess an individual bias and is therefore subject to variation, the one recommended by the American National Tuberculosis Asso- ciation reads as follows :— ** Slight lesions without demonstrable excavation confined to a small part of one or both lungs. The total extent of the lesions, regardless of distribution, shall not exceed the equivalent of the volume of lung tissue which lies above the second chondrosternal junction and the spine of the fourth or body of the fifth thoracic vertebra on one side.” From the radiological standpoint it is often impossible to say for certain whether the lesion is recent or old-standing, whether active, quiescent, or finally arrested. The subject is discussed further in Chapter XIII when considering classification of types of tuberculosis. Thickened Pleura. Provided it is possible to be reasonably sure that the abnormality is a thickened pleura and nothing more significant, and provided there is no parenchymatous lesion visible, this abnormality can be disregarded. An attempt should be made, however, to make certain that the radiological change is not of recent occurrence. Moderately Advanced Disease. ‘This may take the form of a quiescent fibrotic lesion or one exhibiting signs of activity, possibly with cavitation. Treatment will be required in accordance with the type of lesion found. Non-tuberculous Respiratory Disease. A watch should be kept for non-tuberculous conditions in any mass radiographic survey. The conditions generally encountered include — bronchiectasis, cystic disease of the lung, pneumonokoniosis, and tumours of various types including carcinoma of the bronchus. Cardiovascular Disorders. Congenital and acquired lesions of the heart will not uncommonly be discovered by this method. Manifestations of rheumatic carditis, hypertensive heart disease, congenital lesions and unsuspected aneurysm of the aorta are all capable of being disclosed for the first time by routine radiography. Other Abnormalities. A full list of possible lesions will not be given. Diseases of the bony thoracic cage (kyphoscoliosis, fused and bifid ribs, cervical ribs), eventration of the diaphragm and dia- phragmatic hernia, intrathoracic goitre, etc., may all be seen. Administration and Cost of a Mass Miniature Radiography Unit The application of mass miniature radiography to the civilian population after its value had been proved in the Services brought with it a number of administrative problems many of which, even after a number of years, have not been completely solved. Agree- ment has, for the most part, been reached on the staffing of the unit, the method of propaganda, selection of centres and the transport of persons for examination, but on the classification and disposal of those found to be abnormal and the relationship of the unit to existing health services there is still a considerable divergence of opinion. The minimal staff required for each unit consists of a director, two radiographers, one dark-room technician and three clerks. This team is assisted by a radiologist, a general physician and a tuber- culosis expert in the reading of the large films taken as a result of the reading of the miniatures by the director of the unit. In some units it is the practice for the director to make a clinical investiga- tion of all the persons with abnormal chest films, whilst others pass them to the tuberculosis officer. General Public Neuiiee Bin Review by Divector of Unit Films showin no abnormality No Action. Review by panel of. specialists. No significant Lesion Probably AY ignificant non- abnorinality Tuberculous Tubercrilous abnormality Ed No immediate action Report sent Report sent but may be to General to General reviewed again after Practitioner Practitioner a period. with film with film Patient sent to General or special Tuberculosis hospital Jor observation Officer if necessary. Observation at Sanatorium ome or at Or special hospital ; treatment. Fig. 2. Another method—probably more consistent with the fundamental principle that the main function of mass radiography surveys is to discover those with chest abnormalities—is to pass the information obtained to the general practitioner and indicate to him the nature of the abnormality and suggest to him the direction which the H. & R. TUBERC. 4, disposal of the patient should follow. If no action is taken by the general practitioner then disposal can be recommended to the appropriate authority by the director of the unit on the advice of the team which interprets the large films. It has been suggested that mass radiography should be organised as a sorting process which reveals those persons with abnormal chests and should be ancillary to the existing public health services. In London a scheme has been developed in which this is the fundamental principle and the procedure can be represented by the diagram on page 97, which has been based on that drawn up by Stuart Robertson for the London County Council. The cost of a mass radiography unit is of considerable interest as it is often imagined that because the actual film is very inexpensive the unit can be maintained at little cost. The choice of apparatus will always be mainly a matter for the individual but considerable controversy exists as to the relative efficiency of the larger-sized films as compared with the 35 x 35 mm. size. Plunkett, Weber and Katz (21) have compared the value of various sizes and some indication of the superiority of the 4” x 5” film over the 35 mm. film is given in the following table compiled on the examination of 1,000 persons :— No. of persons Percentage of signi- Type of Film ficant existing rd Lesions Discovered 975 1 ieey ph Eres 100 94.4 AES D's 98°3 614 Oi on eo hs 91°8 The total cost of each method including the checking of abnormal miniatures worked out for each case as :— Dollars Iie SeUFS 10.22 eS eA 2.08 35 X 35 mm. . 1.85 Of course the cost per film will depend upon the number of subjects examined as the capital costs remain almost the same for a few or a considerable number of exposures. In 1943 Heaf (22) estimated that the total cost of one mass radiography unit was £30,000 per annum. ‘This figure includes the purchase of the equipment, salaries of the team, maintenance of the depot and the running cost of 100 observation beds which are thought to be necessary for in- vestigating doubtful cases. The full benefit of mass radiography surveys will not be obtained until sufficient units are operating to allow serial radiography to be practised among the age groups most susceptible to the infection, and mass radiography will not exercise its full function in the eradication of tuberculosis until such surveys are associated with mass tuberculin testing particularly among school leavers and young adults. The advantage of such a combination has been fully appre- ciated in Scandinavia, and in Norway a Bill has been drawn up by Galtung Hansen to make radiographic examination, skin testing and B.C.G. vaccination compulsory when recommended by the public health authorities. Tomography The use of the tomograph to eliminate in the skiagram parts of the body lying in front of or behind the lesion and to avoid super- imposition of shadows, has become more general in recent years and no diagnostic centre or well-equipped sanatorium should be without facilities to obtain efficient tomograms. The apparatus can be attached to most good X-ray plants at a comparatively small cost and the technique is not difficult to acquire by a skilled radiographer. The fundamental principles remain the same in all varying types of instruments which are on the market and have been aptly described by McDougall (23) as “ co-ordinating the motion of the X-ray tube and the film around an object which remains fixed during the exposure.” In its simplest form the tomograph consists of a pendulum revolving round a horizontal axis. At the top of the pendulum is the X-ray tube and at the bottom the film. The object to be radiographed rests between the tube and the film, and objects which lie on the particular plane which is in focus are constantly projected on the same point of the film, while objects lying in any other plane (not in focus) throw their shadows on different points of the film. In this way the shadows of all objects above or below the horizontal plane which is in focus are obliterated. The plane in focus can be varied so that a series of tomograms can be obtained -at depths increasing by 2 cm. from the film. The usual routine is to take sections of the chest with the X-ray tube at 40 inches from the film on which the patient usually lies in the antero-posterior position. McDougall states that the actual thickness of the cross- section varies with the extent of the are described by the tube— the greater the arc the thinner the layer—the smaller the are the thicker the layer. The tomograph is very useful in investigating the area of lung in the straight film which is covered by the clavicle, and the first rib. It also is particularly useful in the investigation of doubtful shadows around the hilum and in areas of lung over- shadowed by fluid or thickened pleura. ‘Tomography in the vertical position is not frequently used in chest radiography although it has its advantages when fluid is present in a cavity. It must, however, be remembered that much can be discovered by taking antero- posterior, lateral and oblique films, and by lowering and tilting the X-ray tube or using more penetration and it is often possible to dispense with the use of tomograph. This method of angular radio- graphy has been described by Ramo and Lustok (24). Bronchography and the Bronchopulmonary Segment Accurate information concerning the condition of the bronchial tree may be of considerable practical importance in tuberculosis, and in the last few years bronchoscophy and bronchography with iodised oil have been increasingly practised. The question of the association between tuberculosis and bronchiectasis is discussed in Chapter VI. Foster-Carter (25) (26), and others, have investigated the anatomy of the bronchial tree by means of corrosion casts and broncho- graphy, and have depicted the relations of the main divisions of the bronchi and those segments of the lung supplied by them. From this work has emerged the conception of the bronchopul- monary segment as the unit of pathological anatomy. In a recent publication Foster-Carter and Clifford Hoyle (27) have related the findings to the interpretation of the skiagram. , At the present time this work is more directly applicable to non- tuberculous respiratory disease than to pulmonary tuberculosis, and for this reason, and also because the terminology used by different authors is not yet standardised, the subject will not be discussed further at this point. It is probable, however, that it will become increasingly important. RE ne, TS et References ) MepicaL RESEARCH COUNCIL (1945) Spec. Rep. Ser. No. 251. London. 1) JOINT TUBERCULOSIS COUNCIL (1939) Spec. Rep. No. 16. 3) JESSEL, G. (1941) Brit. J. Radiol. 14, 206. ; ‘) CooPER, E. L. (1940) Brit. med. J. 2, 245. ) DuDLEY, S. F. (1940-41) Proc. R. Soc. Med. 34, 401. }) GALBRAITH, D. (1941) Brit. med. J. 1, 699. ‘) Brooks, W. D. W. (1942-48) Proc. R. Soc. Med. 36, 155. ) Trait, R. R. (1942) Lancet, 1, 609. ) et al. (1944) Brit. J. Tuberc. 38, 116. )) CrivE, F. T. (19438) Tubercle, 24, 63. ) Hatt, A. S. (1942) Lancet, 1, 161. ') British Medical Journal (1945) 2, 932. ) Dick, W. P. (1945) Brit. med. J. 2, 568. ) Epwarps, H. R. (1940) Brit. med. J. 1, 390. ) TRENCHARD, H. J. (1948) Lancet, 1, 366. ) NeEtson, A. (1946) Acta tuberc. scand. Supp. 16. ) Brooks, W. D. W. (1944) Lancet, 1, 745. ) BicceEr, J. W. (1943) Lancet, 2, 699. ) WEBSTER, R. (1943) Med. J. Aust. 2, 61. . ) Epwarps, H. R. (1945) N.Y. St. J. Med. 45, 269. ) PLUNKETT, R. E., WEBER, G. W. and Katz, J. (1941) Amer. J. publ. Hin. 315 772: ) Hear, F. R. G. (1943) Publ. Hlth. 56, 112. ) McDovea.t, J. B. (1940) Tomography. London. ) Ramo L. and Lustox, M. J. (1940) Amer. Rev. Tuberc. 6, 738. ) Foster-CartTer, A. F. (1942-43) Proc. R. Soc. Med. 36, 451. ) (1942) Brit. J. Tuberc. 36, 19. ) and Hovte, C. (1945) Dis. Chest 11, 511. Reprinted in Brompton Hosp. Rep. 1946, 15, 85. ) Banszxy, L. (1942) Lancet, 2, 693. CHAPTER VI CERTAIN COMPLICATIONS AND ASSOCIATED CONDITIONS Haemoptysis THE amount of blood expectorated varies from a sudden massive outpouring due to the rupture of a blood vessel spanning a chronic cavity, to a mere staining of sputum, the result of capillary congestion. Between these two extremes every degree of severity is seen and the haemorrhage may be continuous for several days or recur at intervals. In some women with pulmonary tuberculosis bleeding from the lungs may occur regularly at each menstrual period. Massive haemoptysis due to vascular rupture may be im- mediately fatal or cause death from suffocation within a very short time; there is little chance of averting the outcome. Fortunately, however, this form of haemorrhage is exceptional and haemoptysis is not generally fatal, although it may have serious consequences by blocking the bronchial tubes with blood and so giving rise to pulmonary atelectasis, septic pneumonia or a spread of tuberculous disease. The general principles employed in the management of this im- portant complication do not need special emphasis. The patient is best nursed sitting up or in a semi-recumbent position, slightly in- clined towards the affected side, as this prevents retention of blood’ and spread to the opposite lung. Whether injections of morphia should be used as a sedative is still a subject for debate in view of the danger of damping down the cough reflex, with the result that blood is retained in the bronchial tubes. There is a risk of this if morphia is given in large doses, but smaller doses are without signifi- eant effect upon the cough reflex and serve a useful purpose in calming an excessively anxious patient and in controlling all but essential coughing. Burrell advised an initial injection of morphia to be followed by a bromide mixture if required. The value of the group of drugs which are believed to exert an effect upon the pulmonary blood pressure has yet to be proved. Likewise, there is no satisfactory evidence that a deficiency of calcium in the blood is in any way responsible for the hemorrhage, although administration of calcium in the form of the chloride or gluconate has sometimes been followed by cessation of bleeding. It is, however, with substances used to increase the coagulability of the blood that most of the recent work has been concerned. Morlock and Scott Pinchin (1) found that the intravenous injec- tion of 10 c.c. of a 1 per cent. solution of congo red checked haemoptysis. It is said to reduce the clotting time and increase the blood platelets, monocytes and fibrin content of the blood. It may lead to a slight rigor, and in large doses causes severe shock, but the risk of a rigor can be minimised by using a freshly prepared solution and dissolving the substance in triple distilled water. It is not effective in smaller doses than the one stated. It is important to ensure that none of the solution reaches the subcutaneous tissues round the vein as congo red acts as an intense irritant. The discovery by Dam and Schonheyder of an accessory food factor (“‘ koagulationsvitamin ”’ or vitamin K) which was essential for the manufacture of prothrombin by the liver and the withholding of which from the diet of newly hatched chicks caused fatal haemor- rhages, has been followed by research into the use of the substance in various haemorrhagic conditions. Levy (2) has investigated the pro- thrombin values of the blood in tuberculosis. He found that one- third of his patients with pulmonary tuberculosis had evidence of hypoprothrombinaemia whereas a control group showed no signs of such a deficiency. The hypoprothrombinaemia reached its lowest level in that group which displayed a tendency to haemoptysis. By giving vitamin K Levy regulated the prothrombin deficiency and succeeded in stopping the haemorrhage. Not all workers have been able to confirm Levy’s findings. A number of normal people have been found to have low prothrombin values in the blood. Moreover, there is no strict correlation between the degree of prothrombin deficiency in -the blood of tuberculous persons and their tendency to haemorrhage. Garcia and Lopez de Ines found that in two-thirds only of their patients with haemo- ptysis was the amount of prothrombin diminished, in the other one- third it was normal. From their observations on twenty cases these authors claimed to show (1) that the deficiency of prothrombin is favourably influenced by vitamin K; (2) that a rise in the pro- thrombin level is accompanied by cessation of haemorrhage, and. (3) that vitamin K when taken by mouth is as effective as when given by injection. Further work along these and similar lines is required before the ability of vitamin K to check pulmonary haemorrhage can be regarded as proved. In severe repeated haemoptysis collapse therapy may have to be used to control the bleeding, and of the various measures available the artificial pneumothorax is the one of choice. In view, however, of the natural tendency for pulmonary haemorrhage to cease spon- taneously, and in view also of the possible value of the drugs enumerated, caution should be exercised in employing pneumo- thorax for the sole purpose of combating this one symptom if other features of the case contra-indicate its use. In more chronic cases, or in those with adherent pleurae, the question of whether a thoracoplasty is justified or not is often raised. Here it is even more important than in the case of the pneumothorax to assess the suitability of the disease for the procedure. If on other grounds the operation is indicated the tendency to haemo- ptysis need not be a bar to its performance. To run some risk in the management of this complication is per- missible, but it is probably safer to push the simpler methods of treatment to the limit and to use collapse thereapy in a haemorrhage- free period to forestall a recurrence. Tuberculous Enteritis Tuberculous enteritis is a common complication of far advanced or moderately advanced disease and has been estimated by post- mortem studies to occur in 60 per cent. to 80 per cent. of such cases. The diagnosis in the early stages is not easy. Kruger and Perlberg (4) place reliance upon (1) the presence of a T.B. positive sputum; (2) symptoms referable to the alimentary tract which were present in 96-5 per cent. of their patients, and (3) a chara- teristic ileocaecal spastic filling defect observed in the course of X-ray studies of the intestinal tract. The common symptoms are diarrhoea and abdominal pain but the complication can be suspected if anorexia is associated with a progressive loss of weight for which the condition of the lungs does not seem to be wholly responsible. Rosencrantz and Piscilelli (5) believe that active intestinal ulcera- tion is accompanied by a characteristic temperature response, intermittent in type and with an evening rise of 100° F. as @& mini- mum and 102:5° F. (sometimes 108° F.) as a maximum. These authors claim that in chronic, uncomplicated pulmonary disease, the evening peak is lower, whereas if other complications are pre- sent it is higher, than 103° F. The most important aspect in the treatment of this condition is to cut off the source of the bacilli by converting the sputum from positive to negative. The very nature of the pulmonary disease often renders this impossible. Collapse therapy should be used if the case is suitable. Pneumoperitoneum has been found of value for the relief of abdominal pain due to enteritis and may indirectly exert a favourable influence upon the lung disease by upward ‘pressure upon the diaphragm. Diet is important in the management of tuberculous enteritis and should be light and nutritious, easily digestible, and one which leaves little residue. The personal idiosyncrasies of the patient should be studied. Milk is often best omitted, or advised only in moderation, for it may cause distention and increase discomfort. Attempts have recently been made to treat the condition with a high-calorie, high-vitamin diet without overfeeding. Cod liver oil, vitamin B complex and tomato juice have been used and success has been reported. For example, McConkey (6) studied two almost exactly similar groups of patients, to one of which he gave eod liver oil and tomato juice and found symptoms of intestinal tuberculosis in 1 per cent. : in the other group which did not receive this special treatment the incidence of such symptoms was just over 10 per cent. He believes that this treatment not only alleviates symptoms but causes X-ray evidence of the disease to disappear. Keers (7) believes that enteritis may occur in relatively early treatable disease more often than is generally realised and that the prognosis in such cases is more favourable. He successfully treated five out of six patients with a low-residue, high vitamin diet, with calcium, and with local application of ultra-violet light to the abdomen. Some of his patients were sufficiently improved by this means for surgical collapse measures to be entertained. Tuberculous Laryngitis Involvement of the larynx in the course of pulmonary disease remains, as it has always been, a grave complication. Occurring generally, but by no means always, towards the closing stages it can in such cases be attributed to the free passage over the cords of T.B. positive sputum some of which adheres to and infects them. Some idea of the frequency with which this complication is seen is given by the work of Scott Stevenson and Heaf (8) who investi- gated 2,831 patients with pulmonary tuberculosis (2,180 males and 701 females) and found the larynx involved in 428 or 15-08 per cent. (288 men and 140 women). In 10 cases, or 2-83 per cent., the lesion was symptomless and only discovered on routine examination ; in 18 or 4-2 per cent., laryngeal symptoms were the first manifestations of tuberculous disease. This last finding of a small group of patients in whom the earliest symptoms were referable to the larynx and not to the chest is interesting and has been corroborated by other workers. Thus Donnelly (9) in a series of 1,800 cases of tuberculosis of the lungs found that 26, or 1-5 per cent., had laryngeal symptoms which antedated pulmonary or systemic signs. The symptoms complained of were hoarseness in 16, sore throat in 4, and both together in 6. Seventeen were men and 9 were women. In 15 the intrinsic and in 11 the extrinsic structures of the larynx were affected. In16the pulmonary disease was productive and in 9 it was exudative in type. Donnelly believed that the prognosis was best in those patients in whom affection of the intrinsic portions of the larynx (?.e. vocal chords, ventricular bands or inter-arytenoid space) was associated with an exudative lesion of the lungs. Four years before the appearance of Donnelly’s paper Davis and Wilson (10) observed a type of pulmonary disease having a charac- . teristic X-ray appearance which was invariably associated with involvement of the larynx and in which the initial symptoms were sore throat or protracted hoarseness. The radiological feature of these cases can be quoted in the author’s own words, “. . . a very fine generalised mottling, which is best described as having a ‘ground glass’ appearance. There is rarely definite cavitation. There is not the snowflake appearance of the familiar acute exuda- tive lession, nor the strands or mottling of the proliferative type. The appearance is as though there were a lobar pneumonia with all. its density erased and only the fine, diffuse network remaining. Observation of the films tells much more than verbal description possibly can, and is the only way in which the appearance can be appreciated.” Rusby (11) has also described a small series of similar cases seen at the Throat, Nose and Ear Hospital, Golden Square, which had been sent to that hospital on account of persistent hoarseness, sore throat or aphonia. This small series presented the following characteristics: (1) The patients were males between the age of thirty and forty years ; (2) at the time they were first seen symptoms and signs referable to the chest were either absent altogether or relatively inconspicuous, and had in every instance been preceded by those of the laryngeal disease by some months; (3) the X-ray appearance at the first attendance showed gross bilateral disease of the type described by Davis and Wilson; (4) the prognosis was uniformly unfavourable, death occurring in from four to nine months of diagnosis; (5) collapse therapy made no difference to the ulti- mate outcome and its value is therefore debatable; and (6) the extrinsic portions of the larynx (epiglottis, aryepiglottic folds and arytenoid areas) were the first to be attacked and in some cases remained the only parts affected until the end. It is impossible to be dogmatic but there are considerations which make it difficult to attribute this definite and quite distinctive association, a “‘ laryngo-pulmonary ” form of tuberculosis, to any- thing other than a haematogenous manifestation of the disease. It is reasonable to argue that the lungs and larynx become simul- taneously spattered with tubercles from a common focus. The lungs, by virtue of their reserve of tissue remain clinically “ silent ” for a significant length of time ; the larynx on the other hand, being a neater, more sensitive, and altogether a more compact structure, remonstrates early and causes symptoms almost from the beginning. This series has not been published in full as it lacks the necessary corroborative evidence from autopsy, and it has-been difficult to obtain this owing to the war. Until this necessary gap has been filled it is not possible to urge the full acceptance of this view, for the lymphatics may yet prove to be the channel of spread. But a simultaneous involvement of both organs by the blood stream is at least a plausible hypothesis and is in tune with the work of A. G. Cohen (12) who studied fifty-five examples of haematogenous tuberculosis, in no fewer than twenty-three of which the initial symptoms were related to the larynx. It can be fairly stated, however, that most examples of tuber- culosis of the larynx are secondary to advanced or moderately ad- vanced disease of the lung. Primary tuberculosis of the larynx either does not exist at all, or else is excessively rare, and supposed examples of it described in the past may well have been instances of the laryngo-pulmonary form occurring in the days before radiology of the chest was universally applied. Some work has been done on the diagnosis of tuberculosis of the larynx by X-ray examination. Scott Stevenson (13), however, doubts whether it is possible to make a diagnosis of this complication in the early stages by radiological examination alone, but agrees that in more advanced disease characteristic changes, such as swelling of the epiglottis and arytenoids, may be demonstrable. He quotes Cannyut’s work on tomography of the larynx and considers that tomograms may be valuable in the early diagnosis of those difficult examples of tuberculosis of the larynx in which infiltration starts in the laryngeal ventricle and is not visible in the examining mirror until the disease is well advanced. The most promising fresh line of treatment has been with the use of promine. Tytler and his associates have shown that promine was more effective therapeutically when applied to the surface of tuberculous lesions than when given by mouth. Following this line of research Heaf et al. (14) have treated some examples of laryngeal tuberculosis by local application of promine made up in solution or ouly vehicle. They were impressed by a favourable response in two cases. There are indications that streptomycin may prove valuable in the treatment of this complication. Tuberculosis and Bronchiectasis The association between these two diseases has in the past been only sporadically and imperfectly described. This has been due partly to a fear of introducing iodised oil into the lungs of tuber- culous subjects lest it should precipitate a relapse, a risk which Dormer (15) believes to be overrated for he has performed over 2,000 bronchographies in tuberculosis at all stages without untoward effects, and partly to the fact that the oil may remain in the alveoli for a considerable time, thus masking subtle yet important X-ray changes. Some recent investigations, carried out chiefly by Dormer and his colleagues in South Africa, have shown that the association is, in fact, more intimate than has hitherto been suspected, and the circumstances in which these two conditions are related can be classified as follows :— 1. Bronchiectasis may develop in the ordinary course of phthisis. It is reasonable to expect that dilatation of the bronchi may fol- low any chronic inflammatory process of the lung which under- goes healing, chronic fibroid tuberculosis being no exception, and such dilatations probably exist more often than they are recognised in view of the predominantly apical situation of phthisis and the ease therefore with which natural dependent drainage occurs. . Rilance and Gerstl (16) have carried out a bronchographic study of forty-seven tuberculous patients with bronchiectasis and have noted a considerable degree of distortion and angula- tion of the affected bronchi in over one-half of the cases, a change which is not commonly observed in non-tuberculous varieties of the disease. Dormer, Friedlander and Wiles (15) have studied the bronchi in the exudative types of disease and have demonstrated bronchial dilatation in the affected area. Dormer believes that bronchial and bronchiolar occlusion play an essential part in the evolution of the early tuberculous lesion leading to atelec- - tasis, pneumonitis and later, to bronchiectasis and cavitation. 2. Bronchiectasis may occur secondarily to tuberculous bronchitis. Here also atelectasis of lung behind the point of block is the dominant factor in the production of bronchial dilatation. In some examples, if the disease is localised, resection of the affected part of the lung is the treatment of choice. 3. Bronchiectasis resulting from collapse therapy. If treatment by collapse therapy is followed by complete atelectasis of the lung some degree of bronchiectasis will almost inevitably occur. This has been demonstrated after thoracoplasty by Robinson (17) and by other workers. The secretions from these dilatations often contain tubercle bacilli. After thoraco- plasty the change is permanent and bronchiectasis may domi- nate the clinical picture thenceforward: occurring in the course of artificial pneumothorax—the so-called “ black lobe ’—the widened bronchi are capable of returning to their normal calibre provided reinflation of the lung can be en- sured before secondary infection becomes superimposed. In these examples it is necessary to balance the advantages of complete collapse for the control of tuberculosis against the disadvantages of a potential apical bronchiectasis. 4, Tuberculosis may secondarily infect an established bronchi- ectasis, although it does sorarely. It is Baum and Amberson’s conviction (18) that phthisis becoming engrafted upon a clinical bronchiectasis carries an unfavourable prognosis in view of the ease with which dissemination may be effected by copious expectoration, or by haemorrhage. 5. The appearance of the two conditions in the same _ person may be purely accidental and fortuitous. This independence becomes probable if both diseases exhibit their own special characteristics, if the history of bronchiectasis is a long one whereas the tuberculosis lesion gives every indication of being recent, and if each disease has attacked separate parts of the lung. _ It must be borne in mind that in this variety, as also in the preceding, the acid-fast organisms recovered from the sputum may not be M. Tuberculosis but saprophytic organisms of similar morphology. This requires investigation before the association can be diagnosed with confidence. 6. Lastly, there is good evidence for believing that bronchiectasis may be the end result of the initial tuberculous infection sustained years before. ‘The mechanism is through bronchial obstruction and atelectasis due to the extraneous pressure on the bronchus by enlarged bifurcation or paratracheal lymph glands, the atelectasis persisting after the active infection has died down and the gland become shrunken and calcified. The only certain method of proving this is by demonstrating the calci- fied gland as a broncholith on the rare occasions in which the gland has ulcerated through into the lumen of the bronchus. But in other instances this particular aetiology may perhaps be suspected if there is no history of pneumonic illness to account for the bronchiectasis, but instead a slow and indefinite evolution of symptoms; if the anterior basic branches are affected in association with the middle lobe division on the right or the lingula branch on the left side, for these are the lower bronchi most likely to be picked out ; and if there are heavy calcareous deposits at the lung root in the neighbourhood of the dilated bronchi. ‘The diagnosis must thus be made largely by inference. It is of the greatest importance, however, that this aetio- logical diagnosis should be made by inference in all those examples in which it is the precise mechanism ; for the dangers attending radical surgery in such cases are real. A lobectomy may light up quiescent. tuberculous disease and result either in a tuberculous empyema with a bronchial fistula, broncho- genic spread of disease, and cutaneous sinuses, or in generalised dissemination of the disease with death from meningitis. Tuberculosis and Diabetes The association between diabetes mellitus and pulmonary tubercu- losis is an established fact which needs no emphasis. Himsworth (19) collected a set of figures from several publications in the litera- ture and found that the incidence of clinically detectable pulmonary tuberculosis among 13,330 diabetics was 355 or 2-7 per cent. This figure includes not only those patients who were found to suffer from both diseases simultaneously at their first attendance at hospital or clinic, but also those diabetics in whom tuberculosis developed during the course of treatment. Himsworth himself has investi- gated clinically and by X-ray 230 consecutive diabetics at the time of their first attendance at University College Hospital and found that 15 or 6-5 per cent. showed radiological evidence of tuberculosis, the lung disease being obvious clinically in only two. In several of the patients the disease assumed a pneumonic form starting near the hilum and spreading towards the periphery with a tendency to the formation of multiple small cavities, a location and type occurring sufficiently often to have been commented upon by other observers and to have been.designated as diabetic tuberculosis. It is in the sphere of treatment and prognosis, however, that Himsworth’s work is of particular value, for until comparatively recently it was the prevailing belief that not only did tuberculosis in the diabetic progress, but that this adverse tendency had not been appreciably altered by the introduction of insulin. Himsworth found that these patients did extremely well if placed upon a high-calorie, high-carbohydrate, low-fat diet, balanced by the appropriate amount of insulin, the lung lesion being treated on its merits and according to accepted principles. The results indeed were sufficiently gratifying to warrant an extension of the method, in a modified form, to the treatment of tuberculosis uncomplicated by diabetes, the results of which have been published by Day (20) and described on page 118. Untreated diabetes predisposes to pulmonary tuberculosis and in the overwhelming majority of patients in whom the two diseases are found together, diabetes preceded tuberculosis. an older age group than that customarily found, i.e. in patients around middle age, the time of life at which diabetes is most common. Whether diabetics in whom the disease is properly controlled are also more prone to develop tuberculosis than those without diabetes has not yet been fully settled. signs connected with the majority of tuberculous lesions de- veloping in the course of diabetes, the only certain way to detect the association of the two conditions early is by radio- logy. Every diabetic, therefore, should have routine X-ray pictures taken of the chest. possible with a high-calorie, high-carbohydrate, low-fat diet balanced with insulin. by bed rest and collapse therapy in the same way in the diabetic as in the non-diabetic. vided energetic treatment is carried out on the lines laid down, is as good as if diabetes was not present. Indeed, Himsworth has.expressed the belief that it may even be better in so far as the disturbance of the carbohydrate metabolism can be looked upon as the predisposing factor leading to the development of tuberculosis, a factor which in this instance is known and can be rectified. Tuberculosis and Pregnancy The view, still widely held, that pregnancy is inimical to tuber- culosis of the lungs and should be terminated within the first three months if the disease in the chest is active, has recently been challenged. It is not in the pregnancy itself that the danger lies, for improve- ment in the general condition and the local disease is often manifest during the course of it, but it is during the first three or four months after delivery that a relapse is to be feared. Several factors have been invoked to explain the exacerbation which so often follows the birth of the child: the sudden lowering of the pressure within ‘the abdomen after evacuation of the uterus, with the corresponding augmentation of the diaphragmatic movements; the strain of labour itself; the delayed effect of the nutritive demands of the foetus in the closing months of intra-uterine life; the physical demands which the infant exacts from the mother leading to fatigue and to interference with rest and sleep ; financial stringency in the home; anxiety, real and imagined, concerning the progress of the child ; and the added sense of responsibility which the increase in the size of the family imposes. Some or all of these doubtless add weight in tipping the scales adversely against the mother. Modern work on this subject has brought very much into the fore- ground the view that the environmental and sociological factors among those mentioned are of considerable importance: in the phrase of Friedman and Garber (22) it is child-rearing and not child- bearing which is the major determining factor. For example, R. C. Cohen (23) has recorded his experience of 177 consecutive cases of pregnancy and labour in tuberculous women cared for in the Maternity Unit of the Essex County Sanatorium at Black Notley. Those with quiescent disease were admitted six to eight weeks before confinement and were encouraged to lead an “ active’ sanatorium life ; those with active disease were admitted as soon as the diagnosis was made and were treated as the nature of their case demanded. Labour was assisted by forceps only when necessary. Cohen found that of the 69 arrested or recovered cases 3 retrogressed ; of 50 with quiescent disease 5 retrogressed ; and of 58 with progressive disease, including 10 whose disease was such that the expectation of survival was poor even if pregnancy had not supervened, 15 de- teriorated. The incidence of unsuccessful cases, therefore, in the whole series of 177 patients was 23 or 18 per cent. He considers that by placing the woman under the most favourable conditions the risk attaching to pregnancy can be much reduced, the governing factor being whether the pulmonary disease can be brought under control. He advocates delaying the decision as to termination of pregnancy until the third month in order that progress may be more accurately gauged. The principle of a maternity unit attached to a sanatorium, as in Essex, or of a close affiliation between a sanatorium and an obstetrical unit, as in the Grove Park Tubercu- losis Hospital and Lewisham General Hospital partnership under the London County Council Tuberculosis Scheme, is a sound one and one which should be more widely developed. It enables the woman to receive the benefit of sanatorium routine before and after delivery, with skilled assistance to simplify labour at full term or by prema- ture induction; Caesarean section can be performed at term in those cases for which it is suitable, and the pneumoperitoneum established at the time of the operation can if necessary be main- tained. The infant can be taken from the mother at birth and eared for independently during the early critical months of the puerperium. There is good reason, therefore, to review the whole question of the artificial termination of pregnancy in the tuberculous woman. Jacobs (24) has carefully studied the literature and states that it has failed to show that artificial abortion has any more favourable effect upon the course of the disease than has a full-term pregnancy. He did find, however, that an unfavourable outcome was largely dependent upon the stage of the disease at the time pregnancy supervened. Thus, in some instances, when the disease is either extensive or unusually active therapeutic abortion within the first three months of pregnancy has still to be carefully considered as a preliminary step in treatment. In others, the problem is largely a socio-economic one, and if the management of the case can be planned along the lines indicated above there is good justification for allowing the pregnancy to continue to term. The prospects for the mother are good, and the child is saved. Treatment of active disease should be conducted in a similar way in the pregnant woman to one who is not pregnant. Collapse therapy, with the possible exception of major surgical procedures, is well tolerated and some workers regard pregnancy as an additional indication for its use. Since the risk to the mother is directly related to the extent and severity of the disease it is clearly desirable that tuberculosis, if present, should be detected as early as possible. The best method of doing this is by X-raying the chest of every pregnant woman at her first attendance at the ante-natal clinic, and this group of patients should be placed high on the priority list of future mass radiographic surveys. Of 4,430 women attending the ante-natal clinic of Paddington Hospital, London County Council, Jacobs found that 27 (0-61 per cent.) exhibited active tuberculosis of the lungs requiring immediate admission to hospital, while in 11 (0-25 per cent.) lesions were discovered which were possibly active. These figures agree closely with those published from Chicago by Eisele (25) of a similar survey by screening. References (1) Mortock, H. V. and Pincuin, A. J. S. (1934) Brit. med. J. 2, 762. (2) Levy, S. (1942) Amer. Rev. Tuberc. 45, 377. (4) Krucer, A. L. and PERLBERG, H. J. (1941) Amer. Rev. Tuberc. 44, 73. (5) RosENCRANTZ, E. and PisciLeuui, A. M. (1941) Amer. Rev. Tuberc. 44, 704. (6) McConkey, M. (1941) Amer. Rev. Tuberc. 43, 425. (7) Krers, R. Y. (1947) Brit. J. Tuberc. 41, 33. (8) STEVENSON, R. S. and Hear, F. R. G. (1940) Brit. med. J. 1, 164. (9) DonEtty, J. C. (1942) J. Amer. med. Ass. 120, 675. (10) Davis, S. C. and Wixson, R. A. (1988) Dis. Chest, 4, No. 11, 18. (11) Russy, N. L. (1944) Tubercle, 25, 33 (abstr.) (12) CouHEN, A. G. (1940) Amer. Rev. Tuberc. 41, 426. (13) STEVENSON, R. S. (1938-89) Tubercle, 20, 497. (14) Hear, F. R. G., HuRForD, J. V., Eiser, A. and FRANKLIN, M. L. (19438) Lancet, 1, 702. | (15) Dormer, B. A., FRIEDLANDER, J. and WILEs, F. J. (1945) Amer, Rev. Tuberc. 51, 455. (16) Ritance, A. B. and Gerstt, B. (1943) Amer. Rev. Tuberc. 48, 8. (17) Roxsinson, H. J. (1987-88) Tubercle, 19, 1. (18) Baum, O.S. and AMBERSON, J. B., Jr. (1942) Amer. Rev. Tuberc, 45, 243. (19) Himsworts, H. P. (1988) Quart. J. Med. 31, 373. (20) Day, G. (1942) Tubercle, 23, 215 (21) Tuomprson, B. C. (19438) Brit. J. Tuberc. 37, 87. (22) FRIEDMAN, L. L. and GARBER, T. R. (1946) Amer. Rev. Tuberc. 54, 275. (23) CoHEN, R. C. (1946) Brit. J. Tuberc. 10, 10. (24) Jacoss, A. L. (1946) J. Obstet. Gynaec. 53, 369. (25) E1seLr, C. W., TUCKER, W. B., Vines, R. W. and Batry, J. L. (1942) Amer. J. Obstet. Gynec, 44, 183. CHAPTER VII GENERAL TREATMENT AND CHEMOTHERAPY BuRRELL drew a distinction between treatment designed to im- prove the general state of health and that which was directed against the tuberculous lesion itself. ‘To achieve the best result both should be employed concurrently and the sanatorium is the institution par excellence in which both lines of treatment are practised. The essen- tial functions of the sanatorium, namely, the enforcement of strict bed rest until graduation from rest to exercise and grade work can be begun ; the provision of good food, fresh air, and good ventila- tion; the administration of collapse therapy at the right time to those patients who need it; education in matters of personal and community hygiene ; and instruction in the art of living after dis- charge with regard to both work and leisure, have not changed during the last decade. There have been certain technical developments in the construc- tion and design of sanatoria, which now lie largely in abeyance ; and there is also perceptible a clearer understanding of the distinc- tion between diversional, vocational and occupational therapy, on the one hand, and rehabilitation in its broadest sense, on the other. A great deal more thought is being given to the profitable exercise of the mind of the patient during the tedious months of bed rest and graduated exercise, and in choosing the particular form of occupa- tional therapy, more attention is being paid to individual inclination and aptitude. The introduction of art classes at King Edward VII Sanatorium, Midhurst, is an interesting experiment which is proving successful therapeutically and popular with the patients. Diet Otto Walter introduced forced feeding in the treatment of tuber- culosis in his sanatorium in the Black Forest and claimed good results. While there has been no attempt to underrate the import- ance of diet in the management of the disease, it is now widely believed that overfeeding is unnecessary and may actually be harm- ful in imposing too great a strain upon the digestive mechanism. A mixed diet of 2,800-—3,200 calories daily is adequate for a resting tuberculous person and will enable him, in favourable circumstances, to repair tissue damage and gain weight. Supplementary vitamins may be prescribed with advantage in the early stages of treatment, particularly vitamin C, for there is some evidence which suggests that this substance is often deficient in tuberculosis. Capriciousness of appetite is exceedingly common among the tuberculous. This is no doubt partly the result of prolonged stay in an institution, but it seems also to be an attribute of the disease itself. At all events it should be recognised and the personal likes and dislikes of patients studied. As much variety as possible should be introduced into the diet and free use made of such adjuvants as condiments, sauces, and pickles. Alcohol, if allowed judiciously, is a valuable tonic, and a good stimulus to appetite. The immense influence which quality, variety, temperature, and mode of serving of the diet exerts upon morale and happiness of patients confined to bed for long periods is being only very slowly appreciated, and the extra care and financial outlay required to ensure these can be fully justified. The importance, too, of a warm, comfortable and pleasantly decorated dining room for am- bulant patients in a sanatorium has only recently been generally appreciated. Many attempts have been made in the past to influence the course of the disease by modifying one or other of the main constituents of the diet. Gerson’s advocacy of a salt-free diet may be cited as an example. The evidence that such diets did any good is scanty, and modern work has added little to the subject except that the use of insulin and a high carbohydrate diet has been further exploited. Insulin has been used in certain instances when the patient remains undernourished in spite of an increased diet. An ounce of glucose, in the form of barley sugar which contains 85 per cent. glucose, is given with meals and from 5 to 10 units of insulin are injected afterwards three times a day. Banyai and Jurgens (1) describe forty-three patients treated in this way. It resulted in a gain in weight in 54-1 per cent. of the moderately advanced and in 47-3 per cent. of the advanced cases. They consider it safe to begin with 5 units three times a day after ordinary meals. ‘There is also little doubt that 5 or 10 units of insulin given 15 minutes or half an hour before the principal meals of the day acts as a powerful stimulus to appetite and excites hunger. Day (2) has published some experiments from Mundesley Sana- torium. At different times over a five-year period he divided his patients into four groups. ‘The first group received the unrestricted pre-war diet of the sanatorium ; the second the same diet supple- mented with extra carbohydrate and insulin; the third group received the war-time rationed diet ; and the fourth the same war- time diet but with extra sugar. The amount of insulin given was 10 to 15 units three times a day before the principal meals, with the same amount twice a day between meals buffered with a sweetened fruit drink. Mild hypoglycaemic reactions were not uncommonly observed but were never serious. The progress of these four groups was compared, the criteria of improvement being the gain in body weight and the return to normal of the sedimentin index. Day found that the rate of improvement was greatest in the second group, i.e. the patients who received the unrestricted pre-war diet with extra carbohydrate and insulin regime, and in these the gain in weight was often considerable. So noticeable was this that Day inclines to the belief that not only does improvement in the general condition result in gain in weight, but that an increase in weight, ‘‘ enforced ”’ in the manner described, is itself responsible for an improvement in the lung disease. | Symptoms Compared with the vast amount of work which has been done recently on the specific methods of treating pulmonary tuberculosis, individual symptoms, local and systemic, with the possible exception of haemoptysis, have been largely ignored and there is little fresh to record. A word, however, must be said about postural drainage for its use in the management of lower lobe, particularly “* dorsal lobe,”’ cavi- ties has been advantageously exploited in the last few years. Recent work upon the anatomy of the bronchial tree and the broncho- pulmonary segments now enable dependent drainage of suppurative lung disease to be carried out with greater precision. A tuberculous cavity will often respond in a similar manner to a lung abscess if the patient is placed in the correct position for the dependent drainage of the segment of lung in which the cavity lies. The cavity will get smaller and cough and expectoration diminish. If the sputum is tenacious and difficult to void, expectoration can be made easier by the administration of the following saline draught taken in an equal quantity of hot water a few minutes before postural drainage is begun, and at other times :— | R  Sodiu Bicarbonatis : SORE: Sodii Chloridi . : Bers ine. Spiritus Chloroformi . moe Hl saes Spiritus Rectificati 3 Ss Aquam Anisi. ; SRM: (6 a al | Climate and the Physical Environment For many centuries climate has been held to exert a considerable influence upon the progress of tuberculous disease and the decision as to where a patient should go for treatment is one which has often to be carefully considered. In this, as in other methods of treat- ment, fashions have changed, and Burrell has given a good account of the subject in a previous edition of this book. That meteorological changes can, in some people, occasion sub- jective changes has been suggested by the recent work of Char- nock (3) in this country. This author found that in his sanatorium, between 1938 and 1943, of 754 patients studied, 111 (14:8 per cent.) complained of symptoms related to weather change. These symptoms amounted to tightness across the chest, increase in cough and sputum, muscular pains, discomfort in the joints, headache and lethargy. By correlating the symptoms in susceptible persons with meteorological observations recorded at the time, Char- nock was able to show that these patients complained most when the humidity was rising to a peak accompanied by a falling baro- meter or temperature, or both. On the other hand, they felt at their best with a steady, moderate temperature, a rising barometer and a falling humidity curve. What is true of the short-cycle changes understood by the term weather may equally well apply to the average long-term meteoro- logical characteristics which constitute climate, and while most patients would probably do well, or badly, no matter where they are treated, so long as extremes are avoided, a small proportion would do better at an altitude than at sea-level. The main difficulty is to fore- cast in advance who will derive the additional benefit from residence at high altitude. It is easier to suggest who will not do well, for the bronchitic and hypertensive subjects, those with acute or ad- vanced disease, or with a tendency to haemoptysis, are best treated, in the early stages at least, in a less rarefied and more relaxing atmosphere. It is known that hot, humid atmospheres are danger- ous and it is believed that the prevalence of rain-bearing winds is also detrimental, but the precise factor or factors through which the mountainous environment exerts its influence for good is still imperfectly understood. Nor must it be forgotten that the psycho- logical uplift which results from “ taking the cure ” in a locality the therapeutic advantages of which are widely acclaimed cannot be . lgnored. The modern tendency, however, has been to relegate the import- ance of climate to a secondary place compared with the type of treatment the patient receives. It is accepted that the bracing quality of mountainous air acts as a stimulus to metabolism, and may possibly act in other ways, but they cannot be regarded in any sense as an efficient substitute for proper rest and those ancillary methods of treatment which have proved their worth. The introduction of air-conditioning has now made it possible, within certain limits, to mould the physical environment to suit the patient, and there is no doubt that it has proved invaluable in the management of febrile conditions, including tuberculosis, in the tropics. By means of it humidity can be controlled, temperature regulated and maintained at any desired level with modification of the day-night variation, dust can be filtered, and free ventilation ensured. ‘There is scope for the experimental use of air-conditioning to enlarge our knowledge of the climatic factors in tuberculosis. Mental Factors The importance of the mind in chronic disease has been relatively neglected in the past, and pulmonary tuberculosis has suffered in this respect, as have other conditions. In spite of the pre-eminent position which collapse therapy has for so long occupied, and in spite of the chemotherapeutic advances which crowd into the medical press week by week, there is observable a movement to turn more critically and searchingly to the patient as an individual. It is suspected that not only is physical treatment robbed of its full potentiality if the mind is ill at ease, but also that periods of psycho- logical stress and emotional turmoil may, by lowering general resistance in susceptible people, be a powerful contributory factor in the development of the tuberculous lesion. Investigations into the significance of this hypothesis, of the personality background of tuberculous patients and to what extent phthisis can be regarded as a psychosomatic disorder, are now being conducted. In the short-term pharmacological sphere Houghton and Cor- rigan (4) have recorded some interesting work on amphetamine sulphate (benzedrine), a drug which acts as a stimulant to the central nervous system. They found that 5 mg. of the drug was useful for the depressed and over-anxious patient, changing the mood to one of buoyancy and confidence, and was particularly valuable if prescribed before major surgical procedures or at other times of temporary emotional despondency. The feeling of well-being which this drug engendered was accompanied in some instances by increased appetite and improvement in the general condition. Withthe dosage used, administered early in the day, sleep was not interfered with. Chemotherapy The drug treatment of pulmonary tuberculosis is nearly as old as the disease itself, and an infinite variety of preparations has been employed with the object of eradicating the infection. Referring to these ancient remedies Feldman (5) has said that “‘ faith and hope rather than logic were the motivating factors that permitted the use of the agents mentioned,’’ some of which in comparatively modern times were employed for their supposed action upon tubercle bacilli, while others were believed to owe their effect to stimulation of the reticulo-endothelial system of the body and the general power of healing. Most of the preparations found in the literature up to 1935 bear little resemblance in efficacy or in experimental background to the chemotherapeutic agents that have been synthesised and tested since that date. For full reviews of the whole subject of the treat- ment of tuberculosis by chemical agents the reader is referred to the Mitchell Lectures by D’Arcy Hart (6), and the Harben Lectures by Feldman (5). Within the meaning of the term “‘ chemotherapy ” Hart includes inorganic substances, synthetic organic compounds, and organic compounds derived from natural biological sources (the antibiotics), but excludes methods of immunological approach such as tuberculin, and the purely pharmacological treatment of symptoms. It is a convenient classification to adopt. : Inorganic Substances Heavy Metals. Heavy metals and their salts have figured prominently in the literature of former years, and of these gold salts have been the most promising. Gold Therapy. The use of gold salts was tentatively explored be- fore 1924, but in that year Mollgaard introduced sanocrysin (sodium aurothiosulphate) and such was thé immediate popularity of this and allied preparations (allocrysin, crisalbin, solganol, myocrysin) that Hart refers to the years between 1925 and 1935 as the “ gold decade.” It was Mollgaard’s belief that the drug destroyed tubercle bacilli an vivo, a view which was supported by the fact that in some instances, after injections of sanocrysin, bacilli appeared to vanish from, or become scanty in, the sputum. Later its mode of action was related to stimulation of the reticulo-endothelial system and to the promotion of fibrous tissue in the lungs in which the bacilli become walled off. At the time of its introduction very severe reactions were en- countered which included fever, albuminuria, gastro-intestinal dis- turbance, and skin lesions varying from erythematous rashes to exfoliative dermatitis. The incidence of such complications, while still remaining formidable, was appreciably reduced by the employ- ment of a smaller dosage, by the use of intramuscular watery preparations, and by intramuscular preparations made up in oil which spread the absorption of the drug over a longer period. The indications for the use of gold, as they were held to be during the “‘ gold decade,”’ can be summarised as follows :— 1. To diminish the quantity of sputum and the number of tubercle bacilli contained in it. 2. To check an acute spread of disease of an exudative type before the stage of cavity formation. 3. For the treatment of a fresh exudative focus in the opposite lung of a patient with an artificial pneumothorax. It was believed that in these cases gold supplied a useful adjunct to bed rest in averting the need for a bilateral pneumothorax. 4. As a psychological placebo for a patient who was failing to gain ground and for whom other methods of treatment were inappropriate. Since 1935, chrysotherapy has been used less frequently, although a few authors still have faith in it for judiciously selected cases. Cohen (7), for example, published in 1948 the results of an investi- gation conducted upon 100 cases, all women. He used sanocrysin in weekly injections up to 2-1 g. as a full course. He claimed that the drug was useful in the exudative form of the disease and his series included, in addition, examples of the fibro-caseous form, tuberculous infiltration, soft cavity, and miliary disease. He com- puted that 52 out of the 100 patients derived some benefit which persisted for at least six months. It is probable that the drug still has a place in the management of the early exudative lesion, but, on balance, Hart’s criticism of the use of gold salts is just when he says of it that it was too readily accepted by the clinicians before its experimentation had been controlled and its efficacy proved. Calcium. Calcium has been advocated in the treatment of tuber- culosis, especially for the control of haemoptysis and diarrhoea. In theory it should be of some value, for not only does calcification play an important role in the cure of tuberculous lesions, but some workers have demonstrated a deficiency of calcium in the blood of | tuberculous patients. . In actual practice, however, the administra- tion of calcium is distinctly disappointing. Half the calcium chloride injected intravenously is excreted in the urine within three hours and the remainder within the first three days, so that it is difficult to overcome a calcium deficiency by periodic injections of the chloride. It is possible, however, to overcome it temporarily, which may help to tide a patient over a difficult period, for example during haemoptysis. Calcium has also been tried for the treatment and prevention of effusion complicating artificial pneumothorax, but there is no satis- factory evidence that it is effective. _ Iodine. Iodine at one time enjoyed considerable popularity in the treatment of consumption, but in recent years it has fallen into dis- repute and has even been regarded as positively harmful. Potassium iodide has also been looked upon with disfavour. There is little or no evidence to suggest that iodine or potassium iodide have any place in the treatment of active pulmonary tuberculosis, although the latter salt is useful in the more chronic forms of the disease if associated with bronchitis. Moreover, similar fears were expressed regarding the injection of lipiodol or neohydriol into the bronchial tree in tuberculosis and it was held that such a practice was likely to cause a reactivation. This is without foundation and in recent years bronchography with iodised oil has been used for purposes of investigation in chronic pulmonary tuberculosis. Little harm has resulted and the only valid objection to the practice is that the oil, by persisting in the lung for so long before it is absorbed, obscures subsequent X-ray pictures and thus may mask radiographic change. Organic Chemical Compounds A full list of the organic chemical compounds which have recently been used experimentally against tuberculous infection is given by Hart (6). It includes the sulpha group of drugs, fatty acids and derivatives (chaulmoogra oil and its component acids), the aromatic compounds (para-aminosalicylic acid), the acridine dyes, and a miscellaneous group of which calciferol is a member. Anything approaching a comprehensive discussion of these compounds is outside the scope of this book and the reader is referred to Hart’s paper. Some of these organic substances, however, merit short consideration. The Sulpha Group of Drugs. Following the introduction by Domagk in 1935 of prontosil, the first of the sulphonamide prepara- tions to be placed on the market, a great deal of research has been done upon the effect of the sulphonamide series and the sulphones on tuberculous disease. An excellent review of the work up to 1944. has been furnished by Tytler (8). Soon after Domagk’s discovery Rich and Follis (9) found that sulphonamide exerted a definite inhibitory action upon the develop- ment of tuberculosis in the guinea-pig, and commenting upon this work, Feldman has said that the ‘‘ renaissance of tuberculochemo- therapy began with the recognition of this fact.’ The effect of the drug, however, was purely suppressive and in none of the animals treated did it prevent completely the growth of bacilli. But it was an encouraging start, and since then a large number of compounds have been synthesised and tested which, to anyone who is not a chemist, appear bewildering and haphazard in their complexity. Feldman has made it clear in his Harben lectures, however, that each substance tested was a logical step forward from its predecessor. Progress achieved in this field is not to be measured only by the total number of compounds used experimentally. Of equal significance has been the evolution and adoption of method in this form of re- search whereby each new compound is submitted to a comprehensive sequence of investigations for the evaluation of dosage, toxicity and SULPHANILAMIDE ckeo potency, first on animals and later, if the results warrant it, on man. Feldman has laid down the preclinical requirements of an acceptable chemotherapeutic agent thus :— ‘“* 1. The agent should be well tolerated and should not pee serious or irreversible physiologic derangements. ** 2. The substance should reverse a well-established inoculation tuberculosis, induced by a strain of human tubercle bacilli of standard virulence, from a progressive, destructive process to one that is nonprogressive and will eventually resolve, fibrose or calcify. The obvious consequence of such effects would be the extended longevity of the treated animals. ‘* 3, The substance should eliminate or render avirulent tubercle bacilli from the organs of predilection, such as the spleen, lungs and liver and hence preclude subsequent activity of possible latent infection. “4, The desired results should be obtained within a reasonable period of treatment. In estimating what this time interval should be, one must recall that the lesions of tuberculosis are slow to heal. Experience suggests that in guinea-pigs six months is a reasonable period for such healing.” In addition to these criteria it is important that the infecting organism should not become resistant to the action of the agent used. The acquisition of drug fastness by the organism can seriously interfere with the bactericidal and bacteriostatic properties _ of the chemotherapeutic compound. Furthermore, the excretion of the agent from the body should be at such a rate as to allow sufficient concentration of the drug in the body fluids to be maintained for long enough to achieve the desired end. It is obvious that research work conducted according to an orderly plan will prevent the empirical use of drugs founded upon slender evidence and will avoid the disappointment which so often has followed premature optimism. | — Sulphanilamide and Allied Derivatives. Early work with these sulpha drugs was not so rigidly controlled as have been later studies with the sulphones and antibiotics, so that before the potentialities of the compounds had been fully tested on animals ‘they had been applied to man. The evidence derived from trials upon the human subject suggested that these drugs were of little value. Thus, Zucker, Pinner and Hyman (10) gave large doses of sulphanilamide by an intravenous drip to thirteen patients. They found that this method was not devoid of toxic reactions and that no patient obtained a permanent and complete conversion of sputum from positive to negative. Ellman, Lawrence and Cumings (11) used sulphapyridine in the treatment of forty-two cases of pulmonary tuberculosis with forty- seven controls. They concluded, first, that those with disease of moderate or slight severity showed a higher rate of recovery than the control group but the mortality in the two groups was, similar ; secondly, that tubercle bacilli disappeared from the sputum more frequently in the treated groups, whereas secondary organisms were unaffected in either group ; and thirdly, that patients with advanced disease showed no improvement at all. Promine. The relative failure of sulphanilamide and its immediate successors to exert any beneficial effect upon tuberculosis in animals or man was followed by research into the effect of a kindred class of compounds known collectively as the “ sulphones.” These, when used experimentally against acute infections, were found to be more potent than sulphanilamide although considerably more toxic. Mainly on account of this last characteristic they were abandoned in acute pyogenic diseases but one member of the group, Promine . or Promanide (4—4’-diaminodiphenyl-sulphone N : N’-di-dextrose- sodium sulphonate), was found to possess to an unusual degree the power of inhibiting the development of tuberculosis in experimental animals. Some early experimental results were published by Feldman, Hinshaw and Moses (12) in 1942 and since that date much work has been done and many papers published all of which support a suppressive effect against tuberculosis in the guinea-pig. The result of the application of the drug to the disease in man was eagerly awaited. It was profoundly disappointing, therefore, when the trials showed that promine, chiefly on account of its haemolytic effect on the red blood corpuscles, was more toxic to man than it was to the guinea-pig, and that it was not possible to maintain an effective concentration of the drug in the blood for the requisite length of time. Heaf, Hurford, Eiser and Franklin (13) in a preliminary com- munication have shown that the action of promine on pulmonary tuberculosis in the human subject is not startling, and that the patients who received the drug by mouth exhibited in a mild form such symptoms as headache, cyanosis, nausea, occasional vomiting, and giddiness, which were not so obvious when the intravenous route was used. They found that the development of haemolytic anaemia could be largely checked by giving iron at the same time. It was with the local application of an oily preparation of the drug directly to laryngeal lesions that these workers obtained more promising results. Tytler and Lapp (14) have also had encouraging results from the local application of promine to tuberculous sinuses, thus demon- strating, what is now generally believed, that promine is of more value when applied to a local tuberculous lesion than when. given ‘either by mouth or by injection for pulmonary disease. Diasone. A further step in chemotherapy was the manufacture of a diasone (disodium formaldehyde sulph-oxylate 4-4’ diamino- diphenyl-sulphone) which was first synthesised in 1988. Petter and Prenzlau (15) have published a series of 45 patients who have been treated with it. The amount recommended was 1:0 g. per day by mouth given in divided doses of 0-33 g. with meals. For maximum benefit to be obtained the authors recommended that its adminis- tration should be kept up for at least 120 days, and in their cases the average dose was 0-9 g. diasone daily for 156 days. Mild toxic reactions were observed. These comprised elevation of temperature and pulse rate, nausea, loss of appetite, headache, and nervousness. Reactions were most noticeable early in the course of treatment, improved with continued medication, and in most cases disappeared at the end of four weeks. There was an initial drop in the haemo- globin percentage and the red-cell count which reached its maximum after four weeks, returned to normal in five to seven weeks. There was no evidence of severe agranulocytosis. The blood sedimenta- tion rate improved in 84 out of the 44 patients treated. The authors claim a pronounced improvement in 18 per cent. of the cases, moderate in 50 per cent., and slight in 25 per cent. There was no change in 2-5 per cent. and 4-5 per cent. became worse. The sputum, which was submitted to a fairly searching test for T.B., became negative in 59 per cent. of the cases within 45 to 125 days. The authors regard these results as promising, but emphasize, first, that work with the drug is still in the experimental stage, and secondly, that diasone should not be used unless the patient is under constant expert supervision and a close watch kept on the blood picture. Later experiments with diasone have not been more fruitful. Promizole. 'This member of the sulphone series is the one which has been manufactured and tried most recently. Feldman, Hinshaw and Mann (16) have reported an interesting piece of research on guinea-pigs in which promizole (4—2’-diaminophenyl-5’-thiazolyl- sulphone) was matched against promine. They found that promi- zole exerted a deterrent action upon the development of tuberculous infection which was only slightly inferior to that of promine and in doses which were only half that of the latter drug. It was apparent, however, that promizole failed to fulfil completely the requirements which the authors postulated for a perfect chemotherapeutic sub- stance, in so far as in only four out of fourteen carefully examined spleens were virulent tubercle bacilli not found. Specific tests for toxicity were not carried out, but the incidence is believed to be low. Some destruction of red blood cells occurred, but this was not serious and the regenerative capacity of the bone marrow was unimpaired. Finally, Feldman and his colleagues state that promizole is chemically unlike the drugs previously described as possessing tuberculochemotherapeutic properties ; and point out that it may represent the progenitor of a new series rather than the last member of a line of compounds. ‘ The demonstration that the tubercle bacillus in vivo is vulnerable to attack by drugs must be regarded as the major contribution made by the sulphones. But their toxic action upon the blood-forming organs of the body limits dosage to a point below the effective thera- peutic level, and they have recently become largely supplanted by another and more powerful group of compounds, the antibiotics. The Antibiotics—Streptomycin. Feldman (5) quoting Waksman, a soil microbiologist who originated the term “ anti- biotic,” defines it as ‘‘a chemical substance of microbial origin capable of inhibiting the growth or the metabolic activities of bacteria or other micro-organisms.” The principle of utilising natural antagonisms and of extracting the products of one micro- organism in the hope that they will prove lethal to another micro- organism is not a new one in medical applied science. Over the course of many years several attempts have been made to find an antibiotic capable of destroying the tubercle bacillus, and for a short review of these the reader is referred to Feldman’s Harben lectures. They all, including penicillin, proved deficient until Schatz, Bugie, and Waksman (17), announced that from Streptomyces griseus, of the family Actinomyces, could be extracted a substance with an impressive lethal effect against tuberculosis in the guinea-pig. This substance they called streptomycin. Research on the potentialities of streptomycin was continued by Feldman, Hinshaw and Mann (18) who, after a series of convincing experiments on the effect of streptomycin on artificially induced tuberculosis in the guniea-pig, concluded :— ‘1. Streptomycin, under the conditions imposed, was effective in resolving or suppressing established experimental tuber- culosis in guinea pigs. “2, Although capable of undeniable deterrent effects in com- bating or preventing anatomic changes due to myobacterium tuberculosis, streptomycin in most instances exerted a sup- pressive rather than a sterilising effect on the infective agent. ‘* 3. In more than a third of the treated animals there occurred a reversal of a previously demonstrated sensitivity to tuber- culin. ‘4. The unquestionable ability of streptomycin to reverse the potentially lethal course of inoculation tuberculosis in guinea pigs, and the relatively low toxicity and corresponding safety of purified streptomycin satisfy the prerequisites of a chemo- therapeutic agent worthy of a clinical trial.” They found in addition that streptomycin was not strain specific and that frequent administration was not essential. They showed that the drug was effective against human tubercle bacilli even if a large dose of bacilli was given intravenously to guinea-pigs before treatment was started, a very severe test. Application of this work to man is, at the time of writing, incom- plete and still in progress, but a paper by Hinshaw, Feldman and Pfuetze (19) record some interesting observations. These authors have treated 10 patients with acute haemoto- genous disseminated tuberculosis, with and without meningitis ; 4 were still living 3 to 6 months after treatment was started but the ultimate prognosis is considered to be doubtful. Each of these 4 surviving patients was a proved example of meningitis and received 100-200 mg. of streptomycin daily intrathecally for 2 to 4 weeks together with 1-2-3-6 g. daily intramuscularly for 3 to 6 months. The remaining 6 patients failed to survive, but in them the drug was believed to have modified the course of the disease. The drug has been tried in 24 patients with advanced, in some cases terminal, pulmonary tuberculous lesions. The minimal dose used was 1 g. (1,000,000 units) with an ideal dose of 1° 5-2-0 g. daily. Nineteen (80 per cent.) improved with sufficient rapidity for success H. & R, TUBERO. 5 to be credited to the drug ; in the remaining 20 per cent. the disease remained stationary. Sputum was converted from positive to nega- tive except where thick-walled fibrotic cavities constituted a barrier. Treatment was continued for 3-6 months. The authors found streptomycin successful in the treatment of tuberculous sinuses. In renal tuberculosis, on the other hand, the effect was not lasting and bacilluria recurred. Out of seven cases of tuberculous empyema treated by intrapleural and intramuscular injection in only one was a significant response observed. There is evidence that the drug is effective in tuberculous endobronchitis. The phenomenon of “ drug fastness ” to streptomycin appears to occur rather easily with several types of micro-organisms and this constitutes a most serious drawback to its use. Although the drug is on the whole well tolerated by experimental animals and by man, toxic effects have been observed. These include irritation at the site of injection, histamine-like effects, vestibular disturbances, temporary deafness, and reversible renal changes with albuminuria. It is still, to some extent, debatable which of these effects is attributable to the pure drug and which to impurities. Furthermore, in patients with tuberculous meningitis treated with streptomycin it is probable that the nervous phenomena encountered are the direct result of the disease itself and are due to the process of healing with fibrosis of the meninges. ‘The subject is in need of clarification and the work of Madigan, Swift and Brownlee (20) sug- gest that impurities are responsible for some of the reactions noticed, including the histamine-like effects. It is still too early to forecast the final place which streptomycin will fill in the treatment of clinical tuberculosis. That it has proved the most successful of the antibiotics, and of all chemotherapeutic substances so far employed, will pass unchallenged. That it is capable of reversing a positive tuberculin reaction is of good augury. Nevertheless, it is politic to heed the cautious note sounded by Hinshaw and his colleagues who have written : ‘‘ Streptomycin may represent the first clinically feasible antibiotic remedy for tubercu- losis, but at this time it cannot be recommended as a substitute for accepted therapeutic procedures, the efficacy of which has been proved by long experience.”’ The Fatty Acids and Derivatives. Chaulmoogra oil has been used in the East for the treatment of leprosy for centuries. In view of the analogy which exists between leprosy and tuberculosis it was natural that a successful leprocidal agent such as chaulmoogra oil, the essential constituents of which are chaulmoogric and hydnocarpic acids, should be tested against tuberculosis. The earlier results were not striking. Interest in this subject has recently revived following the isolation by Anderson and his associates of branched-chain fatty acids from the lipoid fraction of tubercle bacilli, fatty acids which bear a functional relationship to chaulmoogric and hydnocarpic acids. A summary of the progress of this work has been given by Ander- son (21). One of these acids, phthioic acid, possesses toxic properties and when injected into guinea-pigs induces lesions similar to tubercles, with epithelioid cells and giant-cell systems. The mode of action of these saturated many-carboned fatty acids is still uncertain. One school of thought relates the bactericidal properties of these compounds to physical effects, either an ability to penetrate the fatty envelope of the bacilli or through a lowering of the surface tension. Robinson (22), who has studied the subject by a synthetical approach, has suggested that if this proves to be the precise mechanism then the exhibition of a fatty acid derivative con- currently with a known tuberculocidal compound might be beneficial. Writing as he was in 1940 Robinson mentioned sulphanilamide or one of the sulphones as the possible active component of this synergism. An alternative explanation for their bactericidal effects takes cognisance of the similarity in structure between them and those acids, such as phthioic acid, which have been isolated from the bacilli, and it is assumed that they enter into competition with these naturally occurring fatty acids and, by “ blocking ”’ an essential biosynthesis, interfere with the internal metabolism of the myco- bacteria. Experimental studies along these lines of tuberculosis in man has not so far been fruitful. Para-aminosalicylic Acid. It has been shown by Bernheim (23) that salicylates and benzoates are capable of increasing the oxygen up-take of tubercle bacilli, and he concludes from this that - they play an integral part in the intermediate metabolism of the organism. Extending this work in Sweden, Lehmann (24) has shown that the effect of salicylates and benzoates is true only in the case of pathogenic tubercle bacilli and that no increased oxygen up-take occurs if the compounds are added to non-pathogenic organisms. Lehmann went further, and on the assumption that salicylates and benzoates are ultimately concerned with the metabolism of T.B., experimented with derivatives of these compounds in the hope of discovering a substance which would enter into competition with the naturally occurring metabolites and by interfering with normal biosynthesis bring about bacteriostasis. He investigated over 50 derivatives of benzoic acid and found that the most active compound was para-aminosalicylic acid which produced an inhibition of 50-75 per cent. in a concentration of 1 in 650,000 or 0-15 mg. per 100 c.c. The substance was non-toxic to rats when given for one or two months in amounts which main- tained a concentration of 3-7 mg. of free amino-salicylic, but in guinea-pigs a decrease in appetite and in growth was observed. No blood changes were seen. The drug could be given by mouth, sub- cutaneously, intramuscularly or intravenously. Trials with this preparation in the treatment of tuberculosis in animals and in man are being pursued in Gothenburg, and by Dempsey and Logg (25) in this country. Vitamins. The vitamins are still relied upon as supportive measures in the treatment of pulmonary tuberculosis. In the light of recent work upon the fatty acid series it is now open to question whether cod liver oil owes its beneficial effect to vitamin A and D contained in it or to the fatty acid of which it is composed. The weight of opinion is still in favour of the former. Vitamin D, in the form of calciferol has been successfully used in high dosage for lupus vulgaris; in the presence of pulmonary disease calciferol should be used with caution as it may cause an exacerbation or haemoptysis. The value of vitamin C in pulmonary disease has been brought into the foreground and investigations have shown that a deficiency may exist in pulmonary tuberculosis. J. EK. H. Roberts has attri- buted bleeding following intrapleural pneumonolysis to a vitamin C deficiency. The evidence that vitamin C plays an important part in the treatment of phthisis is not conclusive. Serum Endotoxoid Anti-tuberculosis serum has been used in an attempt to counteract tuberculous toxaemia, but so far it has failed to win universal approval. Recent work along similar lines has been published by Grasset (27) from South Africa. This author prepared a stable detoxicated vaccine from the auto- genic principles liberated by smooth strains of the tubercle bacillus. This he has called “* tuberculous endotoxoid.”’ By using this for- malised endotoxoid to immunise horses he obtained a specific serum which he believes exerts an. antitoxic action, particularly in acute febrile cases of tuberculosis. Tuberculous endotoxoid is given by injection in doses increasing from 0:50 to 1-5 c.c. over a period of several months, and Grasset has used it either alone or in combina- tion with specific serum in 136 European pulmonary cases and found that 87 (63 per cent.) derived benefit in varying degree. Improvement was also noticed in non-pulmonary tuberculosis. This interesting work is in need of confirmation before a final pronouncement upon its value can be given. Tuberculin When tuberculin was first introduced it was enthusiastically received and was regarded as a cure. Later, however, when results proved disappointing, opinion began to swing to the other extreme and tuberculin was looked upon not only as useless but actually dangerous. Since that time it has practically fallen into disuse as far as pulmonary disease is concerned and is employed by only a few advocates. It still retains, however, a limited value in the treat- ment of some non-pulmonary conditions, particularly tuberculous affections of the genito-urinary tract and of the eye. Intrapulmonary Injections Attempts have been made to influence the course of the disease by the injection of chemical compounds directly into the lung sub- stance. Sir James Roberts (28), for instance, stimulated by some American observations that the phenol series was the most potent of any antiseptic against tubercle bacilli in vitro, employed carbolic acid. He prepared 1 c.c. of a solution containing gr. 4 of carbolic acid with approximately double the amount of glycerine and some local anaesthetic. This amount he injected into different parts of the affected lung each day, in some cases for many days, and claimed 64 cures out of 149 patients treated. Hunter, Peill and Wilson (29) have reported upon the efficacy of gelatine, acriflavine, calcium chloride (G.A.C.C. ‘“B”’) injected directly into the lungs of tuberculous patients and state that pro- vided certain precautions are observed no untoward reactions follow. These precautions are fully stated in the original paper. The rationale underlying the procedure is that G.A.C.C. “‘ B ” induces hyaline change in the affected tissue and that this is followed, sometimes very rapidly, by calcification and clinical improvement. References (1) Banyat, A. L. and JuRGENS, G. H. (1934) Amer. J. med. Sci. 188, 76. (2) Day, G. (1942) Tubercle, 23, 215. (3) CHARNOCK, G. B. (1944) Tubercle, 25, 19. (4) HoucurTon, L. E. and Corrigan, F. L. (1946) Lancet, 2, 864. (5) FELDMAN, W. H. (1946) J. State Med. 9, 267, 297 and 343. (6) Hart, P. D’A. (1956) Brit. med. J. 2, 805 and 849. (7) CoHEN, R. C. (19438) Tubercle, 24, 37. (8) TyTLER, W. H. (1944) Tubercle, 25, 95 and (1945) 26, 23. (9) Ricu, A. R. and Fouuis, R. H., Jr. (1938) Bull. Johns Hopk. Hosp. 62, ties (10) ZucKER, G., PINNER, M. and Hyman, H. T. (1942) Amer. Rev. Tuberc. 48, 292. (11) ELtiman, P., LAWRENCE, J. S. and Cumines, J. N. (1941) Tubercle, 22, 296. (12) FELDMAN, W. H., Hinsuaw, H. C. and Mosss, H. E. (1942) Amer. Rev. Tuberc. 45, 303. (13) Hear, F. G. R., Hurrorp, J. V., E1ser, A. and FRANKLIN, L. M. (1943) Lancet, 1, 702. (14) TyTLER, W. H. and Lapp, A. D. (1942) Brit. med. J. 2, '748. (15) PeTTER, C. K. and PrRENzLAv, W. S. (1944) Amer. Rev. Tuberc. 49, 308. (16) FeELpMAN, W. H., Hinsuaw, H. C. and Mann, F. C. (1944) Amer. Rev. Tuberc. 50, 418. (17) Scuatz, A., Bucie, E, and WAxKsMAN, S. A. (1944) Proc. Soc. exp. Biol. NY 05 OG. (18) FELpMan, W. H., Hinsuaw, H. C. and Mann, F. C. (1945) Amer. Rev. Tuberc. 52, 269. (19) HinsHaw, H. C., FELDMAN, W. H. and PFUETzE, K. H. (1946) Amer. Rev. Tuberc. 54, 191. (20) Manpican, D. G., Swirt, P. N. and BROWNLEE, G. (1947) Lancet, 1, 9. (21) ANDERSON, R. J. (1942-43) Yale J. Biol. Med. 15, 311. (22) Roxpinson, R. (1940) J. chem. Soc. p. 505. (23) BERNHEIM, F. (1941) J. Bact. 41, 387. (Quoted by Lehmann, J. q.v.). (24) LEHMANN, J. (1946) Lancet, 1, 14 and 15. (25) Dempsey, T. G. and Loae, M. H. (1947) Lancet, 2, 871. (27) Grasset, E. (1938-39) Tubercle, 20, 397. (28) Roserts, J. R. (1937-388) HE. Afr. med. J. 14, 221 and 251. CHAPTER VIII THE ARTIFICIAL PNEUMOTHORAX ARTIFICIAL pneumothorax for the treatment of pulmonary tuber- culosis was suggested on theoretical grounds more than a century ago and now is employed all over the civilised world. It is generally recognised by those with experience of tuberculosis that the basis of treatment is rest of the diseased part. The spongy consistency and continual movement of the lung make it easy for tuberculosis to spread, and it is not surprising therefore, to see the rapid improve- ment which so often follows the induction of a pneumothorax. The aim of pneumothorax treatment is to relieve tension and to rest the lung, thus preventing spread of the disease and allowing nature to effect a cure. One of the manifest advantages of collapse therapy in general, and of the artificial pneumothorax in particular, is that it shortens the length of institutional treatment and enables a patient to return to work earlier. It is a mistake, however, to look upon an artificial pneumothorax as a substitute for routine general treatment such as is provided in a sanatorium, for tubercu- losis is a systemic disease and its manifestations may not always be confined to the lung. Collapse therapy has never yet cured phthisis, nor will it ever do so: in the long run success or failure of treatment is absolutely dependent upon the powers of resistance which the patient himself can muster. Employed in its proper place and in full knowledge of its limitations it is possible to find in artificial pneumothorax one of the most valuable and effective weapons against pulmonary tuberculosis. Indications It must not be assumed that the artificial pneumothorax, because it has proved itself exceedingly valuable in certain cases, especially of unilateral disease, is therefore the treatment of choice for all. Hebert (1) in a paper on this subject that repays study, refers to the desired effects of a pneumothorax and urges that the treatment must be placed on a rational rather than on an empirical basis: With this as the guiding principle the main indications for pneumo- thorax can be grouped as follows :— Control of Toxaemia. In most examples of active pulmonary tuberculosis some abatement of toxaemia follows the employment of strict bed rest. There is much to be said in favour of giving this form of conservative treatment a trial, and of withholding pneumo- thorax for a short period after admission, for only rarely is collapse therapy a matter of emergency. A pneumothorax induced when the toxaemia has been to some extent brought under control is less likely to be followed by complications, chief among which is the formation of fluid. Moreover, during this period of preliminary rest the patient becomes attuned to his new surroundings and accepts the prospect of active treatment, when it is suggested, with greater tranquillity of mind. On the other hand, it has been argued that the longer the Helay the greater becomes the chance of pleural adhesions forming. When it is recalled how commonly adhesions are found no matter when the pneumothorax is induced, it is hard to believe that an additional delay of two or three weeks will render divisible adhesions indivisible in more than a very small fraction of the total. For Spread of Disease. Serial X-ray photographs sometimes demonstrate a tendency for the disease in the lung to spread in the absence of obvious toxaemia and objective evidence of activity, and if this advance continues unchecked by bed rest a pneumothorax may have to be employed. Clinically silent spread of this type is a not uncommon characteristic of minimal lesions discovered by routine radiography and for these lesions a shallow or “ mantle ”’ pneumothorax has sometimes been recommended. For the Closure of Cavities. It is in unilateral exudative phthisis with cavitation that the artificial pneumothorax is especially valuable. The importance of obtaining closure of tuberculous cavities, if a subsequent breakdown and a spread of disease is to be avoided, has been realised for many years. Strict bed rest for a sufficiently long period may be followed by spontaneous closure of cavities, but the number of successes is relatively small. The length of time required is often more than most patients can afford, while the danger of a relapse on return to ordinary employment is con- siderable. Wiese (2) found that in only 20 out of 125 unselected cases of pulmonary tuberculosis did the cavity close without treat- ment other than bed rest. Relaxation of the diseased area of lung \ by an adequate pneumothorax is a more certain and more rapid method of converting the focus into a firmly healed scar. _ The use of pneumothorax for cavity closure, however, requires judgment, for not all cavities are suitable for this form of collapse therapy, and such factors as size, position, and chronicity need to be taken into account. A lateral film is essential for the accurate localisation of a cavity. The large cavity is not often amenable; it is one which is fre- quently under tension and requires to be dealt with by different methods (see page 203). The cavity with thin walls which lies at the periphery of the lung should be selected with caution for pneumo- thorax treatment in view of its proclivity to rupture ; likewise the medially placed cavity near the mediastinum often proves refractory to this form of collapse therapy, as well as to others. Apical cavities, on the whole, respond more favourably than do those at the base of the lung; those in the apex of the lower lobe are especially obstinate. The thick-walled chronic cavity may prove resistant. In other words, it is for the soft cavity of reasonable dimensions situated well within the substance of the upper lobe that the artificial pneumothorax is ideally suited. For the Conversion of a Persistently Positive Sputum. The persistent cavity is almost always accompanied by a positive sputum: the converse is also true, and sputum which is persistently bacilliferous generally implies the existence of a cavity or cavities. In some instances, however, these cavities may be so small as to defy recognition by radiographic or tomographic methods. Nevertheless, such examples demand the same consideration as the obviously patent cavity, for unless sputum conversion is achieved the ultimate prognosis is unfavourable. _ An investigation carried out by Brian Thompson (3) upon an industrial population in the North of England is germane to this argument, as it shows the adverse effect of a positive sputum upon the expectation of life of this class of patient. His results are quoted on page 229. A similar survey has also been undertaken by Tattersall (4) in Reading in which he confirms the unfavourable out- look for permanently sputum positive patients. - Control of Haemoptysis. Pneumothorax may be required in the treatment of this symptom, especially if the bleeding is repeated or severe and has defied other methods of treatment. It is sometimes difficult even with an X-ray film to determine from which lung the blood is coming. The patient’s own sensations are often helpful in reaching a conclusion. Once the decision to induce an artificial pneumothorax has been taken, the lung should be collapsed more quickly than is customary and a larger volume of air should be used for the induction and for the first few refills. Amounts of air between 600 c.c. and 800 c.c. are recommended. For the Relief of Pleural Pain. Particularly that associated with chronic pleurisy and accompanied by a friction rub. For the Treatment of Pleural Effusion. After the initial exploration of a tuberculous pleural effusion has been performed, the pleural sac is best left alone unless interference is especially indicated. Some examples, however, require air-replacement, and in a still smaller group, in which active disease in the underlying lung can be demonstrated, the continuation of the artificial pneumo- thorax so obtained may be the best method of treatment. For Economic Reasons. Not all patients are able to afford the time for full sanatorium treatment. Even if the prospect of the disease being controlled without collapse therapy is good, the length of time required would be shortened and the patient’s return to work accelerated if a pneumothorax were induced. It is necessary, however, to weigh carefully the advantages of an earlier return to work against the risk attaching to a pneumothorax. In Children. The adult form of the disease occurring in children under fourteen years of age has an exceptionally bad prognosis, and any measures which are capable of arresting its progress are justifi- able, for to gain time is vital. Little hesitation, therefore, need be felt in attempting pneumothorax if the nature of the case permits. Armand-Delille (5) described the results of pneumothorax treatment in fifty children, and his work did much to dispel the old idea that pulmonary tuberculosis in children is universally fatal. Agassiz (6) has also had encouraging results in young patients. In Pregnancy. A breakdown of resistance against pulmonary tuberculosis is to be feared in the first few weeks after parturition, and the disease may advance. Recently, however, it has been appreciated that if the disease can be brought properly under control before the date of delivery this breakdown can be averted and both mother and child do well.. For the attainment of his aim, in the time allowed, a pneumothorax is often an indispensable adjunct to other more general methods of management (see also page 113). The Presence of Certain Complications. Of these tubercu- losis laryngitis and ischiorectal abscess are the most prominent and provide clear indications for a pneumothorax in view of the import- ance of rapidly converting the sputum from positive to negative. The same applies to ulceration of the intestine unless the disease is already too far advanced. _ Diabetes. Pulmonary tuberculosis found in conjunction with diabetes mellitus requires more energetic treatment than perhaps might have been necessary if it were present alone, and the indica- tions for pneumothorax must be correspondingly widened (see page 111). | Selective Pneumothorax It is a fortunate feature of pneumothorax treatment that the diseased area of the lung more readily collapses than the part which is healthy. It is therefore possible, by adjusting the pressures, ° the spacing of the refills, and the amount of air introduced, to ensure adequate relaxation of the diseased area while preserving the func- - tional efficiency of the unaffected portion. In the early days of pneumothorax treatment the ideal aimed at was the complete col- lapse of the lung, and it was often stated that the best results were obtained when this was achieved. As a result of earlier diagnosis and an increased familiarity with the pneumothorax and its possi- bilities, the procedure is used at a stage when complete collapse is not only unnecessary but undesirable. It is now generally appre- ciated that the ideal pneumothorax is one in which the diseased apex, free from restraining adhesions, is concentrically relaxed, leaving the healthy lower lobe sufficiently expanded to perform its respiratory function with little disturbance. This selective type of relaxation is not always obtainable, but for upper lobe lesions it is the ideal form of collapse. Contra-selective Pneumothorax This refers to a pneumothorax in which the diseased part of the lung is firmly attached to the chest wall by pleural adhesions, while the remainder of the lung which is healthy is collapsed. An attempt should be made to convert this inefficient pneumothorax into an efficient one by the closed method of division of adhesions, and in many cases this can be successfully accomplished. In the most favourable examples a contra-selective pneumothorax can sub- sequently be converted into a selective concentric pneumothorax already discussed. When, however, the degree of pleural adhesion is so extensive that internal pneumonolysis fails, there is little to be gained by persevering with a pneumothorax of this type, although occasionally an attempt has been made to divide the adhesions by the open method, but with little success. In most cases symptoms persist, and there is a constant danger of the occurrence of a tuber- culous empyema. For these reasons it is advisable to abandon the pneumothorax without delay and to proceed, if possible, to other methods of obtaining surgical collapse. Bilateral Artificial Pneumothorax There is a large amount of reserve in the lung so that life can con- tinue even after the greater part of the lung tissue is destroyed or otherwise put out of action. The possibility of maintaining a simultaneous bilateral artificial pneumothorax has been realised for many years. Forlanini (7) had two cases which he published in 1911, while Saugman (8) in 1921 reported seven cases in which he had induced bilateral pneumothorax. In late years it has eae in popularity and is now frequently used. Obviously complete collapse of both lungs cannot be Ren Tees simultaneously. For limited lesions at both apices, however, especially if of a mildly active type with cavitation, or for the control of spread to the opposite lung during the course of pneumothorax treatment, bilateral collapse can be employed without discomfort and with much benefit. Most patients can continue their occupation during treatment without dyspnoea or other symptoms. In bilateral disease the question of which side to induce first may be difficult to answer. As a general rule the lung more heavily involved or the one displaying the more physical signs should be relaxed first. The degree of improvement in the other lung which may follow this procedure is often surprising and may be sufficiently great to eliminate the necessity for a pneumothorax on that side. Jennings and Mattill (9) have investigated this question. They studied 578 patients with bilateral disease who were considered suitable for a pneumothorax on one side. They found that in 40 per cent. the lesion in the contralateral lung did not change ; in 26 per cent. it improved ; in 6 per cent. it remained unstable; while in 24 per cent. it grew worse. | In both pneumothoraces the lungs often assume a selective type of collapse which may be made more perfect by the division of any adhesions which are present. In most cases it is better to obtain a satisfactory pneumothorax by adhesion section on the first lung before the pneumothorax is induced on the epposite side, exceptions being those cases in which the disease is developing at a pace which makes further delay dangerous. When internal pneumonolysis is performed in the presence of an established pneumothorax on the opposite side, care must be taken to guard against over-collapse at the time of operation by keeping the pressure on the negative side. In the maintenance of a bilateral pneumothorax the pressure readings at the beginning and end of a refill are relatively unim- portant. The amount of air introduced is determined more by the degree of collapse seen on the screen than by pressure change. Some workers prefer to refill each side on a separate day. This may be advisable if moderate and transient breathlessness follows a refill, but otherwise there is no objection to refilling both sides on the same occasion, a convenience to an ambulant patient who may have to travel some distance for treatment. The interval, however, between the refills need not be the same on the two sides, and in judging the spacing each must be separately considered. Bilateral pneumothorax therapy is not a difficult undertaking while the patient is in an institution, but complications may arise following the lessened control on discharge. Contralateral Artificial Pneumothorax When the diseased lung cannot be collapsed owing to adherent pleurae, partial pneumothorax has been induced on the healthy side with the object of giving rest to the bad lung. The rationale of the method rests-upon the interdependence of the pressure in the two pleural sacs, a change on one side being reflected to an almost equivalent degree upon the other in the presence of an unfixed mediastinum. Lucacer (10), writing on the subject in 1942, gives the following indications for its use :— A recent exudative lesion in the upper lobe with a miobile mediastinum. Where the integrity of the sounder lung is questionable and a thora- coplasty on the opposite side is contemplated. In severe haemoptysis if a homolateral pneumothorax cannot be obtained and other treatment has failed. Apart from the use of a protective pneumothorax as a safeguard during the performance of a thoracoplasty on the other side, and this is not a contralateral pneumothorax in its true sense, the method has found little favour in this country and is rarely employed. The Unexpandable Lung At the conclusion of pneumothorax treatment it is hoped that the lung will re-expand and fill the pleural space, possibly with the assist- ance of slight emphysematous changes to take the place of lung tissue which has been lost during the process of healing. If the original disease was not extensive and the pneumothorax uncompli- cated by persistent effusion this hope will probably be realised ; but in some cases the absorption of air is followed by compensatory changes in the surrounding structures with the result that, in addi- tion to reinflation of lung, the ribs slant together, the diaphragm rises and the trachea and heart become displaced towards the affected side before obliteration of the space is complete. Indeed, in the majority of re-expanded lungs evidence of such a compen- satory mechanism can be noted and some shift of the mediastinum is accepted as of no consequence unless it is extreme. It is in cases of this kind that a phrenic operation is sometimes useful. In a few patients, however, the lung is so little able to re-expand and the surrounding structures are so unyielding that this compensatory mechanism fails in its object and a_ persistent pneumothorax or “‘dead pleural space” remains. It has been estimated by Farber (11) that this occurs in something approaching 5 per cent. of pneumothorax cases. Farber, in his paper, goes on to discuss the probable causes of unexpandable lung from a study of twenty-seven patients with this condition and found that the more important of these were thicken- ing of the visceral pleura following tuberculous pyopneumothorax, oleothorax or persistent serous effusion; massive pulmonary fibrosis ; bronchopleural fistula; and bronchial stenosis. More than one cause may operate in each case, MAINTENANCE OF PNEUMOTHORAX 148 Consideration of the causes show that in some cases an unex- pandable lung can be anticipated, as, for example, when a pneumo- thorax is contemplated for extensive disease with a fibrotic tendency. In other patients with a persistent effusion the thickening of the visceral pleura is a gradual process and a permanent collapse can sometimes be prevented. In a third group, usually those in whom a small bronchopleural fistula occurs, the condition develops rapidly, is unavoidable, and may be irreparable. A persistent dry pneumothorax is compatible with good health and an active life for many years. Some are known to have con- tinued with small refills at infrequent intervals, for ten, twenty or more years. It is, however, an unsatisfactory end of a therapeutic pneumothorax, for there is always the danger of formation of fluid necessitating a thoracoplasty. With the passage of time this operation itself becomes more difficult on account of calcification or even ossification of the parietal pleura. Maintenance of the Artificial Pneumothorax As the primary object of artificial pneumothorax is to relieve tension in the lung and not to compress it, careful spacing of the refills, using the correct quantity of air, is important. When once a lung is collapsed no special skill is required to put a needle into the pleural cavity and inject air, but it requires considerable ex- perience to judge how much to give and when to give it. The X-ray provides the only accurate means of determining the amount of collapse needed in a particular case, and screening should be done before and sometimes after each refill. Therefore, it is essential for the successful management of a pneumothorax to have at least an X-ray screening apparatus available. Sometimes the air is retained for weeks and even months, so that refills are only required at long intervals; in other cases the air is absorbed much more rapidly and large quantities must be given at frequent intervals to maintain adequate collapse. An extreme example of this, known as pneumothorax insatiable, has been described in which, even after the introduction of a large volume of air, no pneumothorax space is demonstrable radiologically. The pheno- menon is a rare one and the exact mechanism is not fully understood. A common mistake is to leave too long an interval between the ‘ 144 THE ARTIFICIAL PNEUMOTHORAX refills, so that the lung is alternately collapsed and expanded— termed the “‘ concertina’? method by Burrell (12). This does not give the lung the best possible chance of recovery and the pneumo- thorax is not used to the best advantage. It is better practice to use smaller quantities of air at shorter intervals and thus maintain a more consistent and sustained collapse of the affected part. Another common mistake is to maintain the wrong degree of collapse, and an extreme example of this has already been discussed under “‘ contra-selective ” pneumothorax. It is of importance to study the degree of collapse required in an individual pneumo- thorax. Some patients do best with a partial collapse, and if this is increased they begin to get thin, develop dyspnoea, and lose ground ; others fail to improve until a complete collapse is obtained, neces- sitating large and frequent refills. The optimum degree of collapse and the length of time that it will last before another refill is required can only be determined by a careful evaluation of symptoms and signs and of the X-ray appearance. Termination of a Pneumothorax There is some difference of opinion as to the length of time a pneumothorax needs to be maintained. Saugmann in 1920 advocated five years for a complete collapse, and in only a few cases noticed a return of symptoms at the end of that time. Other workers believe that a satisfactory pneumothorax should be main- tained for as long as possible. In many cases the question is decided by obliteration of the pneumothorax cavity by pleural symphysis. Hurst and Schwartz (13), discussing the voluntary termination of pneumothorax, found in their series that the best results were observed in cases in which collapse had been maintained for at least four years. They suggest that an observation period of least three years should elapse after re-expansion has been allowed before the final result is assessed. It is clear that the nature of the original disease must be taken into account. It is unfortunate that even modern standards of investigation fail to show when disease in a collapsed lung is firmly healed, for symptoms and all objective signs of activity may have been absent soon after the inception of treatment, yet a relapse ensues when the pneumothorax is abandoned. It is impossible to generalise and fix precisely the duration of treatment and the period of between three and five years usually adopted is purely arbitrary and based upon accumulated experience, with a suitable margin allowed for safety. It must be emphasised that any calculations should be based, not on the date of induction, but from the time that effective collapse was achieved. This may refer to division of adhesions or to operation on the phrenic nerve. In coming to a decision in each individual patient the following points require attention :— The Nature of the Illness. Before such an important step as the voluntary termination of a pneumothorax is contemplated, a retrospective review of the case from the inception of the disease until the present time should be undertaken. For this the original X-ray, and the last one taken before the induction of the pneumo- thorax, are indispensable. The points requiring special attention are the original extent of the lesion ; the situation and size of the cavities ; the type of disease, whether predominantly fibrotic or exudative ; the type of pneumothorax, whether selective and con- centric or not fully satisfactory ; the progress of the lesion from the time of onset of treatment with reference to relapses and the forma- tion of fluid; and the results of sputum tests, having regard to the methods of examination employed. All these points should be related to the temperament and environmental background of the patient. : Environmental Factors. This is a large and important aspect which includes the type of work and the length of time spent in travelling to it, the home conditions, financial resources, and responsibility for the care of young children. The extent to which unsuitable environmental factors, discovered at the time of diag- nosis, have since been corrected, is of special significance. Personal Factors. There are many people who can never accustom themselves to a needle-prick and who approach each refill with trepidation. In these the treatment should not be maintained longer than is absolutely necessary. Conversely, a number of patients derive a sense of security from a pneumothorax and are reluctant to give up a method of treatment upon which they have come to depend. In the face of such an attitude the wisest course is probably to continue refills after the implications of doing so have been frankly discussed. | Reactions following a Refill. Such symptoms as pain or tightness in the chest or the occurrence of febrile reactions, if sufficiently severe to cause temporary incapacity, may influence the decision as to when to terminate the treatment. Once the decision to terminate has been reached it is better to allow the lung to come up gradually rather than rapidly. Todd (14) advocates slow re-expansion and gives the following reasons : First, that the pleura, if indurated, must be allowed to stretch slowly ; secondly, that any displacement of the mediastinum which occurs has to be accommodated, and thirdly, it may be possible to re-establish the pneumothorax if signs of reactivation appear. A phrenic operation can be done if the pressures become too highly negative, or if there is much displacement of the mediastinum. The performance of a temporary phrenic operation in those patients in whom the disease originally was extensive is often good practice. Complications of Artificial Pneumothorax Collapse therapy is now widely employed and its value is being increasingly recognised, and this wider application of the pro- cedure, especially to patients with early disease, makes it more than ever necessary to balance carefully the obvious advantages of this method of treatment against those complications attaching to it. Gas Embolism and Pleural Shock : Novocaine Reactions.— Gas Embolism is a rare complication due to air entering the pul- monary veins and being carried through the left side of the heart to lodge in the systemic capillaries. The air is derived from three possible sources, air from the pleural cavity, from the alveoli, and from the tubing of the pneumothorax apparatus. Symptoms usually appear soon after the needle has entered or been withdrawn from the chest. The symptoms and treatment of this condition are too well known to need description, except for a warning against the use of artificial respiration as this may lead to more air being sucked into the vein. The manifestations of pleural shock are similar to those of gas embolism but without paralytic or paretic sequelae. The identity of pleural shock, as distinct from gas embolism, has been doubted by some workers who ascribed the symptoms not to a reflex effect from irritation of the pleura but to gas embolism itself. It is not possible to settle this controversy absolutely, and evidence can be marshalled in support of either view. The points in favour of pleural shock occurring as a separate entity are threefold : 1. A state of shock can be produced in animals by irritation of the pleura and the reflex pathway is held to be through the vagus nerve. It can be prevented by ligature of the carotids and by keeping the animal under an anaesthetic. 2. The appearance of severe syncope is known to follow the ex- ploration of a chest for a large pleural effusion. Here the chance of striking the visceral pleurae and damaging the lung is remote; it is certainly far less likely than at the induction of an artificial pneumothorax. 3. Burrell has observed, in some patients, the appearance of symptoms regularly at the time of each refill, and this he held to be more consistent with pleural shock than repeated air embolism. It must be confessed, however, that the distinc- tion between pleural shock and a vaso-vagal attack occurring in a highly-strung or neurotic subject might be in such in- stances, extremely hard to draw. Finally, reference must be made to yet another condition, which, if local anaesthetic is used, enters into the differential diagnosis and may be a source of confusion. This is reaction to or possibly poisoning by novocaine, a drug to which some people are unduly susceptible. Andosca and Foley (15) quote Blumer as recognising two varieties of reaction: (1) that which results in sudden death before any steps can be taken to treat the condition. Here, the drug is very possibly injected directly into the circulation through a small subcutaneous vessel and overpowers the myocardium. (2) A slower but still moderately rapid form in which the patient becomes restless, anxious, excitable, and even delirious, with weak, irregular pulse and rapid respiration. Convulsions supervene, consciousness is lost, the patient passes into coma, and death may result. The drug is quickly removed from the circulation by the liver and if the heart’s action can be maintained by stimulants and the breath- ing by means of artificial respiration until the concentration in the blood has been lowered to a safe level the patient may survive. Phenobarbitone, by the intravenous route, is a valuable drug if given early. Pneumoperitoneum. Direct pneumoperitoneum may occur as a result of the needle being inserted through or below the dia- phragm into the peritoneal cavity. There may be no symptoms or only slight abdominal discomfort, but sometimes severe pain is felt in the chest and shoulder which is worse when standing up. In rare cases air may pass from an established pneumothorax through the diaphragm and produce an_ indirect pneumoperitoneum. Banyai (16) has described cases in which this occurred. The symptoms are relieved by raising the foot of the bed thus shifting the air to the pelvis. Simon and Abrams (17) have recorded a case in which air was seen between the diaphragm and the diaphragmatic pleura on both sides in a patient who was being treated with a left- sided pneumothorax. The only symptom was pain in the lower part of the chest after refills. Puncture of Heart or of a Large Vessel. ‘This complication, which is made evident by blood passing fairly rapidly up the tubing towards the manometer, may be harmless, as in the case recorded by Vere Pearson (18) in which the needle entered the pericardium. Hall (19), however, has reported a case in which a haemopneumo- pericardium was induced when giving a left-sided pneumothorax refill. Transitory electro-cardiographic changes were found similar to those seen in cardiac tamporade. Complete recovery ensued. Displacement of the Mediastinum. Sometimes the media- stinum is resistant and firmly held in position, so that there is no displacement of the lung. In other cases it is extremely mobile and is displaced even though the intrapleural pressure is negative. This is unfortunate for not only may it cause symptoms but it reduces the effectiveness of the collapse as the air introduced tends to deflect the mediastinum rather than relax the lung. It may be necessary to discontinue the treatment. Phrenic avulsion has been advocated on the grounds that the raised diaphragm will prevent bulging of the mediastinum but.it may make matters worse by adding a tone- less diaphragm. One method of treating a mobile mediastinum is to induce adhesions between the lower part of the lung and the chest wall and so anchor the mediastinum. For this purpose Maurer (20) injects 20 c.c. of a 50 per cent. solution of glucose into the pleural cavity and repeats this at weekly intervals increasing the quantity up to 150 c.c. if necessary. This leads to the development of an effusion and subsequently to adherent pleura. Pleural Hernia. Sometimes the pleura forms a hernia which protrudes through the mediastinum to the other side, or between the ribs to give the impression of a superficial tumour. The common sites are through the anterior compartment at the level of the second to fourth sterno-costal articulations, and in the lower part of the posterior mediastinum. Herniae are most clearly brought out in a film taken in full expiration or on the screen ; as a rule they cause no symptoms. | : Accidents due to Needle Puncture. A haematoma may form beneath the skin after a refill but it is exceptional for serious haemorrhage to occur into the pleural cavity unless the needle has passed through the parietal pleura and penetrated a vascular adhesion. Muller and Rinkel (21) have recently described 6 cases of this complication in 15,000 refills, which they attribute to punc- ture of a surface vessel on the parietal pleura. Bleeding may con- tinue for several days. If obliterative pleurisy is to be avoided the authors recommend aspiration and saline washouts. The hypodermic needle used for giving the anaesthetic may break and lodge in the tissues. The break occurs at the hilt and a needle should therefore never be inserted to its fullest extent. It may be impossible to retrieve the needle through the skin, but if there is sufficient pneumothorax space an attempt should be made to remove it by using a thoracoscope and grasping it with forceps. At thoracoscopy the needle may be seen either protruding through the parietal pleura or lying on the diaphragm, and its exact position can be determined beforehand by X-rays. If this intervention fails, the needle is best left alone: the majority become walled off by fibrous tissue and cause no harm, but occasionally they wander and give rise to trouble later. Rupture of the Visceral Pleura. Rupture of the visceral pleura may occur converting the artificial pneumothorax into a spontaneous one. ‘This is a very serious complication if the per- foration remains open and leads to a pyopneumothorax. The symptoms are sudden pain in the chest accompanied by a rise in temperature. The patient is acutely ill, and an effusion soon forms: and may become purulent. The intrapleural pressure may be much increased if the perforation is valvular, and the patient very dyspnoeic until some air is removed. Breath sounds over the pneumothorax cavity are amphoric, “‘ metallic tinkling ”’ is heard, and there is usually displacement of the mediastinum. Rupture results from the sudden increase in pressure during cough and is most common where an adhesion joins the visceral pleura. Occa- sionally a thin-walled cavity or an area of caseating lung may rupture, and it is not uncommon for a pyopneumothorax to break through the visceral pleura and leave a communication between the lung and pleural cavity. MacDermott (22) reports two cases where the perforation was held open by an adhesion and which closed when the adhesion was cauterised. In other instances a small fistula may close spontaneously before irretrievable damage is done. In Burrell’s first 334 cases of artificial pneumothorax (23) rupture of visceral pleura on the treated side occurred in six. Two of these were non-tuberculous patients and both recovered. The other four were cases of pulmonary tuberculosis and all died : a pyopneumo- thorax developed in each case. Thickened Pleura. This may occur when there is no effusion but is especially frequent in cases of long-standing pyopneumo- thorax when the collapsed lung may be so bound down by pleura that re-expansion is impossible. After pneumothorax treatment has finished, the visceral and parietal pleurae are usually adherent and thickened, so that it is not always possible to re-collapse the lung. A pneumothorax can sometimes be obtained a second time, even after a pleural effusion, and Vere Pearson succeeded in reproducing a pneumothorax in one case two years after the last refill. Pleurisy. A small area of pleurisy frequently leads to the pleural layers becoming adherent. If there is a pneumothorax this cannot occur, since the visceral and parietal pleurae are separated by air, and consequently pleural effusion is a common complication. Dry pleurisy may occur as a complication of artificial pneumothorax, and Riviere thought it was not uncommon at the site of puncture, especially if many punctures have been made in the same place. Sometimes intrapleural bodies (so-called “‘ pleural mice ’’) are found either free or on a pedicle. They consist of a coagulum of fibrin and can only be recognised by X-ray which shows them as rounded or oval opacities. They are of no clinical significance. Pleural effusion is the most frequent complication of artificial pneumothorax. There may be no symptoms or a complaint may be made of malaise and slight pain. Sometimes there is vomiting, and the condition resembles an acute gastric disturbance. As a rule there is pyrexia for a few days only but in the more severe cases the temperature is elevated for three to five weeks before settling. Occasionally the temperature remains high and the patient’s condi- tion becomes steadily worse. In these latter examples it is found that the tuberculosis is spreading in the lungs and the development of fluid seems to have been the starting point of a general breakdown. Such cases are uncommon. Various explanations have been given to account for the frequency of pleural effusion in pneumothorax. Irritation by the gas, its temperature, the repeated punctures of the parietal pleura, the use of positive or of extremely negative pressures, have all been described -as playing a part in the production of effusion, but their influence has never been proved. Pisani and Smejkal (24) suggest that pleural effusion is due to the increased permeability of the capil- laries from want of oxygen; to increased osmosis ; to higher con- centration of H ions; to calcium deficiency of the pleura; and lastly to the aspirating effect of the negative pressure. They suggest giving calcium just before and during pneumothorax treatment in the form of a 10 per cent. solution of calcium gluconate intra- muscularly. Bohm (25), in order to test the assumption that calctum exerts its beneficial effect through its action upon the permeability of injured capillaries, investigated the effect of this substance upon effusions and found that it was difficult to raise the blood calcium to any extent by oral administration. He therefore tried injections of parathormone and succeeded in elevating the blood calectum to 13-75 mg. per cent. but without any apparent effect on the exudate. It is more probable, however, that these effusions are true tuber- culous exudates due to tuberculous pleurisy and occur with equal frequency whether the air is heated or not and whether air, nitrogen, oxygen, or other gas is used. The following considerations lend support to this view :— . Pleurisy is a common complication of pulmonary tuberculosis and often leads to adherent pleura. If the parietal and visceral pleurae are separated, an effusion would be expected to form when pleurisy occurred. In almost every case of tuberculous spontaneous pneumothorax effusion develops, but it is rare in the benign variety. | 2. The cytology of the fluid is that of an exudate and not of a transudate. 3. Tubercle bacilli are uncommonly found in the effusion in the early stages, but are more commonly present in long standing examples. 4. Tubercles may sometimes be seen on the pleura at thoraco- scopy. 5. Of the first 309 cases in which Burrell produced a successful pneumothorax for pulmonary tuberculosis, a definite effusion formed in 128;. but of his first 54 cases of non-tuberculous disease where pneumothorax was induced an effusion occurred in one only, and that was but a transient and small effusion in an example of acute pulmonary abscess. These figures give a percentage of 41-4 for tuberculous and under 2-0 for non- tuberculous disease. Hutchinson and Blair (26) have suggested that effusion in tuber- culosis cases is often the result of a small rupture of lung, and support their opinion by the fact that an effusion is commonly preceded by a rise in intrapleural pressure, and that the temperature which accompanies its development is similar to that seen in ordinary examples of spontaneous pneumothorax. Simmonds (27) goes even further and attributes the formation of pleural fluid, serous or purulent, in most instances, to the actual rupture of a cavity. He draws attention to a group of pneumothorax cases in which the cavity increases in size after adhesions have been divided and the affected part of lung completely freed. He noticed this phenomenon in 21 out of 251 patients so treated. Of these 21 patients with ‘‘ ballooning ”’ of the cavity, 16 developed an effusion, the fluid being clear in six, and cloudy or frankly purulent and containing tubercle bacilli in the remainder. Five of the patients did not develop an effusion but one died of haemorrhage from the cavity, two died of spontaneous pneumothorax, and in the others the disease showed signs of spreading. Simmonds examined the lungs of five of these patients post-mortem, and demonstrated a ruptured cavity in four, in all of which the draining bronchus was found to be the seat of caseous bronchitis. He believes that the tuberculous endobronchitis acts as check valve which allows air to enter the cavity on inspiration but not to leave it on expiration. and is responsible for the distension of the cavity and for the rupture of the caseous cavity wall. In his paper Simmonds lists four possible causes for pleural effusion in artificial pneumothorax :— 1. Rupture of a distension cavity already referred to. This he considers more often responsible than is commonly realised and might occur without demonstrable increase in size, or else the phase of enlargement might be missed radiologically. 2. Effusion due to trauma, e.g. cauterisation of adhesions. He found the effusion due to this cause was usually small and transient. 3. Blood-borne tuberculous infection of the pleura. This can hardly be a significant cause, as if it were bilateral effusions would be expected to occur more often than they do. 4, Direct spread of tuberculous disease to the pleura. _ Spread of disease might be responsible for the effusion, mentioned earlier in the text, which is persistent and accompanied by a general breakdown of resistance. To the above list of causes can perhaps be added a fifth, namely, the effusion which follows the establishment of a high negative pressure and which is commonly seen when the pneumothorax is being given up. This has been termed the transudate ex vacuo, but Todd (14) is of the opinion that it is an exudate rather than a transudate. | A small transient effusion is almost the rule in cases of artificial pneumothorax, and if every case were to be examined daily with the X-ray screen its presence would be detected more frequently than it is. Such collections of fluid, however, are soon absorbed and are not important. Pleural effusion is not necessarily a serious complication of col- lapse therapy and it may be beneficial. Sometimes a patient who is not doing well starts to improve as soon as an effusion forms and eventually makes a good recovery. The following table shows the results of effusion on a series of 309 cases from Burrell’s series. They are patients with medium resistance who have failed to improve after other treatment: C1 included those with unilateral disease; C2 those with slight involvement of the other lung; and C3 are those in whom there is involvement of a third or more of the better lung :— | Cl C2 C3 Cases Died Cases Died Cases Died ) Per Per Per cent. cent. cent Total F 126 24 | 19-0 | -1385 AT | 84°8 48 33 | 68-7 Clear fluid 2) BOs Pees Ph CAe 4) CBM oe | any 8 | 72-7 No effusion F 78 13 | 16°6 72 22 | 30°6 31 22 | 71-0 0 18 tl | 62°8 6 3 | 50:0 Pus : 2 6( STE Gr oO" It will be seen from these figures that the development of clear effusion does not increase the mortality rate, but that when the fluid is purulent the outlook is much more serious. When there is extensive disease the mortality is high in all cases. The management of pleurisy occurring in artificial pneumo- thorax can most conveniently be considered under two headings, serous and purulent. Serous Effusions. While each case must be taken on its merits, it may be stated as a general rule that it is unwise to aspirate during the first few days of the acute or febrile stage, and, if pressure symptoms arise at this time, it is better to attempt to relieve them by removing air than by aspirating fluid. If, however, the fluid is left too long it will usually cause obliteration of the pneumothorax by pleural adherence and fibrosis, starting at the bottom of the pleural cavity and working upwards. This is commonly seen fol- lowing the cauterisation of adhesions, especially if bleeding occurred at operation. If obliteration is desired, as it may be if near the time for termination, the fluid should be left, but the patient must be kept under observation lest complications arise. Many cases of pneumothorax which obliterate in this way do very well. In some cases the effusion does not become absorbed for months or even years, or it may never be absorbed. If aspirated it reforms. These chronic effusions are usually localised collections of fluid surrounded by adherent pleura and the general health of the patient may be unimpaired. If, however, it is decided to maintain the pneumothorax, the effusion should be aspirated and replaced by air to prevent oblitera- tion of the pneumothorax cavity. Aspiration is also indicated if the effusion contains tubercle bacilli. The site of election for aspiration is in the mid-axillary line just below the level of the fluid with the patient sitting up or in a semi- recumbent position. The patient is inclined towards the operation during the procedure. Some workers prefer to insert the needle higher in the axillary line, above the fluid, and lay the patient well over towards the affected side. Either technique minimises the chance of sinus formation, as any fluid left will lie below the needle track ; also should a sinus form, it will not interfere with a thoraco- plasty incision if that operation should be required. If the object, however, is to evacuate the pleural cavity completely, the needle may have to be inserted lower down and air run in either through the same needle by means of a “threeway” syringe, or inde- pendently through a pneumothorax needle inserted higher up the chest in front. This latter method has the advantage of enabling the amount of air introduced to be related to the intra- thoracic pressure. Replacement is especially indicated if the fluid appears early in the course of pneumothorax treatment or if tubercle bacilli are demonstrated in it. Usually after one or two aspirations it does not reform, but in a few cases obliteration occurs in spite of aspiration or the use of high intrapleural pressures. It was with _ the object of checking this inevitable obliterative pleuritis that oleo- thorax was introduced, but its use is restricted by the danger of rupture into a bronchus with subsequent infection of the pleural space. Purulent Effusion. The appearance of tuberculous pus during the course of artificial pneumothorax treatment is a serious com- plication. Why it occurs in some patients and not in others and what determines whether an effusion remains serous or becomes purulent are not fully understood. Penington (28), from observa- tions on man and experiments on rabbits, concludes that tuberculous empyema follows the rupture of a caseating tuberculous focus through the pleura. This only occurred in animals which had been previously sensitised. He found that the introduction of tubercle bacilli into the pneumothorax space in rabbits was not by itself sufficient to give rise to an empyema, even after preliminary sensi- tisation, and believes that some other unknown factor associated with caseous material is necessary for the formation of tuberculous pus. Penington’s contention is supported by the work of Gordon and others (29) who also find tuberculous empyema following the rupture of a caseous nodule into the pleural cavity. These nodules were most commonly seen in the front of the lung, and in this situa- tion there is an increased tendency towards rupture, due possibly to the greater movement of the anterior chest. This reasoning is along similar lines to that of Simmonds (27) already quoted, who ascribed effusion in artificial pneumothorax, whether serous or purulent, to distension and rupture of a tuberculous cavity. It is probable that the majority of tuberculous purulent effusions are preceded by a serous exudate even if this phase is only transient, and the formation of pus can occur in one of the following ways :— 1. As a gradual development from a persistent serous effusion. Dumarest (30) called this “‘ benign ”’ pyothorax or cold abscess of the pleura. 2. As the rapid outcome of an acute pleurisy with effusion. The more severe the initial pleurisy the greater is the likelihood of the effusion being purulent and the sooner will it become so, 3. As a sequel to a bronchopleural fistula. It is in this type that the serous phase may be of such short duration as to be missed. It is often difficult to decide when an effusion ceases to be serous and becomes purulent. Tubercle bacilli may be demonstrated in either, and both are sterile on culture for other organisms. Cells are present in greater numbers in purulent effusions and the propor- tion of polymorphs is generally higher. Cutler (81), defining a tuberculous empyema as a turbid or purulent fluid containing tubercle bacilli on direct smear, found it in 59 (12-4 per cent.) of 476 pneumothorax cases. He found it four times more often in ineffective than in effective pneumothoraces, and it was more common in those with advanced disease. It has been suggested that about one out of every ten pneumo- thorax patients develops tuberculous empyema, but the proportion may be less now than formerly. There is no doubt that the condi- tion can be, to some extent, prevented by the observance of certain principles :— 1. A pneumothorax should be cautiously recommended in a patient with advanced or moderately advanced disease. In this class of case it is often better to consider alternative methods of collapse therapy which do not involve separation of the pleurae. 2. Pneumothorax should not be induced for acute pneumonic phthisis, even if strictly confined to one lung, until a period of absolute rest has tided the patient over the acute phase. A phrenic operation, with or without a pneumoperitoneum, can be more safely employed to obtain relaxation. 3. If adequate collapse is prevented by adhesions, an attempt should be made to divide them as soon as it can be done with safety, as adhesions under tension may rupture and give rise to pus formation. Internal pneumonolysis can often be attempted at the end of a month, and if it fails to bring about an effective collapse the pneumothorax should be abandoned at once. 4. The presence of a thin-walled and peripherally situated cavity which remains stationary, or even increases in size, in spite of a mechanically satisfactory pneumothorax is an indication for terminating the pneumothorax and encouraging the lung to re-expand. If this is not done there is a danger that the cavity will rupture. A peripherally situated cavity lying at the base of an indivisible adhesion is also a potent source of danger. The successful management of a tuberculous empyema demands: the careful consideration of a number of factors, all of which must be properly evaluated when deciding upon the course of treatment :— 1. The nature of the pus, whether it contains only tubercle bacilli, or whether it is infected with secondary pyogenic orsarains. . The condition of the underlying lung. . The condition of the opposite lung. . The presence of a bronchopleural communication. . The general condition of the patient. tm Co bo Or It is convenient to divide the cases into two groups depending upon whether the pus is secondarily infected or not. Mized Tuberculous Empyema. This is the more severe variety of the two and has the graver prognosis. It is generally the result of a spontaneous pneumothorax occurring on the top of an artificial one, but may occur as a sequel to an acute infectious Gisease such as influenza. The establishment of a bronchopleural fistula is not invariably followed by secondary infection of the pleural cavity although the appearance of fluid is almost inevitable. Woodruff (32) states that of forty-seven patients with known bronchopleural fistulae, twelve did not develop a mixed infection. In some instances secondary organisms make their appearance some weeks after the acute episode. In a follow-up of sixteen cases known to have had a pure tubercu- lous empyema at one time and which ultimately became secondarily infected, Woodruff found that 25 per cent. of these patients developed their mixed infection within the first six months, another 25 per cent. in the second six months, and in the remaining 50 per cent. contamination occurred some time during the next seven years. Treatment, if it is to be successful, must be prompt. Antiseptics, dyes and chemotherapeutic substances have been used for washing out the pleural cavity but have had only limited application. Penicillin, however, by its action upon pyogenic organisms, has suc- cessfully converted some of these mixed infections back to the state of a pure tuberculous exudate. For example, Roberts, Tubbs and Bates (33) have recorded their experience with penicillin and their work suggests that, although the drug is successful in_penicillin- susceptible strains, a rib resection is not always averted, for the formation of large plaques of fibrin may seriously interfere with aspiration and require to be removed even though the empyema is pyogenically sterile. It would not be out of place here to mention the use of a class of chemical compounds known as detergents, or “ wetting agents,” the essential property of which is the ability to lower the surface tension of solutions to which they are added. In consequence the solution comes more intimately into contact with surfaces, such as cells, than would otherwise be the case and, if an antiseptic, its effect is correspondingly enhanced. One of the most recently introduced members of this group is phemeride, which possesses not only detergent but also antiseptic properties, and which has been submitted to clinical trial by Iland (34). It can be used in concentrations inhibitory to the growth of pathogens, yet harmless to living tissues such as leucocytes. The use of phemeride in mixed tuberculous empyema, in wounds of the thorax, and in fistulae, has been encouraging so far. As no harm results if a little is coughed up through a fistula, it is valuable in the treatment of stubborn sinuses. The application of another member of the group, sodium tetra- decyl sulphate, is discussed later. Few will dispute the need for efficient pleural drainage once the presence of this complication is recognised, and it has been found not responsive to chemotherapy, for the mortality rate that follows more conservative treatment is high. It is better to proceed direct to rib resection, but an intercostal tube can be used as a preliminary expedient if it is thought that the patient will not stand the bigger operation. Considerable improvement in the general condition will usually follow satisfactory drainage, and if there is disease in the opposite lung which looks threatening or is actually advancing, it may be unwise to do anything further. If, however, the opposite lung is sound, closure of the pleural space by thoracoplasty should be carried out, but it requires considerable judgment to gauge the optimum time to perform the first stage of a series of operations upon a very sick patient. Some delay may be inevitable while an effort is made to improve the patient’s resistance, but this period should not be prolonged and operation should be advised as early as possible. Delay not only increases the time the toxaemia acts but leads to thickening of the pleura to a degree which may jeopardise the success of a plastic operation. Furthermore, amyloid disease can sometimes appear rapidly and is always a potential danger. Brock (35) has published the results of treatment of 84 cases of tuberculous empyema with a mixed infection. In 35 of these drainage only was performed: 32 died and 38 are alive. In 49 patients where drainage combined with thoracoplasty was the treatment adopted 14 (29 per cent.) are dead while 35 (71 per cent.) are alive. Among these 35 patients were 15 in whom complete healing without a sinus was achieved. Brock advises early opera- tion and believes that it is no good waiting for the temperature to settle down before beginning thoracoplasty but, on the contrary, regards persistent fever as an indication for operation. This study was undertaken before penicillin became freely available. Some patients are left with a persistent sinus after the combination of drainage and complete thoracoplasty. Attempts can be made to heal these by such operations as “‘ unroofing ”’ the residual space or by the insertion of a muscle graft. Prolonged negative pressure suction and the use of ultra-violet light with a Kromayer lamp, employing special sinus applicators, are sometimes followed by healing. More recently certain chemical agents such as promine and para-aminosalicylic acid have given promising results. Pure Tuberculous Empyema. Considerable diversity: of opinion exists as to the correct treatment for a turbid or frankly purulent effusion containing tubercle bacilli and no other organisms. That many patients lead full and useful lives for several years in spite of sterile collections of tuberculous pus in the pleural cavity cannot be denied. Chandler (36), who was a staunch advocate of the conserva- tive approach to this problem, claimed that the fluid in these cases often did more good than harm. He published the reports of twelve patients in whom the fluid was left, with only occasional aspiration, for ten or twenty years, and proved compatible with reasonably good health. Burrell also had several patients with large purulent effusions who made good recoveries with conservative treatment. Admittedly the progress of some patients under conservative treatment is satisfactory, but it is important to know what propor- tion of the whole these cases form. Woodruff (32), in his report of 154 examples of the condition observed for three to eight years, com- puted that 30 per cent. of uncontaminated empyemata ultimately suffered perforation or secondary infection, and others might later do so. If the problem is considered as a dual one and account is taken of the collapsed lung as well as the empyema space, it is clear that an expectant attitude towards the pus considers only the former and disregards the latter. When the dangers of a_ per- sistent empyema space are remembered it is doubtful whether such a limited view can be endorsed as a general rule. Various attempts have been made to sterilise and “ thin” the pus and to encourage pulmonary re-expansion by the introduction of chemical substances into the pleural cavity. Salts such as normal saline and Dakin’s Solution, and dyes, of which methylene blue is an example, have all been tried. Olive oil with 5 per cent. gomenol was favoured by Chandler and has been found useful in those cases in which a small bronchopleural fistula was present. A definite advance in this form of therapy has followed the intro- duction by Petroff (37) and his colleagues of a mixture of azochlo- ramid and sodium tetradecyl sulphate (Azo-T) as an irrigating solution. Sodium tetradecyl sulphate was added as it was found by experiment to be a suitable depressor of the surface tension of the bacteria or pus cell and so enhanced the bactericidal power of the antiseptic. Petroff found that Azo-T was effective not only in sterilising the fluid and enabling the pneumothorax to be continued, if this was considered desirable, but was also useful in preventing fluid from re-forming. A noteworthy feature of Petroff’s cases was the paucity of skin nodules, sinuses and _ superficial abscesses, the occurrence of which in the past has proved an un- fortunate and not infrequent complication of pleural washouts. Involvement of the chest wall in his series was found in only twenty- two out of 2,500 aspirations, and this low incidence was attributed to the instillation of the Azo-T along the needle track at the close of each treatment. .. Munro-Ashman and Tate (88) have followed up Petroff’s work in this country. They used a 1 in 2000 solution of azochloramid with sodium tetradecyl sulphate 1 in 800 on a series of 32 cases of tuber- culous empyema. Re-expansion of the lung was desired in 26 and obtained in 15; the lung was still expanding in 4 more, and partial re-expansion only was achieved in 2 patients. It was possible to continue the pneumothorax in 6 patients. In only 2 of their cases was the treatment unhelpful and there were 2 deaths. In 19 cases the fluid was rendered T.B. negative and in 3 others pulmonary re-expansion occurred before sterility of the pus was obtained. The authors emphasise the importance of starting treatment early before the visceral pleura thickens and recommend Azo-T replacements three times a week for the first week and subsequently twice weekly until the desired result is obtained. A blunt-ended needle with a sharp stilette of the Houghton pattern was used. They confirmed Petroff’s observation that sinus formation was rare. Azochloramid-T in common with other aqueous irritating solu- tions is contra-indicated if a bronchopleural fistula is present. In this event the best treatment is to keep the level of pus in the chest low by repeated aspirations. Pleural aspiration and lavage will clearly give the best results in those patients in whom tuberculous empyema occurs late in the course of treatment, for by this time the lesion in the underlying lung will probably have healed. If complete re-expansion of lung can be achieved, the result will be satisfactory. Empyema occurs more commonly, however, early in the course of pneumothorax treatment when disease in the underlying lung is still active. In these patients an attempt can be made to sterilise the pus and main- tain the pneumothorax, but if this is unsuccessful a thoracoplasty to close the empyema space must be considered. This operation should be resorted to, if required, as soon as it is practicable pro- vided that the physical condition of the patient and the integrity of the opposite lung permit. Delay will lead to such thickening and rigidity of the pleura as to make the closure of the empyema cavity unlikely. | Brock (85) reports one death in a series of 21 patients operated upon for pure tuberculous empyema. Skavlem and his col- leagues (39) found that conservative treatment with occasional aspiration had a mortality rate of 90-100 per cent. ; whereas in the same period, of 24 patients on whom a thoracoplasty was performed 62-5 per cent. recovered ; 25 per cent. were still in hospital with a good prospect of recovery and only 12:5 per cent. died. Pneumothorax and Aviation A quantity of air enclosed within the body, such as a pneumo- thorax, is subject to Boyle’s law of gases which states that at a constant temperature the volume of the gas varies inversely as the pressure exerted upon it. With increasing altitude the pressure of the atmosphere becomes less and the volume of a given amount of gas correspondingly greater. H. & R. TUBERO. 6 The physical effect of high altitude upon an artificial pneumo- thorax has been known from observations made at many of the Swiss Sanatoria, which are situated in the mountains 5,000—6,000 feet above sea-level. A patient with a pneumothorax becomes noticeably breathless at the conclusion of his journey to such resorts on account of the increased volume of air in the pneumothorax brought about by the ascent. For this reason he is advised to under- take the journey at about the time a refill is due and conversely, on his return to sea-level, a refill should be given before the journey in order to prevent too great a re-expansion of the lung. The influence of altitude upon a pneumothorax has been the sub- ject of recent study on account of the frequency with which battle casualties were transported by air from the forward areas to the base. Many of these men suffered from chest wounds complicated by a haemopneumothorax, and it was a matter of some importance to decide whether aerial transportation was safe for them and, if so, to what altitude they could be taken. But it is not a purely military problem. There is good reason to believe that air travel in the future will be more popular and more universal than it was before the war, or is now, and many pneumothorax patients will seek advice as to the safety of undertaking business or pleasure trips by air. Some idea of the actual problem can be appreciated by Lovelace and Hinshaw’s (40) calculation that 1,000 c.c. of air, saturated with water vapour at 37° at sea-level, will become 1,500 c.c. at an altitude of 10,000 feet. Todd (41) has made some observations upon patients with an artificial pneumothorax who were placed in a pressure chamber. By lowering the partial pressure of the atmosphere within the chamber, it was possible to “‘ take ” these patients to a gradually increasing altitude, which could be measured, and to observe the signs and symptoms which resulted. By means of an X-ray screen and radiography Todd was able to study in detail the effect of the ** ascent ”’ upon the degree of collapse, and by choosing various types of pneumothorax for the experiment he was able to draw some im- portant conclusions. He found, for example, that patients with a free pneumothorax and a mobile mediastinum could be taken to a greater height before symptoms became apparent than could those whose mediastinum was fixed or whose lung was tethered by adhesions. In the latter group the fixity of the mediastinum acted as arigid barrier to the rarefying air in the pleural cavity, with the result that the pneumothorax pressures rose more steeply, dyspnoea and central chest pain were complained of relatively early, and com- pression of the great veins in the upper thorax could be inferred from a noticeable distension of the cervical veins in the neck. Where the mediastinum was freely mobile, however, Todd was able to demonstrate definite displacement of the heart shadow towards the opposite side and the appearance of congestion in the opposite lung. Here, too, the pressure in the pneumothorax cavity became more positive, but the change was not so pronounced as with a static mediastinum, and subjective sensations came on at a higher altitude. The experimental work of Todd and of Lovelace and Hinshaw, when linked up with clinical experience of pneumothorax work in the control of tuberculosis, bring out certain points, consideration of which may be helpful in deciding whether or not it would be safe for this group of patients to travel by air :— 1. The alternate contraction and expansion of the lung which must inevitably accompany a flight is bad for an unstable lesion. In the early stages of pneumothorax treatment, there- fore, before the lesion is reasonably quiescent, flying should be discouraged. 2. There is a danger that pleural adhesions may rupture if the pressure in the pneumothorax cavity becomes much raised. In those patients where frequent travel by air is necessary it is probably wise to divide these adhesions. 3. Patients with a free lung and a mobile mediastinum+stolerate a reasonable altitude slightly better than those with a fixed mediastinum and partially adherent lobes. 4, A flight should not be undertaken, for preference, immediately after a refill has been given but should, if possible, be arranged towards the time that one is due. 5. It is to be anticipated that a patient with bilateral pneumo- thorax will be restricted to a lower altitude than one with only one lung collapsed. 6. Lovelace and Hinshaw state that it is not possible to predict accurately the safe “ ceiling ” for any particular person without first submitting him to a test in a low pressure chamber. At present this cannot be done as a routine in civilian practice, but in the future it might be possible for this individual assessment to be earried out. Todd states that an altitude of 6,000 feet should not be exceeded for any length of time. References (1) HEBERT, G. T. (1936) Brit. med. J. 2, 272. (2) Wiesg, E. R. (1941) Amer. Rev. Tuberc. 44, 92. (3) THompson, B. C. (1942) Tubercle, 23, 139. (4) TATTERSALL, W. H. (1947) Tubercle, 28, 85. (5) ARMAND-DELILLE, P. F. (1924) Rev. Tuberc. 5, 43. (6) Acassiz, C. D. S. (1937-88) Tubercle, 19, 74. (7) ForLANINI, C. (1911) Gazz. med. ital. 42, 41, 51, 61 and 71. (8) SAUGMAN, C. (1921) Paris méd. 41, 59. Lancet (1920) 2, 685. (9) JENNINGS, F. L. and Marri.z, P. M. (1942) Amer. Rev. Tuberc. 45, 461. (10) Lucacer, M. (1942) Amer. Rev. Tuberc. 46, 72. (11) FarBer, J. E. (1941-42) J. thorac. Surg. 11, 424. (12) BurReE Lt, L. S. T. (1924) Brit. med. J. 1, 368. . (13) Hurst, A. and ScuwarmTz, S. (1942) Amer. Rev. Tuberc. 45, 132. (14) Topp, G. (1938) Brit. J. Tuberc. 32, 76. (15) ANDosca and Fo.Ley, J. A. (1945) Amer. Rev, Tuberc. 52, 221. (16) Banyat, A. L. (19338) Amer. J. med. Sci. 186, 513. (17) Srmon, S. and ABrams, H. S. (1933) Amer. Rev. Tuberc. 28, 788. (18) Pearson, S. V. (1919) Lancet, 2, 148. (19) Hatz, I. M. (1944) Tubercle, 25, 66. (20) Maurer, G. (1937) Brit. J. Tuberc. 31, 58. (21) MiuuErR, A. K. and RinKE1, L. R. J. (1947) Lancet, 1, 906. (22) MacDeErmorttT, E. N. (1935) Irish J. med. Sci. p. 608. (23) Burre 1, L. S. T. (1924) Lancet, 2, 167. (24) Pisani, V. V. and SMEJKAL, F. J. (1933-34) Tubercle, 15, 216. (25) Boum, F. (1940) Klin. Wschr. 19, 496. (26) Hurcuinson, R. C. and Buair, L. G. (1925-26) Tubercle, 7, 417. (27) Stmmonps, F. A. H. (1941) Tubercle, 22, 183. (28) PENINGTON, A. H. (1939) Brit. J. Tuberc. 33, 36. (29) Gorvon, B., CHARR, R. and SAvacoo., J. W. (1943) Amer. Rev. Tuberc. 47, 85. (80) DumargEst, F., LEFEVRE, P., MoLLArpD, H., Pavir, P. and Rovuey, P. (1986) La Pratique du Pneumothorax Thérapeutique, Paris. (31) CurteER, I. L. (1941) Amer. Rev. Tuberc. 43, 197. (32) Wooprurr, W. (1937-88) J. thorac. Surg. 7, 420. (33) Roserts, J. E. H., Tusss, O. S. and Bares, M. (1945) Lancet, 1, 39. (34) ILAND, C. N. (1944) Lancet, 1, 49. (35) Brock, R. C. (1943) Brit. J. Tuberc. 37, 18. (36) CHANDLER, F. G. (1942) Brit. J. Tuberc. 36, 103. (37) Prerrorr, S. A., HERMAN, M. and PauiTz, L. (1941) Amer. Rev. Tuberc. 44, 738. (38) Munro-ASHMAN, D. and Tare, M. G. (1943) Tubercle, 24, 181. (39) SkAvLEM, J. H., Pueups, M. L., BAKER, L. E. and CHRISTIANSEN, J. N. (1940) Amer. Rev. Tuberc. 42, 747. (40) LoveLace, W. R. and Hinsuaw, H. C. (1942) War Med, 2, 580. (41) Topp, G. S. (1948) Lancet, 2, 597. CHAPTER IX COLLAPSE THERAPY—SURGICAL PROCEDURES. I Internal Pneumonolysis THE importance of converting an inadequate, contra-selective pneumothorax into one in which the diseased portion of lung is selectively and concentrically relaxed has already been mentioned. One of the simplest and most widely used methods of effecting this conversion is the division of pleural adhesions. Pleural adhesion, as a complication of artificial pneumothorax, iS commonly found and it is rare to obtain complete collapse without any visible adhesions. Admittedly, some adhesions exert no harmful influence upon the satisfactory progress of the case and do not apparently interfere with the adequacy of the pneumothorax ; but the majority constitute a recognised menace to an otherwise favour- able prognosis and the division of these should be attempted. It is important to distinguish between adherent pleura and a pleural adhesion: in Burrell’s phrase the one may be compared to a ship aground and the other to a ship at anchor. In the former it may be dangerous to try to separate the adherent surfaces for fear of injuring the lung, while in the latter the operation can be performed with. comparative safety. | The various types and systems of adhesions which may be seen at an inspection of the pleural space have been listed by Smart (1) as follows :— (i) Cord or band-like adhesions ; (11) Membraneous adhesions ; (iii) Thick, columnar adhesions ; (iv) Sail-like adhesions with only one free edge and which run back to the chest wall or mediastinum ; (v) Surface adhesions, where the surfaces of the lung and the chest wall are opposed ; | (vi) A mixture of the above forming a complicated series of chambers opening one into the other. It is not always possible to tell from a study of the skiagram whether the division of a system of adhesions can be carried out or not, and it is necessary to insert a thoracoscope and inspect the pleural space. Even this sometimes fails to supply the necessary information, and it is only after cauterisation has been started and some progress made that the operator is in a position to judge whether the ad- hesions can be completely or only partially divided. During recent years the operation has been increasingly successful following the adoption of Maurer’s (2) technique of “ enucleation.” By this method formidable lung-containing adhesions can be stripped off the chest wall by blunt dissection in the plane of the endothoracic fascia without injury to the lung itself. The objections to it are that should haemorrhage occur it cannot be so readily controlled, and that there is a risk of the blood supply to the cavity wall being cut off. Technique. The original method for performing closed internal pneumonolysis was introduced in 1913 by Jacobaeus (3), who used two cannulae. There have been several instrumental modifications in the intervening years but the principle has remained the same. A trocar and cannula are inserted through the chest wall under local anaesthetic and the trocar withdrawn. Brock (4) advocates the sixth or seventh intercostal space posteriorly for this preliminary puncture ; in over 98 per cent. of his cases he found it the site of choice. A telescope, which may operate through an angle of 30° or 90° is then placed through the cannula and a thorough inspection of the pleural space carried out. ‘This will enable the operator to decide whether division is worth attempting and will also help him to fix the most convenient spot for the insertion of the second cannula through which the cautery is introduced. ‘The adhesions are then divided with the galvanocautery as near to the parietal pleura as possible. Preliminary coagulation with diathermy can be used if desired to prevent bleeding, but it is not commonly used owing to the danger of delayed sloughing. The most significant development in technique was Chandler’s (5) introduction of the single cannula instrument which dispensed with the double puncture required in the original Jacobaeus operation. In Chandler’s instrument the telescope, cautery, and the needle for locally anaesthetising the adhesion are all introduced together through one rather wider cannula. The advantages claimed for the single-cannula method are :-— (a) Only one puncture of the chest is made instead of two. (b) The adhesions can be inspected under * direct ”? vision and not through an angle of 30° or 90°. ae Pees has been levelled against the single-cannula instrument: on the grounds that a more sweeping division of adhesion can be accom- plished with a two-cannula approach, and that preliminary localisation is required. Neither of these objections is regarded as formidable by those who use the single-cannula method. Sellors has introduced a simplified single-cannula instrument which has been found very satisfactory, and a further modification has been described by Cutler (6) whose instrument includes a bayonet type of trocar to minimise trauma and lessen subcutaneous emphysema, and a mechanism for attaching it to a pneumothorax apparatus. Indications. Internal pneumonolysis should be attempted in all cases of artificial pneumothorax, especially unilateral, in which the degree of collapse is considered to be inadequate for the complete control of the lesion, and in which the type and arrangement of the adhesions as seen on the skiagram suggest that the operation will be successful, wholly or in part. The two absolute indications are the persistence of a cavity in the half-collapsed lung and the per- sistence of a positive sputum. The failure to demonstrate tubercle bacilli by the customary direct method, even repeatedly, is not a sufficiently strict criterion of negativity : the expectoration must be submitted to concentration methods, culture or inoculation into a guinea-pig, or, if there is no spontaneous expectoration, secretion obtained from swabbing the larynx should be used. Apart from the bacteriological and radiological indications just mentioned, the continuance of such symptoms as cough and sputum, failure to gain weight and repeated haemoptyses, or prolonged elevation of the blood sedimentation rate, provide good grounds for interference. Matson (7) also regards as indications those com- plaints which are directly due to the adhesions, of which paroxysmal cough, pain in the chest, and febrile reactions after refills are the most important. Improvements in technique, the small risk attaching to the operation, and the relative infrequency of serious complications have led to a widening of the indications for intervention which pre- viously were more restricted. The conviction has been expressed by some authorities that the mere presence of adhesions limiting the collapse of the vital part of the lung is in itself sufficient justi- fication for thoracoscopy and for the division of those adhesions which can be severed easily and without risk. Assuming the ideal pneumothorax to be one in which selective and concentric relaxa- tion of the diseased part of the lung is achieved, it is not possible, even by modern standards, to infer what degree of concentricity is necessary in order to ensure permanent healing. It is reasonable, therefore, to submit a doubtful case to a thoracoscopic inspection, and to allow subsequent action to be dictated by the appearance of the individual adhesions. Laird (8) has gone further and advocates an inspection of the pleural cavity in every case, even if no adhesions. can be seen on the X-ray. Opinions differ as to whether the operation should be continued if tubercles are seen on the pleura. Providing they are sparse the risk of dividing the adhesions is very slight; if, on the other hand, they are numerous, or can be seen on the surface of the adhesions near the point to which the cautery must be applied, the operation may have to be deferred or abandoned. The presence of pleural exudate before operation is of itself no contra-indication to internal pneumonolysis. The pleural cavity can be aspirated dry at the time of operation before the division is begun. If operation is decided upon it should be carried out in such cases as soon as possible, before the adhesions become covered with fibrinous exudate and the procedure consequently rendered more difficult. Complications and Results. The complications that most commonly follow internal pneumonolysis are haemorrhage and the formation of fluid, which may become purulent. That both these complications can be over-emphasised has become clear from recent reports of large series of cases. Serious haemorrhage may result from damage to an intercostal vessel or to one of the large vessels in the upper thorax. These latter are sometimes pulled out and displaced from their natural bed and become incorporated into the substance of the adhesion. Haemorrhage from either of these two sources may prove fatal unless controlled by open operation. Less severe bleeding occurs from the parietal stump during the course of division but is rarely uncontrollable. Bleeding can be prevented by using diathermy before the cutting current or a cautery point which is not too bright. Brock (4) in 442 operations upon 361 patients had no deaths from haemorrhage and only three in which the bleeding was at all serious and gave rise to haemothorax. Haemorrhage, therefore, is more often annoying than dangerous or fatal. But it has one drawback and that is the irritant effect of the blood itself upon the pleura, This contributes to the formation of a serous effusion as was evident from a close study of the first series of cases described by Chandler (9) in which those of his patients in whom moderate bleeding occurred comprised a rela- tively high proportion of those who subsequently developed fluid. It may also lead to obliterative pleurisy. The appearance of a transient effusion after operation is not uncommonly seen ; for fluid to appear in any quantity is relatively rare. Thus Brock in his large series already alluded to found no fluid or only a very small amount in 87 per cent. of the cases, a | moderate effusion in 8-0 per cent., and much or persistent fluid in 2-2 per cent. Purulent exudates were scarcer and Brock only had 5 eases (1:4 per cent.) in which tubercle bacilli only were demon- strated, and another 5 cases (1:4 per cent.) in which tuberculous pus was secondarily infected with pyogenic organisms. Drash (10) performed 251 operations upon 230 patients and found that a serous effusion occurred in 6 per cent. and tuberculous empyema in 2:6 per cent. The incidence of tuberculous empyema in this series was, in fact, less than the occurrence of this complica- tion in untouched pneumothoraces. It is becoming steadily more apparent that the operation of internal pneumonolysis, by convert- ing an ineffective into an effective pneumothorax, prevents more cases of tuberculous empyema from developing than are caused by the operation itself. , Other complications which are met with include a febrile pleural reaction with a small puddle of fluid, and subcutaneous emphysema which is more annoying than detrimental, although Moore (11) had one patient who lost his pneumothorax on account of surgical emphysema which could not be checked. Occasionally the opera- tion is followed by extension of the disease especially if a large area of the lung is suddenly released. Among the rare sequelae are. Horner’s syndrome, due possibly to the effect of local heat spreading to the stellate ganglion, and the unusual phenomenon observed by Smart (1)in which the lung fell back after the division of a moderately stout adhesion and became secondarily adherent to a fresh part of the chest wall. Results. Chandler (5) described the results of a series of opera- tions on 89 patients :— Goodhealth . A Ait Hy. 5 uta Bamphealthy aay Dead ip Poor health, . Best 'G Lost sight of . a's ane SU Effusion occurred in 24 and of these 20 recovered. Empyema followed in 7 cases being purely tuberculous in 3, a mixed infection in 8, and staphylococcal in 1. Haemorrhage occurred in 15 and the bleeding was always from the parietal stump. It was never severe. Edwards, Penman and Logan (12) have contributed a study of 200 consecutive cases of pulmonary tuberculosis treated by pneumo- thorax with unilateral division of adhesions by closed internal pneumonolysis. ‘The follow-up period was 5 years. The results of these cases (two only of which were lost sight of) were : 133 (66-5 per cent.) survived 5 years ;, 71 (86-5 per cent.) of those in whom a satisfactory collapse was obtained survived 5 years, and 56 of these were well and working after 6 years. In none was there a satisfactory collapse before operation. The authors found that a“ satisfactory ”’ collapse was reached only when the adhesions were divided sufficiently sweepingly to enable the lung to fall below the level of the sternal end of the clavicle. In such a case they found the prognosis to be as good as with a completely free lung, but in anything short of this the prognosis was adversely influenced. In patients with bilateral disease control of the disease in one lung favoured healing in the other. The results of sputum tests were important in assessing ultimate prognosis, for it was found that of those whose sputum was either T.B. negative or absent at the end of three months 79 per cent. survived 5 years, whereas only 40 per cent. with a T.B. positive sputum at the end of three months lived for the same length of time. From his experience Edwards has been led to propound two im- portant dicta: first, “the results of pneumothorax depend on the efficiency of the collapse,’ and secondly, *‘ the abandonment of the pneumothorax without thoracoscopy and the maintenance of an unsatisfactory collapse are both bad practice.” The importance of discontinuing a pneumothorax if selective collapse is not attained cannot be too strongly emphasised. A word must be added concerning the stage in pneumothorax at which the operation should be performed. It was originally customary to allow the pneumothorax to proceed without inter- ference for at least six months before contemplating pneumonolysis in the belief that the adhesions might stretch sufficiently to make operation unnecessary. The modern policy, now fairly widely accepted, of inspecting, and if possible of dividing, all adhesions which run to the affected area of lung as an insurance against the future has been accompanied by a tendency to operate earlier than was formerly the case. Other reasons have been advanced for early operation. Thus, Thompson and Greenberg (13) prefer three to six weeks after starting the pneumothorax on the grounds that selective collapse is more often obtained and the sputum more often rendered negative if operation is carried out at this time rather than later. Jaeobaeus (14) also, in 1938 stated that he now operates much earler (one to two months after induction) than was previously his practice as he had found that the “ older’ an adhesion became the more iibrous tissue it contained. As it is open to doubt whether adhesions stretch to a significant extent with the passage of time, much may be lost and little gained by an unduly long postponement of operation. OPERATIONS ON THE PHRENIG NERVE Sectim or avulsion of the phrenic nerve will cause paralysis of one-hali of the diaphragm, and consequently those movements of the lung which are dependent upon the contraction of the diaphragm will ceae. This fact has been utilised in order to obtain additional rest and relaxation for the affected lung in selected cases, often as a suppEmentary measure to other forms of collapse. If a temporary paralysis only is considered necessary the nerve may be crushed, or injected with alcohol. Crushing is more com- monly practised than injection and is successful in a surprisingly high pioportion of cases, the effect lasting for four to six months, or ever longer. At the end of that time “ screening ”’ will usually show ome return of movement of the diaphragm. Temporary paralyis by phrenic ‘‘ crush ” has in recent years enjoyed a greater populaity than the radical operation for three main reasons : first, shouldphrenic interruption prove a failure no harm is done by the operaton as the restoration of diaphragmatic function is almost always assured. On the other hand, if it is successful and should be mantained, the radical operation can easily be performed. Secondy, in the event of a thoracoplasty subsequently becoming necessary, it is safer to operate with a freely moving dome on the affectd side, for a paralysed diaphragm interferes with the expulsive force »f coughing and the risk of pulmonary atelectasis and spread of dis:ase due to retained secretion is increased. Thirdly, the risks Or To relieve symptoms such as dry cough due to diaphragmatic irritation, vomiting after meals, and persistent hiccough. Symptoms of indigestion are sometimes relieved by the operation. relaxation if a satisfactory pneumothorax cannot be obtained. Although it may achieve the desired end, phrenic paralysis is not always successful and it has been said that it may make the bleeding worse by causing pulmonary congestion. not extensive. That phrenic interruption is more often suc- cessful when applied to a basal rather than to an apical lesion is possibly more apparent than real, for there is evicence to show that the influence of a paralysed diaphragm upon the lung is little less at the apex than at the base. On tle other hand, the effect of a pneumothorax upon a basal lesion is always more uncertain than upon an apical one, and it bllows, therefore, that in lower lobe disease hans operation; enjoy a larger measure of scope. at the apex or to the diaphragm. Elevation and stablity of the diaphragm in such cases relieves tension and may enable the final closure of a cavity to be achieved. This is particu- larly true of lower lobe cavities. 'The modern view, hovever, in such a contingency, has been to swing away from yjhrenic interruption and towards internal pneumonolysis or, ifthis is not possible, towards an apical thoracoplasty after tle lung has been allowed to re-expand. pneumothorax cannot be obtained and whose disease is too active to allow of major surgery. A temporary jrenic paralysis for four to six months combined with appropriate general treatment, will often bring about improvement n the physical condition. to employ the less drastic phrenic paralysis rather than iduce a pneumothorax. If necessary the pneumothorax can be induced later (see also page 156). In this type of case, and in the preceding one, reinforcement of the phrenic paralysis by pneumoperitoneum is now commonly practised. 7. As the last step in the gradual abandonment of a pneumo- thorax. It is particularly valuable if there is evidence of pul- monary ccntraction or displacement of the mediastinum. 8. The discovery by routine radiography of healthy people of an increasingly large number of minimal symptomless lesions has raised the perplexing question of whether collapse therapy is required in the management of these patients, and if so in what form. Many such foci yield no conclusive evidence of activity on the first full assessment, yet the radiological features may occasion a reluctance to pronounce them stable or quiescent. As the lesser of two evils temporary phrenic paralysis is sometimes preferred to artificial pneumothorax in these difficult cases. Complications and accidents following operations on the phrenic nerve have been reported. The subclavian vein has been ruptured during phrenic avulsion. Bleeding may occur as the nerve is being avulsed but it usually stops when the traction ceases. Injury to the thoracic duct with escape of milky fluid has been recorded ; the flow can be stopped by packing the wound with gauze. The brachial plexus and sympathetic nerve have also suffered injury. Fatal cases have occurred as a result of mistaking the vagus nerve for the phrenic. The operation of avulsion is sometimes followed by an acute pleurisy on the same side, rarely with effusion. Bilateral phrenic paralysis is reasonably well tolerated and O’Shaughnessy (15) has described four cases, the intervals between the operations on the two sides ranging from one to six months. In one case the patient became worse as a result of the procedure, but in the other three improvement followed. For some time after its introduction phrenic paralysis rivalled the pneumothorax in popularity. Morin (16) regarded the opera- tion as superior to pneumothorax on the grounds that there were fewer complications, frequent visits to the physician for refills were not required, and sufficient rest was given to the lung to effect a cure. Further experience with the procedure, however, has served to convince most workers that a properly managed artificial pneumo- thorax, supplemented if necessary by the division of adhesions, is a more efficacious method of controlling a tuberculous lesion and converting the sputum from positive to negative. There has been, however, a revival of interest in the procedure attributable to the recent introduction of the therapeutic pneumoperitoneum. Therapeutic Pneumoperitoneum The deliberate application of the artificial pneumoperitoneum to the treatment of pulmonary disease is a comparatively recent innovation and relies for success upon the upward elevation of the diaphragm which follows an increase in the intra-abdominal pressure. It is used in conjunction with phrenic paralysis and enables the rise in the diaphragm to be increased by several centimetres (plate II). Technique. There is a choice of three sites for the induction, all of which have been used: (1) An inch or two below tae umbilicus, in the midline or lateral to the rectus muscle ; (2) An inch or two below the left subcostal margin, lateral to the rectus; and (8) through one of the lower right intercostal spaces in the mid-axillary line. The draw- back to the intercostal route for the induction is the risk of damaging the liver: there is little to choose between the other two, but if the sub- umbilical site is used, it is important to make sure that the bladder is empty. An ordinary standard pneumothorax apparatus and induction needle are used. ‘The skin and track down to the peritoneum are anaesthetised and the induction needle is then introduced through the skin of the abdominal wall. The manometer does not give so ready an indication as to when the peritoneal cavity is reached as it does in the case of the pleural cavity, but if the patient is asked to cough a free swing of the column of fluid in the manometer implies that the needle is in the peritoneal space. It is usual to give 600 ¢.c. to 800 c.c. at the induction : for refills, which can quickly be spaced out to once a week, 1,000 c.c. may be given. Once the pneumoperitoneum has been properly started it is quite simple to give the refills through the lower intercostal spaces, choosing for preference the side on which the dia- phragm has been paralysed. Some workers recommend an abdominal binder tightly applied after the air has been given, in order to support the abdominal muscles and increase the intra-abdominal pressure ; later, massage and exercises can be given to improve the tone of the muscles if the patient’s condition permits. | The treatment is not as a rule followed by any unpleasant symp- toms. Breathlessness and a temporary feeling of distension may (A) (B) Piate II. Left apical pulmonary tuberculosis with cavitation (A) before and (B) after a phrenic “‘ crush ’’ operation with therapeutic pneumo- peritoneum. (By courtesy of Dr. M. H. Jupe.) [To face page 174. : ; 1 ‘ % ’ d . ke ’ ei a a ie a aloes gh FAN gs fy ie 4 ed oe a) , eLefy* a hae : a 43 i. >) - os : . /- 7 sites a aor. 7 rat mie J be complained of just after the refills, but abdominal pain and dis- turbance of bowel action do not usually occur. The treatment can be maintained in patients who are ambulant. Indications. As the pneumoperitoneum is chiefly used for its reinforcing effect upon unilateral phrenic paralysis the indications for the procedure may include, with two exceptions, all those indications which have already been given for phrenic nerve operations. The two exceptions are, first, the use of phrenic paralysis in relieving certain distressing symptoms, and, secondly, as a safeguard at the conclusion of a successful pneumothorax. Artificial pneumoperitoneum has certain additional uses which are not covered by the above :— 1. In examples of bilateral disease which is either too extensive or too acute to permit the use of other methods such as pneumo- thorax or thoracoplasty. 2. After childbirth in a woman with an active, or recently active, tuberculous lesion. This was first suggested by Barnes (17) and has proved an effective way of preventing that recrudes- cence of the disease which may follow parturition. Should the child have been delivered by Caesarean section the “ induc- tion ” of the pneumoperitoneum will have been accomplished at the time of operation and its maintenance for a month or two is a relatively simple matter. 3. For the control of thin-walled cavities of moderate size. Cavities of this nature create a difficult therapeutic problem if a pneumothorax fails, or if the cavity lies so near to the surface as to lead to a risk of rupture once a pneumothorax is begun. The prognosis of this type of disease has been favour- ably altered by the combined use of transpleural drainage and artificial pneumoperitoneum. Hdwards and Logan (18), how- ever, make the point that should the cavity be adherent to the chest wall benefit is less assured. The alternative is lobectomy and several additional factors have to be taken into account before local lung excision is decided upon. 4. Banyai (19) recommends pneumoperitoneum in the elderly patient, provided the cardiovascular system is sound, and also in tuberculosis complicated by basal emphysema and bronchial asthma. Complications Subcutaneous Emphysema. This may occur at the site of puncture and rarely causes more than transient inconvenience. It must be remembered, however, that relatively large amounts of air are given at each session and that the subcutaneous tissue and muscular planes of the abdominal wall can accommodate a large volume of air. Peritoneal Effusion. Effusion follows a pneumoperitoneum in much the same way as pleural effusion occurs in pneumothorax, but is not so frequent. In asmall series studied by Fowler (20) the inci- dence was 3:8 per cent. ; ina larger series recorded by Simmonds (21) this complication was found eight times in 450 patients. The fluid may be present without causing symptoms and may be de- tected only on routine screening ; or it may cause a febrile reaction with abdominal discomfort, loss of appetite and diarrhoea. In the latter the possibility of abdominal disease should be considered. Occasionally it has to be removed, and may lead to the termination of the treatment. Peritoneal adhesions undoubtedly form and in some cases are sufficiently extensive to cause a loculated, encysted collection of air and fluid which makes the management of the case difficult, or leads to the abandonment of the procedure. It would appear, however, that signs of peritoneal irritation and infection are negligible accord- ing to Fowler who studied at autopsy six cases which had been treated with pneumoperitoneum. Peritoneal Shock. This is rare and in Banyai’s opinion is related to too large a volume of air given too rapidly at the initial induction. Haemorrhage into the Peritoneal Cavity. A fatal example of this rare complication has been recorded by Cotton Cornwall and Patridge (22). At autopsy the source of the bleeding could not be determined with certainty but it appeared probable that puncture of an omental vein at the time of a refill was responsible. Air Embolism and Pneumomediastinum. The migration of air from the peritoneal cavity to the brain or thorax is fortunately uncommon. In a series of 450 patients (1,300 air injections) Simmonds (21) found 9 examples: 3 were of air embolism, 4 of pneumomediastinum, while in 2 the clinical features were ambiguous suggesting the simultaneous occurrence of both complications. Through what channels air reaches the brain is a little uncertain. Simmonds suggests that a likely route is via the abdominal seg- mental veins to the vertebral plexus of veins and so to the intra- cranial sinuses. ‘ The manifestations of air embolism occurring in pheumoperitoneum are the same as in pneumothorax. Pneumomediastinum is in most instances the result of air tracking from the abdominal cavity through a hiatus in the diaphragm along- side the oesophageal and aortic openings. Air may thence pass into the interstitial tissue of the lung towards the periphery and may rupture into the pleural space giving rise to a spontaneous pneumo- thorax. Newlyn Smith (23) has recorded a fatal example of bilateral spontaneous pneumothorax following pneumoperitoneum and result- ing from the air passing into the pleural cavities through multiple small holes in both halves of the diaphragm. Pneumomediastinum ean also occur if air is injected into bss tissues immediately outside the peritoneum. Symptoms of Mast eA Hain consist of central chest pain, breathlessness, and sometimes difficulty in swallowing. Cyanosis may be present. A superficial “‘ crepitant ’? murmur, synchronous - with the heart beat, can often be detected on auscultation. The appearance of a subcutaneous emphysema in the superficial tissues of the neck clinches the diagnosis. The conditions which enter most commonly into the differential diagnosis are spontaneous pneumothorax (which may also be established concurrently), pericarditis, and coronary thrombosis. Perforation of Bowel or Viscus. If due care is taken and the technique scrupulously followed this should be an uncommon event for the tendency is for the needle to glance off the bowel rather than pierce it. The danger is greater if there has been a previous attack of peritonitis for the bowel may then be immobilised by matted adhesions or adherent to the abdominal wall. It is advisable to choose for the site of puncture a portion of the abdomen well away from a laparotomy scar. The results of perforating the bowel, are not always serious. Clifford-Jones and Macdonald (24) record a case in which it un- doubtedly happened with no other ill-effects than abdominal pain and a raised pulse rate for two days. Accidental Induction of a Pneumothorax. This may result if the intercostal site for the induction is chosen. Rupture of the Diaphragm. According to Fowler this complication has been seen, but not by him. Cardiac Failure. This may supervene from displacement or torsion of the heart, but is uncommon if the heart is healthy. Death. Aslett and Jarman (25) report two cases in which death occurred during the course of treatment and was related by the authors to the procedure in both instances. Unfortunately no autopsy was possible and the exact mechanism of death was obscure. Fatal complications of pneumoperitoneum, however, are rare ; those most likely to be responsible are air embolism, mediastinal emphysema and cardiac failure. Two contra-indications to the use of pneumoperitoneum should be borne in mind: myocardial disease and weakness of the hernial orifices. *Care should be exercised in the use of pneumoperitoneum after childbirth before the tone of the abdominal muscles has been restored. Pneumoperitoneum has not been in use sufficiently long to allow considered judgment to be passed upon its ultimate value as a therapeutic procedure ; nor will this be possible until the end results have been more closely studied and statistically assessed. But experience to date suggests that pneumoperitoneum has a place particularly in the management of bilateral disease which is unsuit- able for other forms of collapse therapy, in certain types of lower lobe cavity, and in the preparation of a patient for a major surgical procedure such as thoracoplasty. It should be applied on a short- term policy and maintained for no longer than is absolutely necessary. Apicolysis and Extrapleural Pneumothorax The problem presented by those cases in which a pneumothorax cannot be obtained on account of extensive pleural symphysis has always been a difficult one, and the question of how best to treat such patients by collapse therapy has provoked much discussion. One method that has been used has been termed “ apicolysis,”’ an operation in which the parietal pleura is stripped from the chest wall and the space so created packed with various substances. Paraffin wax has been commonly used and possesses the advantage of being malleable and so can be accurately moulded to the shape of the extrapleural space. Sebrechts of Bruges used the pectoralis major muscle. Morriston Davies advocated breast tissue in the ease of women, and, more recently, Matson (26) reported a series of eighty-one cases in which gauze packs were employed and left in position for one to one and a half years without complications and with satisfactory results. Apicolysis with paraffin ‘‘ plomage ” has been used to collapse the more affected side in bilateral apical lesions in which pneumothorax has failed and thoracoplasty is deemed too risky ; and as an alterna-_ tive to thoracoplasty to combat symptoms such as haemoptysis or pyrexia arising from an isolated, thick-walled peripherally situated cavity, incapable of closure by other means. As an established method of treating pulmonary tuberculosis, however, apicolysis with plombage has never been widely adopted and the fact that it is now largely of historical interest only can be attributed to four main causes: (1) It was quickly realised that plombage failed to conform to the essential principle of collapse therapy, namely, that of relaxation ; instead it was the classical and most vicious example of ‘“‘ compression ’’ therapy. Moreover, it was not always possible to effect adequate collapse. (2) Because the element of force or compression was uppermost the complica- tions which attended the operation were both frequent and severe. These consisted of extrusion of the wax through the operation scar to the exterior within six months or nine months of operation ; the occurrence of effusion in, and infection of, the dead space around the compressing medium, a complication from which the use of vital tissues such as breast or muscle did not necessarily confer immunity ; perforation of a bronchus with the piecemeal expectoration of wax ; and occasionally haemorrhage. The appearance of any of these complications often necessitated a further operation of a magnitude which the patient’s general condition made him ill able to withstand. (3) The steady and satisfactory improvement in the technique of thoracoplasty, which has been a feature of the last decade, has resulted in many patients formerly regarded as poor thoracoplasty risks being now suitable for that operation. (4) The reintroduction of air as the “ filling medium,” i.e. a revival of the extrapleural pneumothorax—although in itself but short-lived—nevertheless served to supplant the former procedure and to relegate it into the background. A short discussion of the extrapleural pneumothorax is valuable on account of the practical lessons which have been learned from it. When Graf (27) and Schmidt (28) in 1936 published their tech- nique for the induction of an extrapleural pneumothorax—publica- tions which excited widespread interest—they did not describe an altogether new procedure: the credit for the induction of the first extrapleural pneumothorax has been given to Tuffier who induced it in 1912. But what the work of Graf and Schmidt showed quite clearly was the reason for the failure of those earlier efforts—namely, that the tendency for the apex to re-expand to an appreciable extent, after the first impact of the operation was over, had not been suffi- ciently allowed for at the time the stripping was done, with the result that obliteration of the space quickly occurred. It was but natural, therefore, that those early workers, faced with this seemingly inevitable re-expansion, veered away from the use of air as the filling medium towards the compressive methods of plombage already described. Graf and Schmidt employed extensive stripping of the apex, not only back and front, but laterally and over the cupola of the lung down the mediastinal surface to the lung root. What might be called the “ reactionary recoil ”’ of the lung was thus catered for and the final space, adequate for the needs of the case, could be maintained by refills of air, or, as was often preferred by Graf and Schmidt, converted into an oleothorax. The performance of the operation is frequently one of relative simplicity : initial success or failure largely depends upon the im- mediate post-operative management. Through a posterior incision about four inches of the fourth rib are resected and the loose areolar tissue in the plane of the endothoracic fascia exposed. The parietal pleura is then gently stripped off the chest wall either with the fingers or with gauze mounted on swab holders. The process of strip- ping is patiently continued over the whole apex and down to the lung root on the mediastinal side. Bleeding, not as a rule serious, is easily controlled. When the desired extent of apicolysis has been achieved the chest is closed and a refill given, bringing the pressure up to approximately atmospheric. Fluid collecting in the extrapleural space is removed and replaced with air a few hours after the return of the patient to the ward. It is usually heavily bloodstained. The removal of fluid, which pro- gressively becomes more serous in character, and its replacement. by air is a daily duty until the extrapleural space is dry, and there- after refills are given as often as required to maintain the air space. A common site for the insertion of the needle is through one of the anterior intercostal spaces underneath the clavicle. The induction of an extrapleural pneumothorax can be carried out in the presence of a basal contra-selective pneumothorax. Depend- ing therefore upon the extent of pleural symphysis and the degree of apical collapse desired the operation can assume one of three forms : 1. Where the pleural adhesion is universal. The apicolysis results in a single extrapleural pneumothorax space which is maintained along the lines already indicated. 2. Where the pleural adhesion is confined to the apex, the base being collapsed by an intrapleural pneumothorax. Apicolysis carried out in such a case will result in two pneumothorax spaces separated from each other by a ridge of parietal pleura. These two air pockets can be converted into one pneumothorax space by division of the intervening pleural membrane, a conversion which was at first effected through the thoracoscope some days after the original operation, but which later was done at the same time as the extrapleural apicolysis. The pneumo- thorax which results is then maintained along conventional lines. 3. Where an intrapleural pneumothorax is prevented from being fully successful by a limited area of pleural symphysis indi- visible’ by internal pneumonolysis. Extrapleural stripping is carried out over this adherent area, the freed pleura is divided around it, and the collapse completed. This type of operation which differs only in degree from the preceding, and which is but a variant of the old “open division” of intrapleural adhesions, has been designated by some workers with the specific title of ‘‘ extrapleural pneumonolysis.” The belief that extrapleural pneumothorax would prove an alternative to, and less shocking operation than, thoracoplasty and would thus bring pneumothorax within reach of many patients who had hitherto been denied its advantages, was quickly shown to be questionable. Within two or three years of its revival it had almost followed into desuetude the older operations of apicolysis and plombage. It is possible to group the reasons for its failure under four headings : 1. In practice the operation is often little less severe than thoracoplasty and imposes almost as great a strain upon the patient’s strength. The immediate effects of the operation are partially dependent upon the amount of stripping done, i) and are least in that type of operation referred to as extra- pleural pneumonolysis. always technically possible on account of firm adhesions in the extrapleural space obliterating the plane of natural cleavage. ‘The more difficult the stripping the greater is the Complications are both frequent and severe. Among them can be included : (a) Early re-expansions of the lung before healing had occurred. (b) Haemorrhage, which may occur early and prove trouble- some, or be delayed. The blood sometimes clots in the extrapleural space and although, as Roberts (29) has shown, the clot can be removed through a trocar and cannula such an occurrence tends to militate against complete success. (c) Air embolism. (d) Effusion is not uncommon even after the initial stage is passed. It appears to be absorbed less readily from an extrapleural ‘‘ dead space” than from pleural sur- faces. It requires repeated aspiration. (e) Infection. A serious complication which Geary (380) reported to be as high as 37-7 per cent. of the 74 patients which he observed for three and one quarter years. Tuberculous infection might result from the tearing of lymphatics. Pyogenic infection of the dead space, super- added to the tuberculous, was even more to be feared in the days before penicillin became available. (f) The establishment of a broncho-extrapleural fistula, which Janes et al. (81) found in 5 out of 77 patients that they observed. (g) The occurrence of spread of disease to the opposite healthy lung was found to occur almost as frequently as after thoracoplasty. (h) There is a tendency, particularly if fluid is present, for the extrapleural space to become thickened, rigid and inelastic, and it soon became obvious that in many extrapleural pneumothoraces there was little chance of the lung re-expanding at the conclusion of the treatment, and that the collapse was as permanent as after thoraco- plasty. Many of these cases required a thoracoplasty ultimately to close the artificial space thus created and the rigidity*made this operation more difficult. (i) Hoyt and Tate (82) include acute intestinal tuberculosis and submuscular abscess in the list of complications which they observed in their series. 4. Finally, while the immediate results of extrapleural pneumo- thorax were fair the end results were often much less satis- factory, a finding which prompted a critical review of pre- conceived indications for the procedure. This has been well demonstrated by the work of Roberts. In 1938 Roberts (29) published the results of 33 operations which included 3 hope- less cases. Of the remaining 30 patients, 25 were clinically well after operation, while 2 had died, and in 3 the operation had to be abandoned on account of dense pleural adhesion. From a short-term assessment of these results the author propounded three major indications for the operation : first, if there was reason to believe that after healing the lung may be allowed to re-expand; secondly, if the condition of the patient did not allow of thoracoplasty although a permanent collapse was desirable; and thirdly, in children and young subjects because of the danger of scoliosis after thoraco- plasty. In 19438, at a meeting of the Tuberculosis Association, Roberts (33) presented a five year follow-up of the same patients. Leaving on one side the 3 hopeless cases and the 3 in whom the operation had to be abandoned, he found in the remaining 27 that 2 died at the time of operation, 4 had died in the intervening years, in 6 a thoracoplasty had been performed, 10 were well and working, and 5 remained untraced. Roberts considers that the morbidity of extrapleural pneumo- thorax is greater than that of a modern thoracoplasty and believes that a thoracoplasty should be performed subsequently as soon as the state of the patient allows, the sole remaining indication for operation being, in his view, the preclusion of thoracoplasty by poor general condition or if the operation is refused. Even in the young growing subject a thoracoplasty is - now permissible, as expert physiotherapy before and after operation goes a long way towards maintaining natural posture and preventing deformity. Reports from other sources show a similar modification of view regarding the extrapleural pneumothorax, and although it is still valuable for a small group of cases where thoracoplasty is not possible, there is apparent a decided preference for ‘the modern selective thoracoplasty. References (1) SMART, J. (1989) Tubercle, 21, 81. (2) Maurer, G. (1930) Lancet, 2, 72. (3) JACOBAEUS, H. C. (1922-23) Amer. Rev. Tuberc. 6, 871. (4) Brock, R. C. (1988) Brompton Hosp. Rep. 7, 81. (5) CHANDLER, F. G. (19380) Lancet, 1, 232 and 2, 74. (6) CuTLER, J. W. (1942) Amer. Rev. Tuberc. 44, 722. (7) Matson, R. C. (1929) Amer. Rev. Tuberc. 19, 233. (8) Larrp, R. (1945) Tubercle, 26, 149. (9) CHANDLER, F. G. (1936-37) Tubercle, 18, 298 and 348. (10) Drasnu, E. C. (1937-38) J. thorac. Surg. 7, 411. (11) Moors, J. A. (1987-38) J. thorac. Surg. 7, 417. (12) Epwarps, P. W., PENMAN, A. C. and LoGAN, J. (1944) Brit. med. J. 2, 270. (18) THompson, S. A. and GREENBERG, M. (1941) Amer. Rev. Tuberc. 44, 1838. (14) JAcoBAEUS, H. C. (1987-88) J. thorac. Surg. 7, 417. (15) O’SHaucuNnEssy, L. (1932) Lancet, 2, 767. (16) Morin, J. (1931) Arch. méd.-chir. Appar. resp. 6, 229. (17) Barnes, J. (1939) Lancet, 2, 976. (18) Epwarps, P. W. and LoGan, J. (1945) Tubercle, 26, 11. (19) Banyag, A. L. (1941) Dis. Chest, 7, 402. (20) Fowuer, W. O. (1941) Amer. Rev. Tuberc. 44, 474. (21) Stumonps, F. A. H. (1946) Lancet, 1, 530. (22) CoTTON CORNWALL, V. and PATRIDGE, W. H. (1947) Tubercle, 28, 164. (23) Smiru, C. N. (1948) Brit. med. J. 2, 404. (24) CLIFFORD-JONES, E. and MACDONALD, N. (1948) Tubercle, 24, 97. (25) AsLeTT, E. and JARMAN, T. F. (1945) Lancet, 1, 304. (26)-Martson, R. C. (1942) Amer. Rev. Tuberc. 45, 714. (27) Grar, W. (19386) Dtsch. med. Wschr. 62, 671. (28) Scumipt, W. (1936) Beitr. Klin. Tuberk. 88, 689. (29) Roserts, J. E. H. (1938) Brit. J. Tuberc. 32, 68. (30) GEARY, P. (1942) Amer. Rev. Tuberc. 46, 646. (31) JANES, E. C., Arrcuison, D. B. and ForsBere, A. (1940-41) J. thorac, Surg. 10, 8. (82) Hoyt, W. F. and Tare, J. C. (1940-41) J. thorac. Surg. 10, 551, (33) Roperts, J. E. H. (1948) Tubercle, 24, 124, (Abstr.) CHAPTER X COLLAPSE 'THERAPY—SURGICAL PROCEDURES. II Thoracoplasty Morriston Davies, who considered the operation of thoracoplasty a serious one, wrote of it in 1933 (1): “* For those who win the gain is enormous, whilst those who lose have gambled a year or two of an invalid’s life against health and freedom.” The technique of thoracoplasty has undergone such considerable modification since these words were written that the operation, no longer regarded as a gamble, is now. more commonly employed as a logical step in collapse therapy than as a desperate measure designed to ward off or postpone an inevitably fatal outcome. The ten-rib paravertebral resection of Sauerbruch, the standard pattern of fifteen or more years ago, which resulted almost entirely in a lateral collapse of the lung, has been superseded by the partial apical thoracoplasty embracing the principle of selective concentric relaxation of the diseased part leaving untouched the healthy lower lobe. In other words, the modern thoracoplasty is designed, mechanically, to match the pneumothorax at its best. Following closely in the wake of this fundamental change of principle, and largely dependent upon it, the scope of the operation has become widened and it is being increasingly applied. Moreover, improved methods of case selection, linked with the smaller operative risk of the partial as opposed to the complete resection, has led to the operation being performed earlier than was at one time possible, thus saving time in treatment and minimising the chances of the disease spreading. In the earlier days of the transition from the complete to the partial apical thoracoplasty attention was chiefly focused upon removing increasing lengths of the upper ribs. In order to make this easier the apex of the lung was stripped in the plane of the endo- thoracic fascia, a manoeuvre which enabled the posterior portions of the first and second ribs, with their transverse processes, to be more readily removed. A much improved degree of collapse was obtained, but the procedure was frequently robbed of that complete success which at first seemed assured by the fact that as the sero- sangineous effusion which collected in the dead space was absorbed the apex of the lung expanded to take its place. Several ingenious devices were employed to counter the buoyancy of the lung apex : for example, the periosteal rib beds were partially freed and one end stitched to the chest wall at a lower level in the hope that bone regeneration would occur in time to exert some restraint upon the apex. This was not wholly successful. A significant advance towards the solution of this problem was the operation devised by Holst, Semb and Frimann-Dahl (2) of Oslo in 1935, and called by them ‘ Extrafascial Apicolysis with Thoracoplasty.” The essential difference between this operation and others which preceded it lay in the mobilisation of the apex, which was effected in the extrafascial and not the endothoracic plane. The periosteum and intercostal muscle bundles were sepa- rated from the chest wall and remained attached to the apex of the lung which was freed by the division of apical adhesions and bands which would otherwise have hindered its vertical descent. ‘This operation, in addition to preventing the later riding up of the apex by sheer weight of tissue resting“upon it, possessed one other undeniable advantage—namely, that sufficient mobilisation of the upper half of the lung to ensure selective and concentric relaxa- tion could be achieved in the presence of firm adhesions which might have prevented effective stripping in the endothoracic fascial plane. It is a procedure, however, which imposes a severe strain upon the reserves of a tuberculous patient, and the degree of shock which accompanies it is often considerable. For this reason, it is carried out in two or more stages, the first stage being devoted to the extrafascial mobilisation with the complete excision of the first two or three ribs, and the subsequent operation to grading off the collapse by the removal of the requisite number of lower ribs. If it is possible to apply the term “ standard procedure ” to so variable an operation as thoracoplasty then the extrafascial apico- lysis of the Norwegian School can lay a good claim to the title: since 1986 it has been the basic pattern of all selective thoracoplastic operations. It has, however, not gone unmodified. Price Thomas and Cleland (8) published an important paper in 1942 describing certain variations in technique which these workers now use, and the reader is referred to this paper for a full account of the details. saunoH (4p fo hsaqunoa hg) jeorde dAT}OapoS Indications. Morriston Davies (1) gave the following indica- tions for thoracoplasty : 1. Every case of chronic unilateral tuberculosis in patients up to the age of forty-five which cannot be arrested by simpler nreans. The term “‘ unilateral ’’ does not exclude some fibrosis in the contralateral lung, but does exclude an active process. 2. Every unilateral case with single or multiple cavities with rigid walls. 3. Cases with haemoptysis which cannot be controlled. When the haemoptysis is a danger to the patient’s life some latitude is permissible in respect of the disease in the other lung. Such disease must not, however, be progressive and cavities are a contra-indication. 4, In exceptional cases, thoracoplasty is done when the disease is exudative in character. These indications for the use of thoracoplasty in pulmonary disease are still broadly applicable, but in the light of the recent technical developments which have just been discussed some further observa- tions in amplification are required. First, although it is preferable to try simpler means, such as arti- ficial pneumothorax, before resorting to thoracoplasty, the view is gaining ground that in certain cases it is better to proceed direct to an apical thoracoplasty and exclude the pneumothorax altogether. For example, in sluggish unilateral disease confined to the extreme apex with a constantly positive sputum or a persistent cavity it has been suggested that thoracoplasty is preferable to pneumo- thorax for the following reasons: (1) operation in such a case carries a very low mortality ; (2) a partial operation is all that is required and only that portion of the lung which is diseased and useless is put out of action; (8) it is as successful mechanically as pneumothorax, may be accomplished in one stage, and the need for repetitive treatment in the form of refills extending over years is dispensed with; and (4) the risks attaching to pneumothorax, which are real, are avoided. The decision is not a simple one to make and must largely rest upon individual opinion. Secondly, it is becoming more generally realised that a bad pneumothorax is a greater danger than no pneumothorax at all, and that the sooner it is given up and other methods of collapse therapy substituted the better. In other words, the interval between the induction of a pneumothorax and the recommendation for thoraco- plasty is becoming materially shortened. The practical advantages of this have been well summarised by Roberts (4): (1) it saves life ;_ (2) it lowers the incidence of later spread of disease and re- currences ; (8) it shortens the period during which the patient is capable of disseminating the disease to others ; and (4) it shortens the period of invalidism and restores the working capacity earlier. Thirdly, the adverse effect which thoracoplasty has upon disease in the opposite lung is too well known to need emphasis, and in the presence of bilateral disease the utmost caution must always be exercised in considering operation. But the practice of operating in two or more stages after careful selection and pre-operative pre- paration to some extent allows of greater latitude than was pre- viously possible. Furthermore, thoracoplasty can be uneventfully performed in spite of a selective pneumothorax on the other side, and many surgeons now advocate in doubtful cases a partial or “ pro- tective ” pneumothorax started before operation and maintained for a short time afterwards. Fourthly, the selective apical operation, which is the hall-mark of modern thoracoplasty, is more easily compatible with bilateral collapse therapy. A thoracoplasty on one side with an intrapleural or an extrapleural pneumothorax on the other, or a bilateral apical thoracoplasty, are now possible combinations. ¥ifthly, in deciding upon any form of collapse therapy, parti- cularly so definitive a procedure as thoracoplasty, it is important to appreciate the trend of the disease from its inception until the present time—to view each case in “ longitudinal ” and not “ trans-. verse ’’ section. The classification adopted by Price Thomas and Cleland (8) for chronic disease is useful. There are four headings : (1) the stationary chronic; (2) the relapsing chronic; (3) the slip- ping chronic; and (4) the hopeless chronic. ‘This classification is largely self-explanatory, but, in the authors’ own words: “ The stationary chronic is usually apyrexial, in good general condition, and shows little or no signs of toxaemia; the main symptoms are cough and sputum. The relapsing chronic, as the name implies, resembles the stationary case at times, but has intermittent periods of pyrexia, toxic symptoms, increased cough and sputum and loss of weight. Though recovery follows, he rarely reaches the original state. The slipping chronic is one who gradually retrogresses, although such retrogressions may be slow. Naturally the rapidity of the downward path is of great significance, when rapid it condemns the patient to the category of the hopeless.” The stationary chronic is the ideal case for thoracoplasty for the risk of operation should be minimal and the prospect of cure great. For the relapsing chronic, too, operation holds out an excellent chance of recovery provided it is performed at the right time— namely, during the phase of recovery from a relapse and as near as possible to the crest of improvement. To gauge the opportune moment requires considerable experience in assessing a case, and in interpreting the help that can be derived from radiological and labo- ratory investigation. It can be one of the most difficult decisions in the treatment of tuberculosis. The slipping chronic is less likely to benefit from thoracoplasty, and whether the operation is recom- mended or not depends entirely upon the individual features of each case, particularly the speed at which the disease is advancing. For the majority of slipping chronics it is fair to say that alternative methods of collapse therapy, such as phrenic interruption with sup- plementary pneumoperitoneum, should be given a trial, and if they do not succeed it is doubtful whether the patient could stand up to thoracoplasty, and if he did, that it would turn the tide. If the clinical features are sufficiently grave at the time of assess- ment for the patient to be dubbed a “ hopeless chronic ” the question of thoracoplasty should not arise. It is often tempting in the face | of the question “can nothing be done?” to resort to desperate measures on the reasoning that if it does not succeed little is lost. Such reasoning is unsound for in these circumstances operation can do harm by causing much terminal discomfort in return for a negligible hope of cure, and by lowering the prestige of thoracoplasty, which is important in a closed community like a sanatorium. Sixthly, thoracoplasty is frequently required in certain cases of tuberculous empyema, secondarily infected or not, if other measures have failed to obliterate the pleural space. Here again, the consensus of opinion has veered: towards earlier operation before the pleure are too rigid or too thick to prevent complete obliteration of the: space (see page 158). Lastly, the assistance which ancillary methods of investigation can give is now more highly rated than it was. Serial readings of the blood sedimentation rate or sedimentin index, and of the Houghton index, are useful accessory guides to the trend of activity, and in a difficult case can be used to supplement the clinical assessment based on the age, build and general physical condition of the patient, gain or loss of weight, progress of symptoms, tempera- ture and pulse rate, and the X-ray appearance. Determination of the vital capacity is indispensable, and the V.C., which may at first be a limiting factor, can often be improved by proper exercises. Jacobaeus has devised a method for estimating the V.C. of each lung separately, and the extended use of bronchospirometry is to be anticipated. A total V.C. below 2,000 c.c., unless there is a big difference between the healthy and diseased side, is an unfavourable reading ; but a reading of 2,000 c.c., so long as the contribution of the affected lung is only 200 c.c. or 300 ¢.¢., is compatible with operation. There is, in other words, no short cut or easy way to success in case selection for thoracoplasty : rules are unreliable and individual factors of the highest importance. Consideration of the natural history of tuberculosis and of the factors which influence prognosis, backed by whatever investigations are necessary, is the only way to arrive at a sound and safe conclusion. Contra-indications. Many of these will have become already apparent from what has been written above and little more need be added. Thoracoplasty is essentially a procedure for a stabilised and in- active lesion and when so used is seen at its best and safest. It is not, of course, wholly restricted to this class of case, but it is a fair generalisation to state that the hazards of operation are directly proportional to the degree of activity of the disease, and in the treatment of acute exudative tuberculosis thoracoplasty has no place at all. Age is an important factor, and few patients over forty-five or fifty are suitable for thoracoplasty. But the age of a man, ex- pressed numerically in years, is sometimes a fallacious guide: a man of fifty with good general condition and supple arteries is a better operative risk than an unhealthy and flabby individual of forty. Extra-pulmonary tuberculous disease may or may not contra- indicate thoracoplasty depending upon the type of lesion and the degree of involvement. In the presence of associated bone and joint tuberculosis and tuberculosis of the genito-urinary tract, unless ad- vanced, the lung lesion must be treated on its merits, if necessary, by thoracoplasty, provided the clinical condition of the patient and the degree of toxaemia permit. Tuberculous laryngitis in a reasonably early stage is an indication for thoracoplasty if operation is considered to be the surest and quickest method of converting the sputum from positive to negative. Tuberculous enteritis, on the other hand, if sufficiently well-established to be diagnosed with certainty, generally contra-indicates operation in view of its own extremely poor prognosis. The performance of thoracoplasty in the presence of associated diseases of non-tuberculous aetiology must be undertaken only after very careful consideration has been given to the combined prognosis, and the decision whether to operate or not must depend upon the nature of the complicating disease. The co-existence of bronchitis and pulmonary emphysema with tuberculosis may be enough to contra-indicate operation. So also is cardiac disease. Anaemia, if present, should be corrected before operation is undertaken. Thoracoplasty, if essential for the adequate control of the lung lesion, can be carried out in the presence of diabetes so long as the diabetes is closely watched and adequately treated during the post- operative period. 'Thompson’s case (5) has shown how this can be successfully done. Pre-operative and Post-operative Management. The recog- nition of the importance of team work in thoracic surgery as a whole has been a noticeable feature in recent years. A skilfully adminis- tered anaesthetic, specialised nursing, and expert physiotherapy are just as essential for success as are the experience and judgment with which the case is selected and the operation performed. Attention to detail before and after thoracoplasty by everyone concerned goes a long way towards preventing complications and banishing from the patient’s mind the fear of recognisable deformity. Immediately before the operation the following points have been listed by Price Thomas (3), some of which will be elaborated later :— 1. Physiotherapy. Instruction in diaphragmatic and lower chest breathing exercises should be given before operation in order that it may be utilised afterwards to the very best advantage. Another firm indication for the use of breathing exercises before operation is the increase in the vital capacity which often results from it. | 2. The patient should be made familiar with the methods of administering oxygen, such as B.L.B. mask or oxygen tent, whichever is to be used. A naturally nervous patient is made ‘increasingly apprehensive if the oxygen apparatus is brought into play without any preliminary acquaintance with it. 3. The importance of coughing after the operation and the means that will be adopted to encourage expectoration should be clearly explained to the patient. 4. Price Thomas does not necessarily enforce strict bed rest before operation. There is indeed much to recommend the practice of allowing the patient to be up and about, if his condition permits, for it maintains the tone of the muscular system and is good psychologically. There are several points in the post-operative management of thoracoplasty which deserve particular attention : First, the importance of encouraging expectoration, for the reten- tion of sputum may lead to bronchial occlusion, pulmonary atelec- tasis, and spread of disease to either the lower lobe on the same side or to the opposite lung. The chief deterrent to good coughing and free expectoration is pain and this should be relieved by morphia if necessary. A large dose of morphia may defeat its own object by abolishing the cough reflex, but a hypodermic injection of a smaller dose will be found satisfactory and safe. During the act of coughing the chest should be supported and the patient placed in whatever position is found to be most conducive to his comfort and of greatest assistance in producing sputum. This régime of con- trolled coughing should be carried out regularly at stated times and is facilitated by the administration, in an equal quantity of hot water, of a saline mixture with the following formula :— R Sodiu Bicarbonatis . : ee TY Sodii Chloridi fay sri Spiritus Chloroformi : eae [| Fe Spiritus Rectificati ‘7, ACES Aquam Anisi . : af jae ian Secondly, the important place which physiotherapy has come to occupy in attaining what Price Thomas calls ‘‘ respiratory rehabili- tation ” is still not as widely appreciated as it should be. It is doubtful whether thorocoplasty should be done if the services of a skilled physiotherapist are not available. A short description, therefore, of the deformities which may arise and of the measures taken for their prevention will not be out of place. _ The faulty posture which is so easily adopted after operation con- sists primarily of a scoliosis of the upper thoracic spine with the con- vexity towards the affected side. The remaining components of the final deformity largely arise secondarily to this and comprise : (@) com- pensatory scoliosis of the cervical and lower thoracic and lumbar spine ; (b) deviation of the head away from the affected side by the uneven action of the neck muscles consequent upon the loss of the first rib and of the muscular attachments to it; (c) elevation and rotation forward of the iliac crest opposite to the side operated upon ; and, in some cases, (d) elevation of the shoulder of the affected side. In addition, full range of movement of the arm is reduced as a result of interference with the musculature of the shoulder girdle, the abdominal muscles lose their tone thus impairing diaphragmatic movement, and this may be associated with a lumbar scoliosis. Preventive exercises should be begun ten days before operation, although in an emergency five days can be sufficient. The patient is taught the correct position in which to lie, well supported with pillows and a back rest, and the use of a full-sized mirror at the foot of the bed is indispensable in order that the patient may constantly check the correct position for himself. The hips should be level with the anterior point of the shoulder in the same vertical line as the iliae crest, and the head and neck held straight so that the sternomastoid V is central. In adjusting this posture it may be necessary in the first instance to over- exaggerate slightly the various points. ' Diaphragmatic movements are enhanced by teaching the patient to ** open ”’ the lower costal angle and at the same time relax the abdominal muscles as much as he can; in expiration he is instructed to close down and reduce the diameter of his chest to a minimum. The exereises, simulating the bellows action, increase the mobility of the thoracic cage and the effect should be attained by quiet breathing rather than by forceful inspiration. Arm exercises consist of circling movements, abduction, elevation above the head with the hands together, shrugging and pulling back the shoulders, and of putting the shoulder joint through its full range of movement. Other measures include Dimovemnent in the tone of the abdominal muscles, quadriceps contraction, dorsiflexion of the ankle, and ankle circling. A patient well trained beforehand should assume the correct lying position with the aid of a mirror, and should start simple arm move- ments, on the day following operation. On the second post-operative H. & R. TUBERC. 4 day arm exercises are increased and the posture rectified if necessary, particular attention being paid to the head and neck. On the third day active exercises are begun. ‘Thereafter the physical measures are intensified as rapidly as the condition of the patient allows. Per- severance and constant supervision are necessary and daily visits by the physiotherapist are desirable. The co-operation of the patient must be enlisted from the first if the best result is to be attained, and the personality of the physiotherapist is an important factor in securing this. Thirdly, it has sometimes been assumed that thoracoplasty is the final act of a long course of treatment and that as soon as the im- mediate effects have worn off the patient may leave the institution. This is not so. After operation at least three months, and more often six, of sanatorium routine are required to ensure that the lesion is stable, the cavity firmly closed, and the danger of relapse passed. Complications. The modern type of thoracoplasty with extra- fascial apicolysis is not devoid of accidents during its performance, most of which occur at the time of the first stage. Price Thomas and Cleland (3) record the following : 1. The cavity may be inadvertently entered. This can be dealt with by sucking out the secretions, cleaning the wall with flavine, continuing the mobilisation of the apex and then suturing the cavity wall without tension. 2. The opening of infected pleural pockets. 3. The opening of an uninfected pleural space with the establish- ment of a pneumothorax. 4. Damage to vessels. 5. Damage to the sympathetic nerve and thoracic duct, neither of which need necessarily be serious. Many of the complications which occur later in the post-operative period can be prevented by adopting the measures which have already been described. The following list is again largely based upon the publication of Price Thomas and Cleland : Operative Shock and Loss of Blood. Both may be considerable after an extrafascial apicolysis. Blood transfusion is often necessary and in some clinics is given as a routine. Paradoxical Movement and Respiratory Distress. Atelectasis. In the majority of cases this follows the retention of secretions in the bronchial tubes. Price Thomas recognises three forms: simple atelectasis, atelectasis with suppuration, and the variety followed by the appearance of tuberculosis in the collapsed lobe. The first of these will probably reinflate on its own account and will be helped to do so by physiotherapy ; the second, which may result from a persistent “‘ simple” atelectasis, is a greater danger in view of the risk of bronchiectasis supervening if complete reinflation is not brought about ; the third is the most serious of them all. The part played by a preliminary phrenic operation in predis- posing to atelectasis has been discussed. Should phrenic interrup- tion be deemed advisable in addition to an apical thoracoplasty it should be done after the major operation and not before it. Spread of Disease. The appearance ofa fresh focus in the opposite lung, or the flaring up of an apparently inactive focus, is a real danger of thoracoplasty. A favourite site for the fresh lesion is in the mid-zone of the opposite lung suggesting an aspiration spread from the affected apex. It is thus related to atelectasis. A more _ severe “ flooding ” of the healthy lung may occur if cough is not effective. Pneumonitis. ‘This term is here taken to cover any acute non- tuberculous, inflammatory lesion of the lung. This complication is not confined, therefore, to chest surgery, but is more serious in its effects if it occurs after a major thoracic operation. It can be reduced to a minimum by operating at a favourable time of year, and by postponing operation if there is the least suspicion of upper respiratory tract infection or bronchitis. Infection of the Wound or Dead Space. 'This may be a serious complication and in the past has been responsible for much invalidity and prolongation of convalescence. Chemotherapy, and especially penicillin, has lately materially altered the outlook. Haemorrhage into the extrafascial space. This is sometimes serious and may require an open inspection of the operation area for its control. It must also be regarded as a predisposing cause of infection of the dead space. Spontaneous Pneumothorax has been included by Price Thomas. It more commonly occurs at the time of operation. Anaemia. Some degree of anaemia is not uncommon after thoracoplasty and has been attributed by Braverman (6) to more than one cause, namely, blood loss, intoxication (‘ autotuberculini- sation ’), reduced food consumption for two or three days after operation, and post-operative vomiting. The severest grades of anaemia are found after operations for the closure of tuberculous empyemata. A close watch qronid be kept upon the haemoglobin level of the blood for it is essential that anaemia should be promptly corrected, especially between the stages. Braverman believes that it can be prevented by the pre-operative administration of a high calory-high protein diet with added vitamins, pil. ferrous sulph: gr. 6 t.d.s., and brewer’s yeast. The same measures should be applied for its repair with the addition of blood transfusion if warranted. Cardiac Failure. Myocardial insufficiency occurs rarely after operations performed upon toxic patients with poor general condi- tion, and upon those in middle life. Supplementary Thoracoplasty. Before thoracoplasty was de- signed to produce selective concentric relaxation, and occasionally even now, it sometimes failed to close an apical cavity and convert the sputum from positive to negative. A persistent cavity in a partially collapsed lung is often an extremely difficult surgical pro- position, and various types of revision or supplementary thoraco- plastic operations were undertaken for its closure, in the course of which further lengths of rib either in front or in the axillary region were removed. Judd (7), believing that in many of these refractory cases the lung evades complete relaxation by sinking into the paravertebral gutter, has practised mobilising the lung, rolling it forward and stitching it in this new position in such a way as not to interfere with the blood supply of the cavity. Other supplementary procedures which have been tried include drainage of the cavity, and additional extrapleural apicolysis with the insertion of gauze packing over the site of the cavity. Most of these procedures are of considerable magnitude and are somewhat uncertain in their effects, so much so that many surgeons are coming to regard the thoracoplasty failure as an indication for lung excision. Transpleural Drainage of Cavities The basic principles underlying the treatment of tuberculosis and suppurative disease of the lung have, up to the present, been divergent ; collapse of the affeeted portion of the lung being the accepted method for the former and drainage or excision for the latter. Recently, the gulf which has separated these two types of pulmonary disease has become much narrower. The broncho- graphic studies carried out in tuberculosis by Dormer and his col- leagues in South Africa, and by other workers in this country and in the U.S.A., and the recognition of the importance of tuberculous disease of the bronchi and of pleural symphysis in cavity formation and persistence, have disclosed much common ground between them, and have been followed by the application to tuberculosis, - with some modification, of those methods of treatment which were formerly used for suppurative disease alone. Drainage of certain types of refractory cavity can be quoted as an illustrative example, but before this method of treatment is described it is necessary to devote a few paragraphs to endobronchial tuberculosis and to the modern view regarding the formation and persistence of tuberculous cavities. Tuberculosis of the Trachea and Bronchus. That tubercu- losis can attack the mucous membrane of the trachea and bronchial tree has been established by autopsy studies and has long been known. Heaf (8) in 1924 reported the occurrence of tuberculosis of the trachea in 58 (44 per cent.) of 133 patients dying of pul- monary tuberculosis. Myerson (9), in 580 consecutive patients bronchoscoped at the Sea View Hospital, found a specific lesion of the trachea and bronchus in 160, but does not state to what extent his material was selected. Alexander states that the frequency of this complication in the U.S. is around 11 per cent., a somewhat higher figure than clinical impression would suggest is the case in this country. An accurate figure for the incidence of this mani- festation is hard to reach, for so much depends upon the type of material examined, the methods of investigation employed, and the extent to which these methods are applied. Apart from pressure exerted on a bronchus by an enlarged lym- phatic gland at the time of the initial infection, which may some- times progress to ulceration into the lumen with the discharge of caseous matter, intrinsic tuberculosis of the trachea and bronchus may be broadly divided into four groups, each of which represents a stage in the evolution of the pathological process : 1. An early stage of inflammation with congestion and oedema of the mucous membrane. The process probably starts in the submucous layer. may comprise areas of heaped up, highly vascular, tissue which readily bleeds when touched. tion of fibrous tissue leads to a stricture in the lumen. Cough is troublesome and more commonly complained of than in uncomplicated phthisis. Paroxysms may be accom- panied by blood. streaking of the sputum and by cyanosis. The cough may cause substernal pain. bacilli when other features of the case make this difficult to understand, and the sputum may change, often abruptly, from positive to negative and back again. stridor is constantly present, especially if expiration is forced. An “ asthmatoid wheeze,” if not obvious to the unaided ear, can be detected on auscultation, is maximal over the site of the lesion, and is not altered by coughing. amount of lung tissue apparently involved. become airless and in shrinking it drags the mediastinal structures towards the same side. Once this atelectasis starts it generally progresses moderately rapidly. thorax is attempted in the presence of endobronchial tuber- culosis. First, the lung collapses more readily and completely than is usual, becoming opaque in the affected area—the so- called “‘ black lobe”; and secondly, if the lung contains a cavity this may grow larger instead of smaller as the lung relaxes. Both should engender a cautious attitude towards continuation of this method of treatment. tion of bronchial involvement by Peirce and Curtzwiler (10) and which may be found to be of diagnostic significance. It consists of a thickening along the line of the bronchovascular markings connecting the parenchymatous focus with the lung root (Oechsli’s sign). This is, of course, likely to pass unob- served if the pulmonary infiltration is at all heavy. | 8. Finally, in doubtful cases, inspection of the bronchial tree through the bronchoscope should be carried out. Biopsy of abnormal mucous membrane can be done, but the reaction to such interference is sometimes severe. Treatment of this condition has not so far proved satisfactory. In the early stage of congestion and oedema it is doubtful whether active therapy is needed, and its management should be along con- ventional sanatorium lines. Useless unproductive coughing should be allayed. For the more advanced examples several methods of treat- ment have been tried and an account of these has been given by Ormerod (11). They all labour under the obvious disadvantage that repeated bronchoscopy is necessary. Painting the granulomatous area with 10-30 per cent. silver nitrate, after the preliminary re- moval by forceps of some of the granulation tissue, has been tem- porarily successful and may forestall complete occlusion of the bronchus. Galvanocautery or diathermy has been used on an ulcerating surface, and exposure to ultra-violet irradiation can be effected by means of a special endoscopic technique. In the case of the fibroid structure Ormerod advises conservative treatment pro- vided there is no obstruction ; if there is obstruction, partial removal with punch forceps as a preliminary to galvanocautery or dilatation should be considered. Dilatation should be a gradual process so as to avoid reaction. Indeed, active treatment at any stage is threatened with the risk of exacerbation and dissemination of the infection, and in Myerson’s view the early stages of the disease are best left untreated in view of the tendency to spontaneous healing. It would appear from American reports that streptomycin is valuable in the treatment of this complication and controlled research into this problem has been started in this country. Collapse therapy for the lung disease is regarded by many observers as contra-indicated during the active phase of endobronchial infec- tion. Thoracoplasty is advocated by Alexander (12) for bronchial stenosis by fibrous tissue provided the stricture can be dilated suffi- ciently to enable the retained secretions to escape. If this cannot be done he regards lobectomy or pneumonectomy as the operation of choice. The intrinsic manifestations of tuberculosis of the bronchus are important in themselves; but of even greater significance is the influence which the bronchial changes exert upon the parenchy- matous disease beyond, particularly with regard to the behaviour and persistence of cavities. The Tuberculous Cavity. Recent work has shown that the mechanism of cavity formation is more complicated than was originally believed. Except possibly in some of the advanced and chronic cavities the size of the excavated area can no longer be looked upon as a measure of the amount of lung tissue destroyed ; to this purely “ biological ”’ conception must now be added certain powerful mechanical factors which operate not only in the forma- tion of the cavity but also, in some cases, in its perpetuation. The first is the retractile tendency of the lung tissue itself, which normally acts in response to the difference in pressure between the pleural cavity and the atmosphere; the damaged elastic fibres recoil in response to this pressure difference and a spherical hole results. Secondly, there is the influence of the “‘ chest wall pull ” to which Price Thomas (18) has drawn attention. This is more | concerned with the persistence of a cavity than with its inception, and if the layers of the pleura over the affected area are adherent it becomes a factor to be seriously considered. Thirdly, and most important, is the question of the patency of the main bronchus supplying the cavity. The significance of these factors, both in tuberculous and suppurative disease of the lung, has been freely discussed by Price Thomas; the last of them must be considered at this point in more detail. It is to Coryllos and his associates that the main credit must be given for demonstrating the outstanding importance of the supply bronchus in the formation and closure of the tuberculous cavity. Coryllos and Ornstein (14) in 1938 recognised two types of cavity, each with its own distinguishing features : 1. Those in which the air is under positive pressure. These they term ‘giant’? or “distension” cavities. They have thin walls; they accumulate secretion and show a fluid level ; their size remains unchanged during respiration ; lipiodol or dyes introduced into them through the chest wall are retained for a time; they tend to open and shut spontaneously (the — ‘accordion ”’ cavity); the sputum is usually negative for T.B.; and the general condition of the patient is good. 2. Those in which the pressure within the cavity is atmospheric. The walls of these cavities are thick; no fluid accumulates ; lipiodol and dyes quickly leave the cavity and appear in the sputum ; there is no tendency to spontaneous disappearance ; the sputum is persistently positive for T.B.; and the general state of health is unsatisfactory. Coryllos explains these essential points of difference between the two types by reference to the draining bronchus. In the case of the cavity in which the pressure is atmospheric the bronchial lumen is patent ; in the tension cavity, on the other hand, the bronchus is partially occluded, either by tuberculous changes in its own mucous membrane, or by becoming kinked within the wall of the expanding cavity, with the formation of a valvular mechanism per- mitting air to enter the cavity. during inspiration and trapping it there in expiration. The cavity thus becomes distended to the point at which air can only enter to replace that which is absorbed. Should the block temporarily become complete, as it may through | the agency of a mucous plug, the air within the cavity will be absorbed and the cavity close ; the reinstatement of partial occlusion will be followed by reappearance of the cavity. The evidence upon which this theory of cavity formation rests is derived from three sources : (a) A pneumothorax needle inserted into a giant cavity will record a positive pressure. (b) Cavernoscopic studies of the interior of a cavity have been carried by means of a special instrument and the opening of the drainage bronchus visualised. Coryllos found the open- ing slit-like, resembling the mouth-piece of a saxophone. (c) Dissections carried out. after death have demonstrated tuberculous changes in the draining bronchus. From the results of his work Coryllos was led to the conviction that the essential prerequisite of cavity closure is a block in the draining bronchus, for if there is no hindrance to the entrance or exit of air the cavity persists, whereas a valvular mechanism like the one described paves the way for distension and the formation of a giant cavity. When this view was first put forward it was novel and ran counter to the prevailing teaching of the time which stated that if the bronchus became blocked the cavity persisted and filled with retained secretion. It is in the light of this modified view of cavity formation that the various methods employed to bring about closure must be assessed, for if this view is correct (and it must be admitted that some authorities hold that promoting bronchial drainage is a more rational method of treating distension cavities than by obstruction), it governs the whole rationale of collapse therapy. For the comparatively recent cavity with a healthy supply bronchus, not too near the periphery of the lung, the artificial pneumothorax is ideal; by relaxing the lung and by counteracting the chest wall pull it enables healing to occur. Phrenic interruption acts in a similar though not so effective a manner. But the pneumothorax, even if mechanically successful, may fail in its objective if tuberculous endobronchitis is present, and in many such instances the result of the treatment is not only a persistence but an enlargement of the cavity. There is thus pre- cipitated a situation fraught with the danger of rupture of the cavity, particularly if it lies near the surface of the lung. In order to meet this situation and to render the pneumothorax in such cases suc- cessful, ancillary measures have been tried. The first was the method devised by Brooks (15) for converting the partial into complete bronchial occlusion by means of an in- flatable ‘‘ balloon.”” The balloon was inserted into the lobar bronchus, distended with iodide solution, and the air within the lobe evacuated by suction. The lobe became atelectatic and in favourable examples the cavity closed. This was successful in lower lobe lesions, but for technical reasons has proved difficult to apply to upper lobe cavities. It is advisable to divide all adhesions attaching the affected lobe to the chest wall before this method is used. Secondly, Myersburg et al. (16) have treated three examples of this kind by bronchoscopic suction and have reported benefit which was progressive and apparently lasting. This work requires further confirmation. It must be admitted, however, that in the majority of such cases there is no alternative but to abandon the pneumothorax without delay and contemplate other methods of treatment. The choice of a suitable alternative line of treatment is not easy. The extra- pleural pneumothorax is no less dangerous than the ordinary intrapleural pneumothorax, while experience of thoracoplasty suggests that the operation often serves only to deform the shape of the cavity without effectively closing it. It was largely for the treatment of the distension cavity which was refractory, or was likely to prove refractory, to orthodox collapse therapy that trans- pleural drainage was introduced. Closed Suction Drainage of Tuberculous Cavities. Elliot (17) in the United States has drawn attention to the fact that cavity drainage in the treatment of tuberculosis was discussed by John Hastings in this country in a publication dated 1843. Little work on the subject, however, was published until 1938 when a new technique was evolved, and the method submitted to a fresh trial, by Monaldi (18) and his associates in Italy. The first accounts to appear in English journals were those by Cussen (19) and Roche (20). The principal objectives of this line of treatment are, first, to reduce the positive pressure within a tension cavity and maintain it on the negative side thus enabling the collapsed lung tissue, which it is now believed constitutes the opaque rim of many cavities, to reinflate once more. Secondly, to siphon off constantly the secre- tions which collect in the cavity and so assist endobronchial granula- tions, if present, to heal, the walls of the cavity to become clean preparatory to fusion into a scar, and the patient to surmount the tuberculous toxaemia. Thirdly, if closure cannot be achieved unaided the method appreciably reduces the size of the cavity and brings it within the sphere of surgical collapse. Technique.—Before transpleural drainage can be established it is essential to ensure firm fusion of the pleural layers. The pleural space is tested over the chosen site with a pneumothorax needle and if no negative manometric reading is obtained it can be assumed that the pleural space is obliterated and the operation can be performed forth- with. Should a pleural space be found a small quantity of air is run in and the size of the pocket estimated. The pleurae are then artificially fused by exciting a pleuritis with the help of an irritant solution. Sellors (21) advocates two to five minims of a 10 per cent. solution of silver nitrate, posturing the patient so that the fluid which forms lies over the area in question. When the fluid absorbs the pleurae adhere. If a pneumothorax is present pleural symphysis can be achieved over a wide area by “* poudrage”’; one drachm of tale powder with half | per cent. iodine is sprayed over the lung through a thoracoscope and the air subsequently withdrawn as quickly as possible. The space is tested a second time after the pleural reaction is over. The cavity is then localised in relation to the chest wall at the point through which the catheter is to be inserted. For apical cavities this is usually through an upper anterior intercostal space. Localisation can be done by radiography, including tomography, and by fluoroscopy ; if the latter is used the patient should be screened in the position in which he will be lying during the operation. It is unsafe for the surgeon to operate under fluoroscopic control. A special trocar and cannula with a manometric attachment is used (fig. 3). It is inserted under local anaesthetic through the chest wall towards the cavity, a positive or atmospheric pressure reading indicating when the cavity has been reached ; in case of doubt the effect upon the reading of withdrawing a small quantity of air can be observed. Once the cavity is reached a thin barium-loaded catheter is passed through the cannula, and sufficient length of the catheter is inserted to coil up in the cavity. The cannula is removed and an air-tight’ dressing applied around the tube. The patient may by X-rayed or screened immediately after the operation. The catheter is attached to a motor suction apparatus (fig. 4) with an undine or other convenient glass receptacle interpolated between the patient and the motor to collect the discharge and allow it to be inspected. Continuous suction is begun about twenty-four hours’after operation, at first gently (1-2 cm. Hg) and gradually more forcefully (3-5 cm. Hg). Fresh bleeding is an indication to reduce the pressure of suction or temporarily to stop it. For more complete details the reader is referred to the publications of Sellors (21) and Maxwell and - Kohnstamm (22). The amount of discharge is often considerable at first, but in satisfactory cases it steadily decreases in amount and becomes thinner.and more serous in consistency. Several workers have con- firmed the fact that for the first few days the discharge contains T.B. but is sterile for secondary pyogenic organisms ; after that time secondary organisms appear and T.B. may vanish. As the cavity gets smaller and the discharge lessens the catheter ean be withdrawn by stages; serial X-ray photographs supply guidance as to the speed with which this can be done. Subse- quently, if the procedure has been successful, the cavity becomes represented by a narrow track surrounding the nose of the catheter, and if this is so the catheter may be completely removed. Additional guidance as to how long drainage should be maintained is furnished by what has been termed “‘ cavernography ” or ‘“‘ ascend- ing bronchography ” which consists of running radio-opaque oil into the cavity through the catheter. The oil outlines the cavity radiologically and also enters any bronchi which open into it. This procedure is not done without some risk of bronchogenic spread, and Maxwell urges its postponement until the discharge is T.B. negative. It is believed that the prospect of attaining complete closure of the cavity is to some extent inversely related to the number of bronchi opening into it. Maxwell, for example, found that of three cavities with only one draining bronchus two closed within three months; whereas, of four cavities with four or more draining bronchi closure could not be effected at all in three, and in the fourth it took nine months. It has been suggested that cavities with four or more draining bronchi imply more tissue destruction than distension and are thus unlikely to respond permanently to drainage. A gradual reduction in the number of draining bronchi which remain patent, therefore, is a good sign; not until caverno- graphy fails to outline any bronchi at all is it safe to remove the catheter completely, and not always then. Complications of the method include haemorrhage into the cavity, which may necessitate termination of treatment; gas-embolism, which may rarely prove fatal; pyopneumothorax, if the pleural space has not been firmly obliterated ; and the establishment of a persistent chest-wall sinus with a bronchocutaneous fistula. As experience with this method of treatment widened it became clear that the original expectations reposed in it were not fulfilled, and the last two or three years have been marked by a decline in its popularity. After an initial period of improvement many examples showed little further decrease in the amount of discharge or reduc- tion in the size of the cavity, and in only a small proportion was permanent closure of the cavity effected. For most practical pur- poses cavity drainage is now viewed either as a method of treating cavities which a thoracoplasty has failed to close, or as a procedure to be adopted for certain apical tension cavities as a preliminary to thoracoplasty : when so used it is advisable, as Sellors (23) recom- mends, to perform the anterior stage before drainage in order to leave the track of the catheter undisturbed at the time of the main mobilisation. In the management of the stubborn cavity, particularly if it involves the lower lobe and the remainder of the lungs is clear, it is apparent that the thoracic surgeon is turning more and more away from closed drainage and veering with increasing success towards the more radical procedure of lung excision. It is possible that an altogether fresh chapter in the surgical treatment of pulmonary tuberculosis is opening. Lung Excision In the past there has always been a manifest reluctance to remove a portion of tuberculous lung, however tempting the clinical and radiological features of the case may have been, partly on the grounds that tuberculosis is essentially a systemic disease and that it was therefore fundamentally illogical to perform so definitive yet "906 abnd aonf 0,7 | Cray gy Suosdwoy yy *9 wud, “yg fo fisaj,4noo ig) limited a measure, and partly because in the few cases in which lobectomy was inadvertently performed as the result of an error in diagnosis the results were in fact often disastrous. Within the last few years, chiefly in the United States, there has been a movement towards exploiting the possibility of lung excision for tuberculosis in certain very carefully selected types of disease. Thus, in 1940, Dolley and Jones (24) amplifying the preliminary case reports published by Jones in 1938, submitted an opening paper on the subject to the American Association for Thoracic Surgery and the method of treatment was discussed at length. The results for both lobectomy and pneumonectomy were not good. The chief danger of operation was an aspiration spread of disease to healthy parts of the lungs. Dolley and Jones advocated the performance of a thoracoplasty as a preliminary to resection for technical reasons, and in order to reduce the danger of spread. Moreover, it was not infrequently followed by an improvement in the patient’s general condition which materially reduced the risk of the later operation. Four years later, at another meeting of the same Association, the question was reconsidered in the light of accumulated experience. The results were decidedly better. Thus, Overholt and Wilson (25) were able to report sixty-three operations upon sixty-one patients, thirty-five of which were pneumonectomies, with an operative mor- tality of 5-5 per cent. in reasonable risks and 33-3 per cent. in what were classed as desperate cases in whom collapse therapy had failed. The improvements in the mortality rate and the lowered incidence of complications which this meeting disclosed were largely attributed to the modern operative technique of “‘ dissection ” lobectomy in which the tourniquet was discarded and each individual constituent of the hilum was separately identified and ligatured: In a recent publication Overholt and his colleagues (26) have brought their operative results up to date. The study embraces 88 patients operated upon and observed for 2 to 12 years. A final statistical analysis is not yet possible. The authors performed lobectomy on 33 patients of whom 43 per cent. are clinically well with negative sputum and 24 per cent. are dead ; pneumonectomy was carried out on 58 patients of whom 48 per cent. are now clinically well and 41 per cent. are dead. Exacerbation of disease in the same lung was the most common post-operative and late complication of lobectomy, and it was this which made the results inferior to those of pneumonectomy. It is thought to be partly due to overdistension of the remaining pulmonary tissue, and for this reason a routine thoracoplasty is advised in all cases of upper lobectomy, and should precede resection. During the last two years of the period under review Overholt has modified his technique and now operates under local anaesthesia with the patient in the face-down position. The results for both types of operation have considerably improved in consequence : complications have been fewer in number and the mortality rate lower. Indications. As already stated, several of the earlier examples of lung excision were carried out on a false pre-operative diagnosis. Bronchiectasis and lung cancer are the two conditions which figure most prominently in the recorded accounts and it was only detailed microscopic study of the specimen afterwards which disclosed the true nature of the illness. A tabulated list of indications cannot, at the time of writing, rest upon any sure foundation. The one given below is largely based upon prevailing American opinion which has not yet emerged from the tentative phase. 1. The operation has been successfully performed on patients in whom a thoracoplasty has failed to close a cavity, to convert sputum from positive to negative, to relieve the symptoms of bronchial stenosis, or to abolish other symptoms such as recurrent haemoptysis. In thoracoplasty failures radical surgery is the only procedure left to the surgeon, with the possible exception of cavity drainage. 2. In tuberculosis of limited extent associated with a heavy secondary suppurative infection. 3. For bronchial stenosis with stricture, particularly those’ ex- amples of the condition which have resisted attempts at bronchoscopic dilatation and which are unsuitable for thoraco- plasty. Other forms of tuberculous involvement of the bronchi, such as ulceration, have also at times been included as indications, but care should be taken to make sure that the process has not extended upwards beyond the bifurcation of the trachea, but remains confined to the affected side. Over- holt (26) has shown how common bronchial tuberculosis is in the type of case that is regarded as suitable for resection, and he quotes the work of Meissner (27) who showed that 50 per cent. of the main bronchi and 86 per cent. of the segmental bronchi in pneumonectomy specimens exhibited evidence of tuberculosis. Many such cases are unsuitable for thoraco- plasty, but the antipathy towards this operation in bronchial tuberculosis, at one time strong, seems now to be lessening (Alexander (28) ). 4. For limited pulmonary atelectasis and fibrosis, whether associated with bronchial stricture or not, in which the lung is so shrunken as to seem incapable of, further contraction following thoracoplasty. Even for a lesion of this type Alexander has declared himself impressed with the results of thoracoplasty. A similar lesion situated in the lower lobe is likely to prove even more refractory to thoracoplasty than one at the apex and for this reason provides a more powerful indication for radical surgery. 5. Persistent “tension ”’ cavities, especially those in the lower lobe. These are notoriously difficult to close by collapse therapy even if preceded by transpleural drainage, and if the disease appears confined to a lobe lobectomy offers a possible method of treatment. British surgeons favour lung excision for ‘*‘ dorsal ’”’ lobe distension cavities, even if the fissure is _ fused and a pneumonectomy required. 6. For the isolated collection of tuberculous granulation tissue which is referred to as the tuberculoma. To prove the diag- nosis in this type of disease is frequently difficult and the tuberculoma is often confused with intrathoracic neoplasm. It is obvious that the condition of the opposite lung must profoundly affect the decision ; likewise, the greater the degree of activity in the affected lung the greater becomes the danger of complications. Complications. Quite apart from the tuberculous nature of the underlying disease there are numerous hazards attached to lobec- tomy and pneumonectomy, such as post-operative pneumonia and suppuration in the dead space, all of which may be encountered regardless of the nature of the condition for which operation is performed. The fact that operation is undertaken for tuberculosis leads to the addition of certain specific complications which do not arise in other diseases. Some of the earlier examples so treated died of a generalised spread of tuberculosis with signs of meningitis, and this outcome is still to be feared. A more limited spread of disease, however, to healthy portions of the same or opposite lung occurs more commonly and has been one of the most serious complications. It has been to some extent lessened by technical modifications and by the routine of aspiration of secretions from the respiratory tract during operation. Bronchopleural fistula with a tuberculous empyema is still a real danger and most unsatisfactory to treat. Recent reports suggest that the incidence of this com- plication has been reduced by improved methods of closing the bronchial stump by means of a pleural flap. Operation for the deliberate removal of the affected portion of lung in tuberculosis has not passed unchallenged by staunch ad- vocates of thoracoplasty. This is not surprising for the two pro- cedures are totally different in principle, and the mortality rate and incidence of complications are higher in resection than in thoraco- plasty. Moreover, Chamberlain (29) has made some interesting observations upon respiratory efficiency after thoracoplasty and upper lobectomy based upon bronchospirometric measurements. He has shown that over-distension of the remaining lung which inevitably follows a successful upper lobectomy leads to a pro- eressive reduction in respiratory function, whereas after thoraco- plasty there was no change in respiratory function in about half the cases and an actual improvement in about one-quarter of them. Furthermore, over-distension leads to a lowering of resistance of the lung to fresh disease or to reactivation. The position of lung resection among other active measures commonly employed in the treatment of tuberculosis remains a subject for debate and it would be premature at the present time to attempt to assess its final sphere. It can be asserted, however, with a fair measure of confidence that it will never be applicable to more than a small minority of those patients for whom collapse therapy is now recommended. References (1) Davies, H. M. (1933) Pulmonary Tuberculosis. London. (2) Houst, J., Semsp, C. and FrimMANN-DauL, J. (1935) Acta chir. scand. 76, Supp. 37. (3) Tuomas, C. P. and CLELAND, W. P. (1942) Brit. J. Tuberc. 36, 109. (4) Roperts, J. E. H. (1944) Brit. J. Tuberc. 38, 105. (5) THompson, B. C. (19438) Brit. J. Tuberc. 37, 87. (6) BRAVERMAN, M. M. (1942) Amer. Rev. Tuberc. 46, 27. (7) Jupp, A. R. (1944) J. thorac. Surg. 13, 249. (8) Hear, F. R. G. (1924) Lancet, 2, 698. (9) Myerson, M. C, (1941) J. Amer. med. Ass. 116, 1611. (10) Perrce, C. B. and CurtTzwiteEr, F. C. (1940) Amer. J. Roenigenol. 42, 158. (11) OrnmMERoD, F. C. (1939) Brit. J. Tuberc. 33, 29. (12) ALEXANDER, J. (1941) Amer. Rev. Tuberc. 44, 765. (13) Tuomas, C. P. (1942) Brit. J. Tuberc. 36, 4. (14) Coryuiuos, P. N. and ORNSTEIN, G. G. (1938-39) J. thorac. Surg. 8, 10. (15) Brooks, W. D. W. (1988) Brit. J. Tuberc. 32, 14. (16) Myverspurec, H., GruBER, H. and Lupo, C. W. (1942) Amer. Rev. Tuberc. 45, 368. (17) Exuiot, J. H. (1942) Amer. Rev. Tuberc. 46, 546. (18) Monatpl1, V. (1939) Lotta c. Tuberc. 10, 703. (19) CussEN, J. V. (1941) Brit. med. J. 1, 115. (20) Rocug, H. (1941) Tubercle, 22, 1. (21) Seviors, T. H. (1942) Tubercle, 23, 239. (22) Maxwett, R. J. C. and Kounstamy, M. L. (1943) Brit. J. Tuberc. 37, 24. (23) SEvtors, T. H. Personal Communication. (24) Do.uEy, F. S. and Jones, J. C. (1940-41) J. thorac. Surg. 10, 102. (25) OvERHOLT, R. H. and Wiuson, N. I. (1945) J. thorac. Surg. 14, 55. (26) —— SzZYPuULSKI, J. T. and SANGER, L. (1947) Amer. Rev. Tuberc. 55, 198. (27) MEISSNER, W. A. (1945) Dis. Chest, 11, 18. (28) ALEXANDER, J. (1945) J. thorac. Surg. 14, 47. (29) CHAMBERLAIN, J. M. (1945) J. thorac. Surg. 14, 32. REHABILITATION THE term rehabilitation has been employed so frequently by different authorities during recent years that its meaning tends to change according to the context in which it is used.. The White Paper on a National Health Service described rehabilitation as “ a process or method of completely restoring the whole of the patient’s previous capacities—or doing so as completely as possible—i.e. including the whole of muscle tone to full function of general health and strength, as well as cure of what is wrong.”’ In connection with tuberculosis the term means more than this, and may be defined as the process by which a patient is enabled to return to the nearest approach to normal life and work which his disability willallow. This implies that it is a method which aims at more than providing the patient with suitable employment after the maximum restoration to health ; it embraces assistance to the family, good living condi- | tions, adequate wages and direction towards cultured and creative leisure. To carry out such a programme successfully it is necessary to have a full and intimate knowledge of the individual’s social and domestic environment. In addition to clinical details it is important to know the person’s reaction to work, his habits, temperament and general character. In fact it is not possible to know too much about the individual to plan a scheme for successful rehabilitation. More- over, it is essential that the process is considered as part of the treatment of the disability and, although it assumes increasing importance as the recovery of the patient is realised, the gradual unfolding of the rehabilitation plan for a case should proceed concurrently with each stage of treatment. The peculiar uncertainties characteristic of tuberculosis make the rehabilitation of its victims an intricate problem. The reduced capacity for work, the possibility of relapse and the fear of infection make the employment of the tuberculous an unattractive proposi- tion to industrial concerns. It is therefore necessary to make special provision for such patients to overcome these difficulties. Certain methods can be followed to accomplish this, The one established by the great pioneer of rehabilitation, the late Sir Pendrill Varrier- Jones, and exemplified in Papworth Village Settlement, and the British Legion Village, Preston Hall; the other less developed method of special workshops for the patient living at home as practised in Russia, the Altro Workshops in New York and the Spero Industries in London. The first of these methods will be described as residential rehabilitation and the second as non- residential rehabilitation. Residential Rehabilitation This form is the most beneficial one to all patients who are able to accept the conditions. It aims at providing suitable remunera- tive employment whilst living under the best possible environ- ment with constant medical supervision. To accomplish this it is necessary to have an industrial unit associated with a sanatorium that provides facilities for all forms of modern treat- ment. Wards, chalets, hostels and cottages must be erected along with centres for entertainment and cultural activities. The financial outlay to cover these amenities is considerable, but is fully balanced by the restoration to full working capacity of the many patients who take advantage of the scheme. ‘There are at present six village settlements in England, but so far only two—the Sherwood Colony, under the Nottinghamshire County Council, and Wrenbury Hall Colony, under the Cheshire County Council—have been started by Local Authorities. The other colonies are all controlled by voluntary organisations and are at Papworth, Preston Hall near Maidstone, Barrowmore Hall near Chester, and Woolley Colony in Northumberland. At all these colonies it is easy to find a considerable number of settlers with extensive pulmonary lesions, who would otherwise be on public assistance relief, earning good wages and doing good pro- ductive work. This desirable result is not attained immediately the patient enters the colony. The general procedure is for the man or woman to be admitted to the sanatorium section, where assess- ment is made of the general clinical condition and prognosis of the case. When it is decided that the patient may take up some form of occupational therapy he is given an opportunity to choose the type of work he wishes to do in one of the industries. Here his work is graduated and he receives an “‘ encouragement grant ” up to 10s. | per week. If his progress is satisfactory after a period varying from six to twenty-four months, he is given the opportunity of becoming a colonist, when he will receive wages at trade union rates and quali- fies for residence in a hostel or a house if one is available. If he is married and accommodation can be found, his wife and family may reside in the village and normal domestic life begins under ideal surroundings with every consideration for the welfare of both the patient and his family. Broadly speaking, all tuberculosis rehabilitation settlements are organised on these lines. At certain centres there may be minor differences of procedure. Some visualise that their main function is to return the colonist eventually to obtain employment in the open labour market and to home conditions as an ordinary citizen, whilst in other village settlements attempt is made to persuade as many patients as possible to remain permanently in the village. There is much to be said for both principles, and in most individual eases the ultimate disposal of the colonist depends on clinical, psychological and aetiological factors, but it is important that per- manent settlement shall be mainly reserved for such individuals as are unable to endure the stress and strain of normal industrial life. These people should always have priority of residence over those who are able to compete with their fellow workers without detriment to themselves or others. Special Workshops Not all patients are able to accommodate themselves happily to the routine of village settlement life, although in many cases the objections are more imaginary than real. These patients often run considerable risk if they return to normal industry immediately on discharge from the sanatorium. This has been stressed in the Report of the Medical Research Council Tuberculosis Committee (1) in which it is suggested that— ‘* An intermediate phase is needed during which a _ tuberculous person whose disease has become quiescent can do either part-time or modified work, preferably in normal industry, before resuming full- time employment under ordinary industrial conditions.” In this country little has been done to meet the need of providing modified work for the tuberculous person living at home. Organi- sations like the Spero Industries in London and the Factory in the Fields at Leeds, which employ tuberculous persons in special factories, have had a precarious existence owing to the lack of financial support and the low wages which they offered their em- ployees compared unfavourably with those obtainable in normal industry, particularly in war-time. This handicap has been par- tially removed by the allowances a tuberculous worker can obtain under the Ministry of Health Memorandum 266/T, and through the Ministry of Labour under the Employment of Disabled Persons Act (1944). The City of Hull has a good scheme which provides work for ex-sanatorium patients in the form of car park attendants, but this can only absorb a limited number of persons and, moreover, it does not lead to a permanent form of occupation. In Russia, what is known as the “ prophylactic workshop ”’ has been established in a number of large towns. This provides suitable work for the tuberculous and is under the direction of the Peoples Commissariat for Health and the advice of the tuberculosis officer who visits assisted by the dispensary nurse (2). These work- shops have been combined with night sanatoria where workers can be provided with food and lodgings under suitable conditions. Such arrangements are particularly useful where there is danger of contact infection at home and living conditions are unsatisfactory. Con- siderable importance is attached to the provision of extra nourish- ment for the tuberculous employees in all Russian rehabilitation schemes. The literature on the subject shows that much progress had been made prior to the war and considerable success had been obtained in the successful employment of open positive cases and others undergoing artificial pneumothorax treatment. In our own country the idea of rehabilitating disabled persons in special workshops whilst they live at home has been given official recognition by the formation of the Disabled Persons Employment Corporation which is a non-profit making company designed to establish workshops throughout the country for the employment of disabled persons. Already a number of such factories have been opened for the non-tuberculous disabled, and plans are completed for similar organisations for the tuberculous. The principle is sound and these factories will meet a long-felt need as the majority of tuberculous persons wish to live at home and obtain suitable work nearby. ‘There are many difficulties which have to be overcome, and the experience gained during the twenty years of working such a special workshop at the Spero Factory in Tower Bridge Road, London, will be of considerable value. Here patients are employed at woodwork and receive from 70s. to 100s. per week. During the initial period they may be trained under the Ministry of Labour Interim Scheme for the training of the disabled, but eventually some are able to earn a satisfactory wage from their own productive capacity. Further developments of the scheme include the estab- lishment of a complete industrial clinic with a canteen and a welfare section—all under medical supervision. Employment on the Staff of Sanatoria Another method of rehabilitation which has not been exploited to its fullest extent is the absorption of ex-patients on the staffs of tuberculosis institutions. There are very few posts of this category which cannot be filled in this manner, provided the authori- ties concerned are prepared to increase the total staff employed by approximately one-third over the normal complement to allow for the decreased working capacity and the absenteeism due to tem- porary relapses of the tuberculous worker. Certain administrative difficulties have to be overcome with regard to messing and living accommodation, but the advantages to the patients who can fill such situations and the encouragement it gives to those still under treatment outweigh the difficulties and the risks involved. Employment of the Tuberculous in Normal Industry Many patients on discharge from sanatorium are able to return to normal industry without difficulty if their lesions are healed, but those who are infectious, or whose condition is unstable, should not be advised to attempt such a course unless special conditions exist which overcome the dangers both to themselves and their fellow workers. It is possible for those patients who have completed a course of rehabilitation at an industrial settlement and have proved themselves capable of working under industrial conditions at normal working hours for a number of years without relapse to return to normal industry without undue risk, but the patient coming directly out of a sanatorium, unless there is evidence that the lesion is healed, remains in a precarious state during the first two or three years following discharge if he finds employment in normal industry. Certain large industrial concerns have attempted to open special workshops for tuberculous persons, but the slower rate of work, the necessary medical supervision, and the special canteen facilities have made it difficult to achieve more than partial success. 'There- fore employers are reluctant to engage tuberculous persons, par- ticularly as such a move is often resented by other employees. In the majority of cases it is much more satisfactory to provide separate workshops where special provisions can overcome these difficulties to the satisfaction of all concerned. Assessment of Working Capacity It will be seen that with regard to rehabilitation, tuberculous persons fall mainly into three groups :— (a) Those able to re-enter normal industry ; _.(b) Those only able to work under sheltered conditions either in an industrial settlement or a special workshop ; ; (c) Those incapable of being remuneratively employed in any form of industrial concern. To determine into which category a patient is to be placed, it is necessary to have some method of assessing his capacity for work under conditions simulating normal life. In fact, successful rehabilitation measures depend very largely on gauging the limits of energy output between which a person may safely be employed. Up to the present very little work has been done on tuberculous individuals in this direction. Brieger (3) at Papworth has devised methods whereby an efficiency index is calculated, based on observa- tions on the worker’s general condition, vital capacity, basal metabolism and reaction to known amount of work as shown by pulse rate, temperature range and respiration rate records. It must be admitted that apart from this work and some valuable observa- tions by Edwards (4) on non-tuberculous chest cases, the estima- tion of the limits of a patient’s energy output and working capacity are largely based on the records of pulse, temperature, weight, sedimentation rates and radiographs taken under conditions which have little or no relation to those under which the patient will be living and working on discharge from the sanatorium, and are there- fore inadequate and unreliable for the purpose. Nevertheless, it is particularly important in tuberculosis to attempt to devise methods which will inform us of the patient’s working efficiency under industrial conditions owing to the instability of the quiescent lesion and the long time it takes to establish com- plete arrest of the disease. Rehabilitation as Part of Treatment In order to obtain a correct view of the therapeutic value of exercise and work in the treatment of tuberculosis, it is necessary to view the whole period from diagnosis to reinstatement into industrial work as one continuous process in which each form of exercise, occupation or employment has its special contribution to the final result. In the early stages rest and walking exercises may be prescribed to which are added forms of diversional therapy in the nature of handicrafts, such as making handbags, small fancy goods, needle- work, knitting and small toy construction. Such work is done individually by each patient, and there should be no suggestion of placing any economic value on these productions. The work is prescribed purely to divert the mind away from the disability. Recently the value of artistic pursuits has been tried with success at some sanatoria, and McDougall (5) feels that more could be done for the patient by using diversional powers of music, sketching and painting. At King Edward VII Sanatorium, Midhurst, Todd has developed art therapy under the guidance of Adrian Hill (6) with remarkable success, and finds that it is a valuable factor in aiding the recovery of his patients, both as a means of diverting the mind from the disability and as a step towards a possible avenue of suitable employment after discharge from treatment. The next stage in the rehabilitation of the majority of patients requires equipment to facilitate the employment of patients on remunerative productive work and, although this is still of little economic value, an encouragement grant of up to 10s. per week should be given to stimulate the patient’s interest and confidence. At this period he can be gradually acclimatised to industrial condi- tions in workshops planned as near as possible on the lines of normal industry, provided that the fundamental principle laid down by Varrier-Jones that machines do the heavy work is adhered to and the goods produced are saleable and of a high quality. Although this may mean moderate adoption of mass production methods, the work need not be monotonous provided the managers show some ingenuity in the distribution of jobs amongst teams of workers. It is hardly necessary to emphasize the importance of a good standard of industrial hygiene in the workshop, which should be equipped with modern amenities. As the disease becomes arrested and a certain standard of proficiency has been obtained, the worker can be offered a satisfactory wage, preferably at trade union rates for the particular occupation. Slowly, by easy stages, the previously unemployable tuberculous individual is enabled to earn a living wage and at the same time receive the necessary treatment under full medical supervision. Naturally, there are many kinds of industrial work which cannot be included in this scheme for the rehabilitation of the tuberculous. Woodwork, printing, bookbinding, leatherwork, brush-making, assembling, and the manufacture of hard toys and fancy goods have been found most satisfactory. Government departments and municipal authorities are in constant need of goods which can easily be produced by workshops staffed by ex-sanatorium patients, and even in most sanatoria an industrial side could be developed for the production of useful saleable goods. Provided the articles manufactured are of good quality, it is not an overstatement that the needs of the national and local services in office equipment could easily find employment for all employable tuberculous persons in the country and still leave a considerable margin of orders to be placed to normal industry. It is important in all rehabilitation work connected with tuber- culosis to have a clear conception of the various types of occupations given to patients and their relative places in the process of re- habilitation. The distinction between diversional, occupational and vocational work must be clearly defined. Dzversional therapy, consisting mainly of light handicraft work, is usually given to those patients who are unfit for employment either temporarily in the early stages of treatment, or permanently in the case of the severely disabled. It has a very real value from a psychological standpoint, but has no economic value and does not lead to re- munerative employment. It may be defined as occupation or entertainment provided by or for patients to divert their attention from their disabilities. It need not have any other therapeutic value, and the economic or industrial importance of the work need be of no value. Occupational therapy should be connected with an industrial concern which enables the patient to become associated with condi- tions of work by which his efficiency and productive capacity may be tested with a view to his eventual return to normal or sheltered industry. It should be carried out in a disciplined and realistic environment closely simulating factory conditions, so that, in the final stages, the patient passes from the graduation stages to full productive employment. It is defined as the employment of patients at work which assists them to overcome their particular disability. The work may be productive, and if so the patients should be compensated for the value of the work done, but in all cases the work should follow a definite programme and _ ulti- mately lead to the return of the patient to suitable remunerative employment. Vocational training, although it can be closely associated with occupational therapy, is, as its name indicates, directly concerned with teaching and training the patient for a new trade. It is best carried out after the period of occupational therapy has been completed, when the medical condition of the trainee will not cause anxiety and the need for graduated employment has largely dis- appeared. It is often necessary for certain cases with minimal lesions which may have been discovered by mass radiography and have thereby been pronounced to be physically unsuitable for their present occupation. The training of these individuals to take up suitable work within the limits of their strength creates a need for vocational training centres. Similarly, in the case of young adults who have ‘“‘ dead-end jobs ”’ or have just left school, a period of vocational training is usually needed for complete rehabilita-— tion. Vocational training is a course of tuition in a suitable occupation by which the patient will be able to earn a living. It need have no therapeutic value and is for all practical purposes a term of apprenticeship in employment that will be within the trainee’s eapacity for work. Much care has to be exercised in choosing a new career for a tuberculous person, and it is comforting that the old slogan that a tuberculous person must have outdoor occupation has been finally abolished by the disabled persons employment autho- rities. It is now officially recognised that, generally speaking, tuber- culous patients should have sedentary indoor work as the activity and exposure of an outdoor job is harmful. Indoor occupation should be arranged so that active cases with cough and sputum containing tubercle bacilli only work in proximity to non-tuberculous workmates where the strictest personal hygiene is observed and all precautions are taken to prevent the spread of infection. The first essential is that the patient should be able to limit his exertions to his physical and clinical condition. Recent work on the psychological aspect of tuberculosis rehabili- tation by Witkower has shown that tuberculous persons have a fear of being limited to light repetitive work of a monotonous character. It is not always possible to avoid this type of work, particularly in the middle aged and elderly patients, and in this respect it must be remembered that the incidence in these age groups is rising and therefore the problem is likely to become more serious in the future. It is therefore desirable in all cases undergoing rehabilita- tion to take note of the previous employment, character and habits of the patient and to retain him in work closely allied to his original occupation. Sometimes we are able to allow the patient to return to his previous trade which, of course, should be done wherever possible. The re-training of patients requires considerable patience and money, and the full co-operation of the patient should be assured before the course begins, for often a considerable amount of elementary tuition is required before productive work can be arranged, and the physical disability of the patient makes the course considerably longer than that required to produce the same result in a non-tuberculous person. If a satisfactory scheme for training tuberculous patients can be established it would give them an opportunity to escape from monotonous and “ dead-end ” employ- ment and a chance to compete for work that leads to promotion and a good future. Financial assistance can be obtained for such a scheme. The Ministry of Labour and National Serivce (7) provides grants for the re-settlement of disabled men and women which are payable under three headings :— (a) Training Grant—a weekly payment in respect of a period of instruction of disabled persons by an undertaking with the object of subsequent employment by that undertaking. (b) Deficiency Grant—an annual grant towards any loss incurred by an undertaking employing disabled persons under the o-Sehemie. . (c) Capital Advance—a payment—to be made in exceptional circumstances—to enable a new undertaking to start an employment scheme for disabled persons or to assist an existing undertaking to develop its facilities. The machinery to rehabilitate fully a tuberculous person has been constructed ; it remains for us to put it in motion for the benefit of the patients, and to time the operation of each section so as to obtain the greatest benefit when the patient can take the fullest advantage of the many privileges that have been established to lead him back to normal life. The Magnitude of the Problem In the Fifth Report of the Joint Tuberculosis Council, 1942, on the Rehabilitation and Care of the Tuberculous, it is estimated that there are approximately 30,000 tuberculous males and females for whom part-time or full-time sheltered employment is desirable in England. This figure is arrived at by taking the estimate given in previous reports of the J.T.C. that 15 per cent. of all cases of pulmonary tuberculosis are to be regarded as purely medical problems and 35 per cent. are both economic and medical responsibilities, 50 per cent. being able to return to their original occupation, or otherwise presenting no rehabilitation problem as regards employment. There were 122,621 respiratory adult cases on the dispensary registers on December 31, 1938; 35 per cent. of this figure is 42,917. Of this figure approximately 23,000 are males and the remainder females. A certain number of the odd 40,000 will be married females and elderly people too old for rehabilitation, so putting this figure at a very generous estimate at 10,000 there are still 30,000 tuberculous cases for whom arrangements must be made. A recent attempt to determine the working capacity of persons on a tuberculosis register has been made by England (8). He surveyed all persons on the Oxfordshire tuberculosis register in March, 1946, and found that a high proportion were employed and a low percentage were unemployed and, although the T.B. plus group formed the major proportion of the unemployed, the T.B. minus group accounted for one-third of the total. Taking a total of 619 tuberculous persons, 467 pulmonary and 152 non-pulmonary (828 males and 291 females) and excluding 88 children, 112 undergoing treatment, and 133 housewives, there were 58 persons (45 men and 13 women) unemployed (52 pulmonary and 6 non- pulmonary). Of these 24 were incapable of work, leaving 34 persons “truly unemployed.’ Excluding the above groups this means that 34 persons out of 262 “ truly employable ”’ persons (at least 13 per cent) require rehabilitation. These figures, which include pulmonary and non-pulmonary cases, although small and recorded during an abnormal post-war year, show that the magnitude of the problem is considerable even in years when the possibility of employment for any person was comparatively easy. To provide employment for the large number needing rehabilita- tion requires more than a few industrial settlements scattered here and there throughout the country. It requires a considerable organisation, and the recommendation of the Joint Tuberculosis Council is probably the only satisfactory line of approach. One cannot do better than quote it in full : ** The establishment of a National Rehabilitation Board with Regional Areas throughout the country is suggested as a solution to the problem since this would enable part or whole-time employment to be given to large groups of necessitous cases. The National Rehabilitation Board would act as contractor general to local authorities and Government (departments). . . . The village settlement should be the centre from which regional activities should emanate and this will necessitate the setting up of a sufficient number of such institutions to enable the work of a National Rehabilitation Board to be carried out successfully.” The National Scheme The organisation of a National Rehabilitation Scheme requires the combined administration of the Ministries of Health and Labour. The patient, in the first instance, is wholly a medical problem, but as he becomes physically more stable employment becomes more and more important, so that when completely rehabilitated the medical problem is almost, if not completely, replaced by an economic and industrial one. Fortunately, since the war, considerable progress has been made in the direction of official recognition by both Ministries of the need for a rehabilitation service. The introduction of financial allow- ances for the tuberculous under Memorandum 266/T and the inclusion of tuberculosis as a cause of severe disablement in the Employment of Disabled Persons Act (1944) open up a new era in tuberculosis work. It must be remembered, however, that em- ployment is not the beginning and end of the problem of rehabili- tation of the tuberculous. Along with the privileges which have been granted, it is essential that every possible step is taken to eliminate bad social and domiciliary conditions and to introduce educational methods which will remove the present prejudice against the employment of the tuberculous. The Employment of Disabled Persons Act gives wide powers to the Minister of Labour and National Service, enabling him to form a National Advisory Council and a District Advisory Committee. Furthermore, it gives him power, with the approval of the Treasury, to make arrangements for the provision of a non-profit-bearing company or companies, the objects of which may include all such subjects as appear to the Minister to be requisite for enabling persons registered as handicapped by disablement to obtain employment, or to undertake such work under special conditions, and for the training of such persons for the employment or work in question. Adopting the suggestion previously referred to that existing and new village settlements should form the nuclei of regional schemes, it is not difficult to envisage a plan of special factories and industrial settle- ments forming a series of centres to which the employable tuber- culous may be directed in each area, the authorities of which would negotiate with the National Health Service at regional level. Developments may take place along such lines but, in any case, as the administrative side proceeds, it is necessary that further research be carried out on the clinical side to establish improved methods for the measurement of the efficiency and working capacity of the patients and to educate them to appreciate that it is to their advantage to participate to the fullest possible extent in the facilities provided. These two tasks require immediate and continued attention in order to gain the confidence of both employer and employee, a factor which is essential in successful rehabilitation. General Financial Considerations The most difficult part of all rehabilitation schemes for the tuber- culous is that dealing with finance. This aspect has prevented the development of rehabilitation schemes more than any other, and it has been unfortunate that local authorities have often been dis- couraged in the past from developing industrial village settlements or special workshops for the tuberculous because the capital ex- penditure involved gave no immediate return on the financial side and the venture could not be immediately self-supporting. The rehabilitation of the tuberculous is a public health problem, and the benefits of any scheme should not be measured entirely in terms of finance. Tibbits (9), in supporting this, argues that “‘ The financial resources of large local authorities (County Councils and County Borough Councils) are enormous both as to capital and revenue. Is it wise to encourage the idea that a village settlement must be, per se, a financial success, or at any rate, not a financial charge ? Why should the public be led to expect large potential health profits at no cost? Why should not the rates be burdened with some cost for this ameliorating service just as much as with the cost of ensuring safe motherhood, healthier children and sound sanitary circumstances ? ”’ Generally speaking, expenditure may be divided into two cate- gories.. That needed to maintain the means and facilities for rehabilitation. Under this heading are included such items as workshops, personnel, machinery and the costs involved in running -an industrial concern. In the second category falls the financial assistance needed by the individual, and his family, undergoing rehabilitation. An entirely new light has been thrown on these two problems by the passing of the Disabled Persons Employment Act (1944) and the introduction of financial allowances for certain classes of the tuberculous under the Ministry of Health Memorandum 266/T. The former both assists those who establish organisations for the training of the disabled, and also provides financial assistance for the trainee. The latter is more personal and assists the patient and his family towards recovery, during both treatment and rehabilitation. In providing help for the patient and the trainee, these two measures indirectly assist in the employment of the tuberculous, although it is unfortunate that the chronic case has hitherto been usually ineligible for the grants under 266/T. In all rehabilitation work, and particularly in the case of the tuberculous, there is a con- siderable difference between the wage earned and the wage paid and, although this difference gradually diminishes in a case of successful H. & R. TUBERC, 8 rehabilitation, it is, nevertheless, a dead loss on the industrial con- cern particularly at the beginning of occupational therapy, and must be covered by a scale of allowances. These are now available to many patients and trainees, and the progress of rehabilitation schemes should, therefore, be assured in the future. This does not mean that the 1944 Act and the Memorandum 266/T provide all that is desired. There are many financial difficulties which still remain, but the possiblity of a patient returning to full work by gradual steps is now very real, and the necessity for such a course is Officially recognised. Those patients who do not qualify for the financial allowances under 266/T or who are not included in the Ministry of Labour Interim Scheme have to be supported by other means. If they are under treatment, the cost falls upon the local health authorities, and the care of the family may have to be taken over by the public assistance or social welfare departments. The patients’ income will also depend on payments from National Health Insurance and possibly from the Unemployment Assistance Board. When the National Insurance Act comes into force it may be that Memorandum 266/T will be replaced by the benefits under the Act. If so certain advantages will be gained in that there will be no selection of cases for financial benefit but, on the other hand, there will be a loss to many tuberculous persons in that there are no dis- eretionary grants comparable to those under 266/T. At present there is a delay of three days before National Health Insurance operates and often more than three days before benefit under 266/T is received. This constitutes a serious difficulty immediately a tuberculous person, being rehabilitated, goes sick, in that for a few days there is no income. Recourse has to be made to benevolent funds and to social welfare to cover this preliminary period. Lack of an immediately available grant is one of the great financial diffi- culties of employment of patients in sheltered workshops. Care Committees may help in one way or another, but in spite ot all these valuable contributions towards the income of the patient, he is still liable to find himself and his family in straightened circum- stances during periods when he requires treatment and is unable to work, A rehabilitation centre for tuberculosis runs on principles that are fundamentally opposite to those of normal business. ‘The comparison may be tabulated as follows :— ORDINARY FACTORY Employees are selected on the grounds of efficiency, good health and full-working capacity. Results are measured by the re- turn on the capital invested. Production can be speeded up by faster work and more efficient machinery. The management desires as few changes as possible in the em- ployees. The workers are expected to earn their wages. REHABILITATION CENTRE Rehabilitants are all handicapped by a disability. . When the em- ployee is able to do full and normal work, he is encouraged to seek work in the ordinary factory to make place for a dis- abled person needing help. All types have to be engaged, both inefficient and unskilled workers. Results are judged by the num- ber of persons rehabilitated. Production cannot be greater than the limited capacity and adapt- bility of the workers. The machinery has to fit the dis- ability of the operator. The personnel must continually change to benefit the greatest possible number of disabled persons. The rehabilitant has a production capacity much below normal and yet must be paid an ade- quate wage. In addition to these differences, the rehabilitation factory must provide an efficient welfare service with very careful medical supervision of the workers. With tuberculous employees there is the added complication of infection and also the great danger of recurrence of activity if too much strain is placed on the workers. The industrial environment must be of the highest standard, ensuring good lighting and ventila- tion, absence of dust, correct temperature and humidity, and the provision of comforts that help towards the complete recovery of the disabled person. All these conditions mean considerable expenditure and a subsidy is needed to enable such centres to compete with ordinary business in the open market. Finally, it must be emphasised that the rehabilitation of the tuberculous differs from any general rehabilitation scheme set up for the disabled population as a whole and demands a special organisation to meet the peculiar characteristics of the disability. In a recent treatise by Heaf and McDougall (10) it is clearly demon- strated that the problems of rehabilitating the tuberculous are very specialised and that they form part of the treatment of every person suffering from active tuberculosis. In the rehabilitation of the majority of tuberculous patients the danger of relapse is real and it is this factor, above all others, which necessitates special organisa- tion and close medical supervision at every stage of the rehabilitation programme. References (1) MepicaAL RESEARCH COUNCIL (1942) Spec. Rep. Ser. No. 246. London. (2) ‘* Rehabilitation in U.S.S.R.”’ (1939) Eztract, Bull. Hyg. 1948, 18, 717- 720. (3) Briecer, E. (1938) Papworth Res. Bull. 2, 73. (4) Epwarps, F. R. (1944) Lancet, 1, 81. (5) McDouaat., J. B. (1948) Brit. J. phys. Med. 6, 172. (6) Hix, A. (1947) Studio, 133, 54. (7) Ministry oF LABour (1942) Scheme Grants and Undertakings, Sept. 1942. PL110/1942. (8) ENGLAND, N. (1946) Tubercle, 27, 207. (9) Trpsits, A. C. (1942) Tubercle, 23, 163. (10) Hear, F. R. G. and McDouGat., J. B. (1945) Rehabilitating the Tuber- culous. London. PROGNOSIS To give a reasonably accurate prognosis in pulmonary tuber- eulosis is as important as it is difficult. The ground cannot be covered exhaustively, but certain aspects of the question, particularly those relating to modern work, will be discussed. The problem can be approached in two ways : from the statistical and epidemio- logical angle, and from the point of view of the prognosis of an individual case. By the statistical approach is meant the study of data pertaining to large groups of patients with the object of determining the ex-. pectancy of survival, a method that is generally used either to dis- cover the influence of some particular factor, such as T.B. positive sputum, or else to evaluate the success of a certain form of treat- ment. Thus applied, and within the limits imposed by the particular survey, this approach affords information as to the prognosis of the average case ; it gives less assistance in gauging the eventual outcome of the disease in an individual patient. As an example of this line of enquiry the results of a survey recently undertaken by Thomp- son, (1, 2) can be quoted. Thompson investigated the after-histories of 406 patients with T.B. positive sputum registered at a dispensary in the county of Durham, and observed for up to ten years or more. A positive sputum was chosen as the determining factor for inclusion in the survey on the grounds that diagnostically it was as sound a test as any and more free from error than most others ; moreover, it can be taken as more or less synonymous with cavitatary tuber- culosis of the lungs. The author found a high initial mortality, 42 per cent. of the patients dying within 12 months of diagnosis. Furthermore, he showed that the probability of any patient surviving 1 year and of living a further 5 years was 1 in 4 at the time of diagnosis, becoming 50: 50 if the first 5 years are survived; in other words, half those who were alive at the end of the first 5 years were dead by the time the second 5 years had been completed. Out of the total number 1 in 8 lived 10 years from the time of diagnosis. From additional information placed at his disposal the author was able to assess the influence of sanatorium treatment, and concluded that the expect- ancy of life of a sanatorium patient was better than that of all patients inclusive, by just that period of his stay in a sanatorium. There was no detectable difference between the sexes, but the middle- aged patient fared rather better than the young adult and the elderly. The clinical impression, therefore, that the prognosis of pul- monary tuberculosis with cavitation is bad thus receives statistical support from Thompson’s work, the only mitigating feature of which is that the depressing living conditions of the majority of the com- munity under review, although perhaps rivalled by a few districts in the United Kingdom, could hardly be surpassed. It was an industrial community with bad housing and a low nutritional standard, and which had endured during the years covered by the report a period of profound economic depression. It was just the soil upon which the tubercle bacillus thrives. Several surveys have been conducted with the object of assessing the value of sanatorium treatment, one of the more important in this country being that of Hartley, Wingfield and Burrows (3), who analysed 8,766 patients treated at the Brompton Hospital Sana- torium, Frimley. The material was selected to the extent that hopeful rather than advanced cases were accepted by that institu- tion. The period covered was twenty-seven years. ‘These authors stress the great prognostic importance of the stage of the disease at which treatment was commenced, an observation which can be related to another of their conclusions, namely, the increased prob- ability of survival in those patients who are in a class suitable for artificial pneumothorax. ‘They regarded the first two years after diagnosis as the dangerous period, the prospects of survival increas- ing year by year thereafter. They believed that sanatorium treat- ment conferred considerable benefit upon the patients, but deduced from their material that the prognosis of the average case of phthisis had not changed materially over the last thirty years. It is legitimate to infer from this analysis that the benefit derived from sanatorium treatment is not necessarily lasting and the good that follows from it is in many people lost as soon as they leave the institution. This must not be taken to mean that the sanatorium routine is valueless ; it still remains an indispensable part of treat- ment. But this, and Thompson’s conclusion, should serve to focus increased attention upon the social circumstances and home environ- ment of the tuberculous, for there is where the fault lies. nie oe Numb Number lost Total Classification Decnacd aieAb or fulleted ap Number Percentage A 544 (620) 64(115)} 480 (505) 3865 (871)|76-0 (73-5) BI . | 181 (250), 12 (44)| 169 (206)| 187 (140)| 81-0 (68-0) B2 . (1,914 (2,155) | 111 (178) | 1,808 (1,982); 743 (670)| 41-2 (33-8) B3 632 (998)| 18 (26)| 619 (972)/ 49 (60)| 7-9 (7-2) Total Pulmonary | 3,271 (4,023) | 200 (358) | 3,071 (3,665) 1,294 (1,241) 42-1 (33-9) Non- Pulmonary | 351 (817)| 48 (71)| 308 (246)| 226 (182)|74-5 (74-0) Granp Tora. | 3,622 (4,340) | 248 (429) | 3,374 (3,911) | 1,520 (1,423) | 45-1 (36-4) Classification Dischacce s A 166 (166) eg 8 (2) B2 19 (20) BS 21 (26) Total Pulmonary | 214 (214) Non- Pulmonary | 476 (609) GRAND TOTAL 690 (823) Number lost Total sight of followed up Number 13 (23) | 158 (148) 139 (131) (Ss) 8 (2) 6 (1) een) 19 (18) 10) (6) san CE) 21 (25) see's wee") 13 (26) | 201 (188) 155 (138) 48 (88) | 428 (521) 396 (492) 61 (114) | 629 (709) 551 (630) Percentage 81 (91) 77 (73) 92 (94) 87 (88) Improvement shown for the 1982 over the 1927 discharges may be partly due to the smaller number lost sight of in the 1982 group, but even if all patients lost sight of were alive at the end of the five- year period the percentage of survivors would still show an improve- ment of more than 6 per cent. It would appear, therefore, that in general the prognosis of those discharged from institutional treatment has improved during the last ten years, although in adults the expectancy of life in the B2 and B3 cases is still very poor, as 58-8 per cent. and 92-1 per cent. respectively of these cases die within five years of the date of discharge. The figures relating to children show little change and are too small for any valid conclusions to be drawn from them. | COMPARATIVE FIGURES FROM LANCASHIRE 1930 1940 Pulmonary Tuberculosis ; Number Percentage Number Percentage Number of notified cases | treated under the Tubercu- losis scheme ’ H4 21,280 — LAT Ss tg — Sex: Male é ; 4 670 5A 4 668 56°7 Female ! : : 560 45-5 .| 510 | £48:2 Age Group: 0-14 . ; 79 6-4 43 | 3°6 15—44 . : 874 ,71-0 ~ 862 | 73-1 45 plus s5> =. he) 277 22-5 278 | (28-1 After history for five years | Received institutional treat- ment a , A > 855 69-5 843 res Removal, untraced, refused | | further treatment : : 133 10°8 151 12°8 Deaths from tuberculosis | among pulmonary cases | (removals etc. excluded) . 693 63-1 | 599 58°38 Still under treatment . ; 344 | 27-9. | 896 33-6 These comparative figures, given by Bradbury in his Annual Report for 1945, show a similar trend of improvement of the 1940 over the 1930 cases. Results of Treatment Enquiry into the value of specific methods of treatment is notoriously difficult and apt to be misleading. The paramount difficulty is the finding of a suitable ‘“ control.” If the cases are not subdivided according to the extent of the disease, its activity, the presence of cavities, a tendency to fibrosis, also according to the age, sex and temperament of the patient, comparisons are unreliable ; if they are so divided each group contains too few cases from which to draw useful deductions. This has been made abundantly clear by published work designed to assess the value of the artificial pneumothorax. Of several surveys available two only will be mentioned. The report of the Joint Tuberculosis Council (4) on the survival rate of 3,021 cases of pulmonary tuberculosis treated in forty-two different hospitals by artificial pneumothorax, compared with 1,329 patients in the same hospitals on whom pneumothorax had been attempted but failed, showed that the ratio of actual to expected deaths amongst the pneumothorax cases was approxi- mately half that among the failures. At the same time it was pointed out that a patient with adherent pleurze could not be regarded as a suitable control case for one who had no adhesions. The results of these series were compared with the results in 2,750 patients treated at the King Edward VII Sanatorium, Midhurst, of whom at that time less than 1 per cent. had pneumothorax. The ratio of actual to expected deaths was approximately twice as high in the patients treated with pneumothorax as in the Midhurst group. If, however, ancillary methods such as gold were used, the results in the Midhurst cases were practically the same as those treated by pneumothorax together with ancillary measures. A prominent invalidating factor in the second half of this investigation is that the two groups were drawn from different social strata of society, and Todd’s figures (see later) have shown how important is the home environment to which the patient has to return on discharge. Bentley (5) investigated the fate of 677 new cases submitted to pneumothorax therapy in the London County Council Tuberculosis Service and compared them with 3,309 cases treated conservatively. The period of the review covered 3-13 years. Correction was made for age, sex and clinical classification, and all the patients came from the same social sections of the population. He found that the survival in all cases investigated was 20 per cent. higher in the pneumothorax group than the expected number of those conser- vatively treated. On the assumption that pneumothorax therapy is applied in about 10 per cent. of all patients, the general level of results in all cases undergoing residential treatment would then be heightened by 2 per cent. by the procedure. The prognosis was better with complete collapse than incomplete collapse, the latter being an added source of danger. Similarly, those who left the sanatorium with a T.B. negative sputum did better than those whose sputum remained unconverted. The difficulties inherent in an appraisal of the results of artificial pneumothorax, and of its influence upon prognosis, have been well stated by Bentley who refers to them as the “‘ seven deadly sins ”’ which all investigators in this field must avoid. They are :— (1) Paucity—to draw conclusions from too small a number of cases ; (2) Selection—to write up only certain cases; (3) Precipitancy— to report on cases before a sufficient period has elapsed; (4) False control—to evaluate results by comparison with the fate of patients having extensive pleural adhesions ; (5) Equivocation—to employ equivocal definitions as to the degree of collapse; (6) Failure to trace—to lose sight of a high proportion of patients; and (7) Lack of detail—to fail adequately to describe the extent of the disease. As to precipitancy, Bentley’s minimum period before inclusion in his series was three years ; Thompson’s recent work suggests that ten years should be the limit if the results are to be statistically valid. Failure to define the degree of collapse is also most important for the inclusion of incomplete collapse or contra-selective collapse will vitiate the results. The importance of attaining selective con- centric relaxation of the diseased part of lung, by combined collapse measures if necessary, has been only slowly realised, and a “‘ standard type’ of pneumothorax upon which results can be convincingly judged has only comparatively recently been attained. The difficulties that stand in the way of forming an accurate appraisal of the prognostic value of the artificial pneumothorax apply with equal force to other methods of collapse therapy, of which thoracoplasty is the only one which will be considered briefly at this point. Assessment of the results of thoracoplasty is hampered, as is the artificial pneumothorax, by the many variable factors associated with tuberculosis, by the virtual impossibility of comparison with suitable control material, and by the other “‘ deadly sins”’ in Bentley’s list. Furthermore, in two particulars at least, the odds are more heavily against thoracoplasty than pneumothorax. First, the number of patients operated upon is very much less than the number of pneumothoraces induced, and it becomes correspondingly more difficult to collect a numerically significant series. Secondly, while the “ ideal ”’ type of pneumothorax exists and is known there is no guarantee that the standard pattern of apical thoracoplasty _ has yet been devised. The technique of the operation has been steadily developed from the original paravertebral extrapleural operation of Sauerbruch, from which lateral collapse largely re- sulted, through a procedure in which the apex of the lung was sub- mitted to an extrapleural strip and the upper two ribs and transverse processes wholly removed in order to achieve vertical release, and on to the extrafascial apicolysis with thoracoplasty, introduced ten years ago by Holst and Semb of Oslo, and the modifications of the technique which later followed (Price Thomas and Cleland (6)). Every major change in the technique alters the value that can be placed upon the results of operations undertaken previously and renders them to some extent obsolescent. Nevertheless, some recent figures will be quoted :— Meltzer (7) reviewed 181 cases operated upon up to 1941. The series included “ good” and “bad” chronics and empyemata. Extrafascial apicolysis was carried out when necessary and an average of three ribs were removed at each stage. The results were as follows : arrested 32 per cent. ; apparently arrested 16 per cent. ; quiescent 31-4 per cent.; improved 6-6 per cent.; unimproved 1-6 per cent. Fifteen patients died, 8 from tuberculosis and 7 from non-tuberculous causes. The author found the best results in the 21-30 age group but did not regard middle age as a contra-indication provided the patients were well selected. Valle (8) surveyed 232 cases operated upon between 1931 and 1941 and, on account of differences in the criteria for selection and in the technique employed, he divided the series into three groups depending upon the years in which the operation was performed. Regarding all cases that became arrested or quiescent, or which improved, as having benefited from thoracoplasty, the author found in Group I, operated upon between 1931 and 1935, 49-7 per cent. favourable results ; in Group II, operated upon between 1936 and 1988. 74-0 per cent. favourable ; and in Group III, 1939-41, 78-7 per cent. derived benefit. There were fewer secondary revision operations carried out in the last two periods than in the first. Price Thomas and Cleland (6) collected a series of 120 cases operated upon in the years 1933-40 inclusive. ‘Three types of operation were practised during the period: first, the lateral thoracoplasty with no attempt to mobilise the apex; later, the Semb technique with extrafascial apicolysis; and, finally, the author’s modification of the Semb operation, in which an extension of the mobilisation of the apex was carried on to the mediastinum and paravertebral sulcus combined with the additional resection of portions of the fourth and fifth ribs. They found that the mortality, early and late, improved with the years and was least in their own modified operation ; that the mortality rate was lower if the patient was operated upon within two years of the onset of the disease than later ; and that there was a direct relationship between the mortality rate and the extent of the disease in the ipsilateral and contralateral lung. They concluded that the modified Semb operation was not attended by an increased risk of complications and was followed by _ sputum conversion and closure of cavities more often than was the lateral thoracoplasty. The type of disease was of considerable importance in prognosis, the ‘‘ good chronic ”’ doing better than the less stable examples. _ Hurford (9) published the results of 67 cases operated upon at Colindale from 1933 to 1939 and compared them with an equivalent number of controls made up of those who declined operation after it had been advised. ‘The results for the 54 patients with parenchy- matous disease, based on information received at least one year after the completion of the final stage (the figures for the controls being appended in brackets), were as follows : quiescent 65 per cent. (16 per cent.) ; still active 13 per cent. (13-5 per cent.) ; deteriorat- ing 4 per cent. (25 per cent.) ; dead 18 per cent. (45-5 per cent.). He found the death rate highest in those with the largest cavities. The Houghton index and the erythrocyte sedimentation rate proved useful guides as to fitness for operation. One of the most recent assessments of thoracoplasty for lung disease is that of Sellors (10). The material comprised 633 patients operated upon in the years 1935-46, of whom 45 could not be traced. Death within four months of operation occurred in 17 (2:7 per cent.) ; it took place later in 55 (9-4 per cent.). Conver- sion of sputum from positive to negative was achieved in 84 per cent., and closure of the cavity in 91 per cent. of the series. Working capacity was recorded as full in 59-2 per cent., fit for light work only in 5-5 per cent., while 8-4 per cent. were unfit for work and in a further 8-4 per cent. the working capacity could not be recorded. This imperfect survey of the attempts to assess the long-term prognosis of phthisis by statistical means, and it must be admitted that some of the deductions are very far from encouraging, can perhaps be fittingly rounded off by a recent statement of Stocks and Lewis-Faning (11). These authors have said that “in the period 1923-39, despite the rapid fall in the numbers of notifications of and deaths from respiratory tuberculosis, the average expectation, for a person just notified, of eventually dying of the disease remained remarkably constant at approximately one half in England and Wales as a whole.” If the figures upon which this statement is based reflect the truth, the logical assumption is that the sana- torium regime and those methods of active intervention which have been extensively practised in the last two or three decades have, at the most, only deferred an outcome which was inevitably fatal. It is here, perhaps, that the views of the clinician and statistician differ. Prognosis of the Individual Case Information. derived from the study of the prognosis of the ‘““ average case’ has only an indirect application to a particular patient, and it is with those factors governing the individual prog- nosis, intangible and uncertain as they often are, that the practising clinician is most concerned. Certain examples of tuberculosis, e.g. acute miliary disease or acute fulminant bilateral exudative phthisis in a young adolescent with profound constitutional upset, carry so grave a prognosis that little hesitation need be felt in putting the facts plainly before the relatives, although even in these types the time limit is often hard to fix. In most other varieties of tuberculosis an immediately fatal end is unlikely, but in many the ultimate prognosis must be guanecd or postponed, : Rich (12) states that in order to make a reasonable prognosis on a tuberculous lesion it is necessary to know (a) the number and virulence of the infecting bacilli, (b) the degree of native and acquired resistance at the time of the infection or capable of being developed and maintained by the infected individual, (c) the degree of hyper- sensitivity, and (d) the tissue in which the infection occurs. He expresses the extent and the destructiveness of the lesion in a schematic representation by the formula :— Virulence x No. of bacilli x Degree of Hypersensitivity Lesion «& ; = | WEEE, ose Resistance (native or acquired) This formula, if kept in mind, may prove helpful as a reminder of the interplay of the factors which determine the prognosis of any particular case of phthisis and prevent the exaggeration of one factor out of proportion to others. It will be appreciated that all the items in the formula are difficult to ascertain and to measure, thus emphas- ising how prognosis must be built up by the cumulative weight of evidence derived from many factors of which the following are among the more important :— Age and Sex. Ustvedt considers that the age at which the primary infection is acquired has a significant effect on the sub- sequent course of the lesion. That there are certain periods of life when the body appears to succumb to the disease has been known for many years. These periods are from 0—5 years for both sexes, 17-25 in females and 35-50 in males with a second period in males from 65 onwards. The devastating effect of the infection in the first year of life cannot be over-estimated. Van den Berg (13) has observed that the disease is extremely fatal in the first months of life. The following table taken from his work shows this clearly. | Infected before Morbidity Mortality Period of contact | lst year 2nd year | Ist year 2nd year Ist year 2nd year | Ist three months | of life ‘ re pee a OY. 80°5 32°1 45°6 18°3 30°5 4-12 months of | life . INFLUENCE OF AGE AND SEX 289 the second year there is a marked fall which continues as the higher age groups are reached. This is demonstrated in the figures of Wallgren (14) on a series of 453 children. Age groups 0-1 —3 -7 -16 | Total Number of Child- ren. - : 39 64 225 125 453 Mortality rate per cent. : : 35-9 15-6 4+ 4 0-8 ee 4 Most of these children died of miliary tuberculosis or tuberculous meningitis. The interval between the primary infection and the occurrence of tuberculous meningitis was in the majority of cases from one to two months or, very rarely, after three months. It must, however, be remembered that Margaret McPherson (15) has shown that, although the mortality rate due to tuberculosis was greater in infancy than in later childhood when taken in relation to the mortality rate from all causes, tuberculosis is a much less fre- quent cause of death in young children than in those approaching adult life. But the relative inability of the infant to overcome the primary infection in comparison with children of older years is clearly demonstrated by the investigation of Blacklock (16) on the evidence of healing found around primary foci at various ages : Ape. No. of Foci. Percentage Healing. 0-6 months : 40 0 OS a As : : 58 10°3 i2 years. ; 2 62 37-1 ee fs 40 40-0 3-6. .,; ; é : 44 52-2 6-13 ,, ‘ : : 46 67-4 The factor of greatest importance in the mechanism of healing is the “‘ fixing ’’ and suppression of the bacillus at the site of infection so that the development of fibrous tissue can proceed. As early adult life is approached the prognosis in females becomes graver, particularly in the 15-25 age group. Endocrine instability may have a bearing on this. Since tuberculin surveys have been more often used, the increasing frequency with which young adults escape infection until they enter this age group has been realised and may have a bearing on the lack of resistance shown by those young females who develop progressive lesions immediately after the primary infection eventually causing death in from two to three years. The outstandingly high death rate from respiratory tuberculosis in females in the 20-25 age group has been shown in figures given by Stocks (17) in the table on page 9. It can also be seen that the peak for the males falls much later, so that the prognosis in males becomes increasingly grave up to fifty-five years of age, whereas in females the greatest danger lies in the third decade of life. Temperament. This is of considerable importance. ‘Those patients who find the prolonged course of treatment irksome or who are unable to adjust themselves to a lower tempo of everyday life, both in the sanatorium and afterwards, do not have the same chance of permanent recovery as those of a more phlegmatic frame of mind. On the other hand, it is possible, and singularly easy, to carry this process of adjustment too far and to become morbidly introspective. A sensible middle course between extreme intro- spection and utter abandonment is the ideal one to be steered. Race. It has been known for many years that the prognosis of tuberculosis in some races is more serious than in others. It is accepted that negroes are more liable to phthisis than whites living under similar circumstances ; that certain races in India develop a more severe form of the disease than others was noted by C. A. Johnston as long ago as 1908. Lyle Cummins (18) has done much work on this subject, both in the Army and in South Africa, and comes to the conclusion that the course of the disease in any parti- cular race does not depend on “ allergy ” but on “ the rapidity with which relative immunity is acquired.” In civilised communities where tuberculosis has been indigenous for many generations this relative immunity, or as some would prefer to call it, acquired resistance, develops more rapidly than in the “ primitive” race and at an intermediate rate by the descendants of the latter. The development of the lesion, therefore, in the races that have this | power of rapidly establishing acquired resistance is characterised by fibrosis and a tendency to heal. In the “ primitives ” the lesions show rapid extension with little or no fibrosis and usually end fatally. More research in following up large sections of different races after examination by radiography and tuberculin testing is still needed to elucidate the problem, for in certain parts of Ireland the population show little power to develop acquired resistance, although the disease has been present in the country for a number of generations. The young Irish adult, coming into contact with the infection for the first time, when removed from his or her home environment, often develops a serious form of the disease. This removal from home environment is becoming accepted as an im- portant factor in influencing the progress of the lesion. The Jews show, as a race, a high resistance to tuberculosis and is demon- strated in the survey of Goldman and Wolff (19) who found that for 1924-1926 in Berlin the standardised rate of the death rate from tuberculosis of the Jews was less than half the corresponding rate of the non-Jews. Heredity and Family History. That tuberculosis runs in families is a popular idea which is sometimes tragically true, but whether the development of the disease by successive members of the family is due to frequent contact with the infection or an inherited predisposition to the disease is difficult to determine. Opie (20), after considerable study of the subject, came to the con- clusion that “ the spread of tuberculosis occurs in large part by long drawn out family or household epidemics, in which the disease is slowly transmitted from one generation to the next.’ The relation of frequency of contact to resistance is summarised by Cummins (18) who states that “‘ the fact is established that under the influence of infection an increasing power of resistance can be acquired by the individual and can also, under certain cir- cumstances (poor food, fatigue, stress, alcohol, etc.), be lost.” He thereby attaches considerable importance to environment and living conditions. In the past much stress was laid on the im- portance of a family history in assessing individual prognosis ; after a time this factor received less attention, but recently interest has revived in the subject and the question is being investigated in a systematic manner. The results seem to indicate that heredity does play a very definite part in the development of tuberculous lesions, not so much in determining if a person will contract the disease as by influencing its course when an active lesion has been established. A thorough experimental study has been done in America by Lurie (21) on rabbits. Using successive generations of two groups of animals obtained from widely different parts of the country and observing the different types of lesion which developed in certain generations, Lurie came to the conclusion that resistance of rabbits to naturally or artificially acquired tuberculosis is a function of their genetic constitution and that this determines the type of lesion which develops, either rapidly progressive, chronic, localised ulcera- tive, or of an intermediate character. Usually rapid and intense development of allergic sensitivity was accompanied by a high degree of resistance and slow development of allergic sensitivity with low resisting power. The power of the mononuclear cells to inhibit the growth of tubercle bacilli was found to vary in different animals. In the more resistant the inhibitory function of the cells was good, but in the less resistant it was poor. In the same way the varying power of resistance was demonstrated by the degree of localisation of the infection at the portal of entry. From these observations there seems to be little doubt that heredity played a significant part in determining the type of lesion that developed in these infected animals. In turning from the experimental evidence to the observations on man, it becomes much more difficult to draw conclusions owing to the many uncontrollable variants. The work of Diehl and Verschuer (22) on 87 univitelline and 69 bivitelline twins is interest- ing in that there was 70 per cent. correspondence between the genetic constitution and behaviour towards tuberculosis in uni- vitelline twins and only 25 per cent. in bivitelline twins. Similar results were obtained by Kellman and Reisner (23), who carried out a careful and skilful piece of research on 308 twin pairs, compris- ing 336 cases of adult type pulmonary tuberculosis. In addition they investigated an unselected sample of relatives comprising 930 full brothers and sisters, 74 half sibs, 688 parents and 226 marriage partners. The adjusted morbidity rates in these series which in- dicate the chance of developing manifest pulmonary tuberculosis by the age of 29, were as follows :— For the general population of the State and City of New York 1-4 per cent., for the husband and wives of index cases 7:1, for their half sibs 11-9, for their parents 16-9, for their full sibs 25-2, for their fraternal co-twins 25-6, for their identical co-twins 87°38. The conclusion to be drawn from these results is ‘that human tuberculosis is a disease influenced to a notable extent by inborn inherited constitution—influenced moreover to a greater degree in regard to its behaviour when once contracted than in regard to whether it is contracted at all.” This conclusion is confirmed by the extensive work of Rich (24) who, after prolonged research on the pathogenesis of tuberculosis states: ‘“‘ The more we learn about the factors that govern the development of tuberculosis in the human being the more we are impressed by the importance of the role played by individual native resistance.” _ Mode of Onset.—The more abrupt and dramatic the presenting symptoms the greater is the likelihood of prompt diagnosis and therefore of early treatment. This is especially true of haemoptysis, and those patients in whom the disease is ushered in with frank haemorrhage from the lungs were found by Thompson (1) to have twice as good a chance of surviving five years as the others. To a lesser extent the same is true of the pleuritic onset provided the pleurae do not become so firmly fixed as to prevent the estab- lishment of artificial pneumothorax if this method of treatment is desirable. Stage and Type of the Disease. It was made clear by Hartley and his colleagues in their report (3) that tuberculosis of the lungs passes through a symptomless stage before emerging into a symptom-producing one, and that the chance of survival was pro- portionately greater if treatment was begun in this silent period before the patient had any grounds for believing that he was ill. Before the advent of mass radiographic surveys the “ accidental ”’ discovery of pulmonary tuberculosis was relatively uncommon ; but since the practice of submitting large sections of the apparently healthy population to routine radiography has become widely accepted, symptomless lesions are being unmasked with increasing frequency. It is to be hoped, although not yet proved, that the ultimate prognosis of patients discovered in this way will be much more favourable. The acute spreading exudative type of lesion always gives rise to anxiety ; the more formative “hard” lesions with a fibrotic tendency, on the other hand, being sluggish in development and progression, can be viewed more complacently. The more extensive the disease the worse the prognosis, especially if both lungs are involved. Site of the Lesion. Other factors being equal, apical disease is more readily brought under control than a basal lesion, largely on account of the fact that collapse therapy can be more suitably and satisfactorily applied to the upper lobe than to the lower. Cavities in the “ dorsal lobe”? segment are notoriously resistant to collapse measures. The pneumoperitoneum, reinforcing phrenic paralysis, has recently made a bid to redress the balance, and its effect on ultimate prognosis is awaited. Associated Diseases. Nephritis, recurrent malaria, and above all chronic alcoholism, unfavourably alter the prognosis. Diabetes mellitus is in a slightly different category and has been considered on page 111. : Response to Treatment. Much depends upon the ability of the patient to mobilise his own powers of resistance when placed under ideal conditions, and most examples of active tuberculosis of the lungs, in such circumstances, will exhibit some degree of im- provement in so far as symptoms abate and toxaemia lessens. The extent to which the process can be carried largely determines the ultimate prognosis. Occasionally, bed rest alone, if prolonged, will bring about arrest of the disease; in other instances a pre- liminary period of rest is followed by improvement sufficiently substantial to place the patient within reach of collapse therapy which, at the time of diagnosis, would have been fraught with danger. The prognosis is altered for the worse if a breakdown occurs while under sanatorium treatment. There is yet a third group of advanced or moderately advanced cases, unsuitable for collapse therapy, in whom all that can reason- ably be expected of treatment is the attainment of the “ good chronic ”’ stage. These are often left with an appreciable residual disability but can lead useful lives at a lowered tempo in a pro- pitious environment, such as that afforded by a village settlement. The prognosis as to life will often depend upon whether or not a patient is willing to accept such a mode of living. On a short-term basis, and perhaps even ultimately, there is no doubt that the outlook is more promising for those patients in whom collapse therapy can be successfully applied at the opportune time, provided this active treatment is accompanied by, and initiated during, an adequate period. of sanatorium routine. This enhancement of the prognosis which the successful employment of collapse therapy brings rests not only upon the fact that the extent and activity of the disease in such cases is less, but must also be partly credited to the improved mechanism of healing which follows relaxation of the diseased area of lung. Provided a constancy in recording and a high standard of tech- nique is assured, valuable information can be derived from the serial figures of certain blood tests such as the sedimentation rate and the Von Borsdorff and the Houghton indices, performed regularly at monthly intervals. Such readings, collated with evidence acquired from other sources, helps to assess the trend of the disease and thus simplifies the formulation of a prognosis. Day (25, 26) has recently introduced a modification of the sedi- mentation rate of the red blood corpuscles which he finds of more value than the determination of the rate of sedimentation in the , first hour. His work originated from a study of the ‘‘ Cutler Curves” in which the time of sedimentation was plotted against the distance and Day showed that this time-distance curve was comprised of three periods: (1) the period of acceleration during which the cor- puscles are agglutinating into clumps; (2) the period of maximum velocity ; and (3) the period of slowing due to packing of the clumps. Day regards the second of these three periods as the most important, and from it can be calculated the maximum velocity in millimetres per 100 minutes. The logarithm of the maximum velocity so calculated for any sample of blood he calls the “* sedimentin index ”’ of that sample. He employs the term “ sedimentin” to cover those substances in the blood, whatever they may be, that are responsible for the phenomena of sedimentation, and he takes the sedimentin index as expressing, in arbitrary units, the amount of sedimentin in the blood. From his experience with the sedimentin index Day has been led to regard it as a more sensitive guide to the activity of the pathological process, and subject to less variation, than the first hour sedimentation rate as customarily determined. Moreover, it is unaffected by fluctuations in the total number of red corpuscles. The expectancy of survival in the persistently sputum positive case is not good. Apart from the group designated the “ good chronic ’’ who attains, so to speak, a state of equilibrium with the tubercle bacillus, and it is difficult in the early stages of the disease to forecast who will fall into this group, the majority of those whose sputum remains unconverted do not live longer than three or five years, and many not so long as this. One of the essential aims of treatment, therefore, is to bring about conversion of the sputum, as judged by modern searching methods, and success in achieving this greatly improves the outlook. : Social and Environmental Factors. In making a prognosis in any particular case it is important that our assessment should not rest entirely on clinical data. Knowledge of home and working conditions, to which the patient is returning, is of considerable im- portance and may be the chief factor in determining the permanence i= Al l employed Males 06+ V—Unshilled Males WV--— Semi skilled » 0:55+ +e Skilled * [xxx Professional Y vou 4 rN n = 4 S Lo RH 2 be ° . . .* ux ah PO x oy KKH "Kite pe if I *h + “hy, x Xx % Deaths of cach Age G. 9° R S ms 0-05 “16 220 =25 -35 -~45— -55 -~65 -70 75+ ge in Years Fig. 5.—Social Status and Morbidity Rates. of the improvement which has been obtained by many months of treatment. Social status has a very definite influence on the mor- tality rates. This is seen in the chart above which has been compiled from the Registrar General’s Returns for employed males for 1931-2. The high rate for the unskilled classes contrasts strongly with the rate for the professional classes, being nearly three times as high at the age of 45. That the peak of all the curves for males falls at forty-five irrespective of social status is puzzling, and an explanation of this phenomenon is not easily found. It would seem from these figures that, unless recovery takes place, the course of the disease in the fatal cases is the same for all classes. It may be, however, that a greater number of the Classes I and II cases recover. In fact this is highly probable from the follow-up of patients who have received treatment at the King Edward Sana- torium, Midhurst, where the majority of patients belong to Classes I and II. STATISTICS OF ULTIMATE RESULTS OF SPUTUM POSITIVE CASES Year | Number of Dis- Dis- 1931 | 1932] 1933 | 1934 | 1935 | 1936 | 1937 | 1938 | 1939 | 1940 | 1941) charge | charged’ 1929/30 155 90-6 | 82-4 | 74-6 | 68-5 | 62-4 | 58-5 | 55-1 | 50-5 | 48-5 | 48-5 | 47-1 1930/31 134 94 88-5 | 78 66-7 | 60-7 | 58-5 | 51-7 | 50-2 | 45-8 | 43-5 1931/32 128 92-8 | 77-6 | 68-8 | 64:8 | 62-4 | 51-2 | 51-2 | 49-6 | 48-8 1932/33 141 85 80 72 70 68-5 | 58-5 | 57 52 1933/34 100 84 76 68 57 55 53 51 1934/35 118 ekooe || 7/7/Oal |) Giz 67 62°7 | 57-6 66 Figures showing the percentage “ alive’ in each successive year after dis- charge up to 10 years : compiled from the Annual Report of the Medical Superintendent of the King Edward VII Sanatorium, Midhurst. If these figures are compared with the five-year figures for L.C.C. patients or the ten-year figures for Lancashire patients on page 232, it will be noted that in the former only 43-3 per cent. were alive after five years and in the latter 41-7 per cent. of all pulmonary cases were alive after ten years as against an average of over 60 per cent. for five years in the Midhurst cases. Although the total number of ‘cases reviewed in the London and Lancashire figures is much larger than the Midhurst series the tables do indicate that the superior after-care conditions enjoyed by the Midhurst patients have a con- siderable influence in prolonging life after sanatorium treatment has been completed. The Midhurst figures also show very clearly that fatality rate decreases rapidly after the fourth year from the date of discharge from the sanatorium. In the first five years approxi- mately 30 per cent. of the deaths occur, whereas in the second five years this figure is reduced to the region of 12 per cent. The second and third years after discharge from the sanatorium would appear to be the most dangerous. Further evidence of the importance of environment is gathered from the reports from the village settlements. Here patients with advanced disease often continue to live under ideal conditions and work in sheltered employment for many years. The length of life of these patients is in marked contrast to that of similar cases living in homes in large cities. Varrier-Jones (27) estimated that the average length of life of tuberculous persons residing in village settle- ments is three times that of similar individuals who return to the environment in which they contracted the disease. Certain occupations are definitely harmful, and return to one of these, or to too strenuous work, may change the prognosis of the best of cases. Employment in dusty atmospheres is to be avoided, for although the dusts may not be specifically harmful, as is silica, it may irritate the bronchi and cause catarrhal symptoms. Heavy work is contra-indicated as well as exposure to severe climatic condi- tions of excessive heat, cold, or wetness. This is now being appre- ciated in that those responsible for finding work for tuberculous persons are at last being instructed that outdoor work is not neces- sary, and is sometimes undesirable, for tuberculous persons because of the harm that may result. Prognosis is dependent on the facilities for adequate rehabilitation without which the results of the most successful treatment may be completely dissipated. References (1) THomeson, B. C. (1942) Tubercle, 23, 139. (2) (1943) Brit. med. J. 2, 721. _ (8) HarTiLEy, P. H.-S., WINGFIELD, R. C. and Burrows, V. A. (1935) Brompton Hosp. Rep. 4, 1. (4) Joint TUBERCULOSIS CouNcIL. Report (1986). (5) BENTLEY, F. J. (1936) Med. Res. Counc. Spec. Rep. Ser. No. 215. (6) Tuomas, C. P. and CLELAND, W. P. (1948) Brit. J. Tuberc. 37, 2. (7) MELTZER, H. (1941—42) J. thorac. Surg. 11, 84. (8) VALLE, A. R. (1944) J. thorac. Surg. 13, 36. (9) Hurrorp, J. V. (1941) Lancet, 1, 693. (10) Setiors, T. H. (1947) Thoraz, 2, 216. (11) Stocks, P. and Lewis-FAnIneG, E. (1944) Brit. med. J. 1, 581. (12) Ricu, A. R. (1944) The Pathogenesis of Tuberculosis, p. 703. Springfield and Baltimore. (13) VAN DEN Bere, H. (1929) Rev. Phthisiol. 10, 447. (14) WALLGREN, A. (1988) Lancet, 1, 417. (15) McPHERson, A. M. (1948) Brit. med. J. 2, 98. (16) Buackiock, J. W. S. (1947) Brit. med. J. 1, 707. (17) Stocks, P. (1947) Mon. Bull. Minist. Hlth. 6, 24. (18) Cummins, S. L. (19382) S. Afr. Inst. med. Res. 5, No. 30. (19) GoLtpMAN, F. and WotrFrr, G. (1937) Lancet, 1, 1295. (Abstr.) (20) Opie, E. L. and McPHEDRAN, F. M. (1935) Amer. J. Hyg. 22, 544, see also Editorial (19386) Brit. med. J. 1, 845. (21) Lurie, M. B. (1941) Amer. Rev. Tuberc. 44 (Supp.). (22) British Medical Journal, Editorial (1934) 2, 1055. (23) Editorial (1944) 2, 504. (24) Ricu, A. R. (1944) The Pathogenesis. of Tuberculosis. Springfield and Baltimore. (25) Day, G. (1938-39) Tubercle, 20, 364. (26) —— (1940) Lancet, 1, 1161. (27) VARRIER-JONES, P. C. (1930) J. State Med. 38, 268. (28) L.C.C. Rep. M.O.H. (1938) pp. 27 and 28. CHAPTER XIII CLASSIFICATION AND TYPES OF TUBERCULOSIS Many attempts have been made to classify the various types of pulmonary tuberculosis but so far it has not been found possible to draw up a simple classification which will satisfy all purposes and it is unlikely that this will ever be done, for two reasons : first, because of the many ways in which the problem can be approached ; and, secondly, because the temperament of the individual has an important bearing on treatment, prognosis and the gravity of the lesion and it is not possible to allow for this in any simple grouping. A classification will, therefore, depend on the angle from which the subject is viewed ; generally speaking, this will be either statistical, pathological, radiological or clinical. It is possible to combine two of these viewpoints in one classification and still keep it relatively simple, but, if more than two are incorporated, a complicated table of classes and groups appears which grows larger and more intricate as the sub-divisions are made to separate the many different factors. For statistical returns and general clinical reports the classifica- tion approved by the Ministry of Health is the one generally used. This classification was drawn up in the year 1925, and revised in 1937, and is contained in Memorandum 37/T (Revised). This was again revised in 1947 on the recommendations of the Joint Tuber- culosis Council. As this classification is the basis of all official statistical work in this country it has been quoted in detail. Revision of Section I of the Appendix to Memorandum 37/T (Revised). SECTION I A. CLASSIFICATION OF PATIENTS SUFFERING FROM TUBERCULOSIS For the purpose of the Annual Returns required under this Memorandum, and of the case records necessary to enable these returns to be completed, the following system of classification of cases and of recording results should be used :— I.—All patients should be grouped according to their sex and age ; patients under 15 years of age should be classed as children, and those of 15 years and upwards as adults. II.—Patients should be divided into respiratory and non-respiratory tuberculosis cases as follows : (1) a respiratory case should be one in which there is a tuberculous lesion of the lungs, pleura, intrathoracic glands, trachea or larynx ; (2) a non-respiratory case should be one in which a tuberculous lesion is present in one or more parts of the body other than the lungs, pleura, intrathoracic glands, trachea or larynx. A case in which there are both respiratory and non-respiratory lesions of clinical significance should be classified as a respiratory case. III.—(1) Patients suffering from any form of tuberculosis should then be divided into : Class A, viz., cases in which tubercle bacilli have never been discovered in any exudate, excrement, discharge or tissue. Class B, viz., cases in which tubercle bacilli have been found at any time in any exudate, excrement, discharge or tissue. A patient originally in Class A (T.B. minus) should be transferred to Class B (T.B. plus) at any stage in the course of treatment if and when tubercle bacilli are found, but, for purposes of classification at the time of first observa- tion, if tubercle bacilli have not been found in any excreta or discharge prior to or during the first eight weeks of observation or residential treatment, that patient should be considered an A case. (2) In respiratory cases both Classes A and B should be sub-divided to give indication of :— (a) The extent and degree of the lesion. (b) The degree of toxaemia. The extent of the pulmonary lesion is best described by radiological zones as follows :— The upper zone—that area above a straight line running through the lower borders of the anterior ends of the second ribs. The middle zone—that area bounded by the above line and one run- ning through the lower borders of the anterior end of the fourth ribs. The lower zone—the remainder of the lung below the middle zone. (3) Respiratory cases in both Classes A and B should be further sub-divided in three groups as follows :— Gr@up 1. Cases with slight constitutional disturbance, if any, e.g. there should not be marked acceleration of pulse or elevation of temperature except of very transient duration ; gastro-intestinal disturbance or emaciation, if present, should not be excessive. Obvious physical signs and radiological findings should be of very limited extent. The physical signs should be either present in one lobe only, and in the case of an apical lesion of one upper lobe, not extending below the second rib in front or not exceeding an equiva- lent area in any one lobe ; or, where these physical signs are present in more than one lobe, they should be limited to the apices of the upper lobes, and should not extend below the clavicle and the spine of the scapula. Radiological findings should be limited to mottling involving a total area of not more than one zone. No complications (tuberculous or other) of prognostic gravity should be present. A small area of dry pleurisy should not exclude a case from this Group. . Group 3. Cases with profound systemic disturbance or constitutional deterioration and with marked impairment of function, either local or general. All cases with grave complications, whether they are tuberculous or not, should be classified in this Group (e.g. diabetes, tuberculosis of intestine or larynx). ; Group 2. All cases which cannot be placed in Groups 1 and 3. (4) The classification indicated in the above paragraphs may be demon- strated diagrammatically as follows :— TUBERCULOSIS | | R = Respiratory N.R. = Non-respiratory | Lae | Al A2 A3 Bl B2 B38 A B As the Classes A and B are defined by the success or failure to discover the tubercle bacilli in all cases of tuberculosis it is necessary to sub-divide the non-respiratory as well as the respiratory into these two Classes. It is felt that by doing this the issue is clear-cut and no confusion can arise. The introduction, too, of radiological findings brings the classification into line with modern methods of diagnosis, but the value of other clinical methods has not been overlooked or discarded. (5) Pleural Effusions. Uncomplicated cases of pleural effusion for which no alternative cause can be found should be regarded as tuberculous and placed in Group 1 of Class A and in Group 1, Class B, when tubercle bacilli have been demonstrated in the fluid. (6) The single positive result. Where a single positive bacteriological report is not confirmed by further bacteriological search and is unsupported by clinical or radiological evidence of tuberculosis it may be ignored. B. RESULTS OF TREATMENT The following terms should be used to describe the results of treatment :— ** Quiescent ’’—Cases in which the general condition and exercise tolerance are good, having regard to the extent of the lesion ; which show no evidence of toxaemia ; in which no tubercle bacilli have been found on three consecu- tive monthly examinations by stained film ; and in which changes revealed by other clinical investigations and by serial skiagrams point to retrogression of the tuberculous lesion. ‘ ** Arrested °’—Cases in which the disease has been ‘‘ quiescent ’’ for a con-. tinuous period of at least TWO years, or, if non-respiratory, the disease is ** quiescent ’’ and there is reason to believe it is unlikely to recur. ** Recovered ’’—Cases in which the state of quiescence has continued unin- terruptedly for a period of FIVE years, CLASSIFICATION IN U.S.A. 258 C. DEFINITION OF TERMS EMPLOYED IN THE FORMS OF RETURN 1. ** Dispensary Register.’’—A list of all persons examined by the Tuber- culosis Officer at or in connection with the dispensary, together with the names of any other persons accepted by the Tuberculosis Authority for residential _ treatment, or for observation in residential institutions, or for orthopaedic treatment or supervision under a scheme approved by the Minister of Health for the treatment of tuberculosis. 2. ** Adults.’’—all persons of the age of 15 years and upwards. 3. ** Patient.’’—a person suffering from tuberculosis whose name is included in the Dispensary Register. 4, ** Cases.”—This term, when used without qualification, includes not only ** patients ” but also all doubtfully tuberculous persons whose diagnosis has not yet been completed. 5. ** New Cases.’’—See directions for completing Part (A) of the Annual Return. 6. ‘* Contacts.’”-—Persons coming under review by reason of having lived, worked, or closely associated with a person who has notifiable tuberculosis. 7. ** Domiciliary Treatment.’—Treatment of an insured patient by his insurance practitioner on the recommendation of the Tuberculosis Officer. D. OTHER DEFINITIONS OF TERMS OF DOCUMENTARY SIGNIFICANCE 1. ‘* Active Cases.”°-—Those not quiescent. All cases discharging tubercle bacilli within the preceding three months should be considered as “‘ active.” 2. ** Stationary Cases.’’—Cases in which the signs, symptoms, clinical tests and radiological appearances of the lesions have presented no material new features during the period under review. 3. ‘* Rehabilitation.”’—The remedial process which aims at restoring a patient to the maximum participation in a normal life commensurate with the degree of his disability. Ministry of Health, May, 1947. 93205/9/18 It will be noted that the term “‘ pulmonary ”’ has been eliminated in this new classification and “respiratory ”’ used instead. It is not easy to make the change in routine work, but it would be an advantage to do so in all epidemiological reports and statistics so that the nomenclature conforms with that used by the Registrar General. : It is interesting to compare this classification with one which was approved in 1940 by the National Tuberculosis Association of America and the American Trudeau Society (1)... Cases are divided into three classes according to the severity of symptoms: mini- mal, moderately advanced and far advanced. Minimal. Slight lesions without demonstrable excavation con- fined to a small part of one or both lungs. The total extent of the lesion, regardless of distribution shall not exceed the equivalent of the volume of lung tissue which lies above the second chondro- sternal junction and the spine of the fourth or body of the fifth thoracic vertebra on one side. Moderately Advanced. One or both lungs may be involved, but the total extent of the lesion shall not exceed the following limits :— Single disseminated lesions which may extend through not more than the volume of one lung, or the equivalent of this in both lungs. Dense and confluent lesions which may extend through not more than the equivalent of one third the volume of one lung. Any graduation within the above limits. Total diameter of cavities, if present, estimated not to exceed 4 cm. Far Advanced. Lesions more extensive than Moderately Ad- vanced. Clinical status is defined as apparently cured, arrested, apparently arrested, quiescent, frankly active, or dead. Apparently Cured. Constitutional symptoms absent. Sputum, if any, must be found negative for tubercle bacilli, not only by con- centration and microscopic examination but also by culture or animal inoculation. In case there is no sputum, the fasting gastric juice contents should be obtained and similarly examined. Lesions stationary and apparently healed according to X-ray examination. These conditions shall have existed for a period of two years under ordinary conditions of life. Arrested. Constitutional symptoms absent. Sputum, if any, must be concentrated and found microscopically negative for tubercle bacilli. Lesions stationary and apparently healed accord- ing to X-ray examination; no evidence of pulmonary cavity. These conditions shall have existed for a period of six months, during the last two of which the patient has been taking one hour’s walking exercise twice daily or its equivalent. Apparently Arrested. Constitutional symptoms absent. Spu- tum, if any, must be concentrated and found microscopically negative for tubercle bacilli. Lesions stationary and apparently healed according to X-ray examination ; no evidence of pulmonary cavity. These conditions shall have existed for a period of three months, during the last two of which the patient has been taking one hour’s walking exercise daily or its equivalent. Quiescent. No constitutional symptoms. Sputum, if any, may contain tubercle bacilli. Lesions stationary or retrogressive accord- ing to X-ray examination ; cavity may be present. These condi- tions to have existed at least two months during which time the patient has been ambulant. Active. Symptoms unchanged, worse or less severe, but not completely abated. Lesions not completely healed or progressive according to X-ray examination. Sputum almost always contains tubercle bacilli. In some classifications terms appear such as “ primary tubercu- losis ” and “* epituberculosis.”” These bring us to the classifications based on the pathogenesis of the disease. A considerable amount of debate has centred round the exact meaning of these terms, and three phases have been described in the development of the disease : (a) The Primary Focus. (b) The Primary Complex, and (c) The Post Primary Lesion. Terplan (2) described the three stages as follows :— Primary Focus. The reaction of tissue to, or the structural change brought about by the tubercle bacillus at the site of the first recog- nisable lesion. Primary Complex. The primary focus and the tuberculous lesions in the corresponding lymph glands near the focus. Post Primary Lesions. Any other lesions except those developing an immediate association with the components of the complex in its active state. In most classifications the term primary lesion is usually what Terplan has described under primary complex; a true primary focus being so transient or so insignificant as to be rarely seen. The term Epituberculosis has fallen into disrepute mainly due to the vagueness of its meaning. Burton Wood (3) spent much time in studying the condition and gave an explanation of its development. He concluded that epituberculosis “‘is a manifestation of post primary tuberculosis in childhood and occurs in a period characterised by enlargement of the bronchial glands and a tendency to exudation. The chief factor in its production is atelectasis due to bronchial blockage by tuberculous glands. A secondary factor is probably exudation into the alveoli and engorgement, the result of lymph stasis and vascular congestion. ‘Tuberculous allergy possibly also plays a part for allergic reactions are common in the second stage.”’ Owing to a number of other conditions, tuberculous and non- tuberculous, that can produce radiographic shadows very similar to those due to epituberculosis considerable care must be exercised before using the term. So far the classifications which have been quoted have given very little guide to treatment. For this purpose Burrell suggested four groups : 1. Latent or non-clinical pulmonary tuberculosis. The stage of alarm. Here there is evidence of tuberculosis but not of activity. For example, after pleural effusion. 2. Early progressive or the stage of attack, because here the body has the upper hand and the disease will probably a to proper treatment. ‘There are three subdivisions :— (a) Acute. (b) Sub-acute. (c) Chronic. 3. Late progressive or the stage of defence, because the disease is now firmly established and the individual cannot reasonably expect a cure, but can defend himself to some extent from the spread of the disease. 4, Chronic fibroid stage or aftermath. Here disease is not pro- 3 gressive or only very slowly or intermittently so. The patient suffers from damage great or small, which has been done during the active stage of the disease. Another classification is built on the type of the disease. Acute: Acute Miliary, Bronchopneumonic, Pneumonic. Chronic: Chronic Miliary, Fibrocaseous, Fibroid. | These types are all well known, but considerable interest has centred around the chronic miliary form of the disease. Chronic miliary tuberculosis was not recognised until shown by radiography to exist in certain patients in whom the disease was chronic. Sayé recognised two types: (1) Chronic miliary tuberculosis of primary infection ; (2) Chronic miliary tuberculosis of reinfection. This latter class he subdivided into four groups : (a) Chronic generalised tuberculosis. (b) Chronic miliary tuberculosis or ‘‘ granulie froide.”’ (c) Localised forms of haematogenous origin. (d) Non-apparent forms. Hoyle and Vaizey (4) have collected details of 120 cases and state that more than 200 examples have been reported up to 1937. For the most part the examples are found in adolescents and young adults and both sexes are equally affected. They state that a cardinal feature of the disease is the disproportion between com- paratively triflmg symptoms and signs on the one hand and ap- parently grave disease, judging by radiographs, on the other. Radiographic examination of the chest is essential for the recognition of the disease but a diagnosis is justified only if there is good evidence that the miliary lesions are tuberculous. The chief difficulty in the differential diagnosis is distinguishing the condition from pneumono- koniosis, sarcoidosis and chronic tuberculous bronchopneumonia. Later Fish (5) described ten cases of chronic miliary tuber- culosis in children. He concluded that the disease runs a chronic course more frequently than is generally recognised and that a fair proportion of these chronic cases recover. The pathology of the lesions in chronic and acute cases is essentially the same, but recovery is commonest when nodules are confined to the lungs although it may also take place in generalised cases and even when the onset of the illness is moderately acute. Healing of the indi- vidual tubercles takes place by a process of fibrosis, which usually leads to the complete disappearance of fine mottling from the pul- monary skiagram. Massive caseous glands in the upper mediastinum are a frequent finding in the juvenile type, and the presence of these glands may be responsible for the tendency to recurrent episodes of tuberculous bacillaemia, which is a feature of these cases. Fish gives warning that any one of these episodes may give rise to fatal meningitis ; the risk of which is, however, considerably reduced if strict bed rest is maintained until the X-ray picture is clear. From Holm (6), of Denmark, comes a classification which is useful when the assessment of a case is desired in numerical terms. The chief characteristics of any particular patient can be summarised in a three digit number, the first digit representing the bacilliary report, the second the X-ray report on the type of lesion and the H. & R. TUBERC, 9 OoOmnNtanrh WN = OCMNAARWON HS First Digit (Bacillary Aspect) ..Gastric Lavage TB — .. Sputum Cultures. TB — ..sputum Microscopy. TB — No further examination. ..No expectoration. Gastric lavage not performed. ..Gastric Lavage cultures. TB + ..Sputum Cultures. TB + .. sputum Microscopy. TB + Few bacilli. ..Sputum Microscopy. TB +-+ several bacilli. ..sputum Microscopy. TB +-+-+ numerous. Second Digit (X-ray Report) ..Process Unilateral. No suggestion of cavity. ..Process Bilateral. No suggestion of cavity. ..Process Unilateral. Suspicion of cavitation. ..Process Unilateral. Distinct cavitation. ..Process Bilateral. Suspicion of cavity on one side. ..Process Bilateral. Distinct cavity on one side. ...Process Bilateral. Suspicion of cavity on both sides. ...Process Bilateral. Distinct cavity on one side. Sus- pected cavity on other side. Third Digit (X-ray Aspect) Using this classification a chronic bilateral, markedly sputum positive case, with a cavity in one lung and fairly dense infiltration involving both upper lobes would be coded as 968. Use of this system for summarising cases is valuable in surveying a series of cases either in clinical investigations or epidemiological research. Norman England has drawn up the following classification which he finds satisfactory for statistical purposes and can be used in con- junction with “* Power ” or other types of card designed for modern calculating machines :— TUBERCULOUS DISEASE CLASSIFICATIONS CODE (a) Primary lesion. : : ‘ ‘ : ; ‘ IA (6) Progressive disease of primary focus __. ; : P B (c) Haematogenous dissemination rd Ye ) (d) Isolated bronchogenic pulmonary 1 General. Tuberculous septicaemia 2 Acute miliary tuberculosis 3 Polyserositis 4 Lungs. Simple pleural effusion i) Discrete foci—single 6 —multiple ve —massive § Primary complex : 9 Epituberculosis . : ‘ : ‘ ; ; IIA Atelectasis . B Pneumonic consolidation 0 Tracheo bronchitis 1 Infiltration—unilateral 2 Infiltration—bilateral . 3 Unilateral cavitation ; 4 Unilateral infiltration ++ cavitation 5 Unilateral cavitation + bronchogenic spread . . 6 Unilateral infiltration +- cavitation -- bronchogenic spread a Bilateral disease (multiple type)—moderate 8 —advanced 9 Q * Eatra- Pulmonary. Skin , Lupus vulgaris Cold abscess poi _ — > Eyes Glands - ; Bones and Joints—spine —hip —sacro iliac —other undefined —multiple Synovial membrane Tonsils . : ‘ ; : ; ‘ Brain. : ; ; : : : Ret ME Genital tract . Urinary tract Peritonitis—general —local Intestinal ulceration stricture ischiorectal disease OnbhwonwreoWrponmrounurnwnrowt Larynx . Associated Disease. Erythema nodosum Phlyctenular conjunctivitis Tuberculide ; : ; : 7 Sarcoidosis. : ; : : - : Vv Pneumonoconiosis Healing. Calcification Fibrosis Clearing weowWPromwr The Middlesex County Council have adopted a useful classification for the purpose of treatment. Patients are divided into five groups as follows :— Pulmonary. Group M. A.—Cases for assessment of activity. Group M. B.—Cases for treatment with a view to final arrest, in the best available beds. In this group there are three sub-groups graded according to considered prognosis, i.e. : M.B.1, M.B.2, M.B.3. Group M. C.—Good working chronics. Group M. D.—Unstable chronics. Group M. E.—Terminal bedridden cases. Surgical, and Combined Surgical and Pulmonary Cases. Group M. S.—Cases with surgical lesions only. In cases where there is a lung lesion plus a surgical lesion, the letter *‘ S ”’ is added to the appropriate pulmonary assessment. Thus :—M.B.1.8.; M.B.2./S.; M.B.38.S.; M.C.S.; M.D.S.; M.E.S. Detailed guidance is given in defining the limits of each group so that it is a comparatively simple matter to allocate any particular case to its respective group and _ thereby direct it to bed where suitable treat- ment is available. Complications are dealt with in a special note to the effect that such complications as tuberculous laryngitis or ischiorectal abscess would not necessarily exclude a case from any of the B groups. Severe enteritis would obviously influence the course of treatment and would usually result in a classification of * E.” No attempt is made to graduate toxaemia in formulating this assessment. There is no reference, therefore, to temperature, pulse, night sweats, sedimentation rate, loss of weight, etc. It is con- sidered that these factors will obviously influence the tuber- culosis officer in making his assessment, but they are, none of them, either singly or collectively, sufficiently specific to establish them as criteria for admission to one group or another. The use of radiography, particularly in surveying large numbers of apparently healthy persons, is bringing increasing importance to terms connected with the very early stages of the disease. These are usually summed up in the term “ minimal lesion.” It is not easy to define this term and it is doubtful if it is possible to give anything more than a generalised indication of what is intended. The definition used in the U.S.A. of a minimal lesion has been given on page 254. Another definition, which is entirely dependent on radiography, describes a minimal lesion as one that occupies an area equivalent to a third of a bronchopulmonary segment. These definitions are not wholly satisfactory, because they depend on the size of radiographic shadows and give no indi- cation of the nature of the lesion. Every clinician knows that a small shadow can give most disturbing constitutional symptoms and cause prolonged illness, whereas a shadow twice the size may be completely symptomless and rapidly reach a stage of arrest. Never- theless, if the term is used an attempt must be made to define it, and the simplest way is to limit the size of lesion by the certain area of shadow cast on the skiagram. The majority of clinicians would exclude any lesion with a cavity from the minimal lesion group, but the American definition does not make that proviso. It would, however, be extremely satisfactory if an international standard of classification and terms could be drawn up so that comparable statistics could be obtained from all countries and particularly from the United States, the Dominions and the United Kingdom. Winefield (7) produced an original classification on the con- ception that “ an initial primary infection is followed by a secondary lesion in the lung which probably escapes notice until it has de- veloped into an intermediate lesion giving rise to physical signs and symptoms. In a successfully treated case this intermediate lesion is converted into a pure tertiary lesion without secondary infection. If treatment is unsuccessful the intermediate lesion spreads by direct extension or occasionally by bronchogenic spread, such as occurs in. terminal states, after haemoptysis, and under anaesthesia. ‘* After successful treatment, relapse or spread of disease is caused by the appearance of new haematogenous secondary lesion, which will behave in exactly the same way as its predecessors. ‘These new secondary lesions may occur time and time again.” In the past it has not been uncommon to find lesions divided into groups: the childhood type and the adult type. Such a classifica- tion is unsatisfactory and misleading, as it tends to give the im- pression that the type of lesion usually found in children is uncon- nected with that common in adults and not part of a pathological process characteristic of the disease. It is much better to use the terms recommended by the National Association and the American Trudeau Society and replace Childhood Type by Primary Phase and Adult Type by Re-infection Phase. The Primary Phase is defined as the morbid processes which follow directly and uninterruptedly the first implantation of the tubercle bacillus. The Re-infection Phase is regarded as the development of chronic tuberculosis of the lungs, usually after a latent period has elapsed after the primary phase, due to the reinfection with tubercle bacilli. Re-infection has been differentiated by Terplan (2) from super- infection ; the latter term being used to indicate the occurrence / PRIMARY AND RE-INFECTION PHASE 263 of infection superimposed on an unhealed existing lesion whilst re-infection is used when further infection takes place where all previous lesions are healed. References (1) NATIONAL TUBERCULOSIS ASSOCIATION (1940) Diagnostic Standards and Classification of Tuberculosis, New York. (2) TERPLAN, K. (1945) Amer. Rev. Tuberc. 51, 321. (8) Woop, W. B. (1988-39) Tubercle, 20, 205. (4) Hove, J. C. and Vaizry, J. M. (1987) Chronic Miliary Tuberculosis, London. (5) Fisu, R. H. (1937) Arch. Dis. Childh. 12, 1. (6) Hom, J. (1946) Publ. Hlth. Rep., Wash. 61, 1426. (7) WINGFIELD, R. C. (1938) Brit. med. J. 1, 179. CHAPTER XIV PUBLIC HEALTH SERVICES The Development of the Tuberculosis Services During recent years chest physicians have taken an increasing interest in the facilities offered by the tuberculosis services of Public Health authorities. This is a welcome sign of progress ; for sound administration must always march forward along with improvements in clinical methods, and the development of a good tuberculosis service depends on the mutual co-operation of the clinician with the administrator. It may, therefore, be helpful to outline very briefly the important stages in the control of the disease. The pioneer work of Sir Robert Philip in 1887, by establishing a dispensary system for the diagnosis and domiciliary care of the disease, laid the foundation on which our present legislation is built, At that time all effort to control the disease operated through voluntary agencies, and it was not until 1908 that notification of the disease throughout the whole country was made compulsory, and then only those cases occurring in poor law practice. It took another four years before regulations were passed requiring universal notification of all forms of tuberculosis irrespective of the place or practice in which they occurred. In 1911 the National Health Insurance Act provided “sanatorium benefit’ for all insured persons. ‘This measure marks the beginning of the active develop- ment of tuberculosis schemes throughout the country, and local authorities were encouraged to provide the necessary facilities for the diagnosis and treatment of the disease in all classes of the population, a capital sum of £1,500,000 being made available by the Local Government Board for this purpose. In 1921 it became a statutory obligation under the Public Health Act (Tuberculosis) 1921 for all county and county borough councils to provide adequate arrangements for the treatment of tuberculosis in dis- pensaries, sanatoria and other institutions approved by the Ministry of Health. Power was also given to county councils to make pro- vision for the after-care of all tuberculous persons. The next im- portant step came in 1925 with the Public Health Act of that year. By this Act, county councils and local sanitary authorities were given power to apply to court for an Order for the removal to an institution, in specified circumstances, of persons suffering from pulmonary tuberculosis. It also extended the power of local authorities for educational work in public health, and from thence onwards education in anti-tuberculosis work forms an integral part of the tuberculosis scheme of each local authority. In 1929 the Local Government Act simplified the organisation of institutional care by bringing the facilities of municipal hospitals into use in the treatment of tuberculosis. All these measures were consolidated in the Public Health (‘Tuber- culosis) Regulations, 1930, and, further, the notification of all cases of tuberculosis within forty-eight hours became compulsory. Registers of such notifications had to be kept by medical officers of health ; but no restrictions were to be placed on any notified person, except at they must not work in connection with a dairy, involving the milking of cows, treatment of milk, or the handling of milk vessels. The 1936 Public Health Act (Sect. 171-175) confirmed the duty of county and county borough councils to provide adequate arrangements for the treatment of all persons suffering from tubercu- losis. The Act laid down the conditions and procedure for the com- pulsory removal to hospital of infectious. persons suffering from tuberculosis of the respiratory tract. It also gave county and county borough councils the power to make such arrangements as they think desirable for the after-care of persons who have suffered from tuberculosis, and provided special regulations concerning the treatment of seamen suffering from tuberculosis. An important order issued by the Ministry of Agriculture and Fisheries in 1938 provides for the slaughter of certain types of tuberculous animals, with compensation to owners. In 1943 the Memorandum 266/T was issued, whereby financial aid was granted to all cases of pulmonary tuberculosis in which there was a reasonable possibility of return to work. Although this was a war-time measure, it established a practice which will no doubt be followed and developed in the future. Finally, the tuberculous person has been recognised as a disabled person under the Employ- ment of Disabled Persons Act (1944) and can thereby enjoy the very considerable benefits of the rehabilitation scheme which that measure has established. Having regard to the existing tuberculosis services throughout the country, this brief summary of the legislature dealing with tuber- culosis shows that full advantage has not been taken of the wide powers granted to local authorities and county councils under the various acts. Much more could be done to trim those ragged ends of the present services which should deal with prevention of the spread of infection and the after-care of those who have suffered from the disease. It would also be pertinent to ask if the treatment services of some local health authorities are really ‘“ adequate ”’ to meet the needs of the population in their areas. The power of compulsory removal of an infectious case is rarely used, and rightly so, for force in such matters always brings com- plications which are difficult to overcome ; but in extreme circum- stances it should not be forgotten that the power has been granted for the protection of the community. The Tuberculosis Dispensary Since the compulsory notification of all cases of tuberculosis, the tuberculosis dispensary has become more and more the hub of the service. Founded on the pioneer work of Sir Robert Philip, the dispensary unit has grown to be the main base in all prevention and care work as well as forming the chief centre for the diagnosis of new cases and making statistical returns on the incidence and mortality of the disease. Generally speaking the dispensary is not usually associated with treatment; this is the function of the sanatorium, nevertheless, it is essential that the important but unostentatious work of the dispensary receives adequate recognition and each centre should be properly equipped and fully staffed for the difficult work it has to perform. The area it serves should be large enough, but not too large, to provide employment for a full- time tuberculosis specialist or chest physician, supported by nurses, health visitors and the services of an almoner. ‘This latter post has been made more necessary since the introduction of the financial allowances under Memorandum 266/T. A full team will also include a radiographer and the facilities of a reliable clinical laboratory where cultures and blood examinations can be done. Consultants in thoracic surgery, orthopaedic and pediatrics should be available as their advice will assist in directing patients to centres where the necessary treatment can be obtained. The dispensary unit should serve a population of about 200,000 in a rural and 100,000 in an urban district. It should be equipped with an X-ray plant, capable of taking, with ease, good chest radiographs with an exposure of ;’5 sec. at 4 feet ; this means that the apparatus should be capable of an output of at least 200 MA, preferably 400 MA to leave a good margin of power. In addition, the apparatus should be fitted with Potter Bucky diaphragm and an efficient tomographic attachment. The dispensary should be closely associated with a general hospital for special services and have equipment to carry out artificial pneumothorax refills, routine skin tests, blood sedimenta- tion rates and other diagnostic investigations. The staff required for such a unit will be usually two medical officers, a chief and his assistant, four or five nurses or health visitors, three or four clerks, an almoner, and care committee secretary. In recent years there has been a growing tendency to develop the dispensary unit into a chest clinic. The idea has many advantages, one of the most important being that the stigma and unpleasant associations so often connected with the word “ tuberculosis ”’ are avoided and patients will be less fearful to attend. A further argu- ment in support of the change is that a high proportion of the cases referred to the dispensary for diagnosis are not suffering from tuber- culosis. In one dispensary the average diagnosed as tuberculous was only 30 per cent. of all new cases. The remainder were either free from disease or suffering from a variety of intrathoracic disorders, The introduction of mass radiography surveys will probably increase the discovery of these non-tuberculous conditions. It seems, there- fore, that there is a good case for the term “chest clinic” and regrading of the tuberculosis officer-as a chest physician. This would naturally imply that the physician in charge of the unit would have to be well qualified and experienced in the differential diagnosis of all respiratory and cardiac conditions and have a good knowledge of general medicine. If such posts were adequately remunerated there is little doubt that they would attract suitable candidates who would be willing to devote their whole lives to the study of tuberculosis and diseases of the chest. A possible extension of present services is the inclusion of the mass radiography organisation within the province of the dispensary. The details of mass radiography have been discussed in Chapter V. Here its place in the Public Health Services is considered. Originally it was intended that the mass radiography unit should act inde- pendently of the tuberculosis dispensary and this was suggested in the Ministry of Health Memorandum 266/T, page 5, para. 16, but some local authorities have made the tuberculosis officer the director of the unit and refer all abnormal pulmonary cases found in surveys to the dispensary for diagnosis. So long as this clinic is termed a Tuberculosis Dispensary it would seem to be an unwise policy to cause unnecessary apprehension amongst all such individuals segre- gated by radiography by sending them to an establishment primarily instituted for the diagnosis of tuberculosis. “The designation ‘* Chest Clinic ’? would overcome this difficulty. On the other hand, it is most important that the tuberculosis dispensary does not lose its function as a unit for the prevention of the disease, which is of equal importance to the treatment of those who are already suffer- ing from active lesions. There is a danger that the public health side of the dispensary work might become neglected if the unit assumed the character of a diagnostic centre for chest diseases. Furthermore, it would be unfortunate if the non-respiratory tuber- culosis lesions were diagnosed and observed at a different place to the respiratory ones, for the social and preventive side is essentially part of the work of the centre in every case irrespective of the site of the lesion. The creation of chest centres would tend to break this comprehensive view of the tuberculosis problem and over-stress the division of cases into respiratory and non-respiratory categories. Although the main function of the mass radiography unit is to discover tuberculosis it should be regarded as a public health service which acts as a sieve separating those with abnormal chests from the normals. The diagnosis of the abnormalities discovered should rest with the existing facilities supplied by general hospitals or chest clinics, referrmg to the tuberculosis dispensaries those cases suspected of or diagnosed as tuberculous. As all these services are available already it is unnecessary to develop the mass radiography unit as a diagnostic clinic. It should, however, be intimately connected, through the general practitioners, with all out-patient departments and other clinics associated with chest diseases within the area it serves. In addition to being a diagnostic unit the dispensary must serve as a centre for providing home visits, extra nourishment, boarding out of children, emergency relief for necessitous patients and a scheme for recommending the rehousing of patients where the need arises. ‘The responsibility for the whole care and supervision of the patient when he is not in a sanatorium rests with the dispensary unit. In fact, care work should proceed as regularly and systematic- ally as treatment and prevention, from which it should not be separated. It should be an integral part of every scheme for dealing with tuberculosis and should not just be associated with it. Arrangements for Treatment The treatment of patients falls mainly on tuberculosis hospitals and sanatoria but as the disease presents wide variations in degree of severity and prognosis, a complete scheme should arrange for the different types to be accommodated in institutions designed and constituted to provide the most suitable environment for each par- ticular category. For instance, it is not good policy to treat pleural effusion and minimal lesion cases alongside of patients undergoing major surgical operations, or to associate either of these groups with — chronic advanced cases. The complete treatment scheme should, therefore, provide units for the separate accommodation of these various classes and, provided it serves a large enough population to produce sufficient patients, such grouping would lead to economy and efficiency. : The complete treatment scheme can be represented diagram- matically with arrows showing the main lines of flow of patients as they pass from diagnosis to complete rehabilitation (Fig. 6). The special features to be noted are :— The Unit for Diagnosis and Assessment. This may be at a chest hospital or a special ward in a general hospital and is reserved for those patients presenting clinical difficulties which make further investigation necessary before admission to a sanatorium or tuber- culosis hospital. Such a hospital must be fully equipped for all diagnostic procedures and the staff must be experienced clinicians with a wide knowledge of chest diseases, otherwise there will be a tendency to label as tuberculosis most abnormal skiagraphic lung shadows. It should also be possible to make a fairly accurate assessment of the patient’s disability so that the need for transfer to a sanatorium for prolonged treatment may not be advised un- necessarily. It is during this period of observation in the special chest unit that an indication of the general course of treatment required by the patient may be obtained and the type of sana- torium determined which is most suitable for the patient’s clinical condition. These diagnosis and observation beds are useful, not ” PUBLIC HEALTH SERVICES 270 “QOIALOS SISO[NIIOGN} B OF VWUIBYDS yUIW}ZBII} oJo]dWo0o Surmoys weidserq@—'g “Sup Be SNOWLLOVed WaSN3d | SS a5 ASSHD SO AAYSGNAdSIC “7AOOHDS ANONOD aibky NSdO AYd TIALS AGN | LINO “TOOHDS “TOOHDS ; NOU Daa93S UN3GIeaS Ay aIeANG 2 IN3DS3TWANOD TWNOUBSOAN ‘WORQIYNYS AyYyNOWwInNd SNSYOMHD LINN NOIGST DUEPHdWAT NOIGST TyWiNtn MOISNssS WaANId AtLidSOH DIA DdOH\AO LINO AAADAINS MIDYVAOHL te Se | Uo, SANIaWwod7 “N3ATTIHD LINDA DUSOND HIG “LINA JNIWSS ACSI 3 DJUSONDV!G SPECIAL UNITS O71 only in adults but also in the treatment of children who often do not need prolonged sanatorium conditions but only well-regulated daily routine of rest and exercise and education. The difficulties ex- perienced in determining the nature and significance of pulmonary lesions in children has long been recognised by paediatricians. In many instances it is not possible to decide upon the necessity for sanatorium treatment without a period of observation. It is for this purpose that a unit should be established either in a children’s hospital or as part of a chest hospital. In this way much sanatorium accommodation for children may be saved as many cases on observa- tion will be found fit for either domiciliary treatment or admission to a residential open air school. The Thoracic Surgery Unit. This essential part of a tuber- culosis service must be fully equipped and serve a sufficiently large area to keep it fully occupied. Its work should not, of course, be confined to tuberculosis cases. If it is not in a special hospital it should be attached to a general hospital or a conveniently accessible sanatorium. | 7 One of the most important considerations in the development of this unit is establishing a thoracic surgical team which can be con- tinuously occupied so that efficiency and skill are maintained at a high level. It is not economical nor in the best interests of the patients to run a thoracic surgery unit that operates occasionally. Infrequency of operating sessions leads to dislocation and break- down in team work and the reliance on improvisation to overcome emergencies. A regional development of thoracic surgery services would overcome the drawbacks of separate isolated units and create a comprehensive organisation, the advantages of which have been fully described in a memorandum issued by the Society of Thoracic Surgeons. The Pleural Effusion and Minimal Lesion Unit. It is becoming increasingly recognised that cases of pleurisy, pleural effusions, and minimal lesions are better treated in‘*a unit to which open cases or those with more advanced lesions are not admitted. It may be conveniently attached to a convalescent hospital, or it may be a separate institution. By this special accommodation such patients avoid the possibility of super-infection and also escape the stigma attached to admission to tuberculosis institutions. The segregation of these cases is not recommended solely on the grounds of the possibility of super-infection or re-infection from the more advanced sputum positive patient, as it is doubtful if this occurs except in the pre-allergic state, or the period immediately following the development of hypersensitivity. The main reason for providing a separate unit for pleural effusions and minimal lesions is to avoid the stigma which is still associated with sanatorium treatment and also to avoid the close association of patients with early forms of tuberculosis with those who are having treatment by major thoracic surgery or other special therapeutic measures. The possible reaction of the apparently fit patient thinking: ‘“‘ as you are so I may be,” when seeing advanced cases, may retard recovery and even cause deterioration. The Convalescent Sanatorium is necessary for chronic cases requiring a period of recuperation, or segregation as a preventive measure. Such an institution requires comparatively little in the way of skilled medical and.nursing staff but it does need a depart- ment for diversional and occupational therapy. If these homes are not allowed to develop into sanatoria or hospitals providing all or most of the facilities for modern treatment, but are kept for rest and occupational therapy they can be run economically and relieve the hospitals and other sanatoria of many chronic cases. They can be staffed by a visiting medical staff, resident matron, assistant nurses and instructors. If possible they should be situated on the outskirts of a town. In Amsterdam it has been possible to adapt large barges lying in the canals for this purpose as well as houses in the city. The Open Air School. This institution for the education of children who have either completed treatment, or do not need such careful medical supervision as is provided at a sanatorium, may be residential or day boarding. The residential school, although it has not been established so frequently as the day school, has many advantages as it partially fulfils the function of a sanatorium and at the same time ensures adequate educational supervision. The disadvantage of the day open air school is that the child may return to unsatisfactory conditions at night. The school for physically defective children is a similar institution to the open air school but confines itself to the admission of orthopaedic cases. The Colony or Village Settlement. Every complete tuber- culosis scheme should provide facilities for the rehabilitation of tuberculous persons at an industrial colony or village settlement. The successful development of this unit, which must work in close | SPECIAL WORKSHOPS 273 co-operation with the sanatorium, requires considerable expenditure of capital and a bold constructive policy with expert direction and leadership. It is necessary for it to serve a sufficiently large population to ensure economic and industrial success. This calls for collaboration between local authorities in a regional scheme whereby each contributes to the unit serving the area and in return receives benefits and facilities which could not be provided by a small local authority from its own resources alone. The subject is discussed in greater detail in Chapter XI so that here it is only neces- sary to emphasise the importance of this unit which gives the patient the opportunity of regaining confidence in himself.as a worker and eventually a home with security from want for himself and his family under conditions which reduce the possibility of relapse to a minimum. To the medical officer the unit provides means of accurately assessing the working capacity of patients under industrial conditions and, at the same time, the opportunity of prolonged treatment under close clinical observation. There is little doubt the capital outlay gives adequate return in both preventing the spread of the infection to others and the healing of disease in the individual, provided the right type of case is admitted. The village settlement must not be regarded as a dumping ground for all those patients who are incapacitated by chronic slowly progressive disease and have little or no hope of recovery. Special Workshops. These factories where tuberculous per- sons may find employment under sheltered conditions whilst living at home or lodging at a night sanatorium have not been developed in this country up to the present. Efforts have been made to establish such units by voluntary agencies and a fair degree of success has been achieved in this direction by the Spero Fund for the Welfare of the Tuberculous, but recent work in the U.S.S.R. shows that such workshops are an essential part of all complete rehabilitation schemes for the tuberculous. The place of these institutions has, therefore, been indicated in the treatment scheme discussed in Chapter XI as forming an integral part of the organisation devised to enable the patient to return to normal industry or work permanently under sheltered conditions. Since the passing of the Disabled Persons Employment Act (1944) a scheme for establishing a number of these special workshops under the direction of the Disabled Persons Employment Corporation has been inaugurated so that in future this most important need for the rehabilitation of the tuberculous will be satisfied. These workshops will not be under the Ministry of Health but the medical supervision of the tuberculous employees will probably be mainly the responsibility of the tuberculosis officer who will decide the amount and kind of occupation to be done by each individual. A certain amount of training may be introduced so that although some persons may remain at these special workshops for a number of years, others, it is hoped, will pass eventually into normal industry as skilled, or semi-skilled, workmen, according to their physical and mental capacity. Accommodation for the Combined Case. By combined cases is meant patients presenting both respiratory and non- respiratory lesions. They are particularly difficult to accommodate in an institution as they are usually infectious and cannot, therefore, be admitted to the non-respiratory wards and, at the same time, they require special facilities for the treatment of the non-respiratory lesion which cannot be obtained at a sanatorium for respiratory eases. These patients require beds at a general hospital for the initial forms of treatment and at a specially equipped sanatorium for the recoverable cases. The other features shown in the diagram are units which are familiar to all tuberculosis workers and are included in the majority of local authority schemes and, therefore, need no comment. The organisation of a scheme which has been briefly outlined requires considerable financial outlay and cannot be maintained by all local authorities. Its success also depends upon the number of patients requiring treatment in that their aggregate must be large enough to provide a reasonable demand for the special units which have been described. For instance, it would not be practic- able to establish a unit for thoracic surgery for say ten patients requiring thoracoplasty each year, or a residential open air school for ten or twelve children. The population of the area controlled by the majority of local authorities is too small to carry a tuber- culosis service which will meet the needs of all the patients. The remedy for this lies in fusion of a number of authorities to form a joint body which will be justified in providing a complete scheme to meet the demand from the large number of all kinds of cases requir- ing treatment. Diagnostic and preventive measures connected with dispensary work would still remain the responsibility of each respective local / PRESENT LEGISLATION 275 authority but all residential treatment and rehabilitation measures would be under the joint authority. Such a scheme has been worked out in detail by Lissant Cox in a memorandum to the Joint Tuberculosis Council. It has also been envisaged by the Society of Thoracic Surgeons in a recent publication and in a wider sense forms the basis of the hospital service in the Ministry of Health’s comprehensive national health service. Present Legislation Memorandum 266/T. Since September, 1939, important con- cessions have been granted which have opened up a new field for the benefit of the tuberculous. Acting on the advice of the Com- mittee on Tuberculosis in War-time of the Medical Research Council, the Ministry of Health issued Memorandum 266/T, whereby financial assistance may be given to all persons suffering from pulmonary tuberculosis who have given up gainful occupation to undergo treatment, except in such cases “‘ where treatment cannot do more than alleviate a chronic condition.” The principles upon which this memorandum is based are those which tuberculosis workers have been fighting to obtain for many years and considerable grati- fication was expressed when their labours were successful, but unfortunately the benefits which have been formulated are severely limited in their application as they cannot be granted to chronic pulmonary cases unlikely to recover or non-pulmonary cases. The assistance is regarded as a part of the approved treatment and may be given to the following four categories suffering from pulmonary tuberculosis with the proviso previously mentioned :— 1. Those recommended for institutional treatment who are wait- ing admission and who have ceased work on the advice of the Tuberculosis Officer. ye 2. Those under treatment or observation in an approved insti- tution. 3. Those who have received a period of institutional treatment (a) in all cases for a period of six months, not capable of resuming full employment; (b) thereafter those capable of light work but not full work for a further two periods of six months on certification by the Tuberculosis Officer ; (c) ex- ceptionally for a period of twelve months in cases recom- mended by the Tuberculosis Officer where he considers the. equivalent of sanatorium treatment can be carried out at home. The primary object of the special measures is “ to enable necessary treatment to be undertaken without financial anxiety about the support of the family or the upkeep of the home.” By doing this it is hoped that diagnosis and treat- ment will be received at the earliest possible stage and thereby reduce the sources of infection and improve the results of treatment. Three kinds of payment are possible :— 1. Maintenance allowances based on a standard scale and with- out any test of means. 2. Discretionary allowances on proof of need towards meeting standing charges such as high rent, insurance, etc. 3. Special payments such as travelling expenses, domestic help in the house when the housewife is undergoing treatment and pocket-money where a person without dependants is under- going treatment. Where the Memorandum 266/T does not apply relief can be obtained through the Social Welfare Department. Although the _rates of relief from this source vary in different parts of the country it is interesting to compare the amounts of financial benefit that are granted in a family of husband and wife and three children in each case. Under London Under 266 /T Social Welfare (1946) Husband and Wife . 39s. Od. 33s. Od. Child (11 plus) ; : 10s. 6d. lls. Od. Child (8211) Sts spsee Fae 9s. Od. 9s. 6d. Child (under 8) ; 7s. 6d. 8s. Od. 66s. Od. 61s. 6d. These amounts are only a rough comparison as there are items such as National Health Insurance which is deducted from 266/T but not from Social Welfare allowance. On the other hand, under 266/T there are a number of discretionary allowances for rent, domestic help and fuel which may be, but are not usually, provided under social welfare if a cash payment is made. In 1947 the discretionary allowances under 266/T were in- creased, but both allowances are still a low figure to cover the necessities of life, particularly with the post-war rise in the cost of living. Nevertheless it is a very valuable help, particularly when one considers the findings of the Joint Committee set up by the National Association for the Prevention of Tuberculosis (1942) to enquire into the Income and Food Expenditure of Tuberculous Households in war-time, that seven out of ten households, below the standard of living deemed to be adequate, would go above it if given the maintenance allowance and, if in addition the wife of the householder patient becomes gainfully occupied, the Maintenance Allowances would put all such households above the standard. There is, therefore, no doubt that the granting of these allowances is a step in the right direction, as tuberculosis is a disability that has greater effect on the family income, is more prolonged in its operation at a time when the productive and earning capacity of the individual is the highest, and makes the future more precarious than any other chronic disease. It is to be hoped that when the financial aid under Memorandum 266/T is withdrawn and all monetary aid comes under the National Insurance Act special consideration will be given to the tuberculous so that hardship and privation will be avoided and an adequate standard of living may be main- tained. The Disabled Persons (Employment) Act, 1944. This Act confers wide powers on all local authorities for the rehabilitation of disabled persons. Under Section 15 (c) it is possible for the Minister of Labour and National Service to make financial contributions towards providing facilities enabling registered disabled persons ‘who by reason of the nature or severity of their disablement are unlikely either at any time or until after the lapse of a prolonged period to be able otherwise to obtain employment or to undertake work on their own account ” to obtain employment or to undertake such work under special conditions and for the training of such persons for the employment or work in question. The Act gives the Minister power to make arrangements for the provision of non- profit making companies for the employment of the disabled. Pay- ment may also be made by the Minister : (a) in respect of the expenses of the formation and incorporation of such a company ; (b) to any such company, association or body in respect of ex- penses incurred by them in providing facilities for the employ- ment of the disabled ; (c) to any local authority in respect of expenses incurred by them in carrying out the provisions of the Act and certain travelling expenses of the disabled. To carry out this work the Minister is to establish a National Advisory Council and district advisory committees. In addition there are to be officers appointed for the purpose of administering the Act. The ground is, therefore, now cleared for considerable extension of the rehabilitation services—in fact, if it be so desired, there would appear to be nothing to prevent local authorities establishing or assisting in establishing special employment centres, whenever necessary, for the tuberculous who are unable to work in normal industry. In this way the previously rather neglected part of our tuberculosis services dealing with rehabilitation could now be de- veloped. General Tendencies. During the last fifteen years tuberculosis services have been considerably extending throughout the country. Between 1933 and 1938 the number of beds approved by the Ministry of Health for the treatment of tuberculosis increased from 27,134 to 30,792. This accommodation was sufficient to cope with the demand for treatment, but recently the waiting list has grown to an alarming figure. In England only, during the last five com- plete pre-war years (1934-1938), the total average waiting list varied from 1,748 in 1934 to 904 in 1936. This figure had risen to 4,628 by March 1945, whilst the number of available beds had fallen by over 2,000, so that the position in 1945 in England and Wales was : ree Beds empty, but temporarily | Beds empty and eet ramet Beds provided not available ready for use Waiting lat 29 327 a 975 | 4,628 By December, 1946, the waiting list figure rose to about 7,000. (Lancet, 1947, 1, 349.) It must now be acknowledged that there are insufficient beds to meet the needs of the country and the present position is most critical. It is mainly due to the shortage’ of both nursing and domestic staff which is causing nearly 4,000 beds to be out of use. The problem is a very serious one as the shortage of available beds means that many open cases are among the population spreading the infection to children and young adults and are themselves de teriorating through lack of treatment. At the same time the pro- vision of treatment is becoming more complicated by the extended use of thoracic surgery. The average period of treatment is also becoming longer, and more specialised treatment means an increased demand on beds staffed by trained nursing and medical teams and equipped for major surgical operations. The two currents, therefore, of shortage of staff and more highly specialised treatment run in opposite directions and are causing an impossible situation. Moreover, there is little doubt that during recent years we have concentrated on the treatment of the disease and tended to neglect the treatment of the patient. This is particularly unfortunate as we cannot provide the necessary facilities which we now consider neces- sary to treat the disease, the result being that in a large number of instances neither the disease nor the patient is treated. An interest- ing sidelight, which is a reflection of this general tendency of con- centrating on the treatment of the lesion, is the deterioration in both discipline and individual instruction in hygienic measures at the majority of tuberculosis hospitals and sanatoria. ‘To maintain that a patient goes to a sanatorium for a period so that he can receive education in correct living and precautionary measures, as well as treatment, is very often wishful thinking, for in many institutions there is insufficient effort to ensure that the patients understand the necessity for, and the means of preventing, the spread of infec- tion to others and guarding against re-activating their own lesion. There is no doubt that the extended use of collapse therapy has had a marked effect on the sanatorium routine and that the insistence on keeping to a strict programme of graduated rest and exercises has been relaxed. This change in attitude towards the necessity for maintaining strict rules in a sanatorium brings with it the danger that the patient regards his disability in a casual and irresponsible manner and thereby leads him to take liberties which are incom- patible with his physical condition. The most efficient treatment is obtained when methods of collapse therapy are combined with all the advantages which can be obtained from adherence to a definite programme of graduated rest and exercises leading by progressive stages to occupational therapy and eventually industrial rehabilita- tion. During this period a programme of instruction in hygienic living and precautionary measures should be included as an essential part of sanatorium treatment. Tuberculosis and the National Health Service Act As most of the suggestions embodied in the White Paper issued on “‘ A National Health Service ” (1944) have now been embodied in the Act it is interesting to note the changes with regard to tuberculosis. The White Paper criticised the existing service by stating that “ it tends to be administered as a separate entity, perhaps not enough related to the diagnosis and treatment of other chest and respiratory conditions or to the work of the general hospital, because it has come into being as a separately organised service with one particular object.” , It is not therefore a surprise that the far-reaching changes that have been imposed on the health services by the Health Service Act profoundly affect the tuberculosis services. The general principle seems to be to eliminate as far as possible the tendency to regard tuberculosis as a speciality and to separate preventive measures and care of the patient from institutional treatment. This is an un- fortunate move, for the most satisfactory results are obtained where these services are completely integrated or closely associated with each other. Under the Act the dispensaries become the responsi- bility of the hospital boards, but the local health authority remains in charge of preventive measures and the after-care of the patient. All treatment and medical rehabilitation will be carried out under the officers of the hospital boards but industrial rehabilitation will be the function of the Ministry of Labour and National Service and the local health authority. As the dividing line between medical and industrial rehabilitation is very obscure in dealing with cases of pul- monary tuberculosis it will be difficult to know when a patient passes from the responsibility of the Ministry of Health to the Ministry of Labour and National Service or the local health authority. The scheme to associate the dispensaries with general hospitals is a good one, and the proposal to regard the tuberculosis officer as a chest physician has much to commend it from the point of view of diagnosis and treatment, but it is of the utmost importance that Local “Health Authority | : M. 0. H. ional Hospi 1 Board DISPENSARY OR CHEST CLINIC 4 (Chest Physician) CIIIIITIL LLL LLL LIT LTT TREATMENT CLI IIIIITII LLL LLL LL LLL . Ministry of VLLLLLLLLALAA LAM AAA AA AMA AAA L a bo ur CARE AND AFTER- CARE LLLLLLLLLLLLLLLLL LLL LL PIIIIII ITIL ITI IIL IIL ILI LLL LL LLL} PREVENTION (LOTTI IIT III IIIA LALLA LLL VILLI LLL LAMA AA ALL yee || REHABILITATION WLLL LILILLILLL LAI LL LLL ie Colony ie e ae Care Nigh Committee Contact Examination | Re-employ | | Re-employ | Ce Normal Industry Surveys Mass B.CG. Radiography [— Vaccination Materuity and Child Welfare Clinic NAP T: Fig. 7,—M.O.H. = Medical Officer of Health. N.A.T.P. = National Association for the Prevention of Tuberculosis. this side of the tuberculosis problem does not receive undue atten- tion and the social and economic sides become neglected. The treat- ment of those suffering from the disease is only part of the tuber. culosis service and must not be allowed to eclipse the equally im- portant work of preventing others succumbing to the infection. It is for this reason that the dispensary and not the treatment ward must remain the central point of the service around which the whole service revolves and to which the family should be able to look for guidance, help and assistance in all matters concerning the disease. The tuberculosis officer is the doctor in charge of this unit and it is essential that he retains his duties as public health officer as well as chest physician. Because tuberculosis is still fifth in the causes of death and the major cause of disability in young adults and is an infectious disease which is difficult to prevent, it should have special consideration under the Act. Moreover, it has always been a fundamental principle of tuberculosis schemes that the family must be treated as a unit and that little success in combating the disease will be obtained if the treatment of the patient is the only consideration. For these reasons it is essential that a close relation should exist between the tuberculosis work of the Regional Hospital Board and the respon- sibilities of the Local Health Authority with regard to prevention of the spread of infection and the care of the patient when at home. This may be possible if the chest physicians under the hospital boards realise their responsibilities to the public health authority with regard to prevention and after-care, but they will be handi- capped in carrying out this work if special health visitors are not allocated for tuberculosis work as, at present, successful domiciliary tuberculosis work depends very largely on the efficiency, tact and understanding of the tuberculosis nurse attached to the dispensary. The dispensary or chest clinic is the key to a successful scheme for the prevention and treatment of tuberculosis and in the new Health Service this principle should be maintained. The functions of the various units and their inter-relationships are shown in Fig. 7 (p. 281). Close liaison should be established between the Regional Boards and the Local Health Authority responsible for care and after-care organisation, through the Medical Officer of Health. There is room, also, for voluntary effort. In this way treatment, prevention, and rehabilitation may be co-ordinated and developed equally. Age. See Mortality rates; Resist- ance; Tuberculosis, pulmonary, prognisis in, 120 Air-conditioning in treatment, 120 Air embolism, 176, 182 Air-raid shelters. See Shelter life. para-Aminosalicylic acid, 131, 132 in relation to tuberculous em- pyema, 159 Anaemia after thoracoplasty, 195 Antibiotics. See Chemotherapy. Apicolysis, paraffin plomage in, 179 technique of, 178, 179 use of, 178 extrafascial. techniaue. Artificial pneumothorax, 135 See also Collapse therapy. assessment of results of, 233, 234 aviation in relation to, 161, 162 bilateral, 140 cavity, tuberculous, treated by, 202 comparison of, with thoraco- plasty, 187 complications of, 146 See also Cardiovascular sys- tem ; effusion, pleural ; effu- sion, purulent; effusion, serous; gas embolism; mediastinum displacement ; needle puncture; novocaine, reaction to; pleura, thick- ened ; pleura visceral rup- ture ; pleural hernia ; pleu- risy ; pheumoperitoneum. contra-lateral, 141 contra-selective, 139, 140 endobronchial tuberculosis in relation to, 202 indications for, 135 See also Cavities; children ; diabetes ; pleural effusion ; haemoptysis ; occupation ; pain ; pregnancy ; sputum ; tuberculosis. relation to See Thoracoplasty, Artificial pneumothorax—cont. maintenance of, 1438 optimum degree of, 144 persistent, 142, 148 selective, 139 termination of, 14.4 Assman’s infraclavicular focus. See Focus, solitary. Atelectasis, in children, 31 following thoracoplasty, 194 pulmonary, lung excision for, 209 Aviation. See Artificial pneumo- thorax, aviation in relation to. Azo-T, irrigation of pure tuberculous empyema, 160 B.C.G., oral administration of, 53, 55 production of, 51 vaccination, 51 blood changes following, 57 decrease in complications from, in Scandinavia, 52 duration of immunity from, 54 efficacy of, 53, 54 Joint Tuberculosis Council sur- * vey of work with, 53 Mantoux test in relation to, 52 methods, 52 pathological changes following, 53 protecting against primary in- fection, 53 segregation of patients, 57 ulceration following, 52 | Bacillaemia, 82 Black lobe, 109, 198 Blood sedimentation rate, 245 . Boarding out scheme. See Segrega- tion. Bornholm, B.C.G., vaccination in, 55, 56 Bronchial tree, bronchoscopic ex- amination of, in endobronchial tuberculosis, 199 investigation of, 100 Bronchiectasis, 68 See also Lesions, suppurative. coincidental with pulmonary tuber- culosis, 110 in relation to collapse therapy, 109 to pulmonary tuberculosis, 108, 109 to tuberculous bronchitis, 109 resulting from previous tubercu- lous infection, 110 secondary, tuberculous infection of, 110 Bronchitis, chronic, 68 tuberculous. See Bronchiectasis. Bronchography, ascending, 250 Bronchus, carcinoma of. See Lesions suppurative. tuberculosis of, 197 Calcareous deposits, mosis, 72 Calcified foci revealed by mass radiography, 95 Calcium, in treatment, 123 Cardiac failure in therapeutic pneu- moperitoneum, 178 after thoracoplasty, 196 Cardiovascular disorders, by mass radiography, 96 Case finding, methods, 47 Cavernography, 205 Cavity, tuberculous, bronchoscopic suction for, 202 closed suction drainage of, 203 See also Drainage, transpleural. closure of, in relation to artificial pneumothorax, 136, 202 in relation to thoracoplasty, 196 formation of, 200 persistent tension, lung excision for, 209 relation of, to patency of supply- ing bronchus, 201 types, 200, 201 Chemotherapy: 121 agents, pre-clinical acceptance of, 125 antibiotics, 128 Children, chronic miliary tuber- culosis in, 257 performance of artificial pneumo- thorax in, 138 provision of tuberculous-free en- vironment for, 46 in histoplas- revealed criteria for Climate, in relation to treatment, 119 Coccidioidomycosis, 72 Collapse therapy, surgical pro- cedures, 165 See also Apicolysis; drainage, transpleural; lung excision ; phrenic nerve ; pneumonolysis ; pneumoperitoneum ; pneumo- thorax ; thoracoplasty. Concentration method, 74 Congo red, injection for haemoptysis, 1038 Contact, after history of, 48 history of, 70 definition of, 47 examination of, 47 tuberculosis mortality in, 48 Culture media, 75 Cutler curves, 245 Detergents, 158 in treatment of mixed tuberculous empyema, 158 See also Phemeride. Diabetes, importance of radiography in, 112 predisposition to pulmonary tuber- culosis in, 112 prognosis of tuberculosis coincident with, 112 in relation to collapse therapy, 112, 139 to pulmonary tuberculosis, 111 Diagnosis, 64 differential, 70 radiographic, 64, 73 special tests in, 74-83 Diagnostic unit, 269 Diaphragm, rupture of, 177 Diasone, 127 Diet, 117 Disabled Persons Act, 1944...277 Dispensary, tuberculosis, 266—269 importance of, in tuberculosis services, 282 Diversional therapy, 219 Drainage pleural, in mixed empyema, 158, 159 postural, 118 trans-pleural, 196 cavernography in, 205 complications of, 206 chest (Employment) tuberculous Drainage, transpleural—continued. indications for maintenance of, 205 prognosis of, 205 scope of, 206 serial X-ray photographs in, 205 technique of, 203, 204 Drug fastness, acquisition of, by infecting organism, 125 See also Streptomycin. Dyspnoea, 66 Effusion peritoneal, 176 pleural, in children, 31 complicating artificial pneumo- thorax, 150 in diagnosis of tuberculosis, 68 * occurrence of, 32,33 | special treatment unit for, 271 treatment by artificial pneumo- thorax, 138 purulent complicating artificial pneumo- thorax, 155 pus formation in, 155, 156 serous aspiration of, 154 Electron microscope, use in tuber- culosis investigation, 38 Emphysema, subcutaneous, 176 Empyema, tuberculous definition of, 156 management of, 157 prevention of, in relation to artificial pneumothorax, 156 in relation to lung excision, 210 mixed, 157 thoracoplasty in relation to, 159, 161 pure, 159 Endobronchitis, tuberculous, 197 Enteritis, tuberculous, 104 Environment See also Village settlements. influence on infection, 59, 62, 70 industrial, and tuberculosis, 70 physical, in relation to treatment, 120 Epidemiology, problems of, 1 Epituberculosis, 255, 256 characteristics and theories of, 33 Extrafascial space, haemorrhage into, after thoracoplasty, 195 285 Faeces, examination of, for tubercle bacillus, 76 Family history, 69 See also tuberculosis, pulmonary, prognosis. Fatty acids, 130, 131 Fibrosis, pulmonary, lung excision for, 209 Fistula in ano, 69 Fluorescence method, 77 Focus, primary, 255 solitary, 73 Fungus infections, 72 G.A.G.C, * B,” 133 Gas embolism, 146 Gastric lavage, 75 Gelatine, acriflavine, calcium chlor- ide (G:A.C.C. “ B”’), 133 Ghon’s focus. See Focus, solitary. Gold therapy, 122, 123 Haemoégram, 81, 82 Haemoptysis, 65 degrees of severity, 102 management of, 102, 103 in relation to artificial pneumo- thorax, 104, 137 in relation to thoracoplasty, 104 in sudden onset of disease, 66 use of blood coagulants in, 103 Hamburéger’s test, 79 Heredity in relation to prognosis of pulmonary tuberculosis, 241, 242, Histoplasmosis, 72 Hypersensitivity, 23-30 Immunisation See B.C.G. ; vole bacillus. methods, 50 Immunity. See Resistance. Industry, employment of tuber- culous patient in, 216 Infected material, 39, 40 Infection bovine, 41 control of carriers of, 62 endogenous and exogenous, 34, 35 in the home, 49 See also Contacts ; village settle- ments. Infection—continued. primary, 26 factors influencing 27-30 in children and young adults, characteristics of, 30, 31 reaction of previously infected body to, 26 Influenzal chill and onset of tuber- culosis, 68 Injections, intrapulmonary, 133, 134 Inoculation test, 75 Insulin, in treatment, 117 Iodine, in treatment, 1238 course of, Laryngeal mirror test, 75 swab culture technique, 76 Laryngitis chronic, 69 tuberculous, 105 Legislation, anti-tuberculosis, 264— 266, 275 See also Disabled Persons (Employ- ment) Act, 1944; Ministry of Health ; National Health Service Act. Lesions, classification of, 94 suppurative, confusion of, pulmonary tuberculosis, 72 Lobectomy. See Lung excision. . Loeffler’s syndrome, confusion of with pulmonary tuberculosis, 71 Lung abscess, 72 excision, 206 comparison of, with plasty, 210 complications of, 209 indications for, 208, 209 results (of lobectomy and pneu- monectomy), 207 unexpandable, causes of, 142 Lymphatics, pulmonary, and fection, 32 with thoraco- in- Mantoux reaction, comparison with Vollmer and _ tuberculin jelly tests, 79 test, 47 B.C.G. vaccination in relation to, 52 Mass Radiography, 8 abnormalities, non-tuberculous, revealed by, 96 incidence of tuberculosis, shown by, 8, 9 Mass Radiography—continued. methods, 89 surveys, 90—92 classification of lesions found by, 95 further investigation following 92 lesions found by, 93 value to the’ tuberculosis services, 93 Mediastinum, displacement of, 142, 148 Meninges, bovine tuberculosis of, 43 tuberculosis of, 5 mortality from, in London, 6 Mental factors, influence in tuber- culosis, 120, 121 Middlesex County Council, classifi- cation of pulmonary tuberculosis in relation to treatment, 260, 261 Milk contamination of, after pasteurisa- tion, 44. effect of clean supply of, 12, 41 grades of, 44 pasteurisation of, 48, 44 production, cleanliness in, 44, 45 trade, control of workers in, 44 Milk (Special Designations) Regula- tions, 45 Milk and Dairies Order, 1926—88...45 Minimal lesion definition of, 254 radiography in relation to, 261 special treatment unit for, 271 Ministry of Agriculture and Fisher- ies, 265 Ministry of Health Memorandum 250-253 Memorandum 266/T, 275 See also State. Mortality decline in, 2 amongst young adults, 13 checked by war, 2, 3, 6, 7 Mortality rates by age groups, 10, 11 effect of clean milk supply on, 12 of higher nutritional standards on, 12 of hours of work on, 12 of increased genetic resistance on, 13 37/T (revised), ‘ Mortality rates—continued. effect of living conditions on, 7, 12 of occupation on, 7, 8 of social status on, 8 of tuberculosis services on, 12, 13 National Health Service Act and Tuberculosis, 280 Needle puncture, accidents following in pneumothorax, 149 Night sanatoria, 46 Night sweating, 65 Novocaine, reaction to, 147 Nutrition. See Diet; mortality rates. Occupation artificial pneumothorax in relation ; tos. tas tuberculosis in relation to, 70 Occupational therapy, 220 Oleothorax use .in case of serous effusion, 155 Open air school, 272 Overcrowding, 58 Pain, pleural, relief by artificial pneumothorax, 138 Papworth. See Village settlements. para-Aminosalicylic acid, 131, 139 Paraffin wax, in apicolysis, 178, 179 Penicillin, mixed tuberculous em- pyema treated with, 157, 158 ‘Peritoneal cavity, haemorrhage into 176 Phemeride, 158 Phrenic nerve, 171 Physiotherapy, use of, in relation to thoracoplasty, 191, 193 — Pleura, thickened pneumothorax in reliaon to, 150 pyopneumothorax in relation to, 150 revealed by mass radiography, 95 tuberculosis of, 68, 69 visceral, rupture of, 149 Pleural adhesion, 165 effusion, 31, 150 unit, 271 hernia, 148 shock, 146 symphysis, apicolysis in, 178 287 / Pleurisy, in relation to artificial pneumothorax, 150 dry, 68 Pneumomediastinum, 177 Pneumonectomy. See Lung ex- cision. Pneumonia, confusion of, with pul- monary tuberculosis, 71 tuberculous caseous, in children, 31 Pneumonitis, after thoracoplasty, 195 Pneumonokonioses predisposition to pulmonary tuber- culosis in, 70 Pneumonolysis, 165-170 extra-pleural, 181 Pneumoperitoneum, 147 indirect, 148 therapeutic, 174 Pneumothorax artificial, 135 extra-pleural, 180 comparison of plasty, 1838 complications of, 182 conversion of, to oleothorax, 180 difficulties: in establishment of, 182 end results of, 183 forms of operation for, 181 severity of operation for, 181 technique of Graf and Schmidt, 180 spontaneous, 67 after rupture of visceral pleura, 149 in relation to thoracoplasty, 195 Post-primary lesions, definition of, 255 Pregnancy, 69 dangers of post-partum period in relation to tuberculosis, 1138 in relation to artificial pneumo- thorax, 138 in relation to mass radiographic surveys, 115 management in relation to tuber- culosis, 114 termination of, in tuberculosis, 114 Preston Hall. See Village settle- ments. Primary complex, definition of, 255 focus, definition of, 255 closed internal ; with thoraco- Promine, 126 in mixed tuberculous empyema, 159 in tuberculous laryngitis, 108 local application of, 127 Promizole, 127 Prothrombin deficiency, ptysis and, 103 Psychoneuroses, in relation to differential diagnosis, 71 Pyopneumothorax rupture of visceral pleura and, 149 haemo- Race, comparative susceptibility to infection, 20, 69 in relation to tuberculosis, 19 Radiography, angular, 100 interpretation, 87 miniature, 88 methods in mass surveys, 90 organisation and cost of unit for mass surveys, 96-98 positioning, 84—87 standards in, 85 Rehabilitation difficulties of, in relation to tuber- culosis, 212 problem of, 222 prognosis in pulmonary tubercu- losis in relation to, 248 recommendations of Joint Tuber- culosis Council on, 223 sehemes of, cost of, 225 medical care in, 228 special methods in, 213 state grants in aid of, 221, 222, 225-226 , treatment of tuberculosis, in rela- tion to, 218—222 Rehabilitation, non-residential, 214 employment in special work- shops during, 215 Rehabilitation, residential, 213 Re-infection, 26 phase, definition of, 262 Resistance definition of, 18 hypersensitivity and, 24, 25 lack of, at various ages, 21 relation to age, 20, 21 to exposure to infection, 22 to mental factors, 120 to race, 19 Resistance, acquired, 25 infection and, 26, 29 genetic. See Mortality rates. Resistance—continued. native high, and infection, 29 ~ variation of, 19 natural, 27, 28 Respiratory tract, diseases of differentiation from pulmon- ary tuberculosis, 71 non-tuberculous, 96 Rosenthal’s multiple puncture method. See B.C.G. vaccination. Sanocrysin, 122 Scandinavia, B.C.G. in, 52 Sanatorium advantages of treatment in, 116 convalescent, 272 night, 46 Sedimentation test, 81 Segregation, 46 Serial observation mass radiography in relation to, 99 value of, 838 Serum endotoxoid, 1382, 133 Sexes, comparative incidence of tuberculosis in, 69 Shock, operative, following thoraco- plasty, 194 Skiagrams See also Tomography. interpretation of, 97 Sodium tetradecyl sulphate. See Azo-T. 160 Sputum, collection and disposal of, 39, 40 in endobronchial tuberculosis, 198 obtaining sample of, 75 positive, conversion of, in relation to artificial pneumothorax, 137 tubercle bacillus in, 39 Sputum smear, examination of, 74 State See also Legislation culosis, 264, 275 tuberculosis problem and, 1, 8 Stenosis, bronchial, lung excision for, 208 Sterilisation of infected material, 40 Stoddart solvent cleaning method, 40 Streptomycin drug fastness in relation to, 130 toxicity of, 130 use of, 129, 130 vaccination anti-tuber- Sulpha drugs, 124 Sulphanilamides, 125, 126 Sulphapyridine, 126 Sulphones, 126 Sunlight, lack of, 59 Superinfection, 26 Surveys, case finding, 8 Systemic disease, differential diag- nosis in relation to, 71 Tests, diagnostic, 74-83 Thoracic surgery unit, 271 Thoracoplasty adverse effect on disease of opposite lung, 188 assessment of results of, 235, 236 comparison of, with artificial pneu- mothorax, 187 with lung excision, 210 complications, post-operative, 194— 196 contraindications to, 190 failure of, lung excision following, 208 indications for, 187 operative accidents in, 194 physiotherapy in relation to, 191, 193 post-operative management of, 192 pre-operative management in, 191 scope of, 185 selection of cases for, 189 surgical risk in, 185 technique, 185, 186 Thoracoplasty, supplementary, 196 Tomography, special uses of, 100 Trachea, tuberculosis of, 197 Tubercle bacillus avirulent, injection of, 50 culture of, 75 demonstration of, 37 diagnosis in relation to, 37, (8 eri ar ei destruction of, 45 habitat of, 39 injection of, 50 methods of demonstration of, 74 recovery of, from faeces, 76 resistance of, to chemothera- peutic agents, 38 Tubercle bacillus, avian, 38 Tuberculin, 133 failure of patient to react to, 80 Tuberculin jelly test, 79 Tuberculin test, 77 289, Tuberculin test—continued. methods, 78 value on case finding, 81 Tuberculoma Lung excision for, 209 See also Focus, solitary. Tuberculosis estimated incidence of, 8—10 factors in prevention of, 62 national problem of, 10 post-partum development of, 69 prevention of, 37 See also Infection. secondary invasion by, 69 Tuberculosis, abdominal, 7, 43 acute haematogenous ' dissemi- nated, 129 streptomycin treatment of, 129 avian, 38 bovine, 13 in children, 15 connection between infection in man and cattle, 16 incidence, 14, 17, 42 mortality from, 43 virulence of, 16 cerebral, of bovine origin, 43 congenital, 69, 70 endobronchial, 197 extra-pulmonary, classification for statistical use, 270 meningeal. See Meninges. miliary chronic, 73, 256, 257 in children, 31 Tuberculosis, pulmonary brochiectasis in relation to, 108 classification of, 188, 250-253 American, 254, 255 numerical code for, 257, 258 pathogenic basis of, 255 statistical, 259 treatment in relation to, 260, 261 complications of, in relation to artificial pneumothorax, 139 early active, 95 lesions, revealed by mass radio- graphy, 95 modes of onset, 66 prognosis in, 229 clinical approach to, 237 in children, 239 environment in relation to, 246 Tuberculosis, pulmonary—cont. prognosis, clinical factors in- volved in, 238 family history in, 241 heredity in, 241, 242 influence of age and sex in, 238 influence of associated dis- ease in, 244 laboratory methods in rela- tion to, 245 mode of onset in relation to, 243 occupation in relation to, 248 race in relation to, 240 rehabilitation in relation to, 248 site of lesion in relation to, 243 sputum, persistent positive in relation to, 245, 247 temperament of patient in relation to, 240 treatment, response to, in relation to, 244 type of disease in relation to, 243 village settlements in rela- tion to, 248 statistical approach to, 229, 237 in cases with cavitation, 230 high initial mortality shown by, 229 improvement shown by, 232 sanatorium treatment, in relation to, 230, 231 specific treatment in relation to, 233 respiratory tract diseases simu- lated by, 71 spread of in relation to artificial pneumo- thorax, 136 to lung excision, 210 to thoracoplasty, 195 symptoms, 64 toxaemia of, in relation to artificial pneumothorax, 1386 treatment of. See Air condition- ing ; appetite ; artificial pneu- mothorax ; chemotherapy ; climate ; collapse’ therapy ; diet ; drainage ; environment, physical; injections, intra- pleural; insulin; rehabili- tation; sanatorium; serum endotoxoid ; tuberculin ; tuber- culosis services. Tuberculosis, respiratory, use of term, 253 Tuberculosis services combined case in relation to, 274 consideration of, 278—280 development of, 264 legislation in relation to, 265 See also National Health Service Act. mortality rates, affected by, 12, 13 treatment arranged by, 269 tuberculosis dispensary, 266 Vaccine, B.C.G., 51 et seq. Village settlements infection in, 59, 60 place of, in tuberculosis schemes, 272 preventative value of, 61 prognosis in pulmonary tuber- culosis in relation to, 248 Vital capacity, determination of, 190 Vitamin K. See Prothrombin deficiency. Vitamins, use of as _ supportive measure, 132 Vocational training, 220, 221 Vole bacillus, 57 Vollmer patch test, 79 Wallgren’s intradermal technique of B.C.G. vaccination, 52 Wheezing, in endobronchial tuber- culosis, 198 Whooping cough, effect on hyper- sensitivity, 25 Work, capacity for, in tuberculous patients, 217 Workshops, special, 273 Wound, operative, infection of, after thoracoplasty, 195 X-rays. See Radiography. Ziehl- Neelsen method, 74 ee SS rer ee s Le : ; rot: Ld * ge . Pie * i 33% 3 ~ Canines