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Silicosis and Asbestosis BY VARIOUS AUTHORS EDITED BY A. J. Lanza, M.D. \SSISTANT MEDIC \L DIRECTOR, METROPOLITW LIFE INSUR ANCfc COMPANY; CHAIRMAN, INDUSTRIAL HYCIENE COMMITTEE OF THE NEW YORK TUBERCULOSIS AND HEALTH ASSOCIATION OXFORD UNIVERSITY PRESS LONDON NEW YORK TORONTO Property cf The Library WETRGFCUT-'N L:,T TT no. LZ.37 s PREFACE The industrial age has complicated the scheme of life in many ways, some of them directly affecting the public health ; among these are the diseases due to the inhalation of certain kinds of atmospheric dusts arising directly from industrial operations. Ill effects due to dust contamination of the at mosphere have been recognized from earliest times. This book has for its purpose the presentation of the medi cal and public health aspects of silicosis and asbestods, two definitely industrial dust diseases. Silicosis looms larger in the picture than asbestosis because the former is much more widely spread, affects a much greater number of the indus trial population, has been recognized and studied longer and, consequently, more is known about it. The form of the generic term pneumoconiosis, rather than pneumonoconiosis or pneumonokoniosis, has been adhered to throughout the book. The International Labour Office and both British and American editors have adopted it as preferable. The editor wishes to express special thanks to Miss C. M. Bresnan for reading proof and for making the index and to acknowledge with gratitude the help received from many sources and from many individuals. To them and particu larly those working in the field of industrial hygiene, this book is dedicated. A. J. Lanza, M.D. February 24, 1938 wm CONTRIBUTORS A. J. LANZA, M.D. Assistant Medical Director, Metropolitan Life Insurance Company ; Chairman, Industrial Hygiene Committee of the New York Tuberculosis and Health Association. Formerly in Charge of the Office of Industrial Hygiene, United States Public Health Sendee ; Chief Surgeon of the United States Bureau of Mines; Adviser on Industrial Hy giene to Commomvcalth Government of Australia : Special Staff Member of the International Health Board of the Rockefeller Foundation ; Medical Consultant of General Motors Corporation. R. R. SAYERS, Senior Surgeon, United States Public Health Service ; Chief, Division of Industrial Hygiene, National Institute of Health. Formerly Chief Surgeon, United States Bureau of Mines. EUGENE P. PENDERGRASS, M.D. Professor of Radiology, Medical School, University of Penn sylvania ; Professor of Radiology, Graduate School of Medi cine, University of Pennsylvania ; Associate Director, De partment of Radiology, Hospital of the University of Penn sylvania. S. ROODHOUSE GLOYNE, M.D..D.P.H. Pathologist, Pathological Laboratories and Research Insti tute, The London Chest Hospital. LEROY U. GARDNER, M.D. Director, Saranac Laboratory for the Study of Tuberculosis. - E. L. MIDDLETON, M.D..D.P.H. H. M. Medical Inspector of Factories, London, England. CONTENTS I. Historv of Silicosis and Asbestosis 3 1. History of Silicosis 3 South Africa G Great Britain 8 Germany 12 Australia 14 Italy iG Canada 17 United States 18 2. History of Asbestosis 1 II. Etiology, Symptoms, Diagnosis of Silicosis and Asbestosis 22 31 1. Etiology, Symptoms, and Diagnosis of Silicosis 31 Silica in Nature 32 Occupational Exposure to Silica 33 vii \ viii CONTENTS Factors Influencing the Action of Silica Dust Particles as the Exciting Cause of Silicosis Occupational History Predisposing Causes Symptoms Subjective Symptoms Objective Symptoms Diagnosis The Relation of Silicosis to Disability Prognosis 2. Etiology, Symptoms, and Diagnosis of Asbestosis Symptoms Asbestosis Bodies Diagnosis III. Roentgen-Ray Diagnosis The Healthy Chest The Soft Parts 36 41 47 47 48 50 53 55 57 57 60 60 61 66 67 67 CONTENTS The Bones The Pleura The Mediastinum The Diaphragm The Hilum Shadows The Zones The Lobes The Vascular Markings The Bronchi The Lung Fields Effect of the Phases of Respiration on the Roentgen Appearances in the Chest Roentgen Technic Roentgenological Stages oE Progress First Stage Second Stage Third Stage Other Classifications Simple Silicosis ix 68 70 73 80 82 80 86 87 91 92 97 102 105 106 107 110 117 X CONTENTS Tuberculosis with Silicosis Healthy Lungs and Adnexa Simple Silicosis Silicosis with Infection Roentgenologic Considerations of Silicosis and Silicosis with Infection Silicosis Differential Diagnosis Metastatic Malignant Conditions of the Lungs T uberculosis Mycotic Infections Miliary Calcifications Baritosis Silicons u'ith Infection ( nodular predominance type) Silicn.\i'i with Healed Infection (conglomerate nodular type) Silicosis with Active Infection ( conglomerate nodular type ) 115 124 125 128 132 132 134 *34 *34 *35 136 i39 `39 `44 `45 CONTENTS Differential Diagnosis Infiltrating or Permeating Malignant Metastases Polycythemia or Erythremia Silicosis with Infection and Massive Lesions Further Considerations of Tuberculosis and Silicosis Complications in Silicosis Primary Bronchogenic Carcinoma Cardiac Lesions The Erythrocyte Sedimentation Reaction in Silicosis Asbestosis The Asbestos Industry Autopsy Symptomatology Roentgenologic Considerations Discussion of the Nature of the Roentgenologic Appearances seen in Asbestosis Prognosis xi H5 H5 148 l49 >5i 161 161 165 166 166 166 168 170 172 176 185 Xli CONTENTS Predisposition to Tuberculosis Differential Diagnosis Passive Congestion of the Lungs as a Result of Cardiac Decompensation Advanced Bilateral Bronchiectasis IV. Pathology Introduction Definitions Nature of the Dust The Portal of Entry The Tissue Reaction Silicosis Macroscopical Appearances Lungs and Pleurae Microscopial Appearances The Silicotic Nodule The Complications and Sequelae of Silicosis Silicosis and Tuberculosis 187 188 igo 198 198 198 199 201 202 205 205 205 210 210 214 216 CONTENTS Silicosis with Obsolescent Tuberculosis Silicosis with Manifest Tuberculosis Tuberculo-Silicosis Some Unusual Pathological Varieties of Silicosis Silicosis in Coal Miners Silicosis in Haematite Miners Acute Silicosis Asbestosis Naked Eye Appearances Lungs Mediastinal Glands Other Organs Microscopical A ppearanees The Asbestos Fibre and the Asbestosis Body The Lungs The Pleura Histology of Other Organs xiil 217 2x8 218 221 221 222 223 225 225 226 228 228 229 229 239 243 244 XIV CONTENTS Complications and Sequelae Clinical Pathology and Post-Mortem Examination Sputum Asbestosis Silicosis Blood Urine Autopsies Histology Extraction of Asbestos and Silica Particles from Lung Chemical Analysis of the Lung V. Experimental Pathology Experimental Pneumoconioses Experimental Methods General Tissue Responses to Various Kinds of MineralParticles Silicates Free Silica 244 246 246 246 247 247 248 249 250 252 253 257 257 260 269 271 277 00 -V Cl f-" 1 244 246 246 246 247 247 249 230 252 253 257 257 260 269 271 277 CONTENTS Amorphous silicas Mixtures of Free Silica and Other Minerals Granite Ferruginous chert Gold Inhalation of Various Dusts Xon-siliceous dusts Free silica Inhalation of Mixtures of Free Silica with Other Substances Hematite with 6 per cent Quartz Ferruginous Chert with 30 per cent Silica Artificial Mixtures of Calcined Gypsum and Pure Silica Granite Asbestos Infection and Pneumoconiosis XV 283 286 289 292 2 03 291 297 301 34 307 309 3*3 320 323 327 Xvi CONTENTS VI. Occupational, Preventive and Legislative Aspects Great Britain Sandblasting Prevention Compensation Grinding of Metals Prevention Compensation Refractories Industries Prevention Compensation Manufacture of Abrasive Soap / Powders Prevention Compensation The Sandstone Industry Prevention Compensation Granite Industry Prevention t CONTENTS Compensation XVU 369 Slate Quanting and Dressing 370 17 Prevention 37i )0 Compensation 371 >i Pottery Industry 371 *)- Prevention 375 34 Com pensation 376 35 Tin Mining 377 35 Compensation 377 56 Haematite Iron-ore Mining 378 37 Prevention 379 Compensation 380 57 39 Coal Mining 380 59 Prevention . 384 60 Compensation 385 62 Asbestosis 385 Prevention .63 389 Compensation 390 ;f>5 The Prevention of Silicosis 39i ifi9 Compensation for Silicosis and Asbestosis VII. Public Health and Economic Aspects United States Introduction Silicosis and Compensation Extent and Nature of Hazard Asbestosis Control and Prevention of Silicosis Engineering Control Dust Sampling Medical Control 394 405 405 405 414 419 421 421 422 426 ILLUSTRATION'S Chapter II j__Velocity of Fall for Various Kinds of Dust rA(:E 39 Chapter III 1_Schematic Presentation of Intercostal Muscles 71 2 _Healthy Adult Chest -- Front View 73 2_Healthy Adult Chest -- Side View 75 _j -- Calcified Tracheobronchial Lymph Nodes 85 5 -- Roentgenogram Showing Vascular Markings 89 6 -- Differences in Appearance when Rays Were Directed in Several Planes go 7 -- Composite Diagram of Primary Lobule Lymphatic System 9j 8 -- Diagrams Showing Differences in Expansion in the Various Portions of the Lung 98 9 -- Diagrams Showing Differences in Expansion in the Various Portions of the Lung in a Case xuith Infection 100 10 -- Roentgenogram of a Healthy Chest xix 104 XX ILLUSTRATIONS ii--Simple Silicosis with Uniform Distribution of Small, Round Densities PACE 108 12 -- Silicosis with Infection 109 13 -- Anthracosilicosis with Infection m 14 -- Close-up of a Massive Lesion in Right Upper Lobe 112 15 -- Lateral View of Chest of Individual Having A nthracosilicosis 113 16 -- Massive Lesions in a HardCoal Miner 114 17 -- Metastic Hypernephroma Involving the Glands of the Mediastinum 133 18 -- Miliary Tuberculosis 135 19 -- Miliary Calcification of Unknown Origin 136 20 -- Case of Baritosis 137 21-- Soft Modulation in a Hard Coal Miner 138 22--Soft Nodulation in a Granite Worker 140 23-- Silicosis with Active Infection 141 24A -- Silicosis with a Healed Infection 142 24B -- Close-up of Lesion in Right Upper Lobe 143 25A -- Silicosis with Infection 146 ILLUSTRATIONS v.-B--Same Lung Five Years Later XXI 26 -- Primary Carcinoma of Right Lower Lobe in a Worker l6a --Asbestosis, Early Manifestations 28 -- Lungs of Man Aged 41-- 5/7* Weaver for 20 years. Asbestos Weaver, 5 years j(j -- Examination 5 Years Later -- Asbestosis Moderately Advanced 1 tI 1 /9 ^ ,io -- Close-up of Right Lower Lung Shown in Figure 29 S1--Asbestosis Moderately Advanced :(2--Asbestosis Markedly Advanced W--An Unusual Type of Asbestosis ,g4 l86 .S4 -- Asbestosis with Complicating Tuberculous Lesion in Right Upper Lobe l8 Chapter IV 1 --Silicotic Lung Showing Massive Xodules 2--Silicotic Lung Showing Extensive Xodulation 3 -- Discrete Silicotic Xodules 4 Composite Nodules of Silicosis 208 209 ,,12 213 XXii ILLUSTRATIONS 5 -- Tuberculo-silicotic Nodulation PAGE 220 6 -- Quartz Particles from Stone-masons' Lung 222 7 -- The Asbestosis Lung 227 8 -- Asbestotic Lung Showing Respiratory Bronchioles Packed with Asbestosis Bodies 229 9--Asbestotic Lung Showing Reticular Fibrosis of Alveolar Walls 230 10 -- Asbestos Fibres ( Crocidolite ) 231 11-- Stages of Formation of the Asbestosis Bodies 236 12-- Asbestosis Bodies (low power) in Unstained Section of Lung 240 13-- Asbestosis Giant Cell Showing Phagocyted Asbestosis Bodies and Fibres 242 Chapter V 1 -- Vertical Section through Lungs of White Rat Inhaling Pure Chalcedony for g months 258 2--Intravenous Injections of Pure Silica 264 3 -- Rabbit Livers after Intravenous Injection 266 4 -- Inhalation of Various Dusts 290 5 -- Reactions to Granite and Chert Dusts 298 ILLUSTRATIONS The Course of Rx Inhalation Tubercle in Xannul Guinea Pigs Rl Inhalation in Guinea Pigs Exposed to Carious Dusts xxiii PACE 33 2 334 Chapter VI A Gun Flint from Brandon 348 Localized Exhaust fur Dust Removal at Stone-d rcssing 3C4 Attachment of ihe Expanded End of the Duct and Its Connection with the Suction Apparatus 3G6 Movable Hood Connected with Exhaust Apparatus by a Flexible Tube 368 INTRODUCTION Pathological conditions of the lungs, due to the inhala tion of excessive quantities of dust in certain occupations, have been known to exist for many centuries. It is also true that the frequency of infection, particularly pulmonary tu berculosis, as a complication has been realized for a long time. Pneumoconiosis is a comprehensive term, designating the effects upon the lungs of the inhalation of excessive quan tities of dust, manifested by structural changes in the lung tissue and entirely distinct from the action of poisonous dust, such as lead or mercury, in which case the lungs act merely as the point of entrance into the body without defi nite local influence. At first it was associated chiefly with mining but with the advancement of the industrial age, dusty industries multiplied. It is customary to speak of the dust inhalation effect upon the lung tissue by the name of the chief constituent of the dust breathed, as silicosis when silicon dioxide (SiOo ) is the principal ingredient and asbestosis when asbestos is the offending agent. Silica dust, when the particles are sufficiently small, has the peculiar property of inducing a fibrosis of the lung tissue. This effect is characteristic, as is the resulting roentgenologic appearance. In asbestosis, the pathological process is quite different as is the roentgenologic appearance. These matters are thoroughly dealt with in the text. There is still, however, much to be learned with respect to both conditions. We know the results of the inhalation of these dusts but we are not sure how they are produced. There are two ways in which the pulmonary infections, tuberculosis and pneumonia, may affect or complicate pneu moconiosis. First, there may be infection before the exposure xxiv INTRODUCTION XXV to dust. It is an undecided question whether sucli infection ran so change the pulmonary structure that the later dust effect is more pronounced than it would otherwise be. There seems to be reason to believe that such an enhancement is to be expected, especially if the previous infection were tuber culosis. but this must be left to tiie histopathologist for final proof. Secondly, do such infections upon an already dusted lung become more severe or aggravate the dust effect or other wise change its character? There is even more evidence that any of these effects may result but here again the histopathol ogist must be called upon to tell ns the exact truth. The fust intimation that occurred to us that the character of a silicone lesion could be so changed was when we were searching for an explanation as to why certain individuals with silicosis showed massive consolidations of fibrosis in the lungs and others in the same occupation and apparently exposed to the same amount of dust of the same variety showed a more e%enly diffused nodular fibrotic process. It was a great satis faction to hear a well known pathologist say that a com paratively recent infection like lobar pneumonia might be the answer but that at present there was no definite proof of such theory being correct. It was gratifying to learn that most of us were thinking along similar lines. That most cases of silicosis die of an intercurrent infection, especially tuberculosis and possibly pneu monia, is evidence that silicosis may exert some effect upon the progress of some pulmonary infections. It has not been proven as yet that the same is true of asbestosis. A comprehensive knowledge of the effects upon the lungs of excessive inhalations of dust is not to be quickly gained. The combined efforts of the histologist, pathologist, clini cian, roentgenologist, chemist, physicist and other techno logical experts are necessary. The legal profession deserves a certain share of commendation for stimulating the study of XXVi INTRODUCTION occupational dust diseases and has made a thorough knowl edge of pneumoconiosis a necessity among many of the medi cal men. Were it not for the demand for exactness from out side the medical profession, it is difficult to say how soon curiosity or medical research would have achieved our pres ent accuracy of knowledge with respect to the etiology, symp toms, and pathology of pulmonary dust diseases and their modification by certain infections. A large number of us have, no doubt, taken up the study of pneumoconiosis from the standpoint of interest. Following the experience with silicosis in South Africa, starting several decades ago, text books for the medical student simply men tioned it in a more or less cursory manner as an uncommon condition. We are sure of the necessity of many angles of approach to the subject. The first comprehensive report of silicosis in the United States was made about twenty years ago by one of the authors. It described what was occurring among miners in the south west. Almost simultaneously and without any knowledge of this report, it occurred to a small group of medical men in the east that the best way to study the differences in the appearances of trunk shadows in the roentgenograms of the lungs might be to study the chests of persons engaged in various dusty occupations. The main point learned in this investigation was that organic dusts do not induce lung changes but it further stimulated the study of the effects of inorganic dusts, particularly silica, and later, asbestos. This study has continued up to the present time. Some of the authors of this book were among the pioneers in silicosis and asbestosis ; they have blazed the trail for fu ture investigations. It can be truthfully stated that those who studied these occupational diseases in North America and the British Empire have always had the good of the affected workers in mind. Their researches have saved life and have made many occupations safer for the worker. j i Henry K. Pancoast, M.D. w >U'l:di- >Ut- ion res a le ir idy ing ,`ral tenion of . of Ml'S ing md lall udy the i Of ain do udy ter. j ,`ers furho and ted ave f.D. SILICOSIS AND ASBESTOSIS I. HISTORY OF SILICOSIS AND ASBESTOSIS R. R. Sayers, M.D. SENIOR SURGEON, UNITED STATES PUBLIC HEALTH SERVICE CHIEF, DIVISION OF INDUSTRIAL HYCIENE NATIONAL INSTITUTE OF HEALTH AND A. J. Lanza, M.D. ASSISTANT MEDICAL DIRECTOR METROPOLITAN LIFE INSURANCE COMPANY i. HISTORY OF SILICOSIS Although to the general public silicosis is a disease of recent origin, the history of dust diseases reaches far into the past, and the first recognition of a definite relation between ex posure to dust and pulmonary infection is lost in the mists of antiquity. As Collis 1 states, `In historic times references are to be found in the works of ancient writers who, however, seldom distinguish between the various forms of respiratory disease, but rather refer to a general connection between lung affec tions and dust inhalation.' Probably the earliest recorded reference to the harmful ness of dust exposure is Pliny's description of the devices used by refiners to prevent inhalation of the `fatal dust.'2 The symptoms of a metal digger, as noted by Hippocrates, who lived in the fifth century b.c., are comparable to those ob served among present-day miners suffering from the effects of dust inhalation.3 Other early writers discussed dust phthi sis, and it is believed they had in mind the type of disease described by Celsus,4 a medical writer of the first century, who stated : 3 4 SILICOSIS AND ASBESTOSIS 'By far the most terrible form of emaciation is that which the Greeks call phthisis. It spreads to the lungs. On top of this ulcer ation occurs and a slow fever which at times disappears and at other times reappears.' In `De Re Mettalica,' published in 1556, Agricola described the perils of mining and die `pestilential air' breathed by miners. He also relates how 'the constant dust enters the blood and lungs, producing that difficulty of breathing the Greeks call asthma. When the dust is corrosive it ulcerates the lungs and produces consumption.'5 Lung diseases of miners, smelters, grain workers, etc..* were discussed and described by a number of early writers. Among these, Paracelsus, a Swiss alchemist and physician, was the first to list the occupational diseases of miners and smelters. His book on industrial medicine was published in 1567.6 It is said that Dimerbroek, in 1649, made the first section of a stone-cutter's lung which revealed `lung vesicles completely clogged with fine dust.'7 Ramazzini, in his book published in 1700, noted the effect of dust on the respiratory organs, and reported numerous cases of fatal dust disease. He obtained his information by personal inspection of the trades he dis cussed, and his writings display a recognition of the relation ship between dust inhalation and consumption. According to Collis, Thomas Benson, of Newcastle-under-Lyme, was granted a patent for grinding flints by a wet method. Pre viously, flints were pounded dry, the process proving `very destructive to mankind insomuch that any person, ever so healthful and strong, working in that business, cannot pos sibly survive over ttvo years, occasioned by the dust sucked into his body by the air he breathes.'1 A number of special inquiries into the prevalence of dust-phthisis were made, for example, by Professor Allison9 and Hugh Miller,10 who wrote of the progress of such disease among stone-cutters. HISTORY 5 Thackrah,11 in 1831, began a study of the effect of the dusty trades on British workmen's longevity, and contributed valuable information, including the fact that not all dusts shorten the lives of the workers exposed, as evidenced by the experience in various mines. He noted that, while sandstone workers generally died before forty, there seemed to be little or no unusual incidence of lung diseases in brick and lime stone workers. Dr. Greenhow,1- an instructor in public health, became the first state medical factory inspector in England and made personal investigations of health conditions in industries throughout the country. He collected lung specimens of workers, who had died from dust diseases, for pathological study and he was perhaps the first to use polarized light to identify microscopically the tiny particles of silica in the lungs of a metal grinder. As a result of his work, the first Royal Commission was appointed in 1861 to make a thorough investigation of health conditions in mines. In 1862, Dr. Peacock,13 who had interested himself in the lung diseases of buhrstone cutters and who had detected par ticles of the stone in their lungs, was made a member of the Commission. In his report on the medical aspects of mining, he distinguished between the conditions of the lungs known as `miner's phthisis' and the ordinary type of tuberculosis, noting that the miner's disease occurred in otherwise healthy men with healthy families and that it appeared in them at an older age and was a more chronic type than the usual in fective tuberculosis. Although medical opinion at this period attributed the disease among miners more to bad hygienic conditions than to the dust to which they were exposed, some of the Scottish and English physicians noticed that even in mines where miner's phthisis was prevalent, drillers of rock suffered from more rapid onset of the disease than other miners. This, to- 6 SILICOSIS AND ASBESTOSIS gether with other similar data, gave rise to the supposition that the character of the rock influenced the occurrence of the disease.14 The effects of various dusts on the lungs were reported by other writers, the names given to the resulting diseases being descriptive of the dusts causing them. Zenker 15 provided the anatomical and Kussmaul,15 the chemical proof of the de posit of inhaled dust, especially siliceous dust in the lungs. The name `pneumonokoniosis' was devised by Zenker, who described in detail the anatomical picture of the dusty lung. Visconti, as reported by Rovida,16 in 1870, is accredited with being the first to use the term `silicosis' to denote the pathological condition of the lungs resulting from inhala tion of silica. Commencing in the latter part of the nineteenth century, great interest in the health of miners was being shown throughout the world. A summary of development in some of the principal countries follows. South Africa Too much credit cannot be given to the South African authorities and investigators for their contributions to the whole subject of pulmonary dust diseases. The publications and reports of the Miner's Phthisis Prevention Committee, the Miner's Phthisis Medical Bureau, and the South African Institute for Medical Research have been an inspiration for officials and research workers all over the world. Their in fluence on both the clinical and compensation aspects of silicosis has been enormous. Gold mining started in South Africa on the Witwatersrand in 1886. It was not long before the introduction of machine drilling and the depths of the mines began to produce health problems. The quartz content of the ore bearing rock was . high, containing as much as 80 per cent to go per cent free HISTORY 7 silica. 19 1902, the Government mining engineer noted that miner's "phthisis seemed to be prevalent among rock drillers and a Commission of Enquiry was appointed. Physical ex aminations were made of 3,000 men, the roentgen ray being used in South Africa for the first time in 300 cases. Compensation was inaugurated in 1912 and in 1916, the Miner's Phthisis Prevention Committee issued a compre hensive report. Pre-employment and periodic physical ex aminations were initiated by the Medical Bureau and en gineering methods to improve ventilation and allay dust by the use of water were instituted. The estimation of the amount of silica dust in various working places underground was developed, Sir Robert Kotze having devised an instru ment for this purpose, the Kotze Konimeter. A threshold limit of 300 particles per cubic centimeter ( about 8,500,000 particles per cubic foot) was set as a reasonable (at that time ) standard of safe practice. The Miner's Phthisis Medical Bureau defined diagnostic standards and regulations for compensation. The Bureau established the classification of silicosis into four stages -- ante-primary, primary, secondary, and silicosis with tubercu losis. Watkins-Pitchford and the other medical members of the Bureau -- Watt, Irvine, and Stewart -- made notable contributions to clinical knowledge. The importance of tu berculous infection as an accelerator of lung fibrosis, the marked susceptibility of silicotics to tuberculosis, the progres sive nature of silicosis, were among the important aspects of silicosis which this group described. From the Institute for Medical Research came the important pathological studies of Mavrogordato and Simson. No one interested in the medical, economic, or engineering phases of silicosis can afford to over look the publications that have come from South Africa for the past twenty years. -t 8 SILICOSIS AND ASBESTOSIS Great Britain In 1902, fifty years after Peacock's investigations, a gov ernmental commission was appointed to study the persisting high mortality among the tin miners of Cornwall. Dr. Hal dane, one of the members of this commission, definitely as cribed the disease of these miners to rock dust and stated that the dust itself was what caused the primary injury to the lungs.17 Investigations among slate workers showed that slate dust exposure was related to phthisis, particularly in Wales, where the slate is high in quartz.18 From this time on, frequent and intensive investigations of many of the dusty trades in England were made, and nu merous reports containing valuable information and sug gestions were issued by the British Home Office. Among the industries studied were slate, refractories, sandstone, pot teries, and coal mining. Dr. Collis, in 1915, in the Milroy Lectures, reviewed the status of pneumoconiosis in England at that time. He clearly expressed the theory that `free' or crystalline silica is the causative agent in nearly all dusts that produce serious lung injury and susceptibility to tuberculosis.1 In 1917, an investigation was made of the refractories in dustry, where a species of sandstone shale with a high free silica content is used in making bricks and in 1919, the first scheme of compensation for silicosis was set up for this in dustry. Dr. Heffernan has given an account of the problems connected with this industry.19 The situation in the English pottery industry had existed for many years, Wedgewood having found that his workers employed in grinding flint lived only a couple of years. Several Royal Commissions were appointed to investigate the potteries industry; one by Sutherland and Bryson for- r e v e ig nee vst inms ted tevs avs. .rate for- HISTORY 9 mulnted a scheme for including the potteries in compensa tion laws.2'1 One report of the British Factory Inspectors states that regulations now enforced lor controlling dust in this industry has been so effective that no process in English potteries is now so hazardous as to produce even an early stage of silicosis in less than ten years. The granite industry was also studied repeatedly. In 1930, out of about 500 workers examined, 17 per cent showed evidence by roentgen-ray of silicosis, mostly in the early stages. The free silica content of granite is lower than that of sandstone, usually not over 30 per cent, but the fact that pneumatic tools were generally used was thought to cause more dust than hand methods.21 A very comprehensive report on the metal grinding and casting cleaning industry was issued by two of the Factory In spectors in 1923. It was shown that the occurrence of silicosis, many cases being complicated with tuberculosis, was present almost entirely among those who worked on sandstone grind ing wheels. Silicosis was more frequent and more advanced in the wet grinders examined than in the dry grinders. Sand blasting was rated as potentially a very hazardous process, unless enclosed, or the workers protected. Counts of the dust particles in the air were made with an apparatus developed in 1922, called the Owens' jet dust counter. Petrographic determinations were made and particle size measurements estimated for the dust present in the various processes. De tailed requirements were drawn up for the improvement of working conditions. This report helped to establish the fact that metal particles or hard mineral particles from corun dum or emery were not the source of true silicosis ; that only work on sandstone wheels or on sand cleaning or with other exposure to free silica dust is capable of producing the dis ease.22 *Collis and Yule, in 1933, endeavored to determine the ef- xo SILICOSIS AND ASBESTOSIS fects o exposure to silica dust on mortality by comparing the death rates for a group of occupations having exposure to dust containing free silica with a group having equal ex posure to dusts not containing free silica, working conditions being similar. Comparison was also made with the rates for all occupied and retired males, with correction for age dis tribution. The authors concluded from this analysis that silica dust tends to be a poison to the whole body and that, although it exerts its important influence on the respiratory tract, especially with respect to tuberculosis, it also impairs the circulatory, nervous, and digestive systems and the glands, kidneys, and liver.23 The chemical aspects of the action of silica in the tissues have been painstakingly studied by Gye, Purdy, and Kettle. Kettle has concluded from his experiments that silica, after it has entered the body, dissolves in a colloidal form in the weak alkalis of the lung fluid and is very gradually absorbed, the soluble portion then acting as a tissue poison. He thinks that through its toxic action it paralyzes the phagocytes so that they lose their phagocytic ability and also their power to deal xvith the tubercle bacillus, thus leaving the lung unpro tected.24 Kettle, Gye, Purdy, and S.Lyle Cummins have all proved by experiment that far from being `poisoned' by silica, the tubercle bacillus is stimulated by silica.25 Extensive studies have been made on the health of coal miners. Dr.Middleton, in a five year study of silicosis deaths reported in British industries, showed that during the period from June 1, 1931 to December 31, 1935, there were 147 certified deaths from silicosis and silicosis with tuberculosis and 511 total disablement cases among 139,258 employed coal miners in South Wales and Monmouth. In all the rest of England and Scotland, there were only 22 deaths and 70 total disablement certificates for silicosis in coal miners, in a total of over 600,000 employed.26 Physicians practicing in the of tyi sus lus ves hifc Ste tio ] era wa evt on ab: tiv be< the coi du to ini thi or by fiv C0.` Sri ite sil co iin cal L HISTORY 11 South Wales coal fields believe the silicosis observed there is of the `infective- type ; `infective' is Dr.Irvine's term for the type of extensive fibrosis found in silicotic lungs which is suspected of being produced by the aid of the tubercle bacil lus, but in which the bacillus cannot be demonstrated.14 In vestigations in the iron mining industry disclosed a rather high silica content in hematite miners' lungs at autopsy and Stewart and Faulds felt justified in naming this lung condi tion `sidero-silicosis.' In 1933- W.R.Jynes brought forward the theory that min eral sericite ( a hydrous silicate of aluminum and potassium ) was the chief factor in the development of silicosis.28 How ever, this has not been substantiated. Silicosis has been dem onstrated in experimental animals and in human cases in the absence of sericite and where pure quartz was the only causa tive factor. It is interesting to note that many attempts have been made to find an `antidote' dust to neutralize or delay the harmful action of silica. Carleton,29 in experiments with combined flint and coal dust on guinea pigs, found that coal dust appeared to cause enough initial immediate irritation to promote elimination of some, but not all, of the flint dust inhaled. No definite conclusions have as yet been reached in this work which is still being conducted. Compensation for workers disabled as a result of silicosis or silicosis and tuberculosis has been provided for in England by amendment to the compensation law. From 1925 to date, five schemes have been put into operation dealing with sili cosis in various industries, including the refractories, metal grinding, sandstone, tin mining, coal mining, potteries, gran ite working, and others. Processes not involving exposure to silica dust are exempted, in some cases, the limits of the silica content being specified for the purpose of the law. The most important feature of these schemes is the provision for medi cal certification of physical fitness for work in such exposure. 12 SILICOSIS AND ASBESTOSIS for medical certification of disability with limited compensa tion for non-disabling stages of uncomplicated silicosis, and for post-mortem examination in death claim cases. Germany In Germany, Paracelsus was first to deal with injury to the lungs of miners caused by inhalation of dust and to desig nate such injury as an occupational disease. In the nineteenth century, German pathologists and clinicians made consider able progress in regard to research connected with diseases caused by dust. Arnold succeeded in producing experimental dust fibrosis of the lung and in distinguishing clearly between that and tuberculosis. Eulenberg definitely affirmed that si licic acid causes serious fibrotic disease of the lungs. The connection between inhalation of dust with quartz content and tuberculosis has been shown statistically by various writers : Oldendorff, Sommerfeld, Moritz and Ropke and others showed the high mortality rate from tuberculosis among metal grinders ; Lewin, Hirt, Wilbrandt, and others drew attention to similar conditions among pottery workers. Baumler described the symptoms of silicosis and stressed the cirrhotic character of the accompanying tuberculosis. Staub-Otiker described in detail the roentgen-ray appearance of the silicotic lung as found in metal-grinders and also dis tinguished the various stages of the disease. Stahelin, Ickert, Jotten, Arnoldi, Lehmann-Engel-Wenzel have all given com prehensive expositions of this subject. Koelsch and Kaestle designated the appearance of fine mottling on roentgenogram as the first stage of silicosis, associated with slight dyspnea after effort. While it is admitted that very often tuberculosis is associated with dust fibrosis, the majority of German in vestigators are of the opinion that fibrosis due to dust is a disease in itself and to be distinguished from tuberculosis HISTORY 13 anti that dust inhalation, as such, may lead to extensive pul monary fibrosis without associated tuberculous infection. Scliiuorl, Stauh-Otiker, Arai, Koopmann, lidhme, and Schridde describe such cases. Merkel has concluded from his anatomical findings that simultaneous inhalation of dust and tubercle bacilli occurs and that these exert a double action in the production of the majority of dust fibrosis. A great deal of experimental work has been done in Germany re garding silicosis by Lehmann, Gross, Jdtten, and others. In 1929, `severe pneumoconiosis' (silicosis; was included in the list of occupational diseases subject to compulsory compensation. In the case of severe dust fibrosis combined with tuberculosis of die lungs, tuberculosis is regarded as pneumoconiosis (silicosis) for the purposes of compensa tion. Up to the beginning of the present century, all changes of the pulmonary tissue caused by different kinds of dust were considered as fairly similar. However, the observations of the last few decades, particularly the thorough investigations effected in the last twenty years, have fundamentally altered the former theories. Today it is recognized that the various types of dust must be judged in a different manner and that the decisive factor regarding effect is not the morphological- physical activity of the various types but rather the content of free crystallized silicic acid l quartz ) in the dust. Koelsch began some years ago to investigate conditions in dusty in dustries and in the last few vears, over 1,200 workers in var ious branches of industry involving exposure to mineral dust were examined clinically and roentgenologically. It was found that the most dangerous occupations in regard to pneumoconiosis, as related to dust exposure, were granite and sandstone working. The statistical morbidity and mortality returns, as well as the clinical-roentgenological examinations, 14 SILICOSIS AND ASBESTOSIS show clearly the fundamental principle that the greater the quantity of free silicic acid in the dust, the more dangerous it is for die lungs.15 Australia The rapid increase in Australia's population in the latter half of the last century was due in large part to the discovery of rich alluvial gold fields in several parts of the Continent. This stimulated prospecting and brought about the discovery of other metalliferous deposits. A large portion of the mi grants came from mining districts in England and other countries. Silicosis has been demonstrated in many of the mining fields and a high death rate from pulmonary diseases, in cluding tuberculosis, has been evidenced in connection with the industry.15 In 1902, while a system of sewers was being dug in Sydney, Australia, a Sewer Works Ventilation Board was appointed to inquire into the working conditions and to recommend means of improvement to render the work less hazardous. The board found that miners employed in this type of work suffered from a disease known as `sewer disease' but which was strongly suspected of being due to dust. It was the board's opinion that although fumes from explosives, poor ventila tion, etc., were contributory to the high mortality, the sole cause of the disease was probably the dust from hammering, drilling, and use of the pickax. The Australian government has made many investigations of the mining industry throughout the country and vigorous efforts have been made to control unhygienic conditions. The chief metal mining sections in which health conditions have been surveyed are : Bendigo, Victoria ; Broken Hill, New South Wales ; Kalgoorlie, Kimberley, and Coolgardie in Western Australia.14 HISTORY *5 In 1912, Armstrong investigated a reported epidemic of pneumonia at Broken Hill and found the death rate from pneumonia among underground miners in that locality dur ing 1910-2 was nearly 4 times as great as that for all males in New South Wales. In 1914, the report of a Royal Com mission investigating the mining industry at Broken Hill stared that although the prime cause of pneumonia was sud den changes in temperature, dust inhalation in any form would predispose to disease.30 In 19*9/ the Technical Commission constituted to ex amine the miners at Broken Hill used the roentgen-ray, for the first time in Australia, as a means of diagnosing silicosis as an occupational disease. The Commission made an elabo rate report in 1921 and set up standards for diagnosing the different stages of silicosis.31 In 1924, a very complete investigation of the sewer system situation was made by Dr. Charles Badham, Industrial Medi cal Officer of the New South Wales Department of Health. Dust counts were taken and it was found possible to set a standard for permissible dust concentrations of soo particles per cubic centimeter ( approximately 5,664,000 particles per cubic foot). A special scheme for the compensation of silicosis for Syd ney sandstone workers was put through in 1927 and the whole field was checked again ; surveys were also made among sand stone masons and quarriers in the neighborhood. These were found to be exposed to much the same hazard as the tun- nelers. Open sheds and wet methods were recommended for controlling the dust hazard.14 Since 1926, the mine employees in Western Australia have been examined annually by the Commonwealth Department of Health. Of 2,290 men previously classed as normal, 1.3 per cent were found on re-examination in 1927 to be suffering from uncomplicated silicosis and 0.5 per cent had tubercu- i6 SILICOSIS AND ASBESTOSIS losis only ; o 491 diagnosed as silicotic, 86 ( 17.5 per cent) had silicosis with tuberculosis. In 1929, of 2,293 normals re examined, 100 were diagnosed as silicotic. Silicosis was not found in any case under forty years of age or with less than five years of underground work.30 Italy Italian research workers have furnished interesting contri butions to the knowledge of respiratory diseases resulting from the inhalation of dust. While experimental work was done by Biondi, Tommasi-Crudeli, Feliziana, and others, the report of Devoto and Cesa-Bianchi in 1911 must be con sidered especially notable. In their experiments with guinea pigs, they found that animals subjected to the inhalation of very fine limestone dust are less susceptible to tuberculosis than those which have inhaled silica dust.13 Among other workers who have studied the occurrence of pneumoconiosis in various Italian industries are Pesenti, Rota, and Finzi, who reported on health conditions of workers in lime, cement, and plaster ; Frongia, who noted that the cause of death among Sardinian miners was most frequently an acute infection ( pneumonia) ; Bianchi, who made careful clinical and radiological examination of work ers employed as sculptors, hewers, modelers, and workers in grinding rooms. In regard to the importance of silica dusts as the cause of pneumoconiosis, a report by Giglioli is of real importance. Pieracciui had already remarked that among the workers in the Cornacchino mine, there occurred a high incidence of broncho-pulmonary affections and pulmonary tuberculosis ; a later inquiry by Puccinelli and Ginanneschi confirmed this fact. Giglioli found that in many of the miners at Cornacchino, and in almost all who worked where the air is rich in silica dust, there occurred, after two to three years of- work, broncho-pulmonary affections, with coughing, HISTORY 17 breathlessness, emphysema, and in general, after a more or less lengthy period, all the signs of pulmonary tuberculosis. There is almost always a well-marked, pre-tuberculous pe riod, which may evolve slowly without tuberculous compli cations corresponding to so-called miner's phthisis. More recently, Mazzi, in 1913, on the basis of animal experiments and clinical observations, has come to the conclusion that silicon (in the special form of silicates) causes chronic in toxication of the system and acts especially on the blood in exercising a general anemia producing action.15 Canada In 1875, Sir William Osier, in one of his lectures, demon strated two specimens of miners' dusted lungs. His description of the pathology of this disease compares favorably with modern descriptions of silicosis. Pneumoconiosis or silicosis or miner's phthisis has been scheduled as a compensable oc cupational disease in quarrying, stoneworking, metal grinding or polishing, and mining for a number of years in Ontario, Alberta, and Saskatchewan. Silicosis has been studied from time to time in the gold fields of Ontario, at Porcupine, Kirkland Lake, Cobalt, and Sudbury. Granite cutters in Ontario were examined in 1928. Other examinations have been made among foundry workers and among sandblasters, as well as workers in marble, talc, cement, brick, grain elevators, and artificial abrasives. These investigations were carried out by the Industrial Hygiene Division of the Ontario Health Department, where Cunning ham, Riddell, and their associates have done work on cor relating clinical, roentgen-ray, and pathological findings in lungs of workers. Belt of Toronto University has made com parisons between the silica content of the ash of silicotic lungs and the number of particles to be seen in the same lungs with i polarized microscope. The method brings out `invisible 18 SILICOSIS AND ASBESTOSIS silica' so often predicated by pathologists working on silicosis. Outstanding experimental research on silicosis is being car ried out at the Banting Institute of the University of Toronto, under the direction of Banting, by Doctors King, Fallon, Irwin, Stantial, Franks, and others. Irwin has developed a micro-incineration method which makes it possible to de termine amounts of silica in tissues with considerably greater accuracy for the purpose of relating it quantitatively to the degree and location of fibrosis present in the lungs.14 Recent experimental work by Denny, Robson, and Irwin showed that animals dusted with quartz, to which less than 1 per cent of metallic aluminum dust had been added, showed practically no fibrosis.32 United States As early as 1887, Dr. Frederick Peterson14 of Pough keepsie,33 New York, presented a report of an autopsy upon a foundry worker which unmistakably indicated silicosis and called attention to the prevalence of this type of disease among fellow employees of his patient. In the same year, a series of patients employed in a cutlery factory were presented to the Franklin District Medical Society by Dr.F.J.Canedy of Shel burne Falls,14 Massachusetts.34 Dr.William W.Betts of Nevada, in 1899,14 described 3J a series of cases of pulmonary disease among employees of a gold crushing plant. Not until 1915 was the first study of silicosis and allied dis orders initiated by the United States Bureau of Mines and the United States Public Health Service, jointly, in the lead and zinc mining district of southwest Missouri.3* This in vestigation was followed by similar studies in hard rock metal mining regions in other parts of the United States.37 In 1924, the United States Bureau of Mines established a clinic in the Tri-State Lead and Zinc mining district (Mis souri, Kansas, and Oklahoma) which was later (1927) ex- HISTORY 19 panded into a co-operative enterprise by the Bureau of Mines u-ith the Tri-State Producers Association and the Metropoli tan Life Insurance Company. This clinic tvas maintained for nine years. Over 60,000 complete physical examinations of 27,000 individuals were performed at this clinic while it was maintained under Government auspices, including roent genogram of the chest and a blood Wassermann or Kline test. The results are partially summarized in Technical Papers 545 and 552 of the United States Bureau of Mines.38 The general tenor of these studies in the United States was in dose con formity with those of South Africa and England. Attention was later directed to the anthracite coal mining industry, in which a disabling pulmonary disease, locally known as miner's asthma, had long been recognized. In 1933, the United States Public Health Service, in co-cpcration with the coal mine operators, the United Mine Workers of America, and the Pennsylvania Department of Labor and Industry, undertook a survey of pulmonary disease in the anthracite mines, the results of which were published in Bulletin 221 of the United States Public Health Service.39 This study confirmed what many had suspected -- that dis abling pulmonary fibrosis among coal miners was due to silica and not to coal dust, although the coal might modify the clinical and pathological picture. Other studies of the United States Public Health Service in bituminous coal mines failed to establish a disabling fibrosis in the absence of silica. Brundage of the Public Health Service had demonstrated from mortality records that bitu minous coal miners had a low rate of tuberculosis. To the condition found in the anthracite mines, where silica bearing rock is often adjacent to the coal. Sayers and his colleagues gave the name anthraco-silicosis and demonstrated that in the older age groups, the incidence of tuberculosis as a complica tion was very prevalent. In the age group forty-five to fifty-five. 20 SILICOSIS AND ASBESTOSIS the tuberculosis rate was five times that of the general popula tion and above age fifty-five, ten times as large.39 About the same time, Gardner and Cummings of the Saranac Laboratory started their extensive studies of pul monary disease in the iron ranges of northern Michigan and Wisconsin. The general conclusions of all these field studies indicated that the incidence of silicosis and the resulting clinical picture were directly related to the severity of ex posure to quartz dust and to the presence of infection and that other substances, in combination with the silica, might and often did modify the action of the silica. These conclusions are supported by the results of investiga tions of foundries. Foundry studies were conducted at various times by the United States Public Health Service,40 by the Industrial Hygiene Division of the Metropolitan Life In surance Company,41 by the Saranac Laboratory and the American Foundrymen's Association,42 the State of Con necticut,43 and the State of Massachusetts.44 A number of investigations were also made in the granite industry, notably in 1918 by the Committee on Mortality from Tuberculosis in the Dusty Trades,45 under the leader ship of Dr.Frederick. L.Hoffman, and later, in 1929, the im portant study by Russell of the Public Health Service.45 The sandstone industry was investigated by Hayhurst in 1926;47 the marble industry by Dreessen of the Public Health Service in 1934 ; 48 and the pottery industry on a number of occasions.49 The cement industry also has been thoroughly studied, beginning in 1915 by Tucker,50 and later by the Public Health Service 51 and also by the Saranac Laboratory.14 These various investigations of the cement industry revealed little or nothing in the way of occupational pulmonary disease and served to confirm the so-far accepted principle that disabling HISTORY 21 pulmonary fibrosis is dependent upon exposure to the dust of uncombined or free' silica and not `silicates.' The manufacture of abrasives received considerable atten tion as did metal grinding. The United States Public Health Service,5' the United States Department of Labor, Dr.C.-E.A. Winslow" in Connecticut, Dr.W.Irving Clark54 in Massa chusetts, Dr.H.H.Kessler 35 in New Jersey, and others have re ported on the abrasives industry ; and Winslow and Green- bur^,36 W.H.Drury 37 and others on metal grinding. During the years that these investigations were carried on, much laboratory and clinical research was under way. In Philadelphia, Stengel, Pancoast. Landis, T.Grier Miller, and Henrv Field Smyth, interested in tuberculosis in industry, had conducted studies in the relationship of industrial dusts to pulmonary disease ; numerous articles and reports came from this group, both collectively and individually, com mencing about 1914. During the years 1914-30, in association with the Bureau of Mines and later on their own behalf, the Public Health Service combined field studies with laboratory research in an effective manner. Miller in the Public Health Service demon strated the technique of intraperitoneal injections of silica and other dusts to determine the tissue reaction.35 Gardner and his associates at the Saranac laboratory demonstrated that attenuated tubercle bacilli in the presence of quartz dust would, in experimental animals, produce fatal tuber culosis widiout increasing the virulence of the bacilli.58 In 1922, Greenburg and Smith introduced the impinger, a dust sampling device, which resulted in the impinger method becoming the standard for the United States Bureau of Mines and the Public Health Service.60 The intimate relationship of roentgenological diagnosis to the silicosis problem was recognized early. In 1926, Pancoast 2 a SILICOSIS AND ASBESTOSIS and PendergTass published the first book to appear on this subject.41 These authors, together with Sampson and others, have carried on experimental work in technique and in elaborating standards of diagnosis.42 The determination of disability in silicosis has proved vexatious to both clinicians and workmen's compensation officials. At the University of Rochester, McCann and his associates have been working on physiologic methods of estimating pulmonary impairment. Harrington of the United States Bureau of Mines, Philip Drinker at the Harvard School of Public Health, Cummings at Saranac, Bloomfield and Dallavalle of the Public Health Service, Fehnel and his associates at the Metropolitan Life Insurance Company, have contributed a very large amount of work to the engineering and chemical methods of dust de termination and control. Here again, the reports and publica tions are far too numerous to detail and the reader is referred to the original sources. In addition to all the publications made available by all this field and laboratory work, the Harvard School of Public Health, the Saranac Laboratory, and the Division of Indus trial Hygiene of the United States Public Health Service have undertaken direct educational activities. A recent organ ization is the Air Hygiene Foundation, sponsored by various industries to encourage research into atmospheric pollution and pulmonary disease and to carry on educational work. 2. HISTORY OF ASBESTOSIS Asbestos was'mined and the fibres were separated from the mineral and_used in the making of fire-proof fabrics several centuries b.c. Attention is called by Cooke 43 to a cremation cloth described by Herodotus in 450 b.c. Materials made of asbestos have been used ever since but in the past three dec ades, the industry has grown tremendously owing to the HISTORY 23 greatly increased use of fire resisting and insulating materials as well as brake linings in the automobile industry. Asbestos is a magnesium silicate, containing a small amount of iron and a trace of aluminum. The fibres are long and flex ible and for many purposes are combined with cotton to undergo regular textile processes of spinning and weaving. Most of the asbestos used in the United States comes from Canada. The first report of a death resulting from asbestos dust in halation was presented by Murray in 1900.64 A second case was reported by Cooke 65 in 1924 and again in 1927.63 At that time, Cooke described the unusual and characteristic asbestosis bodies. In 1927, Oliver66 reported 2 cases, to be followed by McDonald 67 and Seiler.68 In 1928, Simson 69 reported 2 cases in South Africa. Other cases were reported by Wood and Page 70 in 1929, Haddow 71 in 1929, and Wood and Gloyne7in 1930 ; in that year appeared the comprehensive report of Merewether and Price.73 In the United States, Lynch and Smith 74 reported the first cases in 1930. The first investigation of the asbestos industry in the United States was made in 1930 and 1931 by Lanza, McConnell, and Fehnel.75 In the last few years, much atten tion has been given both to the clinical aspects and diagnosis of asbestosis and to its pathology. In 1936, Shull reported a roentgenological review of 71 cases.76 Recently the United States Public Health Service 77 has published several reports of dust control methods in asbestos plants and of the industry in general. BIBLIOGRAPHY 1. Collis,E.L. Industrial Pneumoconiosis with Special Ref erence to Dust Phthisis. Milrov Lectures, 1915- H.M.Stat. Office, London, 1919. 2. Plinius Secondus, Caius. Naturalis Historias: Book II. 24 SILICOSIS AND ASBESTOSIS Trans, by Kenneth C.Bailey under the title 'The Elder Pliny's Chapter on Chemical Subjects,' pt.i, 1929. 3. Sayers.R.R. Silicosis among Miners. Bur. of Mines Tech. Paper 372, 1925. 4. Mavrocordato.A.E. The Etiology of Silicosis. Rept.4th Meeting of Permanent Internat. Commission for the Study of Occupational Diseases. Lyon, 3-6, Apr. 1929. 3. Agricola, Georgius. De Re Metallica : Book I. Trans, from first Latin ed. of 1556 by Herbert C.Hoover and Lou Henry Hoover. Mining and Scientific Press, San Francisco, 1912. 6. Koelsch, Franz. Theophrastus von Hohenhcim, called Para celsus. Of the Miners' Consumption and Other Miners' Dis eases. DeuLGesell.Gewerbehyg., N.F. 12, 1923. 7. SchOrmann.S. Industrial Dust: Its Control with Special Ref erence to Legal Measures. CentraIbl.Gewerbehyg.il. Unfallverh., Sup. 15, 1929. 8. Ramazzini.B. (Cited by Collis, Ref.i ) 9. Allison, ( Cited by Collis, Ref. 1) 10. Miller, Hugh. My Schools and Schoolmasters. 12th ed. 1869. Wm.P.Nimmo, Edinburgh. 11. Thackrah,C.Turner. The Effects of Arts, Trades and Professions. 2nd ed. 1832. Baines & Newson, Leeds. 12. Greenhow,E.Headlam. (Quoted by Collis, Ref. 1) 13. Peacock,T.B. On French Millstone-makers' Phthisis. Med ico ChiruiTgical Rev., 25, 1860. (Cited by Collis, Ref.i ) 14. Silicosis and Allied Disorders. Medical Series, Bulletin No.i. Air Hygiene Foundation of America, Inc., Pittsburgh, Pa. *93715. Silicosis. Records of the International Conference held at Johannesburg, p-S39, 13-27. Aug. 1930. 16. Rovida, Carlo LE0p01.n0. Un case di silicosi del pulmone, con analist chimica. Plli Annalli di Chimica, 1871. 17. HaldaneJ.B.S., Marint,J.S., and Thomas,R.A. Report to the Secretary of State for the Home Department on the Health of Cornish Miners. Cd.2091. H.M.Stat.Office, London, 1904- HISTORY 25 18. Report of the Departmental Committee upon Merioneth shire Slate Mining. Cd.yfiye, H.M.Stat.Office, London, 1895. 19. 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Path. 12:245, 1931. 26. Miodleton.E.L. Industrial Pulmonary Disease due to the In halation of Dust. Lancet, 231:18:59, 1936. 27. Stewart.M.J. and Faulds.J.S. The Pulmonary Fibrosis of Hematite Miners. J.Path.Bact.3g:233, 1934. 28. Jones,W.R. Silicotic Lungs -- The Mineral They Contain. J-Hyg.S3:37. i9S329. Carleton.H.M. Pulmonary Lesions Produced by the Inhala tion of Dust in Guinea Pigs. J.Hyg.22:438, 1924. 30. Harrincton.D. and Davenport,SaraJ. Review of Literature on Effects of Breathing Dusts with Special Reference to Sili cosis. Part I. U.S.Bur.of Mines. Inf.Cir.6835, Mar. 1935 31. Report of Technical Commission of Inquiry: The Preva~ lence of Miners' Phthisis and Pneumoconiosis in the Metal- 26 SILICOSIS AND ASBESTOSIS liferous Mines at Broken Hill. No.6 Report, Dec. 1,1921. Dept, of Labour and Industry, New South Wales. 32. Denny,J.J., Robson,W.D., and Irtvin.D.A. The Prevention of Silicosis by Metallic Aluminum. I. Preliminary Report. Can. Med.Assoc.J.37:1, 1937. 33. Peterson,F. Anthracosis Pulmonum. Med.Rec.23:113, 1887. 34. Canedy.F.J. Grinders' Consumption. Boston Med.Surg.J., 117:198, 1887. 35. Betts,W.W. Chalicosis Pulmonum or Intestitial Pneumonia Induced by Stone Dust. J.Am.Med.Assocs4:7o, 1900. 36. Higcins,E., Lanza,A.J., Laney.F.B., and Rice,G.S. Siliceous Dust in Relation to Pulmonary Disease among Miners in the Joplin District, Missouri. U.S.Bur.of Mines Bull. 132, 1917. Lanza,A.J., and Childs,S.B. Miners' Consumption : A Study of 433 Cases of the Disease among Zinc Miners in South western Missouri. U.S.Pub.Health Bull.85, 1917. 37. Harrington,D., and Lanza,A.J. Miners' Consumption in the Mines of Butte ( Montana ). U.S.Bur.of Mines Tech.Paper 260, 1921. 38. Sayers,R.R., Meriwether,F.V., Lanza,A.J., and Adams,WAV. Silicosis and Tuberculosis among Miners of the Tri-State District of Oklahoma, Kansas, and Missouri. I. U.S.Bur.of Mines Tech. Paper 545, 1933. Meriwether,F.V., Sayers,R.R., and Lanza,A.J. Silicosis and Tuberculosis among Miners of the Tri-State District of Okla homa, Kansas, and Missouri. II. U.S.Bur.of Mines Tech. Paper 552, 1933. 39. Sayers,R.R., Bloomfield,J.J., Dallavalle.J.M., Jones,R.R., Dreessen,W.C., Brundage,D.K., Britten,R.H. Anthraco-Silicosis among Hard Coal Miners. U.S.Pub.Health Bull.221, Dec. 1935. 40. Bloomfield,J.J., and Greenburg.L. Sand and Metallic Abra sive Blasting as an Industrial Health Hazard. J.Ind.Hyg.15: 184, July 1933. 41. McConnell,W.J., and FehnelJAV. Health Hazards in the Foundry Industry. J.IncLHyg. 16:227, July 1934. Industrial Commission of Wisconsin. Proceedings of the HISTORY 27 Conference Concerning the Effects of Dusts upon the Respira tory System. Nov. 16-17, i932-(Feb- t9S3 ) 42. Papers and Discussions Presented before the American Foun- drymen's Association Annual Gmvention, Toronto, Can., 21- 23, Aug. 1935. 43. Report of Bureau of Occupational Diseases of the State of Connecticut. Fiscal Year ending 30, June 1935. 44. Commonwealth of Massachusetts. Report to General Court of Special Industrial Disease Commission, Boston, Feb. 1934. 45. Hoffman,F.L. Mortality from Respiratory Diseases in Dusty Trades. U.S.Bur.of Lab.Stat.Bull.231, 1918. 46. Rlssell,A.E., Britten,R.H., Thompson,L.R., Bloomfield, J.J. The Health of Workers in Dusty Trades. II. Exposure to Siliceous Dust ( Granite Industry ) U.S.Pub.Health Bull. 187, July 1929. 47. Hayhlrst.E.R., and Kinpel,D.J. Stereoscopic X-Ray Exam ination of Sandstone Quarry Workers. Am.J.Pub.Health, 17: 818, 1927. Hayhurst,E.R., Kindel.D.J., Nieswander,B.E., and Bartlett,C.D. Silicosis with Low Incidence of Tuberculosis. J. Ind.Hyg.i 1:228, 1929. 48. Dreessen.W.C. Effect of Inhaled Marble Dust as Observed in Vermont Marble Finishers. U.S.Pub.Health Repts.4g:724, 193449. Landis,H.R.M. The Pottery Industry in Relation to Tuber culosis. AmJ.Pub.Hcalth., 4:739, 1914. Miller,T.Grier. and Smvth, Henry Field. The Dust Haz ard in Certain Industries. J.Am.Med.Assoc., 70:599, 1918. Qi/aintance.P.A. Silicosis: A Study of 106 Pottery Workers. Am.J.Pub.Health., 24:1244, 1934. Schramm, Edward. Dust Elimination in the Pottery Industry. J.Am.Ceram.Soc., 16:205. >93350. Tucker,G.E. Physical Examination of Employees Engaged in the Manufacture of Portland Cement. Am.J.Pub.Health, 5: 560, 1915. 51. Thompson,L.R., Brundace.D.K., Russell,A.E., and Bloom field,J.J. Health of Workers in Dusty Trades. I. Health of r 28 SILICOSIS AND ASBESTOSIS Workers in a Portland Cement Plant. U.S.Pub.Health Bull. 176, 1928. 52. Holmes.P.M. Health Hazards in the Industries of Niagara Falls. U.S.Pub.Hcalth Repts-35:i, 1920. 53. Winslow,C.-E.A., Greenblrg.L., and Greenberg.D. The Dust Hazard in the Abrasive Industry. U.S.Pub.Health Repts. 34:1171. 1919. 54. Clark,W.I., and Simmons,E.B. The Dust Hazard in the Abra sive Industry. Indus.Doc., 4:53, 1926. Clark,W.I. Dust Hazard in the Abrasive Industry. Second Study. J.Ind.Hyg., 11:92, 1929. Clark,W.I. Dust Hazard in the Abrasive Industry. Third Study.J.Ind.Hyg., 13:343- '9Si55. Kessler,H.H. Silicosis in the Abrasive Powder Industry. Am. J.Pub.Health, 21:1390, 1931. 56. Winslow,C.-E.A., and Greenburc.L. Study of the Dust Haz ards in the Wet and Dry Grinding Shops of an Ax Factory. U.S.Pub.Health Repts., 35:2393, 1920. 57. Drury.W.H. The Incidence of Tuberculosis among Polish ers and Grinders in an Ax Factory. U.S.Pub.Health Repts., 36:159, 192.1. f 58. Gardner,L.U. Studies in Experimental Pneumonoconiosis : Reactivation of Healing Primary Tubercles in the Lung by the Inhalation of Quartz, Granite, and Carborundum Dusts. Am.Rev.of Tuberc., 20:883, 1929. 59. Miller,J.W., and Sayers,R.R. The Physiological Response of Peritoneal Tissue to Dusts Introduced as Foreign Bodies. U.S.Pub.Heaith Repts.4g:8o, 1934. 60. Greenburc.L. and Bloomfield,J.J. The Impinger Dust Sampling Apparatus as Used by the United States Public Health Service. U.S.Pub.Health Repts., 47:654, 1932. Bloomfield,J.J. and Dallavalle.J.M. The Determination and Control of Industrial Dust. U.S.Pub.Health Bull.217, 93561. Pancoast.H.K., and Pendergrass,E.P. Pneumoconiosis (Sili- cosis ) . Paul B.Hober, Inc., New York, N.Y., 1926. HISTORY 29 C)2. Pancoast, H.K., Pendergrass,E.P., Riddell,A.R., Lanza,A.J., McConnell, W.J., Sayers,R.R., Sameson.H.L., and Gardner, L.U. Roentgenological Appearance in Silicosis and the Un derlying Pathological Lesions. U.S.Pub.Health Repts-5o:889. 1935(3^. Cooke,W.E. Pulmonary Asbestosis. Brit.Med.J.2:1024, 1927. (14. Murray,M. Charing Cross Hosp. Gas., 1900. ( Ref. to by Cooke) (j-. Cooke,W.E. Fibrosis of the Lungs due to the Inhalation of Asbestos Dust. Brit.Med.J., 2:147, 1924. GG. Oliver,T. Pulmonary Asbestosis in Its Clinical Aspects. J. Ind.Hyg., 9:483, 1937. G7. McDonald,S. Histology of Pulmonary .Asbestosis. Brit.Med. J,, 2:1025, 1927. G8. Seiler.H.E. A Case of Pneuntonoconiosis : Result of Inhala tion of Asbestos Dust. Brit.MedJ., 2:982, 1928. 6g. Simson.F.W. Pulmonary Asbestosis in South Africa. Brit.Med. J., 1:885, 1928. 70. Wood.W.B., and Page.D.S. A Case of Pulmonary Asbestosis. Tubercle, 10:457, 1929. 71. Haddow,A.C. Clinical Aspects of Pulmonary Asbestosis. Brit. Med.J., 2:580, 1929. 72. Wood.W.B., and Gloyne,S.R. Pulmonary Asbestosis. Lancet, 1:445. l93. 73. Merewether,E.R.A. and Price,C.W. Report on Effects of Asbestos Dust on the Lungs and Dust Suppression in die Asbestos Industry. H.M.Stat.Off., London, 1930. 74. Lynch,K.M., and Smith,W.A. Asbestosis Bodies in Sputum and Lung. J.Am.Med.Assoc., 95:659, 1930. Lynch,K.M., and Smith,W.A. Pulmonary .Asbestosis II. Am. Rev.Tuberc., 23:643, 1931. 75. Lanza,A.J., McConnell,W.J., and Fehnel.J.W. Effects of the Inhalation of Asbestos Dust on the Lungs of Asbestos Work ers. U.S.Pub.Health Repts.. 50:1, 1935. 76. ShullJ.R. Asbestosis : A Roentgenologic Review of Seventy- ^ One Cases. Radiology, 27:279, 1936. 30 SILICOSIS AND ASBESTOSIS 77. Page,R.T., and Bloomfield,J.J. Dust Control Methods in an Asbestos Fabricating Plant. U.S.Pub.Health Repts., 52:1713, 1937Dreessen.W.C., DallavalleJ.M., Edwards,T.I., Miller, J.W., Sayers.R.R., A Study o Asbestosis in the .Asbestos Tex tile Industry. U.S.Pub.Health Bull.241, 1938. II. ETIOLOGY, SYMPTOMS, DIAGNOSIS OF SILICOSIS AND ASBESTOSIS R. R. Savers, M.D. SENIOR SURGEON, UNITED STATES PUBLIC HEALTH SERVICE CHIEF, DIVISION OF INDUSTRIAL HYGIENE NATIONAL INSTITUTE OF HEALTH AND A. J. Lanza, M.D. ASSISTANT MEDICAL DIRECTOR METROPOLITAN LIFE INSURANCE COMPANY x. ETIOLOGY, SYMPTOMS, AND DIAGNOSIS OF SILICOSIS Silicosis has been variously defined : Dorland ( Diet. 16th ed. pp.68) 'Pneumoconiosis due to inhalation of the dust of stone, sand, or flint(Webster's New International Dic tionary, 1930, p. 1956) `An affection of the lungs occurring in stone cutters, caused by the inhalation of quartz dust.' The Committee on Pneumoconiosis of the Industrial Hy giene Section of the American Public Health Association, recently defined silicosis as `a disease due to breathing air containing silica ( Si02), characterized anatomically by gen eralized fibrotic changes and the development of miliary nodulation in both lungs, and clinically by shortness of breath, decreased chest expansion, lessened capacity for work, absence of fever, increased susceptibility to tuberculosis (some or all of which symptoms may be present), and by characteristic X-ray findings.' 1 The compensation law of West Virginia defined silicosis as `an insidious fibrotic disease of the lung or lungs, due to prolonged inhalation and accumulation sustained in the course of and resulting from employment, of minute particles 31 32 SILICOSIS AND ASBESTOSIS of dust containing silicon dioxide ( Si02) over such a period of time and in such amounts as result in the substitution of fibrous tissue for normal lung tissues ; and the term silicosis shall also include silicosis accompanied by tuberculosis of the lungs evidenced by the presence of tubercle bacillus in the sputum.'2 While the foregoing definitions express somewhat different viewpoints, they have this in common -- the cause of silicosis is silica or quartz. Although other dusts, when inhaled in sufficient concentrations over a long enough period of time, have been shown capable of producing a definite pulmonary fibrosis, nevertheless the pneumoconiosis characterized 'by nodular fibrosis has to date been shown clinically and ex perimentally to be associated only with the inhalation of dusts containing free or uncombined silica. Silica in Nature Silica is the most abundant constituent of the minerals and rocks that make up the crust of the earth. It occurs in two forms, free and combined. The free silicas, as a group, are definite compounds in the form of SiO. The combined forms are silicates. Of free silicas which occur in nature, that known as quartz is by far the most common. Quartz is a hard mineral and chemically resistant to reagents. It is an abundant con stituent of granite, schist, and other rocks, and the chief component of sandstone and quartzite. Many ores are de posited in veins that consist nearly wholly of quartz. Probably the next most common form in which free silica exists in nature is the amorphous hydrated form known as Opal ( SiO.,-H.,0 ). Opal is a silica of colloidal origin and-occurs abundantly in the diatomaceous earths. It is less resistant to reagents than quartz. Another type of free silica is flint and with flint is found chalcedony, a waxy, translucent form of silica interpreted as consisting of fibres of quartz with a small 2! ' ETIOLOGY, SYMPTOMS, DIAGNOSIS 33 amount of interstitial opal. Other forms of free silica occur ring less abundantly in nature are tridymite, cristobalite, and siliceous glass or vitreous silica. Occupational Exposure to Silica As the earth's crust contains so large an amount of silica, it is obvious that those occupations concerned with mining and the driving of tunnels are associated with a silicosis hazard. Other occupations exposing the workers to this hazard are those concerned with the processing and industrial use of mineral products, such as smelting and refining, the use of sand and gravel for structural purposes ; the cutting of stone, particularly granite ; the manufacture and use of certain abrasives ; and the processing of the various forms of free silica. According to Knopf,3 the most common forms of free silica used industrially are massive crystalline quartz, quartz ite, sandstone, flint, tripoli, diatomaceous earths and silica sand. Table 1, from Ladoo,4 illustrates the great variety of uses to which silica is put in industry and the kind of silica adapted to each purpose. TABLE I USES OF SILICA Abrasive uses : In scouring and polishing soaps and powders In sandpaper In sand-blast work Metal buffing, burnishing, and pol ishing TYPES OF SILICA USED Quartz, quartzite, flint, chert, sand stone, sand, tripoli, and diatoma ceous earth ; all in finely ground state. Quartz, quartzite, flint, sandstone, and sand ; coarsely ground and closely sized. Quartz, quartzite, sandstone, and sand, crushed into sharp angular grains uniform in size. Ground tripoli and other forms of ground silica. 34 SILICOSIS AND ASBESTOSIS USES OF SILICA For jawing and polishing marble, granite, etc. As whetstones, grindstones, buhr- stones, pulpstones, oilstones, etc. Tube-mill lining Lithographers' graining sand Tube-mill grinding pebbles In tooth powders and pastes Wood polishing and finishing Refractory uses : In making silica fire brick and other refractories Metallurgical uses: In making silicon, ferrosilicon, and silicon alloys of other metals, such as copper As a flux in smelting basic ores Foundry-mold wash Foundry parting sand Chemical industries: As a lining for arid towers As a filtering medium In the manufacture of sodium silicate In the manufacture of carborun dum Paint: As an inert extender TYPES OF SILICA USED Sharp, clean sand graded into var ious sizes. Massive sandstone from very fine to moderately coarse grained. Chert, flint, and quartzite in dense solid blocks. Medium to fine sand or rather coarsely ground silica and tripoli. Rounded flint pebbles. Various forms of pure silica finely ground. All forms of silica ground to me dium fineness. Fairly pure quartzite known as ganister: not less than g- per cent SiO , nor more than 0.40 per cent alkalis, tightly interlocking grains desired. Moderately pure sand, massive crys talline quartz, sandstone, quartz ite, or chert. Massive quartz and quartzite. Ground sandstone, quartz, and tripoli. Fine sand and ground tripoli. Massive quartz or quartzite. Massive diatomaceous earth and tripoli, sand, finely granular quartz or quartzite, finely ground tripoli, diatomaceous earth, and other forms of silica. Pure pulverized quartz sand, pure tripoli, and diatomaceous earth. Pure quartz sand. Finely ground crystalline quartz, quartzite, and flint; also finely ground sandstone, sand, and tripoli. ETIOLOGY, SYMPTOMS, DIAGNOSIS 35 USES OF SILICA TYPES OF SILICA USED Mineral fillers : yV* a wood filler In fertilizers In insecticides As a filler in rubber, hard rubber pressed and molded goods, phono graph records, etc. In road asphalt surfacing mixtures Ceramic uses : In the pottery industry as an in gredient of bodies and glazes In the manufacture of ordinary glass In the manufacture of fused-quartz chemical apparatus such as tubes, crucibles and dishes Decorative materials: In the manufacture of gems, crystal balls, table tops, vases, statues, etc. Insulation: Heat insulation for pipes, boilers, furnaces, kilns, etc Sound insulation in walls, between floors, etc Structural materials : Sand-lime brick Optical quartz: For the manufacture of lenses and accessories for optical apparatus Finely ground crystalline quartz, quartzite, flint, tripoli, and other types of ground silica. Finely ground silica of all types. Flint, tripoli, and chert. and other amorphous silica preferred : also all other forms of very pure silica, all finely ground. Very pure massive quartz preferred. Rock crystal, amethyst, rose quartz, citrine quartz, smoky quartz, chrysoprase, agate, chalcedonv, opal, onyx, sardonyx, jasper, etc. Massive and ground diatomaceous earth. Moderately pure, sharp, angular sand, preferably finer than 20mesh, together with a small per centage of finely pulverized silica. Clear, colorless, flawless rock crys tal or massive crystallized quartz. In a recent survey,5 carried on in a large manufacturing center, it was found that about 9 per cent of the industrial workers were employed in occupations where the silica hazard required consideration. According to the census from 1930, there were gainfully employed in the manufacturing and 36 SILICOSIS AND ASBESTOSIS mechanical industries in this country approximately 14,000,000 persons. If the above survey can be accepted as repre sentative of the occupational distribution of these workers, it would appear that there are nearly 1,200,000 individuals possibly exposed to a silicosis hazard in the manufacturing and mechanical industries alone. Lanza and Vane,6 in their discussion concerning the prevalence and effect of silicosis, state : `Our very rough, but obviously conservative estimate of the number of workers exposed to silica dust to a harmful degree in the United States is, therefore, upwards of 500,000.' Factors Influencing the Action of Silica Dust Particles as the Exciting Cause of Silicosis Although it has been accepted that silica is the exciting cause of silicosis, there are certain factors which must be considered as influencing its action. Early workers were in clined to consider that the injury produced by the dust particle was due to the mechanical irritation of its hard and cutting edges. Gardner 7 has shown experimentally that the inhalation of finely divided carborundum dust, which has sharp edges and a greater hardness than silica, does not produce the nodular reaction characteristic of silicosis. Collis8 was one of the early workers to draw attention to the chemical action of dust. Gye and Kettle 9 have shown that silica in solution or non-crystalline form exerts a toxic action upon the tissues which leads to the proliferation of fibroblastic cells. Lately, Miller and Sayers 10 have reported results of experi mental studies and have classified the reaction of peritoneal tissues to certain dusts. Only the silica containing dusts have uniformly produced the proliferative harmful reaction. Other dusts have been either completely absorbed, leaving no scar tissue, or have remained unaltered in the form in which they were injected. These latter reactions are classed as ab sorptive and inert. ETIOLOGY, SYMPTOMS, DIAGNOSIS 37 Since dust, to exert its harmful action, must enter the finer divisions of the lung, its particle size bears a definite rela tionship to its injurious effects. The silica must be present in the air in particles small enough to enter the finer air spaces and of such dimensions that the phagocytic cells may engulf them. The natural defenses of the respiratory tract probably prevent many particles larger than 10 microns from reaching the finer divisions of the lung and such as do are likely to be expelled with the bronchial secretions. The solubility of the silica may play a definite part in the production of disease and the size of the particle also affects the rate of solution as the smaller the particles, the greater the total surface area exposed to the action of solvents. Table 2 shows the size distribution of various industrial dusts as compared with the dust particles observed in the out door air in the general atmosphere. About 70 per cent of the particles found in industrial dusts generally are between 0 .5 and 3 microns in diameter. There are, no doubt, a great many particles too small to count by the method used but experimentally it has been shown that such sub-microscopic particles are not retained in the lungs but pass out with the expired air. Sayers 11 has shown that less than 15 per cent is retain^! when finer particulate matter, such as lead in the form of fumes, is inhaled. The majority of particles found upon microscopic examination of lung tissue also fall within the limits of from t to 3 microns. Another reason for considering the size of the particles as affecting the harmfulness of the dust, is that the larger ones settle out with comparative rapidity from the atmosphere while the rate of falling for the smaller particles is very slow. Figure i illustrates graphically this difference ; particles under 1 micron falling at the rate of from 1 to 3 feet per hour, vary ing with the specific gravity, while particles 5 microns in diameter and of specific gravity 7 fall about 60 feet per hour. M ' 'min wpyi 3 Q N j < w J P3 -< 3za / h 3Ov) >3< iot. 0z 1 to I Q >u* u ? M J5 ETIOLOGY, SYMPTOMS, DIAGNOSIS 39 Particles oE more than io microns settle out in a relatively short time. Thus we may say that the harmfulness of a given dust is directly influenced by the number of particles it contains of free silica less than 10 microns in diameter and that probably the most damage is produced by those between 1 and 3 microns. The relationship of dust concentration and duration of exposure is closely associated in their etiological significance. The rate at which silicosis will develop, excluding certain factors considered as predisposing, depends upon the dosage Figure 1 - Diameter of Dust Particle in Microns -- Density of Dust Particle in Grams per CC. 40 SILICOSIS AND ASBESTOSIS of free silica. This dosage is obviously dependent upon the amount of silica in the air inhaled and the duration of ex posure. In this lies a point of great practical importance which explains the apparent discrepancies between the reports ol different investigations with respect to the time necessary for silicosis to develop. In 1902, a committee, of which Dr.J.B.S.Haldane 12 was a member, reported upon an investigation made to determine the cause of excessive mortality rates from tuberculosis among Cornish tin miners. These investigators pointed out that it was evident that the inhalation of stone dust by these miners was the cause of permanent damage to the lungs. Further more, they noted that the condition developed gradually in the case of the ordinary miner but rapidly in the case of the machine workers who were exposed to greater amounts of dust. Dr.Watkins-Pitchford13 and Dr.Mavrogordato,1* as well as other South African investigators, emphasize the relation ship of the concentration of dust and duration of exposure to the degree of lung changes produced. Intermittent employ / ment has been suggested as an aid in preventing silicosis but aside from the fact that it does delay the ultimate result, it has not been shown that such interruption of work can safely be relied upon where harmful concentrations of dust are involved. In the United States, the reports of the Picher Clinic15 have indicated the effects of varying periods of ex posure to silica in the mines of that district. Similar studies of the health of granite workers 1617 likewise stress the dura tion of exposure necessary to produce definite degrees of silicosis. Various investigators have stated that the presence of other substances in silica containing dust may influence the action of silica tending either to aggravate or retard the usual reac tion. The question was raised by Heffernan 18 in 1926 as a result of a study of a group of brick makers in Derbyshire. He ETIOLOGY, SYMPTOMS, DIAGNOSIS 41 concluded that the clay present in the silica dust was re sponsible for the absence of silicosis in this group of workers. Gardner is strongly of the opinion that the action of silica is modified by other substances which may be in combination with it and this is supported by the recent Canadian reports with reference to the action of metallic aluminum.19 What the implication of this may be with respect to specific dust problems in various industries remains to be determined. Cases of so-called acute silicosis, resulting from the presence in highly siliceous dust of alkali in a fine powdered form, have been reported by Chapman,20 Kessler,21 MacDonald,22 Kil gore,23 and others. Some have suggested that the action of silica is made more rapid by the presence of these alkalis because silica is more soluble in alkaline solutions. Kettle 24 failed to demonstrate such action experimentally and states that proof is still lacking that any action of the kind may occur. The effects of inhaled coal dust in conjunction with silica have been reported at length by the Public Health Service 25 in their study of anthraco-silicosis among hard coal miners. Taken all in all, the available data indicate that other components of silica laden dust are not merely inert diluents whose effect is to reduce the amount of silica inhaled. Some of these substances may act in this manner ; others apparently aid in removing the silica particles from the atmosphere ; and others may accelerate or retard the action of silica. More over, when inhaled with silica, these latter tend to alter the anatomical form of the silicotic lesion. The degree of modifi cation is determined by the character and amount of the adulterant dust. Occupational History Most important in determining the significance of a given dust exposure is a complete, carefully taken occupational SILICOSIS AND ASBESTOSIS history, whereby the total dust exposure may be estimated and compared with other cases of a similar nature. Tables 3, 4, and 5 illustrate a practical method of analyzing and record ing occupational factors in the study of a dusty industry.25 TABLE 3 Occupational Record Division of Industrial Hygiene -- United States Public Health Service Dated : August 8, 1933 Name K...........M......... Age began work : is Office : Industrial Hygiene Present age : 49 Number of years worked : 34 Specific Occupation Specific Industry No- f y*wi TM Hard Cod Non-dusty Present Section foreman Anthrac:iitte coal Preceding 1 -- Contract miner ( chamber) " ' t -- Miners' laborer ( chamber ) " ` 3 -- Mule driver (dry mine) "` 4 -- Patcher (dry mine) "` 5 -- Slate picker ( dry breaker ) " ` 6 -- Farm laborer ( Pa.) Agriculture 5 *3 3 3 2 2 r Remarks : Estimating the total time idle during working life -- 3 yean Table 4 shows the occupations and associated dust ex posure of chamber miners and laborers. Each occupation en gaged in by these coal miners was studied separately. Ex perience has shown that the various occupations comprising the activity of any dusty industry are usually associated with dissimilar dust exposure. Table 5 shows a method of analysis used in estimating an individual's total dust exposure. With such occupational histories available and the knowl edge of the percentage of total dust exposure revealed by detailed occupational analysis, it was found possible in a recent study to predict in 9 cases out of 10 approximately the ETIOLOGY, SYMPTOMS, DIAGNOSIS TABLE 4 43 Dust Exposure of Contract Miners and Helpers ( Laborers ) Chamber Mining Occupation Jack-hammer drilling Hand loading After firing Taping and wiring Setting up prop*, and in main airway* Number of Samples Average Dust Count Millions of Number of {millions of ParticleHours in particles Hours Per Activity per cubic Cubic Foot foot of air) 23 1 22 2 57S 1,138 373 *,376 7 X 834 209 2 X 40 20 8 Totals 6* 6X -- 3,itat 3, x a 1 million particle-hour* per cuit. * 480 million partide-hours per cu.ft. 6pi his. pulmonary condition that would be found upon physical ex amination, insofar as changes due to dust inhalation were concerned. A statement on the effect of variations and concentrations and composition was developed by the Committee on the Prevention of Silicosis through Medical Control.24 An abstract of this report follows. The effects of the variation in concentration of silica in the air breathed must be judged by data from those field and laboratory studies which have reported results that can be compared. The following concentrations have been accepted as permissible for particular industries in the localities in dicated. "It is believed that the effects of other substances associated 44 SILICOSIS AND ASBESTOSIS with silica in atmospheric dusts are sufficiently marked and well defined to preclude comparison of silica hazards merely on the basis of the amount of free silica in the atmosphere. It is concluded that atmospheric concentration of silica, which may have proved incapable of producing silicosis in one industry, will not necessarily be harmless under other condi tions. The reverse is equally true. If these premises are as TABLE 5 Estimation of the Individual's Total Dust Exposure Name K.......... M Occupation Foreman Dust Concentration Number of in Millions of Millions of Years Particles Per Cubic Particle-Years Foot (average) Per Cubic Fool Slate Picker (dry mine) 3 3o Patcher ( dry mine) 3 71 Mule driver ( dry mine ) 3 7i Miner's laborer ( chamber) 3 480 Contract miner ( chamber) ij 480 Section foreman 57 760 I4J JI3 1.440 7,300 35 Total 3 -- 9,790 0.700 millions particle-year, per cu. ft _ ^ mmionf of plrticie.yein ^ 3 {t. sound as they seem, there can be no universal regulatory standard of permissible dust concentration at the present time. Separate standards must be set for different industrial dusts and processes. When all of the factors determining such standards have been more accurately measured and correlated it may become possible to use them as a basis for the general regulatory standard. `It is recommended that clinical and engineering studies be carried out as rapidly as possible to establish the necessary r ETIOLOGY, SYMPTOMS, DIAGNOSIS 45 scientific data upon which we may base practical and effective regulatory standards. `The factors necessary to establish a safe concentration of atmospheric dust are the following : `1. The relative number and size of the free silica and the other particles suspended at breathing levels in the different parts of the industrial atmosphere. Industry (1) South Africa Gold Mines ( 1) Ontario Gold Mines (1 ) Australia Sandstone (*) Barre Granite (a) Pennsylvania Anthracite Mines (1) Broken HOI, Australia Lead-Zinc Mines Percentage of Silica in the Dust Permissible Maximum Safe Dust Concentration Millions per cubic foot 80% about 35% (in the rock) 90% (in the rock) 31% to 33% 35% X3% 5% :o% to 17% 6 tO tO 30 S to to to to TS so 14 `2. The proportion of the workmen's time actually spent in the various dust concentrations. `3. The effects of exposure to environment, as revealed by the occupational and medical histories of old employees, by physical examination and by the roentgenological appearance of their lungs. `From the viewpoint of silicosis prevention, the standard of safe atmospheric dust concentration is the maximum in which persons can spend their entire industrial lives without / I 1I 46 SILICOSIS AND ASBESTOSIS producing demonstrable evidence of significant reaction in their lungs. `There is evidence that for prolonged exposure, a concentra tion of more than 5,000,000 particles per cubic foot of a highly siliceous dust is dangerous. Therefore, it is now considered good practice to hold concentrations of highly siliceous dust at 5,000,000 particles per cubic foot or less. `Since standards of safe atmospheric dust concentration, based on medical findings, have been established but for a few industrial dusts, and in view of the fact that to establish such standards for other industrial dusts will require con siderable study and investigation, some arbitrary standard to serve tentatively as a measure of good practice may be useful. This arbitrary standard should be based upon what is believed to be within the limits of good engineering prac tice and that which, from a medical viewpoint, it is judged will largely control the silicosis hazard for most industrial exposures. It has been suggested that the maximum permis sible concentration of silica in the air breathed might be expressed by the following formula ( Determination of dust concentration according to the technique described by the United States Public Health Service in Reprint 1520 from Public Health Reports, March 18, 1932 ) : Multiply the per centage of free silica by the total particle dust count. If the result is under 5,000,000, the condition may be considered permissible. If the result is over 5,000,000, the condition may be considered too high. For example, 10 per cent free silica with an average total dust concentration of 30,000,000 par ticles per cubic foot would give 0.10 times 30,000,000 which equals 3,000,000 (good practice ) ; 30 per cent with an aver age total dust concentration of 50,000,000, would equal 0.3 times 50,000,000 or 15,000,000 (unsatisfactory). This for mula is not applicable to any dust containing less than 3 per cent free silica.' ETIOLOGY, SYMPTOMS, DIAGNOSIS 47 Predisposing Causes The wide distribution of silicosis indicates that all races are susceptible and that no nationality is exempt. Although available data show that the incidence of silicosis is higher among the younger miners in districts where the percentage of free silica is high and among older miners where the per centage of silica is low, age, in itself, is probably not a factor. The'history of previous dust exposure and of previous respira tory infection is obviously of the utmost importance in the study of either an isolated case or of an industrial group. In dividual susceptibility is frequently mentioned but the weight of evidence is that it may be considered an acquired and not a congenital condition. Lehmann's 27 experiments to determine the functional ef ficiency of the upper respiratory tract, in the removal of dust, suggest that abnormalities of the nasal passageways may af fect the time element in the development of silicosis. Infections of the upper respiratory tract may be of im portance. Sinus infections may act by decreasing the efficiency of the upper respiratory tract in the removal of dust from the air passing to the lungs and also may be responsible for the spread of infection to the lower respiratory tract. Acute pneu monic conditions as well as the more chronic lung changes such as chronic bronchitis, bronchiectasis, and bronchiolectasis, emphysema, and pleurisy, all tend to lessen the ability of the lung to rid itself of foreign materials, through im paired lymphatic drainage and inability to force the bron chial secretions and foreign matter from the lungs. Symptoms The Committee on the Prevention of Silicosis through Medical Control26 has summarized the symptoms associated with silicosis both in the presence and in the absence of in fection, as follows (condensed) : 48 SILICOSIS AND ASBESTOSIS Subjective Symptoms Dyspnea. The complaint most frequently mentioned is - shortness of breath. Depending upon the extent of the in volvement, this varies from slight dyspnea, following exer tion, to marked dyspnea upon the least exertion or even when at rest. The shortness of breath noted in silicotics pre sents one peculiarity in that it is seldom accompanied by orthopnea, the individual being no more short of breath ly ing down than when in an upright position. This may not be so, however, when silicosis is complicated by cardiac dis ease or by true asthma. Silicosis Noted as a rule only after sud den or extra exertion. Seldom so marked as to interfere with routine duties. However, in cases with extensive pulmonary fibrosis, it may limit the in dividual's activities. Silicosis with Infection If complicating infection is not widespread, may be no more marked than in cases of simple silicosis but as infection and fibrosis increase, it becomes disabling. Cough. Many silicotics complain of a troublesome cough. This cough differs from that resulting from simple irritation due to dust which clears up upon removal from exposure. When present, it is more pronounced in the morning or upon beginning work after a rest period. Silicosis The typical silicotic cough is dry and non-productive. It usually parallels shortness of breath in degree and may con tribute to disability. Silicosis with Infection The cough usually becomes more troublesome and is pro ductive. The sputum varies from thick, tenacious, mucous material to that of a foul, purulent or purohemorrhagic consistency. ETIOLOGY, SYMPTOMS, DIAGNOSIS 49 Microscopic examination or animal inoculation frequently reveal tubercle bacilli or, in some cases, organisms of tlve fusiform spirochetal group. In advanced cases, coughing at tacks are often of such severity as to leave the individual ex hausted. Chest Pain. This symptom is complained of by a majority of silicotics. It varies from a feeling of tightness in the chest to the sharp pain typical of pleurisy. (Since chest pain is offered as a complaint in many conditions, it cannot be stressed as especially characteristic of silicosis.) Silicosis A late symptom in cases of simple silicosis. Then seldom more than a sense of tightness or feeling of substemal pres sure. Silicosis with Infection Pleuritic pain is suggestive of a complicating infection. It is increased by exercise and by coughing and may be distress ing in advanced cases with ex tensive infection. Hemoptysis. True hemoptysis seldom occurs. Frequently, however, the sputum may be blood-streaked following a se vere coughing attack. Hemoptysis must always be considered as suggestive of tuberculosis. Silicosis Occasional blood-streaked spu tum. May result from alveolar rupture following sudden ex ertion in advanced cases. Silicosis with Infection May be the first indication of tuberculous infection. May be consequent upon the develop ment of pneumothorax. May occasionally be excessive if cavities are present. SILICOSIS AND ASBESTOSIS General Complaints. Weakness, loss of weight, digestive dis turbances, night sweats, insomnia, dizziness, and edema of the extremities are not characteristic of uncomplicated sili cosis but are apt to be present if infection supervenes, espe cially when the infection becomes extensive. Objective Symptoms Changes in the general appearance are infrequent in sim ple silicosis unless far advanced. Such changes as are mani fested are usually due to complicating conditions. Silicosis Silicosis with Infection Early cases appear unchanged ; The appearance sooner or later in fact, it is common to find becomes that of chronic phthi these individuals showing a sis. The bony landmarks of the slight increase in weight, possi thorax become prominent and bly because they are less active. there is an increase in the an As the disease progresses, re terior-posterior diameter of the spiratory embarrassment is chest, possible hypertrophy of noticeable and there is a gen the accessory respiratory mus i eral loss of muscle tone. cles of the chest, and in the final stages, retraction of the supra and infra clavicular spaces. Cyanosis and clubbing ;1 !i of the fingers are not promi nent except in those cases of long standing, with cardiac i > disturbances. Chest Expansion. Decrease in the expansion of the chest may be demonstrated in cases with extensive pulmonary fibrosis. Silicosis In early cases it is usually not possible to demonstrate de- Silicosis with Infection Decrease in expansion may not be noted in early silicosis with r ETIOLOGY, SYMPTOMS, DIAGNOSIS 51 creased expansion. In advanced cases, expansion may be less ened by o to 30 per cent but remains equal on both sides. slight infection but as the con dition progresses, a definite decrease is readily observed. When infection is more pro nounced in one area of the lung, expansion may be more markedly decreased on the af fected side, particularly if there is pleural involvement. Prolonged Expiration. In most cases, decreased chest ex pansion is preceded and later accompanied by a definite change in respiratory rhythm. Close observation reveals that even at rest there is a distinct tendency to prolongation of the expiratory phase, which, as silicosis advances, becomes more marked. Following exercise, the silicotic may breathe less rapidly than the normal person under similar conditions as the lungs cannot be emptied rapidly enough to permit more rapid respiration; but although the respiratory rate is not so rapid, as in the normal person, it will persist for a longer period. Silicosis Early in the development of simple silicosis, prolonged ex piration may be evident only after exertion. Later the degree of prolongation usually paral lels the increase in pulmonary fibrosis. Silicosis with Infection In cases of early silicosis with slight infection, prolongation of the expiratory phase may be no more marked than in simple silicosis. As the condition progresses and fibrosis in creases, it may simulate char acteristic asthmatic respiratory rhythm. Signs Revealed by Palpation of the Chest. Except in the late stages of silicosis with infection, little is revealed by pal- I 52 siLrcosrs and asbestosis pation of the chest. However, where there is a measurable decrease in expansion, one may note by palpation that, upon forced inspiration, the anterior chest wall is lifted forward by the accessory muscles of respiration. Silicosis No change noted until ex tensive fibrosis has taken place, when there may be an increase in tactile fremitus generally. Silicosis with Infection When infection is extensive, tactile fremitus is increased and occasionally friction rubs may be elicited. Extensive thickening of the pleura or pneumothorax may result in a decrease or absence of tactile fremitus over affected areas. Percussion. There is usually an impairment of the percus sion noted over the whole chest but unless one is particularly observant, this may not be detected. Silicosis Since impairment in resonance is general over all lung areas, it is difficult to demonstrate until advanced fibrotic changes have developed. Decrease in diaphragmatic excursion may sometimes be revealed by per cussion. Silicosis with Infection Increase in loss of normal resonance. When massive areas of fibrosis have developed, this may amount to absolute dull ness over areas involved. Am phoric resonance may be elic ited where there is pneu mothorax. Decreased diaphrag matic excursion may readily be shown in advanced infec tion. Auscultation. Breath sounds are usually decreased in in tensity and the characteristic prolongation of expiration is readily noted. ETIOLOGY, SYMPTOMS, DIAGNOSIS 53 Silicosis Silicosis with Injection Decrease in brcaih souiuU rftieral and more marked as Tlie condition progresses. Sub crepitant rales, which dear up after coughing, are occasionally lu-ard. Usually heard, some of the following : Persistent post-tussic crepitant and sub-crepitant rales; coarse rhonchi associated with productive coughing, wheezing or musical rales in creased by exertion and cough ing, amphoric breath sounds over cavities and areas of pneu mothorax ; pleural friction rubs occasionally. Diagnosis The diagnosis of silicosis must be based upon information furnished by past occupational and medical history, the rec ord of present complaints, and the evidence revealed by a careful physical examination of the chest, including a roent genogram. The past and present occupational history should, as far as possible, detail the specific jobs in each industry in which the worker has been employed during his entire working life and estimate the time spent at each job and the duration and nature of previous dust exposure. The medical history should include all disabling illnesses and any history of contact with cases of active tuberculosis. The dates of all illnesses should be recorded. Physical examination of the chest should be carried out in a systematic and thorough manner. Subjective symptoms and positive clinical signs are usually absent or difficult to elicit in early and uncomplicated silicosis ; there are no signs or symptoms which may be considered as pathognomonic. Where the disease has progressed to the point when there is 54 SILICOSIS AND ASBESTOSIS decreased capacity for work, there will usually be clinical evidence of pulmonary changes. Included in the diagnosis should be a statement whether there is evidence of tuberculous infection, either active or latent, or infection of other nature. A positive diagnosis of silicosis should not be made with out a good roentgenogram of the chest, revealing nodular shadows throughout the lung fields. Although it is not ad visable to make a diagnosis of silicosis based upon roentgenray findings alone, nevertheless the chest conditions revealed by fluoroscopic and roentgenological examinations of the chest furnish the most convincing evidence of pulmonary fibrosis. Diagnosis by roentgen-ray is discussed in a separate chapter. A fluoroscopic examination is of distinct advantage. Par ticularly is it possible, by such procedure, to study diaphrag matic movements and note the presence of areas of increased density which, of course, are better shown in detail by film examination. The general information regarding pulmonary density furnished by fluoroscopic examination is of benefit in deciding the particular technique to use to secure the best roentgenogram of the lungs. Laboratory Examination Laboratory examination of the blood, urine, and sputum are of value when correlated with the clinical manifestations of silicosis. There are no blood characteristic of simple sili cosis. When infection is present, blood examinations are sometimes helpful in determining its severity and progress. Cases complicated by tuberculosis often show an increase in the sedimentation rate, paralleling the activity of the tuber culous complication. Urinalysis offers little of particular value in silicosis. Uri- ETIOLOGY, SYMPTOMS, DIAGNOSIS nary silica determinations may show an increase in silica pres ent, paralleling the silica exposure.25* The chief value of sputum examination is to determine the presence of tubercle bacilli. As in the case of chronic fibroid phthisis, too much dependence must not be placed upon microscopic examinations of the sputum. Where many sputum examinations have been negative for tubercle bacilli, guinea pig inoculation or sputum culture may indicate their presence. The Relation of Silicosis to Disability A diagnosis of silicosis does not necessarily mean disability. Since it is a slowly developing disease, roentgenological evi dence of silicosis may exist for many years prior to the dem onstration of any decreased capacity for work. The term `disability' is usually employed to indicate less ened capacity to do the work required of an individual in the course of his usual occupation. It may vary from partial to complete. Disability may persist as partial, but when the fibrosis is complicated by pulmonary tuberculosis, it becomes serious and permanent. Individuals with active tuberculosis are considered unsuitable for further employment in even a minimal silica exposure, regardless of whether or not they may also be silicotic. The existence of marked m complete disability is relatively easy to establish. Howes er. the clinician may find it possible to arrive at such a conclusion only after repeated examina tions, made over such a period of time as to afford him an opportunity to determine definitely the nature and severity of infection and other complicating conditions. The matter of partial disability is far more difficult to determine satisfactorily. The cause and extent of partial dis ability frequently requires careful examination to be ac- 56 SILICOSIS AND ASBESTOSIS curately gauged before proper placement of a worker can be effected or a fair settlement of a compensation claim achieved. To declare whether or not a workman should be allowed to continue at his work is a grave responsibility and calls for the utmost care, as well as experience, on the part of the ex amining physician. Fitness for work may be expressed as fol lows : I. Partial disability due to silicosis without infection : (a) May continue at usual occupation, if environment is satisfactorily controlled as regards dust concen trations and tuberculosis contact; ( b ) Degree of fibrosis and rate of development may re quire that the individual seek less arduous em ployment and avoid even minimal exposures to silica-containing atmosphere. II. Partial disability due to silicosis with complicating pul monary infection : ( a) Primary silicosis. Infection mild and non-tuberculous. In most instances, after successful treatment of non-tuberculous complicating infection, may be allowed to return to usual work, provided environ ment under which they are working is safely con trolled. ( b) Primary silicosis with pulmonary tuberculosis as complicating infection. Those individuals with silicosis who develop pulmonary tuberculosis are considered totally unfit for further employment in an industry affording even minimal exposures to free silica. This disability is obviously total, so long as active tuberculosis is present. Following success ful treatment, these cases regain their health to the point where they can be safely employed at other work. ETIOLOGY, SYMPTOMS, DIAGNOSIS 57 Prognosis There is hut a limited amount of factual data regarding the progress of silicosis and the relationship of a previous or superimposed infection to the progressive nature of this con dition must he considered. Nor is there adequate informa tion as to the ultimate results to silicosis cases after removal from exposure, and the extent of their subsequent pulmonary infection. It may be stated that the prognosis of the individual case of silicosis is almost as variable as are the industrial condi tions which cause the disease. Where the hazard is not verv serious and the resulting damage to the lungs of slight or moderate degree, with removal from further dust exposure, there may be little to apprehend either in the way of dis ability or shortened life. Tubercle infection occurring in such cases tends to become chronic and the patient may live for a long time with no marked disability as do other cases of fibroid phthisis. Where the pulmonary damage from silica is considerable, the outlook is usually unfavorable and when, as so often hap pens, this type of patient becomes tuberculous, his prognosis is very grave. Everything considered, the silicotic who is re moved from further dust exposure has a fairly good prog nosis. When tuberculosis supervenes, he may go the quick route or the slow one. His chances of securing an arrest of his tuberculosis are much less good than if his lungs were not previously damaged by silica. 2. ETIOLOGY, SYMPTOMS, AND DIAGNOSIS OF ASBF.STOSIS Asbestosis lias been defined by Merewether 19 as `a specific occupational disease of the lungs caused by the inhalation of asbestos dust and characterized by progressive replacement 58 SILICOSIS AND ASBESTOSIS o the essential active functioning tissue of the lung by in active non-functioning fibrous or scar tissue. It is essentially a pneumoconiosis, a fibrosis of the lungs, caused by the in halation of dust and, therefore, is in the same category as silicosis, which disease it resembles in some respects, while differing considerably in others.' Asbestos is a hydrated magnesium silicate. More than 90 per cent of the raw mineral used in manufacture in the United States and Great Britain is Canadian chrysotile. While most of the asbestos dusts in industrial plants are made up of very small particles, asbestos fibers exceeding 200 mi crons in length have been found in the lung tissue of asbestos workers. Asbestos is subjected to two main manufacturing processes. It may be combined with diatomaceous earth and other simi lar inert substances to be used for packing, insulating and fireproofing materials, or it may be combined with cotton or other materials and submitted to the usual textile processes of cleaning, mixing, carding, spinning, twisting, and weav ing. The asbestos cloth may in turn be subjected to further processes of impregnation with various substances for special purposes. Merewether and Price,J0 in their comprehensive report, state that approximately 2,200 individuals are exposed to practically pure asbestos dust in the factories of Great Britain. They examined 363 workers and the following table gives the result. Yean at Work o to 4 5 to 9 to to 14 15 to 19 so and over Cases Examined 89 141 84 28 si Showing Fibrosis 0 36 *7 >5 7 Per cent 0-0 *5-5 5*-i 53*6 80-9 ETIOLOGY, SYMPTOMS, DIAGNOSIS 5g This table does not apply to any one group of workers in the factories. The authors have collected also, outside of these statistical cases, records of ten deaths resulting from asbestosis, nine of which were verified by autopsy and the tenth, by repeated clinical and roentgenographic examinations. Nine of these deaths occurred from 1928 to 1929. The ex posure of the ten cases varied from nine to twenty-four years. In a study commenced in 1929, Lanza, McConnell, and Fehnel31 arrived at the following conclusions : 1. Prolonged exposure to asbestos dust causes a pulmonary fibrosis different from silicosis and demonstrable by roentgenogram. Clinically, it appears to be of a type milder than silicosis. 2. Definite cardiac enlargement was frequently found to be associated with asbestosis. 3. A predisposition to tuberculosis, due to asbestos dust, was not indicated although it was not known how much asbestosis may add to the mortality from pneumonia and acute non-tuberculous pulmonary infections. Page and Bloomfield,32 of the United States Public Health Service, have given a comprehensive report on dust control methods in an asbestos fabricating plant, and Dreessen, Dallavalle Edwards, and Miller,33 of the United States Public Health Service, have made a recent study of the asbestos in dustry. This study included physical examinations of 541 asbestos workers and of a control group. No cases of asbestosis were found among workers exposed to dust concentrations below 2,500,000 particles per cubic foot of air. Three doubt ful cases were found in the 2,500,000 to 4,900,000 particles range. The definite cases were found where the exposure had exceeded 5,000,000 particles. The authors suggest 5,000,000 particles per cubic foot of air as a threshold limit pending further investigations. Carders showed the highest proportionate amount of as- 6o SILICOSIS AND ASBESTOSIS bestosis, next were mule and ring spinners, and then weavers. As with silicosis, it was found that the incidence of asbestosis increased rapidly with increasing dust exposure. A fifth of those with an exposure of 50,000,000 to 99,000,000 particle years and one half of those with more than 100,000,000 par ticle years, had asbestosis. No free silica was found in the dust of the factories studied. Symptoms The onset is gradual and depends upon the nature and extent of exposure to asbestos dust. There is a general im pression that asbestosis comes on more quickly than silicosis and whereas the roentgenogram may show considerable in volvement in silicosis with few, if any, symptoms, the reverse is apt to be found in asbestosis. Cough is variable and ex pectoration little or none, unless there is an accompanying infection. Anorexia is a fairly constant late symptom and Haddow 34 regards it as an indication to stop work. As in silicosis, dyspnea is the most striking symptom. It is progressive and severe and is due to impaired elasticity of the lungs and to interference with blood supply. Cyanosis and clubbing of the fingers are common late in the disease as is loss of weight and emaciation. There is a typical skin lesion found in asbestos workers known as the asbestos com. The fine asbestos fibers penetrate the superficial layers of the skin and produce small corns or hypertrophies of the epiderm. No asbestosis bodies have been found in these lesions. Asbestosis Bodies Asbestosis bodies are, perhaps, the most interesting feature of pulmonary asbestosis. They have been described in de tail by numerous authors, notably Cooke,35 McDonald,36 Simson,37 Gloyne,38 Merewether and Price,30 and Lynch and ETIOLOGY, SYMPTOMS, DIAGNOSIS 6l Smith.39 The description given by Cooke is abstracted as follows : The `curious bodies' so characteristic of pulmonary asbestosis are found in the alveoli and bronchioles and in the fibrous and necrotic areas. They measure 20 to 100 microns in length. One or both ends are bulbous, giving a clubbed or dumb-bell appearance. The shafts are either homogeneous 01 segmented crosswise. They are golden yellow to brownish in color. They do not stain but give a Prussian blue reaction to iron. The Bragg roentgen-ray spectoscope showed that they were not altered asbestos fibers. Most of them are soluble in strong acids and alkalis and Cooke, McDonald, and Gloyne have been able, by this means, to identify a slender mineral core derived from the asbestos fiber. Lynch and Smith 39 were able to see this core as a central filament with slightly green ish tinge. These bodies are not essentially iron, but contain it. They are not found in the lungs of iron workers. These curious bodies have been induced experimentally. Simson 37 states that Mavrogordato gave him for examination the lungs of a guinea pig which had been exposed to asbestos / dust from the mines two hours a day for fifty days. The ani mal died from other cause. The microscopic examination of lung structure showed a slight generalized fibrosis and the curious bodies similar to those found in the human. Gloyne 38 injected asbestos dust into animals and after twelve days found foreign body giant cells but no curious bodies. From a diagnostic standpoint, it is generally agreed that the `curious bodies' signify exposure to asbestos dust but cannot be depended upon for a diagnosis of asbestosis.40 Diagnosis The diagnosis of asbestosis must be predicated on the his tory of exposure, including the essential factors of length of exposure and its extent, as well as a characteristic roentgeno- 62 SILICOSIS AND ASBESTOSIS logical appearance, together with definite symptoms that cannot be ascribed to other organic disease. Because the pul. - monary fibrosis o asbestosis tends to cause cardiac enlarge ment and impairment, caution should be taken to avoid diagnosing, as asbestosis, cardiac or cardio-renal vascular dis ease in an individual merely because he worked in an asbes tos plant, even though there may be asbestos bodies in the sputum. With the complications o pulmonary tuberculosis or cardiac disease present, the occupational factor may be difficult to determine even by the roentgenologist after a series of films and a post-mortem may be necessary to ascer tain to what extent asbestosis, if present, contributed to dis ability or death. The roentgenological diagnosis of asbestosis is discussed in another chapter. BIBLIOGRAPHY 1. Sayers,R.R., Chairman, Committee on Pneumoconiosis. Pneumoconiosis. Am.Pub.Health Assoc. Year Book, 193a- SS2. State o West Virginia: Workmen's Compensation Law. Amended by Chap.23, Official Code of W.Va. 9, Mar. 1935. Charleston,W.Va. 3. Knopf,Adolph. Description of Silica. U.S.Pub.Health Bull. 187. The Health of Workers in Dusty Trades. II. Exposure to Siliceous Dust. ( Granite Industry) 1929. 4. Ladoo,R.B. Nonmetallic Minerals; Occurrence, Preparation, Utilization. McGraw-Hill Book Co., New York, 1925. 5. BloomfieldJ.J., Johnson,SAV., Sayers,R.R. Potential Prob lems of Industrial Hygiene in a Typical Industrial Area. U.S.Pub.Health Bull.216, 1934. 6. Lanza,A.J., Vane.R.J. The Prevalence of Silicosis in the General Population and Its Effect upon the Incidence of Tuberculosis. Am.Rev.Tuberc.29:8, 1934. 7. Gardner,L.U. Studies on Experimental Pneumoconiosis : Re activation of Healing Primary Tubercles in the Lung by the I i ETIOLOGY, SYMPTOMS, DIAGNOSIS 63 Inhalation of Quartz, Granite, and Carborundum Dusts. Ain.Rev.Tuberc.2o:883. 1929. 8. L.,Collis,Edgar Grfenu<<od,Kajor. Health of the Industrial Worker. P.Blakiston's Son and Co., 1921. (j. Gye.W.E., Kettle.E.X. Silicosis and Miner's Phthisis. Brit. Jour.Exper.Path.3:24i, 1922. 10. Millf.r,J.V Sasers.R.R. The Physiological Response of Peritoneal Tissue to Dusts Introduced as Foreign Bodies. L'.S.Pub.Health Rcpts.49:80. 1934. 11. Sayers.R.R. Experimental Studies on the Effects of Ethyl Gasoline and Its Combustion Products. U.S.Bur.Mines, Mono graph 2. 1927. 12. Haldane,J.B.S., Marint.J.S., Thomas,R.A. Report to the Secretary of State for the Home Department on the Health of Cornish Miners. Cd.2ogi, H.M.Stat.Office, London, 1904. 13. Watkins-Pitchford.W. Miners' Phthisis: Its Cause, Nature, Incidence and Prevention. Pan-Pacific Sc. Congr. Melbourne, 1923. Med.J.of Australia, 13, Oct. 1923. 14. Mavrogordato.A. Etiology of Silicosis. Intern'l Conf. on Silicosis. Johannesburg, South Africa, 1930. 13. Sayers,R.R., Mf.riwether,F.V., Lanza,A.J., Adams,WAV. Silicosis and Tuberculosis among Miners of the Tri-State District of Oklahoma, Kansas, and Missouri. U.S.Bur.Mines Technial Paper 545, 1933. 16. Russell,A.E., Britten,R.H., Thompson,L.R., Bloomfield, J.J. The Health of Workers in Dusty Trades. II. Exposure to Siliceous Dusts. (Granite Industry) U.S.Pub.Health Bull.187, 1929. 17. BloomfieldJ.J., DreessenAV.C. Silicosis among Granite Quarriers. U.S.Pub.Health Repts.4g:679, 1934. 18. Hefferman.P. Exposure to Silica Dust without the Occur rence of Silicosis. J.Ind.Hyg., 8:481, 1926. 19. Denny.J.J., Robson,W.D., Irwin,D.A. The Prevention of Sili cosis by Metallic Aluminum. Can.Med.AssocJ.37:1, 1937. 20. Chapman,A.M. Acute Silicosis. J.Am.Med.Assoc., 98:1439, ~ 1932- 64 SILICOSIS AND ASBESTOSIS 21. Kessler,H.H. Silicosis in the Abrasive Powder Industry. Am. J.Pub.Health, 21:1390, 1931. 22. MacDonald,G., Pigcot,A.P., Gilder,FAV. Two Cases of Acute Silicosis. Lancet, 2:836, 1930. 23. Kilgore,E.S. Pneumoconiosis, Unusually Acute Form. J.Am. Med.Assoc.99:1414, 1932. 24. Kettle,E.H. The Action of Harmful Dusts. Proceedings oE 43rd Session, 1933-34. Institution of Mining and Metallurgy, London, 1934. 25. Sayers,R.R., Bloomfield,J.J., Dallavalle.J.M., Jones,H'.R., Dreessen.W.C., Brundage.D.K., Britten,R.H. Anthraco-Silicosis among Hard Coal Miners. U.S.Pub.Health Bull.221, 1936. 26. R.R.Sayers, Chairman : Report oE the Committee on the Prevention of Silicosis through Medical Control. U.S.l)cpu>[ Lab., 20, Nov. 1936. 27. LliI.mann.G. The Function of the Nose as a Dust Filter. Arbeits-physiol. 7:167, 1933. 28. Goldwater.L.J. The Urinary Excretion of Silica in X'onSilicotic Humans. J.Ind.Hyg., 18:163, 1936. Bloomfield.J.J., Sayers,R.R., and Goldman,F.H. The Uri nary Excretion of Silica by Persons Exposed to Silica Dust. U.S.Pub.Health Repts., 50:421, 1935. 29. Merewether,E.R.A. A Memorandum on Asbestosis. Tuber cle, 15:698:109, 19338:15:152, 1934. 30. Mere\vether,E.R.A., and Price,CAV. Report on Effects of Asbestos Dust on the Lungs and Dust Suppression in the As bestos Industry. H.M.Stat.Office, London, 1930. 31. Lanza,A.J., McConnell,W.J., and FehnelJ.W. Effects of the Inhalation of Asbestos Dust on the Lungs of Asbestos Work ers. U.S.Pub.Health Reports, 50:1, 1935. 32. Page.R.T., and Bloomfield.J.J. Dust Control Methods in an Asbestos Fabricating Plant. U.S.Pub.Health Repts., 52:1713, 937- 33. Drefssen.W.C., Dallavalle.J.M., Edwards,T.I., Miller.J.W., ETIOLOGY, SYMPTOMS, DIAGNOSIS 65 Sayers,R.R., A Study of Asbestosis in the Asbestos Textile Industry. U.S.Pub.Hcaltlt Bull.2 n, 1938. 34. Haudow,A.C. Clinical Aspen* <>f Pulmonan Asbestosis. Brit. Med.J., 2:580, 1929. 35. Cooke,W.E. Fibrosis of the Lungs Due to the Inhalation of Asbestos Dust. Brit.M.J., 2:147, *924Cooke,W.E. Pulmonary Asbestosis. Brit.M.J., 2:1024, 1927. Cooke,W.E. Asbestos Dust and the Curious Bodies Found in Pulmonary Asbestosis. Brit.M.J,, 2:578, 1929. 3G. McDonald,S. Histology of Pulmonary Asbestosis. Brit.M.J., 2:1025, 1927. 37. Simson.F.W. Pulmonary Asbestosis in South Africa. Brit.M.J., 1:885, 1928. 38. Gloyne.S.R. The Presence of Asbestos Fibre in the Lesions of Asbestos Workers. Tubercle, 10:404, 1929. Glgyne.S.R. Reaction of Tissues to .Asbestos Fibre, with Ref erence to Pulmonary Asbestosis. Tubercle, 11:151, 1930. 39. Lynch,K.M., and Smith.W.A. Asbestosis Bodies in Sputum and Lung. J.Am.Med.Assoc., 95:659, 1930. Lynch,K.M., and Smith.W.A. Pulmonary Asbestosis II, Am. Rev.Tuberc., 23:643, 1931. 40. Lynch,K.M. Pulmonary Asbestosis. J.Am.Med.Assoc., 109: '974- >936- III. ROENTGEN-RAY DIAGNOSIS Eugene P. Pendergrass, M.D. PROFESSOR OF RADIOLOGY, MEDICAL SCHOOL, UNIVERSITY OF PENNSYLVANIA PROFESSOR OF RADIOLOGY, GRADUATE SCHOOL OF MEDICINE, UNIVERSITY OF PENNSYLVANIA ASSOCIATE DIRECTOR, DEPARTMENT OF RADIOLOGY, HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA For many years, pneumoconiosis, in spite o its often rather spectacular roentgenographic appearances, was very largely regarded in the light of an interesting disorder. More re cently, however, the extreme importance of roentgenograms as a means of accurate diagnosis in indicating the exact patho logical condition present in connection with pneumoconiosis has received considerable recognition. At the present time, it is generally conceded that the roentgenographic examina tion, properly carried through, is the most precise method at our command for determining lung pathology in a case of suspected pneumoconiosis, or for differentiating this affec tion from another one that may be present. The proper roentgen interpretation of pneumoconiosis cases is dependent upon certain important qualifications. These may be enumerated as ; ( 1 ) a knowledge of the anat omy of the chest and the many physiological problems asso ciated with its anatomical constituents ; ( 2 ) a thorough familiarity with normal roentgenographic and fluoroscopic appearances and their permissible variations therefrom; ( 3 ) an understanding of the histology of the lungs and more especially of the lymphatic system ; ( 4 ) a clear preception of the pathology of pneumoconiosis and of all conditions which may simulate its roentgenographic appearances 1(5) 66 ROENTGEN-RAY DIAGNOSIS 67 an experienced intimacy with the roentgenographic appear ances of pneumoconiosis and of those which may resemble it, based upon a fundamental knowledge of the pathology represented ; ( 6 ) a keen insight of the physical factors in volved in the production of the suspected or alleged pneu moconiosis ; and, ( 7 ) the use of the proper tei hnic to show, 10 full advantage, any or all of the abnormalities present. Technic may completely enlighten, may so modify appear ances as to be confusing, or may mislead entirely. The Healthy Chest 1 Familiarity with the roentgen appearances of the healthy chest is a prerequisite for anyone who attempts to properly interpret chest roentgenograms. Unfamiliarity with normal variants and with the modifying influences of a faulty tech nic not infrequently results in misinterpretation, with an attendant chain of difficulties. A common example oE such an error is the diagnosis of pulmonary tuberculosis, pneu moconiosis, and silicosis based on the presence of prominent truncal shadows. Within recent years, improvements in cer tain technical factors and apparatus have created marked variations and changes in the roentgenographic appearances of some of the chest structures. In view- of such facts, there fore, a review, and where necessary a revision, of the more pertinent aspects of the chest problem, both in health and disease, seems a necessity. The various tissues demonstrable in the chest roentgeno gram will be discussed individually and in the order in which they are taken up in our routine consideration of such an examination. To follow a definite system in the study of any roentgenograms is to prevent the overlooking of, in some instances, obvious conditions. The Soft Parts. -- The approximate development of fat and "musculature can readily be determined from the roent- 68 SILICOSIS AND ASBESTOSIS genogram. The density of the axillary fold frequently serves as an index of the patient's state of nutrition. A loss, as well as a gain, in weight can easily be determined by comparison of the thickness of the soft parts in those instances in which repeated chest exposures have been made. Sometimes, ap parent roentgen evidence of diffuse pulmonary haziness and lung pathology may be explained by unusually thick soft parts. Examples of such instances include the well-developed pectoral folds in men, and the large breast shadows in women. The nippies of the breasts and pigmented moles may pro duce shadows in the roentgenogram that simulate those of metastatic nodules or other pathological processes. Other soft tissue shadows, such as calcifications of vessels, angiomas, tumors, thyroid, and lymph nodes, may be observed in the neck and axillae. Shadows of soft tissue masses ( benign ut malignant) and enlarged lymph nodes can be demonstrated in the axillae, neck, or supraclavicular fossae. The Bones. -- The bony thorax can be fairly well visualized in the chest roentgenogram in the anteroposterior, posteroanterior, and lateral projections. In the posteroanterior and anteroposterior views, with the sternal ends of the clavicles equidistant from the spine, in order that the chest be symmetrically placed, one can see the clavicles, the upper end of the humeri and the scapulae, the ribs, the cartilages when ossified, and the alignment of the thoracic spine. In a few instances, one can see the irregular appearance of the rhomboid fossae on the under surface of the inner fifth of the clavicle. This may be unilateral or bilateral and should not be mistaken for a bone lesion. Oc casionally, one can see the shadow of the foramen of the supraclavicular nerve, near the upper aspect of the middle of the clavicle.2 The epiphyseal development of the inner end of the clavicles can be readily demonstrated, as can epiphyseal centers in the humeri and scapulae. The normal variants of ROENTGEN-RAV DIAGNOSIS Go the ribs, such as bicipital and cervical rib. should be noted. A mental note should be made as to the density of the ossifi- cation.of the bones. Not infrequently, decreased bone density, caused bv some condition such as parathyroid disease, or even localized areas of bone destruction from metastatic malig- nancv, will assist in directing the attention of the clinician to the primary cause of the patient's complaint. Recognition of erosion of the under surface of the ribs may lead to a diagnosis of coarctation of the aorta. Ossification of the costal cartilages is of very little significance. We place no reliance on the old dictum that ossification is evidence of a chronic bron chitis. In general, ossification increases with age. but occa sionally it is found well advanced in thin young women. In such instances, it may be difficult, at times, to interpret struc tures near the midline, due to the superimposed shadows of the costal cartilages. Oblique views are of great assistance in these patients. There seems to be very little difference in the width of the intercostal spaces in the absence of pleural in volvement. In older individuals with increased aeration or emphysema, the intercostal spaces may be slightly wider, but the important manifestation is that the ribs assume a more right-angled position with the spine. The alignment of the thoracic spine can be readilv demonstrated. Minor degrees of scoliosis do not interfere with study of the chest, but marked scoliotic changes, on the other band, tend to obscure the shadows of the structures in both lung fields, due to the shadows of the spine on one side and the closeness of the ribs on the other. In the lateral view, one can see the r ibs, portions of the shoulder girdle, and the thoracic spine. The spine is readilv visualized, hut superimposed shadows of lung structures are confusing in evaluating hone detail. In adults, the body of the vertebrae may, or may not. show hypertrophic changes, and even calcification oi the nucleus pulposus. Usually there 70 SILICOSIS AND ASBESTOSIS is a gentle, double curve to the spine, concave posteriorly above and slightly convex, or straight, below. In kyphotic individuals, the anteroposterior diameter of the chest may be greater than the transverse. The vertical diameter of the body of the vertebrae and the intervertebral discs increases slightly from above downward. The Pleura. -- The parietal pleura is so thin that it does not cast a shadow which can be seen in the roentgenogram unless it is thickened and diseased or obliterates some portion of the costophrenic sulci. Very slight thickenings of the parie tal pleura may be suspected in those instances when there is interference with the costal expansion, especially when the process is unilateral. In anteroposterior roentgenograms of the chest made with the Potter-Bucky diaphragm, the reflection of the pleura, liga ments and muscles over the vertebral column produces a straight line shadow on each side of the spine. Disturbance in this normal straight line may occur in spinal caries, bone tumors, some spinal cord tumors that emerge from the spinal canal, and pleural collections occurring in the vicinity of the vertebrae. In this country particularly, where one finds many refer ences to the apical cap (thickening of the visceral pleura over the apices of the upper lobes), it is a wise roentgenolo gist who recalls that there are other structures whose shadows create a similar appearance in a similar position. Subcostal muscles, in the oblique views, may be misinterpreted as thick ened pleura. The roentgen appearances of these various anatomical structures have been emphasized by Knutsson,3 whose obser vations are briefly abstracted. On the posterior portion of the thoracic wall, the internal surfaces of the ribs are covered with subcostal muscles. In the lateral aspect of the thorax, the muscle lining disappears. The narrow muscle layer on ROENTGEN-RAY DIAGNOSIS 7* the inner aspect of the ribs produces a shadow, seen only in the oblique view, with one exception, which gets thinner from above downward and disappears entirely in the region of the costophrenic sulci. In pleurisy, on the other hand, the pleural thickening usually gets thicker from above downward, a. Schematic presentation of intercostal muscles demonstrating the decrease in the thickness of the muscles as they approach the diaphragm, b. Schematic presentation of pleural thickening which becomes more prominent near the diaphragm. ( Knutsson.') and may obliterate the sulcus. ( Figure 1 ) The thickness of the muscle shadow depends upon the muscular development of the individual. In the upper thorax, the muscles extend laterally, far enough to be seen in the posteroanterior and the anteroposterior projections. This structure is called the `companion shadow of the second rib.' Mesial to the angle 72 SILICOSIS AND ASBESTOSIS of the second rib, there are no subcostal muscles, and the shadow here is produced by the connective tissue. The first rib, likewise, has a companion shadow which is produced bv a sheet of connective tissue interposed between the posterior part of the dome of the pleura and the first and, to a certain degree, the second rib. The following structures are situated in this interspace : the last cervical ganglion of the sympa thetic, the supreme thoracic artery and vein, and the first thoracic nerve. The `companion shadows of the first and second ribs,' as well as those produced by the subcostal mus cles in the oblique views, are symmetrical on the two sides. This fact should be of assistance in differentiating these shad ows from those created by pleural thickening. The pleura does not calcify under normal circumstances. The visceral pleura covers the different lobes of the lungs and ordinarily does not cast a shadow that can be seen in the roentgenogram, except in the instance of the azygos and other accessory lobes. At times, straight and very thin shadows of the interlobar lines can be seen in the chests of healthy individuals. We have felt that such pleural shadows represent a permanent thickening of the pleura from a pre-existing infection. Furthermore, such slight thickening of the inter lobar pleura is capable of producing shadows because the roentgen rays are projected in their axial plane. This con clusion is supported bv the frequency with which a shadow of the interlobar pleura is found in one roentgenogram of a stereoscopic pair and not in the other. Any interlobar thick ening not observed in an axial plane will, nevertheless, pro duce shadows in the roentgenogram, which, when superim posed upon those of the lung fields, will create an increased density. If such a density is not recognized in its true relation, it may be mistaken for an intrapulmonary lesion. In disease, the visceral pleura rarely, if ever, becomes as thick as the pa rietal pleura. Clark4 believes that, when adhesions have ROENTGEN-RAY DIAGNOSIS 73 formed, the increase in the thickening of the pleura in the lower chest and around the heart, as compared to that occur ring in the upper chest, is due in pan to the relatively more powerful movements of structures such as the domes of the diaphragm, the flaring of the ribs, and the pulsation of the heart. The visceral pleura is reflected over the mediastinal structures and does not cast a recognizable shadow. In disease, however, it may produce changes which can be observed in the roentgenogram. The Mediastinum. -- In roentgenograms of the chest, we prefer an exposure that will show the shadow of the trachea down to, and including, its bifurcation. In the posteroanterior or anteroposterior roentgenograms, with the patient placed correctly, the shadow of the trachea in the neck will be seen in the midline. Deviation to the right or left of the midline above the level of the clavicles may result from rotation of the head, and must be differentiated from displacements of other origin. Below the clavicles, the trachea continues in its midline position until it reaches the level of the aorta, where it deviates slightly to the right in roentgenograms exposed during the inspiratory phase of respiration. In adults, in roentgenograms made in the expiratory phase, the trachea is displaced slightly to the right throughout its thoracic posi tion. In all instances, the shadow of the lumen of the trachea is fairly uniform, although its lumen decreases slightly from above downward. Just above the trachea, the laryngeal por tion of the upper respiratory pathway is narrowed and pro duces a funnel-shaped shadow, with the apex of the funnel cephally placed. The tracheal cartilages, especially when ossified, aid greatly in the demarcation of the trachea.5 Careful inspection of the shadow of its contour will not infrequently show evidences of. compression or deviation that may prove significant. As a "rule, the lumen of the trachea is larger in men than in 74 SILICOSIS AND ASBESTOSIS women. Its caliber is not uniform throughout, becoming pro gressively narrower as it approaches the bifurcation. The level of the bifurcation of the trachea varies with age. In adults, it usually divides at the level of the intervertebral disc between the fourth and fifth, or as low as that between the fifth and sixth, vertebral bodies. It is well to remember, however, that the relationship in the cadaver may vary con siderably from that in the living. Likewise, the level of the roentgen tube may cause discrepancies in the level of the bifurcation and the carina. The angles made by the bifurcating bronchi with the trachea vary with age and from one another. In adults, the angle of the right bronchus is approximately 20 degrees and the left, 40 degrees. The eparterial bronchus sometimes branches directly from the trachea. The shadows of the trachea and the right and left bronchus can readily be seen in the oblique and lateral projections of the chest. In the lateral view, the trachea may be followed from the suprasternal region down to its bifurcation. During inspiration, the entire trachea moves downward and slightly forward, unless fixed by mediastinitis. The soft tissues flanking and surrounding the trachea have been discussed by Dann.6 His investigators have helped sub stantially in identifying the structures producing these shad ows. The right border of the supracardiac portion of the mediastinum is formed by the superior vena cava and in nominate artery, while the most lateral margin of the medias tinal shadow is almost invariably formed by the superior vena cava. ( Figure 2 ) The more medial density is a combination of the vena cava and the ascending aorta, which lies slightly anteriorly and to the left.7 The space between the vena cava and aorta, as described by Dann in his studies in young cadavers, is rarely seen roentgenographically. However, a markedly distended aorta may approach the right border of / F igures 2 a n d 3. Healihy adult chest. a. su|>erior vena cava ; b. trachea ; r. Iiilm n or root /one ; d. preaortic space ; e. a coni|>osite shadow, made up of the inferior vena cava, the phreno|K.ricardial liga ments, and possibly also (luid in die <ul cle-sac. 76 SILICOSIS AND ASBESTOSIS the superior vena cava and, in some instances, actually forms the right border of the superior mediastinum. When en larged shadows of this general configuration arc seen, one should consider a substernal tumor, aneurysm of the innomi nate artery, and diverticulum of the esophagus. Roentgenoscopic observations of the changes in the shadows during the grunt of forced expiration and a study of the esophagus may assist in differentiating between substernal thyroids, innomi nate aneurysms and esophageal diverticula. The left border of the supra-aortic portion of the superior mediastinum is formed by the soft tissue shadows of the left common carotid and subclavian arteries. The recurrent laryn geal nerve lies to the left of the trachea. The shadow of the aortic arch is usually seen extending beyond the left border oE the spine. With increasing age, its knob-like contuiu be comes more prominent, until it is most pronounced during the arteriosclerotic period of life. The left posteroanterior oblique view of the chest permits excellent visualization of the aorta and, when used in conjunction with roentgenoscopy, gives valuable information concerning aortic dimensions and elasticity. The aorta follows a more sagittal course in narrowchested individuals than in flat-chested persons. Increases in prominence in the outline of the shadow of the aortic knob may result from syphilis or hypertension, while an absence or decrease in the outline of the knob suggests either coarctation or right aortic arch. The pulmonary artery is seen best with the patient in the anteroposterior or right antero-oblique positions. It lies just to the left of the base of the aorta, nestled within the con fines of the aortic arch. Sometimes it is seen better after a cough, which serves to separate it from the aorta.* In recent communications, O'Kane, Andrew and Warren 8 and Margolies 9 reemphasize the importance of the roentgenographic and roentgenoscopic examinations in determining ROENTGEN-RAY DIAGNOSIS 77 the size and shape of the heart. In addition to these estima tions, the roentgenologist must concern himself with the pul- .sations and the mobilitv of the heart and am abnormal den sities. There are many conditions, suc h as congenital deformi ties of the chest and acquired affections, such as pneumothorax and hydrothorax, which may exert profound influences upon the heart. Examinations must be made in the anteroposterior, posteroanterior, oblique, and lateral views, in order to assure adequate study of the heart. The most important view is the left antero-oblique view, but the degree of rotation and the optimum position for a roentgenographic demonstration must alwavs be guided by the preceding roentgenoscopic impres sions. Under normal conditions, the heart in thin individuals lies in the vertical position, whereas in the more stocky, broad- chested person, it assumes a more transverse position. Further more, patients with round chests more frequently have a rounded heart than patients with flat chests.10 In the latter type of patient, the heart has a more oval circumference. Normally, with the patient facing in an anteroposterior direction, the right border of the heart is formed, from above downward, by the right auricle, the inferior vena cava and the cardiophrenic ligament.9 (Figure 3 ) In some patients, paracardial fat pads form part of the cardiac border. Roent- genographically, however, the shadow of the outline of the heart may sometimes be seen as a density within the less dense fat pad. The left cardiac border is formed by the pulmonary artery, the left auricle, and the left ventricle.9 With the patient in the lateral position, the anterior border of the cardiac silhouette is formed, from above downward, by the base of the aorta, the pulmonary conus and the right ventricle. The posterior border is formed, from above downward, by the arch _ of the aorta, the pulmonary artery, the left auricle, the left ~ ventricle and the inferior vena cava. The cardiac silhouette. 78 SILICOSIS AND ASBESTOSIS with the patient in the right anterior oblique position, is formed by the right auricle and the inferior vena cava on the right side, with the aorta, the pulmonary artery, the pul monary conus, and the right ventricle, mentioned in order, from above downward, forming the left border. With tiie patient in the left anterior oblique position, the right border is formed by the superior vena cava, the right auricle and the right ventricle, whereas the left border is made up of the silhouette of the aorta, the pulmonary artery, the left auricle and the left ventricle, mentioned in order, from above down ward. These cardiac contours bear a definite relationship both in size and degree of expansion with one another. Normally, the average anteroposterior diameter of the heart is about two-fifths of the transverse diameter of the chest.10 While empirical judgment of the size of the heart is used con stantly to decide increases in cardiac size, it is by no means sat isfactory. The cardiothoracic ratio, diagonal measurements and cardiac area determinations are much more satisfactory. As a rule, however, the average anteroposterior diameter of the heart is less than three-fourths of the average transverse diam eter of the heart. Realizing that the average anteroposterior diameter of the heart in females is 8.7 cm. and in males, 7.8 cm., one can obtain a fair impression as to size.10 The oblique diameter of the heart is about one-third larger than the aver age anteroposterior diameter. In the lateral view, the attachment of the pericardium may be seen extending down from the posterior edge of the heart shadow. (Figure 3) It is seen as a faint shadow with its posterior border straight, or slightly concave, extending to the superimposed diaphragmatic shadows. This shadow is a vantage point for observing slight pericardial effusions,11 which tend to distend the cul-de-sac and distort its normal concave appearance. During deep inspiration, especially in tall, thin persons, I ROENTGEN-RAY DIAGNOSIS 79 the right and left phrenopericardial ligaments exert a pull upon the domes of the diaphragm, by virtue of their attach ments to the diaphragm, which is synchronous with cardiac pulsation. .As this frequently occurs in healthy individuals during deep inspiration, it must not be confused with the abnormal diaphragmatic tug produced by adhesions between the domes of the diaphragm and the pericardium, which may be seen during the expiratory phase of respiration also. Chances for error are minimized by roentgenoscoping patients in the horizontal posture, the patient lying on the right side and the rays projected anteroposteriorly. This allows the mediastinum to drop toward the right, permitting the ex aminer to see more of the left dome of the diaphragm and its connections with the heart. Phrenopericardial tugging observed in this position nuy be evidence of adhesions. With the patient lying on one side, the entire mediastinum shifts to the lower side. This evidence can be recorded when the rays are projected in a horizontal plane.1- The horizontal position may also be used to advantage in identifying pericardial efEusions. One must be well acquainted with the normal appearances of the heart and aorta in this position before using it for refinements in diagnosis. In this position, the transverse diameter of the heart is larger than in the erect position and the width of the shadow of the aorta is greater. This may be due partly to the elevation of the diaphragm. Roesler13 thinks that there is also an actual increase in the cardiac volume in the horizontal position. Occasionally, a swallow of barium, with the patient in the horizontal position, will outline a cardiac or aortic aneurysmal dilatation, which might otherwise be overlooked. Under normal conditions, the space between the pericar dium and epicardium is very small. It was our good fortune to examine a healthy student with air in the pericardium, as a result of an accidentally inflicted wround. The space between 8o SILrCOSIS AND ASBESTOSIS the pericardium and the epicardium, as outlined by air, was almost negligible when compared with the pneumopericardiogram of tuberculous pericarditis. While practically even portion of the heart may become calcified in disease, the calcification associated with old age must be considered physiological. In the past, roentgenolo gists constantly overlooked calcifications within the heart.14 Calcified valves may be seen in the anteroposterior view near the middle or lower half of the heart. The aortic valves are usually seen overlying, or just to the left of, the spine and are, therefore, more adequately seen on slight rotation. Mitral calcifications, however, lie well to the left of the midline, and when seen in the lateral projection, are situated more pos terior than the aortic calcifications. Roentgenoscopically, these shadows have to and fro movements, going toward the apex during systole and returning during diastole. The Diaphragm. -- The right dome of the diaphragm is about 1.5 cm. above the left dome, in most instances. When transposition of the viscera occurs, the opposite obtains. In certain other instances, the shadow of the left dome of the diaphragm is either on the same level or above that of the right dome. We presume that, in the absence of eventration or herniation, such instances may be regarded as normal va riants. The splenic flexure of the colon is usually highly placed in such individuals, or there may be a large collection of air in the fundus of a cascade type of stomach, which may be responsible, to some degree, for the position of the diaphragm. In the anteroposterior and posteroanterior projections, the right and left halves of the diaphragm are dome-shaped. The attachment of the mesial portions of the domes is on a higher level than its attachment to the ribs. This results in a costophrenic sulcus of varying depths. The domes of the dia phragm are regular in this plane and, during inspiration, any peaking may be the result of either pleural adhesions or ROENTGEN-RAY DIAGNOSIS 81 localized areas of inelasticity oE the lung structures. The domes of the diaphragm may be wavy at their outer aspect or produce a shadow of multiple arcs over its surface, due to variation in attachment or hypertrophy of the constituent muscle bun dles. This has been described as individualization of the costal components. Occasionally, in the posteroanterior and lateral projections, one finds a rounded hump of the mesial aspect of the right dome of the diaphragm. This observation has been reemphasized 13 as being due in the healthy individual to a weakness of the anteromedial portion of the diaphragm as compared to that of the posterolateral portion. In addition, the inferior vena cava may play a part in preventing down ward excursion oE the diaphragm. Tumors of the liver and subphrenic lesions may produce an appearance that simulates such a condition. An anomalous enlargement of the right lobe of the liver will produce a shadow in the lateral view that may simulate that of an interlobar collection.16 In the lateral view, the domes are higher anteriorly and the posterior costophrenic sulcus is much lower than the anterior, rendering it possible for a relatively large localized pleural collection to escape detection in the dorsoventral roentgenogram. The upper sur face of the shadows of the right and left domes runs from before backward. These shadows may be parallel or may cross each other, either anterior or posterior to a point that cor responds to the middle of the domes. During the inspiratory phase of respiration, the shadows of the domes lose their dome shape and become relatively straight. The movement of the domes of the diaphragm is extremely variable. The most correct impression of its movement is obtained during ordinary respiration. Frequently, efforts to study diaphragmatic excursion during forced respiration are confusing, due to the influence of costal and abdominal mus cles.'The movement of the domes of the diaphragm is usu- 1 82 SILICOSIS AND ASBESTOSIS ally more pronounced in men than in women. The domes are higher and the excursion is greater in the horizontal posture than in the erect. Therefore, anyone interested in detecting slight restriction in movement should examine the patient in the erect posture. Lateral roentgenoscopy of the diaphragmatic domes, with the patient lying on the back and the rays projected from the opposite side, is difficult because of the increased dome shape of the diaphragm and the en croachment upon the costophrenic sulci. IE the patient is studied roentgenoscopically in the horizontal plane while lying on one side, and the rays projected ventrodorsally, the dependent diaphragm will become more cephally placed and will have a greater excursion. These observations have also been noted by Pierson and Newell.12 Such positions or modi fications thereof allow a study of the costophrenic sulci and aid in differentiating between thickened pleura and pleural collections. The Hilum Shadows. -- The structures in the hila include the bronchi, the pulmonary arteries and veins, the tracheo bronchial and aortic lymph nodes, nerves, and connective / tissue. The lymph nodes are classified as follows (a) bifur cation nodes, located between the right and left main bron chi ; ( b) tracheobronchial nodes, situated above the bronchi and along the trachea ; ( c) the aortic nodes ; and ( d ) the paravertebral nodes. Sukiennikow17 states that there is a greater number of lymph nodes on the right side. Miller 5 says that there is a greater number of nodes associated with the eparterial bronchus than with the bronchi supplying the middle and lower lobes. The hilum shadow is irregular in outline with ill-defined borders. The density of these structures, as seen in the roent genogram, varies considerably with the type of roentgenographic exposure. In the arbitrary properly exposed roent genogram, the shadow has varying densities and is not homo ROENTGEN-RAY DIAGNOSIS 83 geneous. It would seem that if roentgenologists could agree upon what a properly exposed film consists of, varying densi ties could be regarded as significant observations. We have placed considerable reliance upon individual ability to see varying densities in the liilum shadow, i.e., the bronchial shadow is different from that of the vessels. When the density of the shadow is more or less homogeneous, it is our impres sion that one can be fairly certain that abnormal changes have become manifest. The National Tuberculosis Committee 11 has described the limits of the hila as follows : `On the right side, the normal shadow may be said to ex tend, from above downward, from the top of the right main bronchus to approximately a point where the right lowerlobe bronchus, below the origin of the middle-lobe trunk, begins to subdivide into its lower-lobe branches ( or trunks ) . This includes the anatomical hilum, the greater portions of the larger bronchi, and some lung tissue in front and behind. The extent of this hilum shadow from above downward is approximately two interspaces and a rib. `On the left side, the pulmonary artery passes above the left bronchus, and from above downward, the left hilum shadow may be said to extend from the upper border of the pulmonary artery down to approximately a point where the left lower-lobe bronchus begins to subdivide into its lowerlobe branches (or trunks 1. Such a hilum shadow on this side is slightly shorter than the one on the right and is slightly less than two interspaces and one rib in length. `While the top of the right bronchus is higher than the left, if the tops of the hilum shadows be limited in the manner just described, they are on a plane approximately level. `The thickness of the hilum shadow in the anteroposterior direction is a matter that requires further study, and prob ably largely from the lateral view. Measurements from lateral 84 SILICOSIS AND ASBESTOSIS views are very uncertain and subject to considerable per sonal equation. One should learn to acquire the idea of depth as well as length and width when interpreting hilum shad ows.' In the lateral view, the shadows of the hila are superim posed and it is impossible to define their limits, even within wide margins, because of so many variable factors, such as target film distance, length of time of exposure, and disturbed shadow outline due to transmitted pulsation from adjacent vessels. We suggest, however, that one can develop an individ ual impression as to their normal extent by studying roent genograms of the chest of healthy individuals, made with a Potter-Bucky diaphragm in an almost lateral projection, with the patient so placed as to prevent the superimposition of the hila. Such films allow one to see shadows of the varying den sities of the hila, and, if a thorough understanding is obtained, it becomes possible to determine deviations from the normal with a high degree of precision. In the dorsoventral and ventrodorsal roentgenograms, the outer boundary is regarded as normal when it lies within the inner zone of the lung field. Everyone familiar with the inter pretation of variations of hilum shadows realizes how difficult it may be. Oblique and lateral views often assist in detecting glandular enlargements that might otherwise escape notice. Calcified lymph nodes occur frequently in the hila of healthy individuals. They represent, as a rule, evidence of a pre-existing active tuberculous process. Calcification of a lymph node does not necessarily mean that the node may not contain viable tubercle bacilli which, under certain con ditions, are capable of multiplying and setting up an active disease. In adults, we have felt that nodes that are calcified in a relatively homogeneous manner are probably healed, whereas those in which the calcification is punctate and ap pears as a mottled shadow have a much greater potentiality Figure 4 Calcified tracheobronchial lymph nodes. Note the irregular calcification oE the nodes. They are somewhat punctate in type. These are examples oE nodes in which infection may become reactivated. 86 SILICOSIS AND ASBESTOSIS for reactivation. ( Figure 4 ) Chests of children with calcified nodes of this type should probably not be regarded as healthy. While it is true that calcified nodes are usually regarded as evidence of past tuberculous infection, it is entirely possible for them to be due to some other process. It is important to evaluate the dense, circular shadows, due to vascular trunks obtained in an axial plane, and appearing in the roentgenogram as densities similar to those cast by calcified nodes. These shadows are readily seen roentgenoscopically and, should any doubt arise as to their nature, slight rotation of the patient will permit identification of their true nature. Calcified shadow densities do not disappear on rotation, whereas vascular shadows do. The Zones. -- The chest has been variously divided into different zones for convenience of description of the single film. The classification in most frequent use is that which divides the one side of the thoracic cavity into 3 zones ; the inner or hilum, the middle or truncal ( or vascular mark ings ), and the peripheral, which contains the finer subdivi sions of the vascular tree in which the only shadows visible consist of fine linear markings. In stereoscopic films, there is very little occasion to use such a classification, except so far as the various zones have different capacities for expansion.18 The hilum zone expands and contracts less than the truncal or vascular zone, and the peripheral zone has more expansile and contractile power than the truncal or vascular zone. The Lobes. -- Ordinarily, the right lung is divided into 3 lobes and the left, into 2. Not infrequently, there is an ac cessory lobe on the right side called the azygos lobe.19 This lobe is recognized by the fine pleural line which extends from the apex of the lung downward, to end as a dense oval shadow near the upper aspect of the right border of the superior mediastinum. The dense oval shadow is due to the ROENTGEN-RAY DIAGNOSIS 87 azygos vein, which maintains its foetal position and carries with it a reflection of the parietal pleura, down to the point of entrance into the superior vena cava. The size of the azygos lobe is quite variable, depending upon the position of the vein. More recently, other accessory lobes have been described in roentgenologic literature.20 An accessory lobe may occa sionally be found at the base of either lung, either partiallv or completely formed. These lobes are variable in size and represent a division of the lower lobe. They can be recognized by the presence of interlobar pleural shadows, extending up ward from the mesial portion of the domes of the diaphragm toward the hila. This lobe may occasionally be the site of a pathological process and, therefore, readily recognizable. On one occasion, we observed two lobes only, on the right side. The observation tvas later confirmed by post-mortem exami nation. The position of the various lobes is readily observed in those instances where either interlobar shadows are visible or after introduction of an opaque medium into the bronchi. It should be emphasized, however, that the size and extent of the lobes are quite variable. On occasions, the lotver lobes may extend very high posteriorly, so high that physical signs, and even shadows in the roentgenogram, may be misinter preted as representing lesions in the lower portion of the upper lobe. The Vascular Markings. -- Extending from the hilum on either side are heavy shadows passing into each lobe. These shadows are more pronounced in the lower lobes and, in roentgenologic literature, are described as truncal shadows. It has seemed to us, however, that such a terminology conveys an impression that a bronchus is responsible for, or at least associated with, these visible shadows. From the work of Miller,21 Miller -- 22> 24> 2S 5 and Greineder,26 such an inter- 88 srucosis AND ASBESTOSIS pretation may not be true. For years, roentgenologists at tempted to localize foreign bodies and pathological lesions according to the distribution of these shadows as they passed into each lobe. It was recognized that only very large bronchi were visible, and these were restricted, for the most part, to the hilum zone. On the other hand, the roentgenologist thought that the truncal shadow, as seen and described in the roentgenogram, consisted of bronchus, artery, vein, nerves, lymphatics, and connective tissue. Wherever one of the large branch shadows was seen, there was thought to be a bronchus. We know now that such is not the case. Miller 2i has shown that `the pulmonary artery follows, in all of its subdivisions, the subdivisions of the bronchial tree. As each main branch of the pulmonary artery arches over its corresponding stem bronchus, it comes to occupy a position posterior (dorsal) and slightly lateral to the bronchus. The relation of the main trunks of the pulmonary vein to the bronchi is quite differ ent ; they are situated anterior (ventral) and mesial to their stem bronchi and in their ultimate distribution are situated as far removed from bronchi as possible.' Miller,21 interested in another phase of the same subject, made similar observations, as did Greineder,24 with even more striking demonstrations by tomography. If one can be certain that veins, as a rule, have a larger diameter than the arteries, it is our belief that the shadows of the larger veins can be differentiated from the larger arteries in roentgenograms of excellent detail made during the diastolic phase of the cardiac cycle. We appreciate that the above discussion may be considered academic and of no practical importance so far as the distribu tion of the bronchi is. concerned, because of the improved methods for delineating bronchi after the instillation of opaque media and the increased use of the bronchoscope. Nevertheless, it is our firm belief that too many roentgenolo- ROENTGEN-RAY DIAGNOSIS 89 X4 Figlre 5 Illustration of a roentgenogram showing the vascular markings in the right upper lung field. The pulmonary artery and vein were ligated in this instance. In the left upper lung field, the blood has been allowed to drain out. Note the difference in size of the vascular markings. (Reproduced by permission from / Miller.11) gists are misinterpreting normal variations of the vascular markings in terms of pathology. ( Figure 5 ) Miller,23 in 1919, recognized and warned us of such a possibility. Notv, it has become necessary for industry to have pre-employment as well as follotv-up examinations and, unfortunately, many roentgenologists, upon whom the burden of the roentgen ex amination has fallen, are, all too frequently, misinterpreting vascular shadows as fibrosis, and thereby imposing an unnec essary hardship on both the employee and the employer. Vascular shadows are otherwise confusing in interpretation, particularly with regard to the dense, circular shadows, due to blood vessels recorded in an axial plane, which may simu- 9 SILICOSIS AND ASBESTOSIS Figure 6 Curved paraffin cylinders in c. were examined to demonstrate differences in appearance when rays were directed in one plane, a. and in another plane, b. Note the differences in density of the cylinders in a. ana b. d. vessel shadows in roentgenogram of in flated normal lung. (Reproduced by permission from Miller.21) late an appearance of thoracic calcium21 and, in the more peripheral portions of this zone, may produce an appearance of beading or early nodulation, when the roentgenogram is made during the systolic phase of the cardiac cycle. The ap pearance of beading may simulate that of a pathological process, such as that seen in silicosis, baritosis, or a mycotic infection. Stereoscopic dorsoventral films may not be sufficient to identify the exact nature of the shadows, but films exposed in an oblique view and rotation of the patient during the roentgenoscopic examination will usually be of aid. If the dense shadow is due to a blood vessel, slight rotation will cause the shadow to disappear; if due to a calcified lesion, the shadow will remain. Furthermore, the blood vessel shad ows are circular and homogeneous, whereas a calcified lesion > I I ROENTGEN-RAY DIAGNOSIS gi may be irregular and less homogeneous, or even mottled. (Figure 6) Millex5 called attention to another structure, the ringshaped cartilage which occurs where bronchi leave the main stem bronchi. This cartilage may produce a dense, circular shadow in the roentgenogram. McPhedran and Weyl17 2` have emphasized the importance of synchronizing the roentgen exposures of the chest during the late diastolic phase of the cardiac cycle. They have per formed important experiments in an effort to evaluate this phase of the general problem, but further investigation is necessary. This work, thus far, serves to show that vascular displacement and vibration cause considerable blurring of roentgenographic detail. Likewise, kymograms illustrate clearly what a marked influence the cardiac pulsation exerts on the lung structures close to the heart. The Bronchi. -- The first subdivision of the right bronchus is the right upper lobe bronchus ( eparterial), which comes off at an angle of almost 90 degrees and passes abo' . the pul monary artery. This bronchus gives off a branch, the vertebral, which passes upward to the apex of the lung parallel to the spine. This bronchus gives off branches which extend an teriorly and posteriorly. The upper lobe bronchus gives off another important branch which is designated as the second interspace bronchus, because it comes off behind the level of the second interspace in front. Likewise, this bronchus gives off anterior and posterior branches. The portion of the right bronchus between points from which the upper and middle lobe bronchi come off is termed the stem bronchus. Foreign bodies frequently lodge in this region. The middle lobe bronchus comes off the stem bronchus anteriorly. It divides into many branches, but there are 2 main divisions, as a rule ; ( a) the branch which passes down- 92 SILICOSIS AND ASBESTOSIS ward and anteriorly, and ( b) the branch that passes upward and laterally. The lower lobe bronchus bifurcates into several main branches which have been variously described as the anterior, middle, posterior division branches in the lower portion of the lower lobe, and the apical branch in the upper portion. All of the main subdivisions give off many branches. Disease of the mesial and posterior division bronchi produce shadows that border upon the shadow of the heart in dorsoventral roentgenograms. Further identification of the bronchi can be obtained in the oblique and lateral projections. The left upper lobe bronchus ( hyparterial) passes below the pulmonary artery. Its subdivisions are similar to those of the right side, except that there is a branch which goes to the lingual tip of the upper lobe which is that portion in front of the heart. The left lower lobe bronchus has a longer course than that of the right side before it gives off any subdivisions, other wise it and its subdivisions are similar to those of the right side. The Lung Fields. -- Medicine owed a debt of gratitude to William Snow Miller whose life has been dedicated to the study of the anatomy of the lung. No discussion of the healthy lung can possibly be complete without frequent reference to Miller's work, and much of that which we shall discuss has been gleaned from his reprints and recent book.5 In the discussion of the healthy lungi we have approached its consideration from the standpoint of the smallest function ing unit in the lung, the primary lobule. It is obvious, there fore, that the following discussion is of more importance his tologically than roentgenologically. As the bronchial tree is followed to its ultimate divisions, there occurs a lack of the regular bronchial outline and the gradual appearance of an air passage, whose walls are lined ROENTGEN-RAY DIAGNOSIS 93 with variable, irregularly placed air spaces. These terminal air channels arc called the respiratory bronchioles, which, in iurn, divide into smaller brant lies known as the alveolar duets. These alveolar ducts are smaller than the respiratory bron chiole from which they spring and are lined by more alveoli than the aforementioned bronchiole.-1" 24 The alveolar ducts, in turn, lead into from 2 to 5 spheroidal cavities called atria. The atria, in turn, open into numerous air sacs around the periphery of which are situated the alveoli. The bronchial musculature forms sphincters about the channels leading into the atria and around the alveoli which line the smaller bronchioles.JS These sphincters probably play an important role in the muscular spasm known to occur in asthma. Normally, air passes unimpeded by these sphincters. With muscle contraction, the air channels reduce in size pre venting the egress of air, which produces an increase in re sidual air with the formation of emphysematous lobules. The structures described above comprise the anatomical unit or primary lobule of the lung, which may be defined as a ductulus alveolaris, the air spaces connected with it, and all their associated vessels, nerves, and lymphatics. The pri mary lobule has the form of a truncated pyramid, with its base directed toward the periphery of the lung."- 24 Its air passage (ductulus alveolaris) usually enters the primary- lobule at the side rather than at its apex. Primary lobules vary in size from 0.45 mm. to 0.845 mm., the larger units situated in the peripheral and basilar portions of the lung. It is obvious that these lobules are not seen in the roentgenogram. It is only barely possible that one sees, roentgenographically, the larger, secondary lobules, which are made up of 50 to 250 of these primary units. The primary lobules receive relatively little blood from the bronchial blood vessels.22- 24 The pulmonary artery, on the other hand, follows the course of the respiratory bron- 1 p 94 SILICOSIS AND ASBESTOSIS r I Figure 7 Composite diagram (modified from Miller) of the primary lobule lymphatic system, indicating the primaiy distributions or accumulation points for dust which will lead to predominant phases of pneumoconiosis, b.r., respiratory bronchiolo ; d.al., alveolar ducts ; a., atria; s.al., sacculi alveolare ; a.p., alveoli ; a.p., aveoli opening into respiratory bronchioles and alveolar ! ducts in close relation with the origins of peribronchial and perivascular lymphatics ; A, branch of pulmonary artery, accom panying the air passages ; V., branch of pulmonary vein in inter lobular septum; P., pleura ; P.B., peribronchial lymphatics ; P.V., perivascular lymphatics; 1, 2, 3 and other dotted areas, lymphoid deposits. (By previous permission of Dr.W.S.Miller.) chiole and the alveolar duct into the center of the primary lobule.5 Each atrium is supplied by a branch of the pulmonary artery, which then divides into enough smaller tributaries to supply the alveolar sacs. The pulmonary vein, in contra- ROENTGEN-RAY DIAGNOSIS 95 distinction to the pulmonary artery, courses along the periph ery of the primary lobule at a distance from the air channels.5 (Figure 7 ) Its branches arise from the pleura, the end of the alveolar duct, the walls of the alveolar sacs and the points of division of the bronchi and bronchioles. The lymphatics of the lung may be divided into the deep lymphatics and the superficial lymphatics.-* The deep lym phatics include all of the channels which follow the bronchial tree and its associated blood vessels toward the hilum. The superficial lymphatics lie within the pleura. The bronchial lymphatics in the primary lobule are 3 in number, with no lymphatics present in the air spaces as ves sels. The lymphatics of the pulmonary artery lie between the artery and the bronchiole, anastomosing with i of the 3 bron chial lymphatics. These, in turn, unite with others to form a rich network, running toward the hilum. The lymphatics of the pulmonary veins follow the course of the veins from the various points of origin described previously, with one excep tion. Since no lymphatics lie in the walls of the air sacs, there are no lymphatics along the veins arising from their walls. The pleural lymphatics form a rich network which drains into the lymph nodes in the hilum. There is some evidence supporting the belief that the superficial pleural lymphatics, covering the diaphragmatic surface of the lower lobes, drain into the abdominal pre-aortic nodes by way of the ligamentum pulmonale.'4 The numerous valves in the superficial lym phatics point in no particular direction. The valves are less numerous in the deep lymphatics and lie close to the hilum in the large vessels, allowing flow in the direction of the hilum only. Similar valves lie in some of the deep lymphatics close to the pleura. These valves point toward the pleura, allowing lymph flow into the superficial pleural lymphatics without permitting a reflux of superficial lymph into the deep set of lymphatics. 9G SILICOSIS AND ASBESTOSIS In addition to the lymph vessels, the primary lobule con tains small masses of lymphoid tissues, which mav he liumil in ilie walls of ihe primary lobule."' besides these distinct lymphoid masses, one can identify a sheath-like dispersion ol lymphoid tissue along the pulmonary artery and along the air channels. This faintly defined sheath of lymphoid tissue is rarely found in the lungs of humans under thirty years ot age. With the advent of middle life, however, these lymphoid deposits become moie conspicuous until they are quite promi nent at approximately sixty years of age. The lungs in healths individuals over sixty frequently show the alters and bron chus completely surrounded by this lymphoid tissue.-"' Per haps tills accounts for the prominent linear markings fre quently associated with advancing age, markings which are usually lacking in children and young adults. It is impoitant to know the distribution of these lymphatic masses and lym phoid networks as they are the centers about which disease processes often commence. Considerable ev idence has been accumulated substantiating the belief that massage, passive motion, capillary wall injury, increased venous and capillary pressure, and decreased blood proteins accelerate lymphatic flow.30- 31 The importance of these findings may be appreciated when one realizes that the rate of lymph flow and the progress of phagocytes within lymph vessels are negligible when the part being studied is at rest. Without the former observations, one would be at loss to explain the rapid appearance in the hilum glands of foreign particles ducted into the lung. In one set of experi ments, ink particles were demonstrated within the hilum nodes several minutes after their injection into the lung.30 Drinker and Field 30 demonstrated that phagocytosis was not entirely responsible for the transfer of foreign particles into the perialveolar spaces. Perhaps alveolar pores really do exist, allowing free interchange of such material.32' 33 This, in part, ROENTGEN-RAY DIAGNOSIS 97 helps explain the vapid appearance of foreign bodies in the hilum nodes, as the finding obviates complete dependence jtpon phagocytosis in the transfer of foreign material from the alveolus into the perialveolar tissue. Dollev and Wiese 14 recenth found that unilateral pneumo thorax produced a decrease of about 45 per cent in the lvmph flow from the lungs. Such data, correlated with those previ- ouslv referred to. would seem to indicate that the respirators excursions of the 1 tings and the massaging action of the pleura play an important role in pulmonarv lymph flow. It also seems reasonable to conclude that the rate of lymph flow might van- in different portions of the lung, depending ii[v>n differences in respiratory excursions in various portions of the lung. That such differences in the amplitude of pulmonan expansion do occur seems well substantiated bv the work of Keith. Miller. Scott, et al. While there is gncxl evidence indicating that lvmph con stantly courses through the lung toward the hila. no absolute proof concerning the magnitude of this hniph flow is avail able. Drinker and Field were unable to demonstrate am appreciable flow in their animal experiments. If little is known concerning this particular factor, certainly less is known of the true function of the lymphatics. Effect of the Phases oj Respiration on the Roentgen Appear ances in the Chest. -- Dining inspiration, the first five ribs ro tate up and out. earning the sternum forward and upward. These movements imlease the anteroposterior dimensions of the chest, therein- expanding the upper lobe in an antero posterior direction, allowing an influx of air.1* The ribs main tain a constant relationship with the upper lobe in its antero posterior excursions, with the result that the impressions of the first five ribs may frequently be seen in post-mortem speci mens on the anterior surface of the upper lobe. Such mark ings, however, are unusual in the lower lobes. During inspira- p e ROENTGEN-RAY DIAGNOSIS 99 cion, the lower lobes are expanded by the descent of the power ful diaphragmatic muscles, which increase the depth of the chest, and by the action of the lower intercostal muscles, which increases the transverse diameter of the chest.1'* These forces are much greater than those influencing the upper lobes, be cause of this, the lower lobes are drawn downward during inspiration, thereby massaging its pleural surfaces against the long axis of the ribs, which explains the absence of the rib markings previously referred to as being commonly found in the upper lobes. The evidence concerning the formation ol rib impressions in the upper lobe is indirect. Clark 4 has called our attention to the relatisc lack of pigmentation of the lung surface where rib impressions are found, whereas more pig mentation is found in the lung tissue adjacent to the inter costal muscles. Such evidence is in favor of Keith's13 ideas concerning the mechanism of respiration. Clark 4 also believes that these observations support the premise that the massage effect of the ribs is an important factor in lymphatic flow. This seems reasonable in view of the fact that other portions of the lung, such as the lung around the heart, the tip of the lung extending into the costopln enic sulcus ( where it is mas saged by the diaphragm ), and the posterior surfaces of the lower lobes, are less pigmented than the inside of the lung and the lung surfaces where massaging action is minimal. The summation of these inspiratory forces produces expansion in a forward, downward and outward direction, with consider ably more expansion taking place in the lower lobes than in Figure 8 Diagrams showing the differences in expansion in the various portions of the lung. Note decreased expansion in upper lobe and in peravertebral gutter. (Reproduced bv permission from Maeklin.") ROENTGEN-RAY DIAGNOSIS lOl the upper.1'* The trachea and its ramifications also feel the effects ol these inspirators lorces as the trachea and hila mmc downward and loiuard. uliilc the bronchial iree and die vascular strut tines he< onto elongated.* Keith l!< has staled that, when more is learned about normal respiration, the lobation of the lung and the great fissures will be found to be of functional significance. Working against these inspiratory mechanisms are the heart, die \ertebral column and \enebra) portions of the ribs. These portions of the chest are antagonists to pulmonary ex pansion bv virtue of their anatomical characteristics.13- 10 Being relatively fixed structures, they cannot move to ali-u- the nearby lung to expand. ( Figures fj and 9 ) I11 like fashion, the apex of the upper lobe does not expand as fully as the lower portion of the upper lobe, which is not inhibited by the peculiar conical shape of the upper thoracic cage. One can conclude, therefore, that the amount of air entering the lower lung field and periphery of the lung is greater than that which enters the upper lobes or hila. Attention should again he directed to the importance of respiratory movements upon the lymphatic flow and its pos sible influence upon the distribution of a pathological process. While the evidence is purely deductive, it seems reasonable * Keith and Miller believe that the bronchial tree spreads and elongates during inspiration. Macklin's work, while not conclusive, does not support the spreading of the bronchi, although it dues show the elongation vers well. Figure 9 Diagrams showing differences in expansion in the various por tions of the lung in a case with infection. The shaded portion of the diagram in the upper, mesial and posterior portion of the lung field represents the area of infection. Note the marked de crease in the expansion of the lung. Compare with Fig. 12. (Re produced by permission from Macklin.M) 102 SILICOSIS AND ASBESTOSIS that adequacy of lymphatic flow and degree of respiratory mobility go hand in hand. Perhaps this might account for the frequency of upper lobe tuberculosis and for the mid-lung field changes of silicosis. Perhaps it might also account for the clear peripheral and paracardiac zones in the lung fields in patients with pronounced changes due to silicosis with a quiescent infection. Roentgen Technic. -- Considerable data have been ac cumulated showing that the diagnostic value of chest roent genograms depends upon certain film characteristics which are determined by the technical factors used for the examina tion. J7- 33 For this reason, certain fundamental technical re quirements have been defined which, when adhered to, have produced a high quality of chest examination. Briefly, these factors may be summarized as follows : 1. Time. Exposures made in from 130 to second are essential to overcome lack of detail resulting from vascular motion. Synchronization of the roentgenographic exposures with the late diastolic phase of the cardiac cycle further re duces vascular blurring. This method, if coupled with some means of determining full inspiration, would be ideal, as one could then be reasonably sure that slight vascular changes in different films of the same patient were, or were not, due to physiological variations.37- 33 2. Distance. Focal-spot film distances between 4 and 6 feet are most satisfactory, as distances under 4 feet produce con siderable distortion, while exposure made at distances over 6 feet are not sufficiently superior to warrant the expense of bulky high tension apparatus. 3. Screens. Screens should be chosen for excellence of de tail, although high-speed intensifying screens are of con siderable assistance in avoiding blurred images. Screens must be kept clean and care taken that contact is maintained throughout their surfaces. ROENTGEN-RAY DIAGNOSIS IO3 4. Voltage. The roentgen tube voltage should be so chosen that the densities in the diagnostic areas of the him nil! lie between the limits of 0.4 and o.G. This depends upon die other physical factors employed, but, as a rule, will vary from 30 to 80 kv. ( peak). 3. Current. The choice of the tube current also depends upon each of the factors previously considered. Bearing these factors in mind, that tube current should be chosen which will produce proper roentgenographic densities. 6. The Roentgen Tube. The line or band focus tubes have been recommended as they combine the detail pro duced by a small effective focal-spot with the durability of the broad focal-spot tube. 7. Film Processing. Unless a time-temperature method of development is employed, in which all factors are carefully calibrated and controlled, it is useless to follow the technic described. Warm solutions, impure chemicals, over or under developing will ruin any fdm, no matter how perfect its ex posure may have been. In addition to these factors, it is necessary to use accurate methods for measuring patients. One must also be careful to make all measurements through the same anatomical points. An impulse timer, a cathode current stabilizer, suitable in dicating meters, adequate power supply, full wave rectifica tion for the high tension equipment, and 1 kv. per step auto transformer control, are all essential for obtaining roent genographic results which can be repeated on different occa sions. Stereoscopic examinations made in the anteroposterior or posteroanterior directions are desirable in chest roentgenog raphy. The gross exaggeration of vascular markings and other abnormal densities, seen in single flat films of the chest, is avoided and properly evaluated by stereoscopy, which places these questionable areas at their right depth. Lateral, F ig ijr k id . See c a p tio n o n p a g e io r,. ROENTGEN-RAY DIAGNOSIS 105 oblique, recumbent, or any other position, determined roentgenoscopicallv, will add valuable information. Most chest cassette changers are equipped with some type of fixation device, such as a windlass and binder, which en circles the patient's back for immobilization. After immobili zation has been accomplished, care must be exercised to de termine whether or not the patient is rotated. Even slight rotation will cause a difference in density of the two sides of the chest. Such differences in density have been regarded, by some, as evidence of pleural thickening or hypoventila tion. (Figure 10) Roentgenological Stages of Procress 49 Roentgen appearances represent pathological changes. At first, in the study of pneumoconiosis, it seemed logical that the stages of progressive changes should be based upon a sequence of advancement which could be shown by such a simple means as the roentgenogram. Clinical groupings must necessarily be based upon such phenomena as increasing dyspnea and incapacity for work, together with certain clini cal signs. Even these, when -he first classifications of pneu moconiosis were based upon similar industries, rather closely followed the roentgenographic demonstration of the progres sion of pathological changes. It is unfortunate that the roentgenological groupings of the various countries have differed. In the United States, the roentgenological classification of Lanza and Childs,39 who Figure 10 a. healthy chest; l>. same patient. .Vote the increased densitv over the right hemithorax which is due to slight rotation. This was produced by the supporting strap when the patient was plactxl against the film changer. io6 SILICOSIS AND ASBESTOSIS divided the condition, as shown by the roentgenogram, into 3 well-known stages, designated numerically, was followed until comparatively recent years, when it no longer seemed feasible. In South Africa, where the disease received prob ably the greatest amount of study in the early years of our more extensive knowledge of silicosis, three pathological stages were first recognized -- early, intermediate and ad vanced silicosis.40 The roentgenographic appearances ascribed to these were quite similar to those of our own three stages. Later on, the condition was legally divided into three clinical stages -- ante primary, primary, and secondary. Roentgeno graphic appearances were grouped to conform to iJiese in showing progression or extent. Compensation laws elsewhere, as in Ontario, have been based, to a considerable degree, upon the highly successful legislation in force in South Africa. As a result, the roentgenological classification of silicosis has fol lowed the same designations of stages as that of the legal classi fication, which is quite natural. With no federal laws in this country directly governing the condition, and no clinical classification of the disease, the roentgenological classifica tion first adopted has held priority. In order to make comparisons with the groupings used elsewhere, it is necessary to give a brief r6sum of the roent genological stages of silicosis as described in this country. First Stage. This stage has been characterized roentgenographically by a definite increase in the prominence and ex tent of the hilum shadows, an increased prominence and thickening of the trunk shadows, and a greater prominence of the linear markings of the peripheral zone. Enlarged glands may be interpreted in the hilum regions. This stage must be subject to certain modifications. Frequently, appear ances are detected in the central portions of the lungs, usually more or entirely on the right side, consisting of a slight haze, with or without fine lines. Within these areas, ROENTGEN-RAY DIAGNOSIS 17 there occasionally become manifest a feu- small, faint, hazy spots, which are probably the beginning of lymphoid deposit enlargement. In many cases, the definite appearances of the first stage, as just described, are not apparent. In a flat roent genogram, these hazy areas often have the appearance pre sented by a very small female breast or a pectoral muscle in a male, but in the wrong locality. This manifestation is prob ably due to the beginning of the interstitial fibrosis and of the visibility of a few of the individual nodules. One who has observed the effects of dusts in many occupations will find that individuals who follow certain dusty trades do not present progressive appearances that run true to form or that can be made to conform to the usual general stages, for the reason that there are types of the condition peculiar to cer tain industries, and, possibly, to certain individuals. The general manifestations of this first stage are not char acteristic of pneumoconiosis alone, but may be simulated by many other conditions, especially, passive congestion, acute or chronic respiratory infections, chronic bronchial catarrh and bronchiectasis. Moreover, the hilum and trunk shadows are subject to considerable normal variations in appearance in the adult. As a numerical stage, this one implies, theoretically at least, an early period in progression, yet individuals may remain in this phase for years, or indefinitely. As the mani festations of a typical first stage, with prominent hilum and trunk shadows and linear markings, are not characteristic of pneumoconiosis alone, I am inclined to doubt the fairness of giving this stage a definite medicolegal status, or of using it as a basis for compensation. Second Stage. This most typical stage has been charac terized by the distinctive distribution of small, rounded densities, varying in size from a pinhead to a pea, through out both lungs. (Figure 11 ) The nodules appear first on r i Figure ii Simple silicosis showing the uniform distribution of small, round densities throughout both lungs, in a hard coal miner. the right side, around the root of the lung, and usually be come quite perceptible here before they are seen on the left side. This predominance is apparent until the distribution becomes quite general throughout both lungs, and then there ROENTGEN-RAY DIAGNOSIS 109 Silicosis with infection and beginning coalescence of the nod ules in both lung fields, especially in both upper lobes, in a hard coal miner with an active tuberculous infection. There is a small pneumothorax in the right side. is no appreciable difference. The spots are alwass more numerous around the hila and less in the basilar portion of the lungs. The densest and most sharply defined nodules are usually found in association with the more rapidly fibrosing no SILICOSIS AND ASBESTOSIS dusts, such as those to which many abrasive tool grinders are exposed. There is always more or less evidence of diffuse fibrosis present, as a continuation of that often visibly started ' in the first stage, and as a forerunner of the essential process of the third. It may not be apparent because of emphysema. When not apparent, its presence may be suggested by lack of lung expansion and diaphragmatic excursion, or sharp peak ing of the domes. Theoretically, one would expect this second stage nodulation to be superimposed upon first stage appearances, but very often, the latter are not apparent. They may be obscured by emphysema, but this is not the sole cause. Third Stage. This stage has been characterized by mani festations due to a predominance of diffuse fibrosis, which may present three fairly definite and distinct appearances, although all of them may be observed in the same case: ( i ) The larger nodules of the second stage, where most prevalent, either may coalesce into very much larger and ir regular masses, or be found close together with more or less haze between them. It may be difficult in such cases to differ entiate between second and third stages, except by a lack of expansion and diaphragmatic excursion, and the presence or absence of diaphragmatic irregularities. ( Figure 12) ( 2 ) A more or less diffuse fibrosis, somewhat similar in appearance to the fibrotic process representing the late result of an extensive bilateral chronic pulmonary tuberculosis. Usually, definite nodules are still present, although not al ways. ( 3 ) The presence of massive fibrotic areas presenting the appearance of extensive pulmonary consolidations. In the late period of the stage, there is usually one such area on each side, rather symmetrically located subapicallv, but sometimes unilateral, or more extensive on one side than the ~ other. (Figures 13 and 14 ) In an earlier period of the stage, Figure 13 Anthracosilicosis with infection. Some of the lesions are healed. Other lesions, such as the one in the right lower lobe, extend to the periphery of the anterior chest wall. Note that the massive lesions in the upper lung fields have a clear zone of lung around them. Another interesting feature is the absence of any evidence of nodulation. 1 r lobe. The lesion is centrally placed and does not extend to the periphery at any point. From the roentgen standpoint, this lesion is regarded as silicosis with a quiescent infection. ROENTGEN-RAY DIAGNOSIS US FiCL'RE 15 Lateral view of the chest of an individual having anthracosilicosis. Note that the major portion of the lesion is in the upper half of the lower lobe and the lower half of the upper lobe. when small, they may appear quite asymmetrical. Lateral roentgenograms have shown us that many or most of these 114 SILICOSIS AND ASBESTOSIS Figure i 6 Massive lesions in a hard coal miner. Note the symmetrical posi tion of the masses. subapical masses are in the apices of the lower lobes, and numerous autopsy reports in the literature have confirmed this location. (Figure 15) Often, associated with these ROENTGEN-RAY DIAGNOSIS 11 r> manifestations, dense, fibrous bands are found extending in various directions, but prominently downward, and fre quently causing marked diaphragmatic deformities. They often resemble thickened trunks. The heart and vessels are I quite likely to be displaced when these bands are present. Diaphragmatic excursion is very much restricted or entirely absent. (Figure 16 ) Other Classifications. The present general classification of South Africa is as follows : 1. Rather more fibrosis than usual 2. More fibrosis than usual 3. More fibrosis full 4. More fibrosis to com mencing fibrosis 5. Commencing fibrosis 6. Commencing fibrosis plus Ante primary 7. Commencing to early 8. Early commencing 9. Early to medium 10. Medium fibrosis 11. Medium to advanced fibrosis 12. Advanced fibrosis Primary Secondary Complicated classifications are more apt to become popu lar in the examinations of individuals in a single industry than when several industries are studied, as seems to have been the case in connection with the South African gold miners, and as was the case with Jarvis 41- 42- 43 in his studies of the Barre granite cutters. They are, no doubt, admirably adapted for use when practically the entire work of an in- Mi 4 1 id SILICOSIS AND ASBESTOSIS dividual or board is restricted to the examination of silicotic persons, especially in 011c industry, but they are hardly prac ticable for roentgenologists in general, who are more favor able to simple classifications. In the formulation of the most excellent Workmen's Com pensation Act of Ontario, especially in respect to silicosis, the clinical classification of the South African Board has been embodied. This section of the Ontario Act reads as follows : ( 9 ) -- ( a) `Silicosis' shall mean silicosis of the lungs ( a fibroid condition of the lungs caused by the inhalation of silica dust). ( b) A person shall for the purpose of this Act be deemed to have or to have had silicosis. -- (I) In the ante-primary stage when it is found by the Board that the earliest detectable specific physical signs of silicosis are or have been present, whether or not capacity for work is or has been impaired by such silicosis ; (II) In the primary stage, when it is found by the Board that definite and specific physical signs of silicosis are or have been present, and that ca pacity for work is or has been impaired by that disease, though not seriously and permanently ; (III) In the secondary stage, when it is found by the Board that definite and specific physical signs of silicosis are or have been present, and that ca pacity for work is or has been seriously and permanently impaired by that disease, or when it is found by the Board that tuberculosis with silicosis is or has been present. The 1925 South African law defines three legal stages of silicosis practically identical with the above Ontario specifi cations. In view of the greatly altered aspect of the disease in South Africa, it has become necessary to recognize addi- ROENTGEN-RAY DIAGNOSIS tional clinical groups of cases, which Watkins-Pitchford41 Miiimian7c\s somewhat as follows : ^_a t Simjilc Silim.'.i.s. The condition in an individual win* reflfeins tree of oveit tuberculosis. It is non-progressive and produces but little effect upon the health. From the patho logical standpoint, these subjects present numerous small, inert nodules of dense fibrous tissue, symmetrically distrib uted. l-'.ach nodule is sharply defined from the surrounding tissue, and is so well encapsulated as to be easily shelled out. They vary in size from 3 to 4 millimeters and are rarely over G millimeters. If closely aggregated, they may produce a cer tain amount of disability, mainly shortness of breath. The roentgenological examination is more reliable than the clini cal one. ( b j Tuberculosis with Silicosis. This is a progressive and serious disease associated with larger nodules unsymmetrically distributed and composed of young connective tissue dements among which tubercle bacilli are found. Adjacent nodules are frequently aggregated into masses. There are 2 classes of cases in this group : ( 1 ) The individual may have had simple silicosis at first, followed by the development of unsymmetrical tuberculous lesions (tuberculosilicosis). This change may occur after many years. ( 2 ) The tuberculous lesions may be manifest first, followed by the silicotic ones in close association (silicotuberculosis). Here again, the roentgenographic findings are important. In tuberculo silicosis. the hitherto uniformly mottled areas are now in vaded by one or more unsymmetrical areas of shadow with mottling around them. The Miners' Phthisis Act now pro vides separately for these two general groups of cases, as has been the case in Ontario. At the meeting of the First International Conference on Silicosis 45 at Johannesburg, in August, 1930, the three clinical stages recognized locally were accepted by the Conference. 118 SILICOSIS AND ASBESTOSIS They were as follows : First Stage -- Respiratory symptoms slight, few or no physical signs and capacity for work little impaired. Roentgenograms show the linear shadows in creased and present discrete shadows of nodulation. Second Stage -- All physical signs are increased. The nodular shad ows are increased in number and size and show a tendency toward confluence. Third Stage -- All signs and symptoms are greatly accentuated, and there is a total loss of working capacity. When tuberculosis is present, the stage classification must be based more or less upon a loss of working capacity than upon physical signs and roentgenographic appearances. It was recommended that an internationally comparable roentgenographic technic and terminology be adopted, and that a further study be made of the correlation of roentgen appearances, pathology' and symptomatology of silicosis with or without tuberculosis. In 1931, Dr. Pancoast and I decided that it was more ra tional to dispense with any attempts to employ general stages of progression in any of the ways so far discussed and to substitute a pathologic-roentgenological classification, which could be combined with the clinical aspect peculiar to any one industry, or with all of them. Those who have studied a single phase of pneumoconiosis in one occupa tional group, such as asbestos workers, coal and hard rock miners, granite cutters, and sand pulverizers, for example, have found it most difficult to apply any definite numerical order of progression by stages such as that used for other oc cupations. Likewise, those who study a large number of oc cupations and industries find it difficult to adhere to a general division into stages, such as that, for example, as had its origin in the study of hard rock miners, without making exceptions or creating certain variants. This becomes more complicated with each new occupation studied. Pneumoco niosis implies a condition of fibrosis, occurring, so far as we ROENTGEN-RAY DIAGNOSIS 1 ig know, in only one general wav, but with certain variations dependent upon uncertain or unknown influences. Xoftv, the clinical phenomena must, ut necessity, depend upon*-obvious forms of pathological changes. Furthermore, roentgenographic appearances portray these pathological changes as soon as they become macroscopic, or reveal their influences while the actual changes are still microscopic. Therefore, it seemed wiser to substitute, for a numerical progression of pathological changes typical for a few of the occupations, a general pathological classification which would include the typical and the variants, and, at the same time, lie applicable to both clinical and roentgenological studies for each industry or occupation. A study of the diagrammatic representation of the lym phatic system of the lungs, such as that of Miller/6' and an application of the pathological features of the condition to this serves to indicate that there are practically three simultaneous primary distributions or accumulation points for dust, which correspond to later possible manifestations of fibrosis. ( Fig ure 7) T1 jse have been summarized as follows: (1) Blockage of the peribronchial and perivascular lymphatic systems, with later intensification of trunk shadows, linear markings, and pulmonary lymph nodes ; ( 2 ) Lodgment in lymphoid deposits, with subsequent development of nodular fibrosis ; (3) Thoroughly interstitial fibrosis following a rapid block of lymphatic channels. To these are added the pleural side-track, which is more or less common to all cases and needs no special classification. From a study of various industries, it seemed evident that fibrosis might exhibit predominance in any of these distribu tions in individual occupations. For example, in coal mining, the driller may show predominance of the nodular type, whereas the man in the breaker may exhibit only the first stage for many years ; in hard rock mining, the nodular type 120 SILICOSIS AND ASBESTOSIS predominates until diffuse fibrosis supervenes ; in the granite flitter, the interstitial type predominates, although the nodu-|ar may. exceptionnlh, do so ; in die asbestos worker, the interstitial type is characteristically predominant. Interstitial predominance, l'apidly progressing, will develop into diffuse fibrosis without nodular predominance. And so we might run through all the fibrosis producing dusty occupations. The following pathologic-roentgenological classification was offered as a suggestion to overcome the existing con fusion : 1. Peribronchial-perivascular-lymph rapid node predominance slow 2. Early interstitial predominance ( interferes with diaphragmatic movement) with nodular appear ance without nodular ap pearance rapid or slow 3. Late or advanced interstitial pre dominance 4. Nodular predominance 5. Advanced diffuse or terminal fibrosis non-progresstve progressive conglomerate nodu lar type interstitial type massive fibrosis type It was thought that many individuals might show, or oc cupations be characterized by, various combinations of these types ; and that, in one industry or occupation, there would be a sequence of predominant appearances which would correspond closely to the clinical aspect and progression of n ROENTGEN-RAY DIAGNOSIS 121 the disease. This has not been true in my experience, how ever, even in studies of individuals exposed to pure silica without contaminating dusts. We found it difficult to understand, or to explain, all of the underlying factors in the rapidly developing interstitial fibrosis. Gardner,48 however, offered an explanation. He stated that the obstruction in the deep pulmonary btnphatics diverts the lymph flow and dust cells toward the pleura, where counter-resistance is met. Consequently, dust cells pass through the walls of the lymph vessels and accumulate in the surrounding connective tissue at a point where the two lymphatic systems communicate. In support of the theory first advanced,411 of the choking of lymphatic channels by dust cells and the contraction of their lumen, which has been open to criticism, Gardner believed that the point of actual obstruc tion could be in the pulmonary lymph nodes, which would produce stasis in both deep and superficial lymphatics. He further suggested that the previous condition of these lymph nodes, as to changes induced by childhood tuberculosis and other agencies, might have some influence on the rapidity of onset and progression of silicosis. It is my feeling that ac tive-infection may exert an important influence upon the roentgen manifestations. These roentgenological phases of the condition, which we have described previously,49-50-101 may be briefly summarized as follotvs : 1. The perivascular-peribronchial-lymph node aspect due to the relaying of phagocyted dust to the pulmonary lymph nodes and their subsequent enlargement and ultimate par tial fibrosis to the gradual enlargement of lymphoid deposits along the course of lymph vessels and the subsequent thick ening of these vessels and stasis of contents. This is charac terized roentgenographicallv by increased prominence of the hilum and trunk shadows and linear markings. This appear 122 SILICOSIS AND ASBESTOSIS ance is by no means characteristic of pneumoconiosis alone, and even if it does indicate the condition, the phase is abso lutely not incapacitating. It, together with a barely percepti ble appearance of macroscopic nodules, corresponds to the so-called first stage. 2. The nodular aspect is due to the gradual enlargement of lymphoid deposits and their coalescence into quite appar ent macroscopic nodules symmetrically scattered throughout both lungs. This corresponds to the so-called second stage. It is conspicuously absent in many instances, especially when the silica intake is rapid. 3. The interstitial tvpe of the condition results from a hilumward and pleural ward block in the lymphatics and the escape of dust phagocytes in large numbers into the in terstitial interalveolar tissue and subsequent fibrosis. It ap pears as a faint homogeneous haze, first on the right side, then on the left. If the silica intake is comparatively slow, it may accompany the perivascular-peribronchial-lymph node aspect, but if more rapid, it may be associated with the nodu lar type, or may progress without the latter directly into the terminal stage of the condition without any evidence of nodulation. The unprotected or inadequately protected sand blaster, sand pulverizer, and sandstone abrasive worker have been among those especially prone to present this rapid interstitial aspect. 4. Terminal and incapacitating silicosis is characterized by two general appearances, -- a terminal diffuse fibrosis of a conglomerate nodular type, one which is quite similar in ap pearance to a generalized chronic fibroid tuberculosis, and the terminal stage characterized by large consolidated areas. In 1935, another classification or silicosis terminology was suggested because it was felt that, if objective terms, descrip tive of the type of pathological change, could be generally adopted, material progress would result. The committee's ROENTGEN-RAY DIAGNOSIS 12j report,51 given below, will certainly be revised from time to time as experience directs. Abstracts from the report are as follows : It should be distinctly understood that the tabulation which follows applies only to silicosis, that form oE pneu moconiosis resulting from the inhalation of dust with a high silica (SiOj ) content*. Other forms, like asbestosis, are excluded from this consideration because their pathology is essentially different from that of silicosis. The tabulation contains two columns ; on the left, the roentgenological appearances; and on the right, the corre sponding pathological lesions. There is further subdivision to describe the appearance of; ( 1 ) the healthy lung, ( 2 ) the uncomplicated silicotic lung, and (3) the lung of silicosis with infection. The changes described under the first divi sion are those compatible with a state of good health ; and, while they may be produced by the inhalation of relatively small amounts of silica dust, they are not sufficiently charac teristic or advanced to substantiate a diagnosis of silicosis. Similar or identical appearances may also result from the in halation or nonsiliceous dusts, from certain infections, from cardio-vascular disease, and from certain other rare condi tions. The changes involved are, for the most part, confined to the lymphatics and perilymphatic connective tissues and do not affect the parenchyma of the lung. Since, by defini tion, silicosis is a disease characterized by nodular fibrosis in the parenchyma of the lung, these alterations, even when they may have been caused by inhaled silica, do not constitute a basis for a diagnosis of silicosis. The second group covers the discrete and conglomerate nodular fibrotic reactions of sim- * Some of the nonsiliceous components of certain industrial dusts seem to modifv the pathological reaction, but the character of shadows cast by the'C modified lesions is not sufficiently defined at the present time to include them in the tabulation. Later, ten more information has accumulated, tertain other terms mav hasc m lie included. 124 SILICOSIS AND ASBESTOSIS pie silicosis. The last group deals with silicosis complicated by infection. In the majority of instances, the infecting organism is the tubercle bacillus, but the classification is sufficiently broad to include other types of infection. Certain criteria by which one attempts to differentiate various forms of infection will be discussed. Roentgenological Appearances Histological Appearances Healthy Lungs and Adnexa 1. Healthy lungs.--As defined by the N.T.A. Committee report. Irregular exaggeration of the linear markings, with possibly some beading con fined to the trunks. 3. Increased root shadow. 1. Essentially the normal tis sues of the vascular tree, the mediastinum, the bronchi, and trachea. Cellular connective tissue proliferation about lympha tic trunks in the walls of vessels and bronchi. Bead ing may be due to various causes, as blood vessels seen end on, arteriosclerosis, minute areas of fibrosis in lymphoid tissues along the trunks. 3. Cellular reaction in the tracheo-bronchial lymph nodes with extensions along afferent lymphatic trunks. These changes come within normal variations when not accompanied by recognized organic disease. Irregular exag geration of the linear markings, irith possibly some beading. belongs in the healthy chest group even when found in per sons with a history of considerable exposure to silica, for such changes are nonspecific in character and they do not involve the parenchyma of the lung. Silicosis as a clinical ROENTCEN'-RAV DIAGNOSIS *3 disease begins only when the lung proper is affected. Like wise, under Increased root shadow may be of nonspecific- origin and hence is not diagnostic. In the early stages of sili cosis. the mediastinal shadow may be widened, owing to the enlargement of the tracheobronchial lymph nodes from ac cumulated dust and cellular reaction to it; later, when spe cific fibrosis develops, the tissues generally contract and the nodes decrease in size. The changes described under 2 and 3 may be caused by many forms of irritation ; if they are due to silica, they are identifiable only by microscopic examina tion. They do not. apparently, interfere with respiratorv function, and they are not of diagnostic significance. Rnrulgrnnlugiuil . 1 j/j>rnranees Histological .-f[jjicaranccs Si.mpi.e Silicosis 4. Xodnlatinn. -- Discrete shadows not exceeding 6 mm. in diameter, tending to uniformity in size, density, and bilateral distribution, with well-defined borders surrounded by apparently normal lung shadow. The outer and lower lung fields characteristically show fewer nodules. Conglomerate shadows that appear to result from a combination or consolida tion of nodulation usually with associated emphysema manifested by -- a. Localized increased trans parency of the lung with ~ loss of fine detail. 4. Circumscribed nodules of hyaline fibrosis located in the parenchyma of the lung. Occasionally, some of these nodules may show micro scopic foci of central necro sis. 5. The result of coalescence of discrete nodules ; an area in which the nodules are closely packed and most of the intervening lung is re placed by more or less hyaline fibrous tissue. The lung architecture is par tially obscured. No demon- 126 SILICOSIS AND ASBESTOSIS Roentgenological Appearances Histological Appearances Simple Silicosis -- continued b. Intensification of the trunk shadows by con trast. c. Depression of the domes with possible tendency toward individualization of the costal components of the diaphragm. d. Lateral view : Increase in the preaortic and retrocardiac space with exag gerated backward bow ing of the spine. Widen ing of the spaces between the ribs may or may not be present. strable evidence of infection. Emphysema is a compensa tory dilatation of the air spaces with or without thickening of the septa. The second group of changes is limited to simple silicosis uncomplicated by demonstrable signs of infection. This con dition is characterized by the presence of small, discrete nodules of fibrous tissue disseminated throughout the func tional parts of both lungs. The lesions and the shadows cast by them tend to be spherical, hard, sharply defined, and vary in size from 2 to f mm. While the distribution is usually uniform throughout both lungs, the extreme apices and the outer portion of the bases are frequently uninvolved. Ih less advanced cases, the nodules remain discrete and separated by air-containing tissue. Number r, deals with the conglomerate shadoxvs of simple silicosis, which appear to develop from a combination or consolidation of discrete nodules. The resultant lesion and the shadow that it casts are often difficult to distinguish from the massive shadows of silicosis with infection, 9. It is gen- ROENTGEN-RAY DIAGNOSIS 127 erally assumed that conglomeration results from accidental overlapping and fusion of discrete nodules when they be come very numerous ; but since conglomeration is usually a localized affair and does not occur in the same position of the lung of every individual, it is logical to enquire why the nodules happen to fuse in one portion of the lung and not in others. Microscopic examination of the tissues from such areas reveals no evidence of active infection. The nodules seem to be much closer together than in other portions of the lung, they are less uniform in size, and they are usually embedded in a matrix of diffuse fibrous tissue having the same characteristic hyaline appearance as that forming the nodules themselves. It seems probable that conglomeration tnav have occurred because the portion of the lung in ques tion was previously damaged by a localized inflammatory process occurring before or during the early period of dust exposure. Because the tissue was injured, more dust would tend to accumulate-in- the-area, the nodules would develop irregularly and would frequently be very close together. The silica lodging in pre-existing granulation or scar tissue would exert its characteristic effect, and a diffuse hyalinization would result. This explanation for conglomerate reaction is, at present, hypothetical ; proof will come from long con tinued serial roentgenographic studies of groups of persons exposed to silica dust and from the chance autopsy that may be obtainable. To differentiate conglomerate shadows from tiie massive shadows of infection, 9, reliance must be placed upon the absence of change in size and character of the shadows in serial films taken over an extended period of time and upon the clinical findings in the case. Emphysema is usually associated with far advanced silico sis and it is particularly liable to complicate conglomerate nodulation. It occurs in the immediate vicinity of the con glomeration as a result of the distortion produced by con- 128 SILICOSIS AND ASBESTOSIS trading scar tissue ; there is. also, a generalized `compensa tory' emphysema found along the borders of the lung, par ticularly at the bases. The latter type is also common in faradvanced generalized nodulation. Author's Note : I am not at all certain that conglomerate shadows and even nodulation should be included under a classification of simple or uncomplicated silicosis. My experi ence in an industry of pure silica workers rather points to some complicating factor. I am almost convinced that shad ows, such as described above, can be explained by a compli cating healed infection. This will be discussed later. Roentgenological Appearances Histological Appearances Silicoms with Infection The characteristic appearances described under simple silicosis are modified by infection as follows : G. Localized discrete densities and/or string-like shadows ac companying those of simple silicosis described above. 7. Mottling. -- Shadows varying in size with ill-defined borders and lacking uniformity in density and distribution, ac companying simple silicosis. 8. Soft nodulation. -- The nodular shadows described under sim ple silicosis, 4. have now as sumed fuzzy borders and/or 6. Strands of fibrous tissue, often along trunks and septa, with or without areas of cal cification ; indicative of 'healed' infection. 7. (a) Areas of broncho pneumonia with or without caseation, i.e., acute infection. ( b ) Lobular areas of proliferative reaction with or without case ation, i.e.. chronic in fection. 8. Pcrinodular cellular re action either exuda tive or proliferative in character. ROENTGEN-RAY DIAGNOSIS 129 Roentgenological Appearances Histological Appearances Sn u:<is w 1111 l mi < 1 u>\ -- 1 on 1 i luted irregularities in distribution. This change may or may not acrompanv the simple mot tling of 7. p. Massive shadows of homogene ous density not of pleural origin symmetrically or asym metrically distributed. 9. Extensive areas of fi brosis probably due to organized pneu monia of tuberculous or nontuberculous or igin superimposed, upon a coexisting sili cotic process. Out lines of normal struc tures may be partially dcstrmed. In the last group, silicosis with infection, are included all cases with detectable evidence of infection whether active or inactive. In this respect, we depart from the South African procedure, which includes here only active infection. The difficulty of determining activity, particularly in the silicotic subject, is our chief reason for this arrangement. Number 6 covers loci nt healed infection. Identification of such changes dejn-nds ujron the same criteria that are generally employed in otherwise normal individuals. In the silicotic subject, the shadows usually occur upon a back ground of generalized nodulation. although in some cases, there may be a distinct tendency toward excessive nodula tion in the immediate vicinity of the scars left by the infec tion. Where the exposure to dust has been limited, the major evidence of nodulation may occur about the foci of healed infection with much less reaction in the remainder of the lung. The string-like shadows of healed fibroid tuberculosis 130 SILICOSIS AND ASBESTOSIS are not difficult to interpret if they occur in the classical loca tion, i.e., in the upper third of the lung. In the lower lung, they present a problem whose solution depends largely upon the experience of the roentgenologist. The term, mottling, 7, we have reserved to describe the shadows of infectious lesions in contradistinction to nod-ulation, which is restricted to those of the silicotic dust nodule. It is essential that this distinction be appreciated and re corded in the terminology. In tuberculosis, mottling is due to bronchogenic or aspiration foci of disease which exhibit a characteristic clustered arrangement. The lesions may be exudative ( acute ) or productive (chronic ) in type ; the difference will be registered in the roentgenogram by a mottling which is fluffy and ill-defined, or hard and sharply defined, as the case may be. The distribution of the mottled foci, together with the presence of large foci of older disease interpreted as tuberculosis, and clinical and laboratory find ings establish the character of the infection. Mottling due to chronic infection that has developed previous to or simul taneous with the relatively early periods of dust exposure may exhibit little or no effect from the inhaled silica for many years. In nontuberculous broncho-pneumonias, the large chronic foci are absent, and the disseminate mottling may involve different parts of one lung or of both lungs. In many instances, the nature of the infection must be estab lished by serial examinations over considerable periods of time and by careful correlation with clinical and bacterio logical findings. Soft nodulation, 8, is a term that has been coined to de scribe a rather uncommon combination of silicosis with in fection, usually tuberculous. The ordinary hard, sharply de fined nodular shadows of simple silicosis, under these circum stances, appear to have enlarged and lost definition. Their 'borders are now fuzzy and blend imperceptibly with the sur- ROENTGEN-RAY DIAGNOSIS 13' rounding lung structure. Such lesions generally occur in association with localized conglomerate shadows in the apex or other portions of the lung. Histologically, the infection appears to have localized in and about pre-existing silicotic nodules, so that each is surrounded by a zone of exudative or productive cellular reaction. Massive shadou's of homogeneous density, 9, are cast bv the areas of combined silicosis and infection, usually chronic in nature. The two processes appear to have developed simul taneously and unusual amounts of dust accumulate in the diseased area. Generalized nodulation usually occurs throughout the remainder of the lungs. Pleural densities can be differentiated in stereoroentgenograms, and by overexpo sure, it often becomes possible to penetrate the extremely dense intrapulmonary areas and analyze their internal struc ture. Not infrequently, cavities may be visualized that were completelv overlooked with the usual technic. When due to tuberculosis, such lesions are often bilaterally symmetrical. If the process extends to the pleural surface, a tuberculous etiology is postulated, while other infections are more often deep-seated. Histological examination of such lesions shows conglomer ations of simple nodules embedded in masses of more or less perfectly organized granulation tissue. Often the fibrous tis sue has undergone the same peculiar hyalinization that characterizes the interior of the silicotic nodule. Usually, the outlines of the original lung architecture are completely de stroyed. Manifestations of infection depend upon the nature of the process. If tuberculous, there will be foci of caseation and possibly small cavities. Calcification is not infrequent. If the process is inactive, the presence of fibrous tubercles, which do not exhibit the hyalinization of silicosis, may be present. The occurrence of giant cells is helpful. A partially organized nontuberculous pneumonia usually contains foci 132 SILICOSIS AND ASBESTOSIS of acute exudation of variable size. Clinically, such unre solved pneumonias Frequently exhibit periods of exacerba tion followed by regression. They may be due to a great variety of organisms, including the Friedlander group and oral anaerobes. Where all manifestations of activity have dis appeared, the lesion is probably best classified as a conglom erate shadow of simple silicosis, 5. Roentgenologic Considerations of Silicosis and Silicosis with Infection 10- Many of the dusty industries with a silica hazard present certain unusual or interesting features, which have beeilargely attributed to the contaminating dusts. Since this con sideration is concerned chiefly with silicosis, the individual industries will not be discussed separately. It is my belief, however, that various types of lesions found in different in dustries can be explained as being due to the mollifying in fluences of infection. Possibly infection and contaminating dusts play a major role. Silicosis: Nodulation, slow in progression, is one of the most characteristic of all appearances occurring in pneu moconiosis (when present). It results from exposure to dust in many industries, such as, mining hard coal, foundries, sand blasting, and sand pulverizing. The nodular aspect is due to the gradual enlargement of lymphoid deposits and their coalescence into quite apparent macroscopic nodules, in many instances, symmetrically scattered throughout both lungs. This corresponds to the beginning so-called second stage. It is conspicuously absent in some instances. In early nodulation, where the progression has, presum ably, been slow, the roentgen findings are as follow-s : The hila may be enlarged. The trunk shadows and linear mark ings are increased in prominence. The nodules are small, discrete, slightly dense, fairly uniform in size, and evenly i 134 SILICOSIS AND ASBESTOSIS distributed throughout the lung, more on the right at first. There is a slight homogeneous haze, beginning in mid-lung fields. At this time, there is no interference in diaphragmatic movement. There is, occasionally, thickening of the inter lobar pleura. ( Figure 11 ) The above observations are included under simple silico sis only because of the fact that those most interested in this subject support such statements. I have always accepted early nodulation as evidence of simple silicosis, until it was possible to study a group of workers in a pure silica industry in which some of the workers were exposed to large quanti ties of finely divided silica over a period of years. In some instances, the exposure period was over forty years. In spite of such exposures, a large percentage of the workers showed no changes in their lungs. Individual lack of susceptibility has not seemed an adequate explanation to me for such ob servations. Differential Diagnosis. -- There are many conditions that will cause lung changes which simulate the roentgen findings of silicosis. Some of these affections have been definitely identified, others have not. Metastatic Malignant Conditions of the Lungs.-- Most cases of this kind are readily differentiated from nodular silicosis, but occasionally, one encounters a case in which ap pearances are very similar, because the metastatic nodules are large and widely separated. ( Figure 17 ) Tuberculosis. -- These nodules are small, soft and fluffy, unlike the smaller, dense ones in silicosis, yet in some cases, it is impossible, either with clinical or roentgenographic evi dence to differentiate the two conditions. The history will greatly aid in reaching a definite conclusion. Roentgeno- graphically, the main variation may be the difference in size and density of the hila, although this is not always the same. (Figure 18) ROENTGEN-RAY DIAGNOSIS lS5 FlGLRE 18 Miliary tuberculosis. This appearance could readily be mis taken for that of a nodular type of silicosis. Mycotic Infections. -- Actinomycosis, sporotrichosis, leptothrix, and other fungoid infestations may cause nodulation in the lung and simulate silicosis. Such nodules, however, are usually larger, softer, and of considerable variation in size. In proven mycotic infections, dyspnea has been an outstand- Figure ig Miliary calcification of unknown origin. This patient had a carcinoma of the stomach and the miliary calcification in the lungs was a coincidental finding. He had never been exposed to dust and had never worked in the wheat fields. Dr. LeRoy U. Gardner studied pathological sections obtained at post-mortem examination and was unable to determine the cause of the calci fication. ing symptom. Fawcitts2 believes that these conditions are more prevalent than is commonly thought. Miliary Calcifications. -- Most roentgenologists have had L ROENTGEN-RAY DIAGNOSIS 137 Figure 20 Case of baratosis. This individual worked in barium rock and had worked in this industry for a number of years. The findings in his chest roentgenograms were entirely coincidental and were not causing any symptoms. The individual was not incapacitated, in fact he had few, if any, symptoms. A study of the roentgeno grams made approximately seven years before the one illustrated above showed a fine, discrete nodulation at that time, but not nearly so marked as is evident at present. the experience of seeing one or more cases of multiple sym metrical lung calcifications, and most of us have regarded thenr as evidences of healed miliary tuberculosis, with or JUH 138 SILICOSIS AND ASBESTOSIS Figure 31 Soft nodulation in a hard coal miner, diagnosed as silicosis with infection. Note the tendency toward coalescence in the mid dle third of the right lung. without good reason to so diagnose the condition. The ap pearance is not likely to be confused with silicosis. Sayers and Meriwether had the unusual experience of finding 125 ROENTGEN-RAY DIAGNOSIS 130 such cases in an examination of 18,285 men at the Pilcher, Oklahoma, Mining Clinic. Many, but not all, of these men had been miners, and some of those, who had been, showed real evidences of pneumoconiosis in addition. (Figure 19) The lungs showed a diffuse distribution of dense, discrete, ap parently calcified, shot-like spots throughout the lungs. They were of all sizes up to 1 cm. in diameter, and were variously ascribed to fungus infections, pneumomycosis, and healed miliary tuberculosis. Baritosis. -- I have seen several patients with widespread dense nodulation. typical oE that seen in so-called simple silicosis, and similar to the cases seen in Italy.5J These individ uals have been exposed to barium dust, which may be re sponsible for the changes observed in their lungs. ( Figure 20 ) Silicosis -with Infection ( nodular predominance type).-- Pulmonary tuberculosis is a frequent complication of pneu moconiosis. The latter condition may be a predisposing fac tor in the frequent incidence and serious consequences of the infection, especially when the progress of the pneumo coniosis is rapid. The two conditions often must be differen tiated when only one exists, or pneumoconiosis is present in only a minor degree and presumably not sufficient to exert any predisposition. Differentiation is necessary' because the two conditions may produce quite similar roentgenologic ap pearances. ( Figure 21) Tuberculous infection may be present in what appears to be a purely nodular type of silicosis. ( Figure 22 ) It is far more likely to be a superimposed process, and presumably exoge nous in the absence of any typical adult lesion. When the nodules tend to become conglomerate, or there is the appear ance of considerable interstitial change between them, we may suspect a superimposed tuberculosis, although it can not be absolutely proven. In the typical nodular type, the -shadows vary in size from those barely visible to that of a 140 SILICOSIS AND ASBESTOSIS FlCLRE 22 Perinodular or soft nodulation in a granite worker. Compare with Fig. 21. The nodules in Fig. 22 are much larger than those seen in Fig. 21. small pea; they are more or less regular in outline and rather sharply circumscribed. The density depends consid erably upon the size. The question of superimposed tuber culous infection may also arise when the nodular shadows ROENTGEN-RAY DIAGNOSIS 141 Ficlre 23 Silicosis with infection. The infection is actise and there seems to be a general coalescence of most of the nodules. One would expect die infection in such an individual to be more active than that illustrated in either Fig. 21 nr Fig. 22. are larger, and have a hazy, or fuzzy and irregular, and much less dense periphery, especially toward the apices. If the less dense periphery is spreading rapidly under serial studies, one may suspect superimposed tuberculosis of the Worked in Breaker _ Coal for 20 gedfflF Figure 24A A rather typical lesion seen in an individual having silicosis with a healed infection. These lesions are often bilateral and often found in the upper third of the lung fields. Note the aerated lung surrounding these areas. ROENTGEN-RAY DIAGNOSIS U3 FlfURF. 2jB Close-up ul tlic li-Mott in the right upper lobe. perinodular type ( Finnic 22 ) especially if this is occur ring in some nodules and not in others. To make this distinction by a single examination is likely to be guess work. F.ven serial observations must be made by the use of exactly identical technic. It is entirely possible that other infections may complicate an already established silicotic process in the lungs, and, in the absence of other clinical or laboratory observations, it may be impossible to identify the nature of the contaminating i i 144 SILICOSIS AND ASBESTOSIS influence. Unless the infection be active, as indicated by changing roentgen appearances, determined by serial roent genograms or by clinical obsenations, one may justifiably re gard the lesion as silicosis with healed infection. ( Figure 23 ) Silicosis with Healed Infection (conglomerate nodular type). -- The roentgen findings are as follows: The hila may be inc reased in prominence, but usually are not notice able. The trunk and other lung markings may be increased. There are conglomerate masses and beginning massive fibrotic masses which do not extend to the periphery of the lung and are usually found in the upper two-thirds of the lung fields, involving either the upper lobe bases or apices of the lower lobe. ( Figure 24 ) The lower third of the lung is emphysematous, as a rule. The trachea is not displaced, un less there has been a pre-existing tuberculous process. There is moderate interference with diaphragmatic movement, with possible peaking, humping or waviness of the domes. Not infrequently, there is thickening of the interlobar pleura. In previous communications on this subject, I have re garded the above findings as indicative of a simple silicotic process. Increasing experience with pure silica workers has lead me to believe that such roentgen appearances represent silicosis with a healed infection, or at least a quiescent period in the infective process. During the active period of the infec tion, the lesion extends to the periphery of the lung. As the infection subsides, the conglomerate mass is found more mesially, with a clear lung area peripheral to it. Such observa tions as these have taught me to feel more optimistic as to the future in the treatment of silicosis with active infection. ( Figure 25) I have considered, under the healthy chest, a possible ex planation for the location of the conglomerate lesions. It is in such lesions as these that the massage action of the thoracic cage, heart, and diaphragm upon the lymphatic flow may be ROENTGEN-RAY DIAGNOSIS 145 of major importance. With the subsidence of the acti\e in fection and its accompanying fixation, the lung structures can again begin to move relatively freely. In my experience, it has seemed that the extent of the lesion has progressed more readily in those areas of the lung (upper lung fields) that are more susceptible to fixation or interference with respiratory movements. (Figures 9 and 23) Silicosis with Active Infection (conglomerate nodular tvpe ) . -- Pulmonary tuberculosis may be present before a .silicotic process becomes predominant, or it may occur after ward. If the infection is active, the lesion extends to the peripherv, usually. It should be borne in mind that oblique or lateral views ma\ be essential to diagnose or excluile jierijjheral extension of a lesion situated in certain portions of the lung. If the silicotic process was present before the tuberculous infection, the trachea usually remains in the midline, whereas, if the tuberculous process was present first, the trachea is more likely to be displaced, either to the side or anteriorly or posteriorly. Usually, pulmonary tuberculosis, with the pos sible exception of Friedlander's pneumonia, can, for practical purposes, be regarded as the cause of tracheal displacement. In the larger lesions, heavily exposed roentgenograms, or those made with the aid of the Potter-Bucky diaphragm, may assist in demonstrating a cavity or calcium nodules, as a means of identifying the nature of the infective process. I have seen only a feu- individuals in whom silicosis with active infection was complicated by a spontaneous pneumo thorax. All of these patients did poorly. One wonders, there fore, if such observations may not be regarded as collateral evidence against the use of collapse therapy in the treatment of silico-tuberculosis. Differential Diagnosis.TM0 -- Infiltrating or Permeating Ma lignant Metastases. -- Quite frequently, metastatic malignant Figure 25A Silicosis with infection. There are a few small, discrete nodules distributed throughout both lung fields. In the right upper lung field, there is a massive lesion which extends to the periphery. Figure 23 B Five years later. The lesion in the right upper lung field has contracted down to a relatively much smaller mass, and there is non- aerated lung around it. Elsewhere, the nodules in the lungs have not changed. This individual is working in pure silica dust, which contained high concentrations of finely divided silica up until a few years ago. This individual, at one time, had a silicosis with active infection. He now has silicosis svith an inactive infec tion. 148 SILICOSIS AND ASBESTOSIS processes in the lungs are of such a character as to take on an appearance closely simulating that of pneumoconiosis of a conglomerate type. Naturally, the individual is incapacitated, and often in a manner similar to a silicotic patient. Polycythemia or Erythremia. -- This condition may be re garded from two points of view. As an independent disease, it usually has an associated increased prominence of the hilar and trunk shadows, due to the engorged pulmonary vessels. On the other hand, high red cell counts, even sufficient to suggest polycythemia, are very frequently associated with pneumoconiosis. There seems to be reason for believing that lung fibrosis and pulmonary arteriosclerosis can produce a condition akin, perhaps, to polycythemia and due, presum ably, to impaired interchange of oxygen and carbon dioxide. Yater and Constain u reported two cases of primary pulmo nary arteriosclerosis, one an anthracotic patient with emphy sema, and the other with a mitral stenosis. They stated that secondary pulmonary arteriosclerosis involves the larger ves sels and may be due to mitral stenosis, emphysema, congenital heart disease, and conditions in which the lung volume is re duced, as tuberculosis and tumor. Polycythemia is one of the clinical phenomena. Rosenthal33 reported three cases of workers in dusty atmospheres or with irritating gases in whom there developed cyanosis and dyspnea, and true polycythemia in one. Moschowitz :'s believes that secondary pulmonary arteriosclerosis is vers common. He found it in 6.5 per cent of autopsies and plates the causes in the order of frequency as, mitral stenosis, emphvsema, pulmonary fibrosis, extensive pleural adhesions, kvphoscoliosis, and congenital heart lesions. We have been interested in determining any relations between pneumoconiosis and polycythemia, and, in our search for any true associations, we have been inclined to ac cept the views of Wood,3' that there are really two conditions * to be considered. One is a compensatory mild polycythemia ROENTGEN-RAY DIAGNOSIS `49 from lung fibrosis, and the other, the true erythremia origi nating in bone marrow changes and capable of producing alterations in the roencgenographic appearances of the chest referred to at the beginning of this paragraph. Silicosis with Infection and Massive Lesions.--Terminal and incapacitating silicosis with infection is characterized by three general appearances -- a terminal diffuse condition of a conglomerate nodular type, one which is quite similar in ap pearance to a generalized chronic fibroid tuberculosis, and the terminal stage characterized by large consolidated areas, which quite frequently closely resemble tuberculous consoli dations. Some of the lesions seem to be quiescent, with the roentgen findings as follows : The trachea or hilum is not displaced. The hila may be prominent, but often is not noticeable. The lung markings are increased, but usually ob scured by emphysema. The lesions are usually in the upper two-thirds of the lung fields and do not extend to the periph ery. The nodules are not particularly prominent. There is marked emphysema of the lower one-third of the lung field. As a rule, there are no cavities ; if present, they may or may not be due to vascular injuries. The Potter-Bucky film shows trabeculation of massive areas without calcification or cavity. Frequently, there is marked interference with diaphragmatic movement. Peaking of the domes of the diaphragm occurs often, and sometimes, there is thickening of the interlobar pleura. If the tuberculous infection teas present before the silicosis became manifest and the infection is active, the roentgen findings are as follows : The trachea and the hila may be dis placed, if pneumoconiosis was not the predominant lesion originally. Usually, lung markings are largely obscured by emphysema. The massive lesions are usually in the upper two-thirds of the lung fields and extend to the periphery. Nodular formation, if present, is generally best seen in the P 150 SILICOSIS AND ASBESTOSIS lower lobes. Emphysema is marked. A Potter-Bucky film shows a homogeneous density of the lesion, with occasional cavity formation. At times, there are evidences of calcification. Almost invariably, there is interference with diaphragmatic movement, with peaking of the domes of the diaphragm. One frequently observes a case in which there is a rather extensive consolidated lesion in the upper chest, more marked on one side, or limited to one side. In addition to this, there are nodular lesions, usually lower down, on one or both sides. This type of case represents a most difficult one for differential diagnosis. If the case is essentially one of tuberculosis, the massive lesion is most likely a rapidly progressive one and the nodular appearance may be due, in part at least, to a bronchopneumonic spread to one or both sides. The differentiation really lies between massive consolida tions of the terminal stage of silicosis with a healed infection and massive tuberculous lesions which are made up of a large amount of fibrosis as a result of the accompanying pneu moconiosis. Such lesions have the contracting characteristics f of any large fibrosing tuberculous areas. This may be bilateral, but the chances are that one side started before the other, or progressed further and fibrosed more than the other. One must regard these lesions as of tuberculous, or partly tubercu lous, origin when they are peripherally located. The uni lateral or older bilateral lesion of this nature will cause homo lateral displacement of the trachea and possibly of the vessels, and because it must retract upward and outward, the hilum shadow is apt to be similarly displaced. These displacements were brought to our attention in the first American paper on the roentgenological aspect of silicosis by Lanza and Childs 39 in 1917. Silicotic consolidations with infection will not dis place the mediastinal structures unless the tuberculous in fection preceded the silicotic process. ROENTGEN-RAV DfAGNOSIS When there are bilateral con lidations, one of which is obviously tuberculous because of the effects of retraction, the lesion on the opposite side may not extend to the pe riphery, and yet be tuberculous, as indicated by upward dis placement of its corresponding hilum shadow. This lack of peripheral location is explained by the fact that it cannot re tract upon and displace the central movable structures, like the trachea, because they have already been fixed by the contralateral lesion. There is still further differentiation to be made by roentgen ological studies. If the individual, consolidated lesions are intentionally over-exposed, especially with the use of the Potter-Buckv diaphragm, considerable difference trill be noted in the structures. The silico-tuberculous consolidation shadow will appear generally homogeneous, and any stringy appearance due to tuberculous fibrosis will be coarse and far apart, and cavities, or calcifications, or both, may be found. The purely silicotic consolidation with healed infection trill not be nearly so homogeneous. In addition, there is apt to be a close trabeculation. Further Conmim rations of Tuberculosis and Silicosis95 Throughout the tollowing paragraphs and to some extent throughout the chapter, the terms `silico-tuberculosis' and `tuberculo-silicosis' nic used. These terms are rather confus ing and possibh the terms should be dropped entirely. On the other hand, these terms are frequently referred to in compensation legislation and in the literature on this sub ject. The terms Mliro-tuberculosis' and 'tuberculo-silicosis' have gained a great deal of notoriety in the radiologic litera ture particularly and in those instances, this author at least, implies one of the following ideas. 152 SILICOSIS AND ASBESTOSIS a. silico-tuberculosis 1. The patient has had a well developed silicosis before tuberculosis became superimposed. In such instances, the trachea remains in the midline. 2. Silico-tuberculosis may mean that the tuberculous lesion although predominant, has had its clinical and radiologic manifestations modified to such an extent that the roentgen and clinical signs are not those of tubercu losis alone, even though the tuberculous process is out of proportion to that of silicosis. b. tuberculo-silicosis 1. The term tuberculo-silicosis is employed in those in stances in which tuberculosis was the primary lesion and silicosis was superimposed. In these individuals, one does not refer to childhood tuberculosis, but only to the adult type and in such instances, the trachea is usually dis placed toward the tuberculous process. It has seemed advantageous to discuss the relations of tuberculosis and silicosis under certain definite groups of cases, which will be dealt with in numerical order as follows : 1 : The first group to be discussed comprises those cases of pulmonary tuberculosis in which there can be found no roentgenological evidences of silicosis after several years of service in a dust-laden atmosphere, and the condition present is obviously only tuberculosis. We must bear in mind that dust exposure does not preclude the possibility of anyone contracting tuberculosis. A consideration of this group must include the differentiation of the evidences of the infection from all of the phases of pneumoconiosis. We have seen all phases of silicosis interpreted from roentgenograms when tuberculosis was obviously the only condition present. In some of these cases, compensation had been granted and in others, claimed on the basis of silicosis simply through lack of diagnostic experience, and because the claimants worked 1 l R.OENTGEN-RAV DIAGNOSIS 153 where the production of a silica-laden atmosphere was as sumed as a possibility. The differential diagnosis in this group resolves itself into the ahiliis to recognize evidences of any of the above-mentioned phases of silicosis, on the one hand, and those of pulmonary tuberculosis on the other. There seem to be many roentgenologists who are not able to do this, although they make the attempt, and especially in con nection with compensation cases. A further discussion of this group would entail a prolonged dissertation on both diseases. It should be borne in mind that this group does not include cases which may have both conditions, but that tuberculosis is the only one present. 2 : The second group of individuals to be discussed in cludes those cases of obvious pulmonary tuberculosis in which there are evidences of a very mild degree of silicosis or pneu moconiosis after several years of service in an industry, but in which it seems reasonable to believe that the latter condi tion is not a predisposing factor. Bv the term, `mild degree.' is implied a very moderate nodular appearance, which mav have been produced or have been found after ten to fifty vears' occupation in the same industry. In many instances, it is easy to draw the line between predisposition and lack of it, but in some cases, this is a very difficult question to settle, and the value of the decision must be governed to a consid erable extent by the diagnostician's ability and experience. The law in some countries gives every worker the benefit ol the doubt when both conditions are present, justly so in many instances and, no doubt, unjustly in others. Unfortu nately, animal experimentation is of little or no value in helping us to decide whether a very slowly progressing pneu moconiosis, requiring many years to become evident in even a minor degree, is in any way a predisposing cause nf the in fection, because it is impossible to obtain proof of the action of silica or other dusts when inhaled in moderate quantities 154 SILICOSIS AND ASBESTOSIS upon animals over a period of very many years. Ordinarily, one recognizes two distinct types of human pulmonary tuberculosis, childhood and adult, which are, in many re spects, almost different diseases. Anyone familiar with silicosis must recognize a third type, namely, silicotuberculosis, which presents many points of difference from the other two, and which will be discussed later. In the group of cases now under discussion, we would not use the term silicotuberculosis. In these individuals, one would expect to find the usual appearances of adult tubercu losis, throughout its course. In many instances, we have noted evidences of a tendency to heal with only the usual amounts of fibrosis. Complete clinical and roentgenological healing of such lesions would almost always imply lack of predisposition by reason of dust. Lack of complete healing may leave one in doubt as to future predisposition and change in type, whether the individual changed his occupation or not, and subsequent serial examinations would have to be the deciding factor. In this connection, it should be borne in mind that silicosis with an active infection may be a progressive condition for many years after cessation of the dusty occupation, and predisposi tion may become manifest a long time after the dust exposure. Our greatest experience with the group of cases under dis cussion has been in connection with coal-miners. The fre quently alleged protection against tuberculosis afforded by coal-dust is well known to everyone interested in pneumo coniosis. In discussing this problem, we must not lose sight of the fact that, in the coal-miner, we are dealing with two different kinds of dust, and, therefore, two entirely different conditions ; one, anthracosis, due to coal-dust alone and rela tively harmless ; and the other, best designated by the term anthraco-silicosis, or silico-anthracosis, recently used by Cooke,3 and due to a mixture of coal-dust and silica. Pure coal-dust by itself, does not produce more than a mild degree ROENTGEN-RAY DIAGNOSIS ^5 of pneumoconiosis and probably does not, in itself, or through its own effects alone, predispose to tuberculosis. If tuberculosis occurs in the pure anthracotic, it is likely to take the usual form of adult tuberculosis. On the other hand, there seems to be conclusive evidence presented by Cummins,59 Middleton,0 and others, that coal-dust ag gravates the action of silica when the latter is inhaled in large amounts, but Mavrogordato,61- - Heffernan,65 and Hef- fernan and Green,64 and others, believe that, when the in take of silica is slight, the action of coal-dust may be a retard ing one on the silica. Certainly the excessive inhalation of both dusts is productive of a predisposition to tuberculosis. Cooke 5S quotes from Cummins 39 that retention of coal-dust to any serious degree does not occur unless the lymphatics of the lung have been previously damaged by the action of silica, in which case the coal-dust is capable of accumulating and leading to serious, and even fatal, disease. 3 : The third group of cases for discussion comprises a very important one in which the individuals present obvious tuberculosis associated with slight evidences of silicosis, after a comparatively short period of occupation, and yet, it is most likely that the silicosis is a definite predisposing factor in the infection and its progress. There may be another factor of the silica-saturated lung to be considered, which will be discussed later in connection with group 4. This present group has been a very interesting one to us and one which confused us con siderably until we became oriented, because it was a new experience. We refer particularly to sand pulverizers and workers in some other industries, who are exposed to unusu ally large amounts of dust containing a very high percentage of silica. In the incapacitated individuals, tuberculosis was the striking feature. In most cases of this group, the evidences of silicosis were slight. The tuberculous manifestations were al most invariably those of a diffuse pneumonic process, unlike 156 SILICOSIS AND ASBESTOSIS the cases of more chronic silicotuberculosis. Moreover, the clinical aspects differed. There was a vapid onset of dyspnea, cough, hemoptysis, niglu-sweats. asthenia, and extreme weak ness, in contradistinction to the characteristic comparative freedom of die more chronic cases from serious symptoms until near the end. We have no way oE determining whether anv of those cases had tuberculous lesions before starting work, or whether some or all contracted the disease during their comparatively short time at their occupation. All ol these workers were cases in which a complete knowledge and understanding of the physical factors incident to the industry were absolutely es ntial in the correct roentgenological in terpretations. 4 : The fourth group, which merits separate considerations, embraces cases of obviously advanced tuberculosis in which there are no demonstrable evidences of silicosis, or, if present, they are entirely masked in individuals working under condi tions in which the physical factors in the occupation would lead one to suspect the possibility of a rapidly developing sili cosis, as in group 3. The essential theoretical point is that the intake of silica has been unusually rapid, but there has not been sufficient time for demonstrable fibrosis, or even demon strable prefibrotic stages to become established. The question arises as to whether a silica-saturated lung, with the prelimi nary stages of silicosis in progress, can act as a predisposing factor in the incidence of tuberculosis, or can reactivate old but unhealed lesions. We have frequently come in contact with cases in which these questions have arisen and it is an issue that we can no longer evade. These two aspects of the situation must be considered sep arately, and the second will be discussed first. It would seem that the question of reactivation would have to be answered largely by the results of animal experimentation. Gardner65 states that it has been generally assumed by clinical investi- V ROENTGEN-RAV DIAGNOSIS 157 gators that the terminal tuberculosis, which causes the deaths of at least ay per cent of silicotic subjects, is the result of inlection tutjuircfl dining industrial life. Hence, lie carried out a series of animal experiments to determine whether or not certain dusts might not reactivate old, partly healed foci, and from this source produce endogenous reinfection. Guinea pi'^s were infected through the air passages by the author's usual attenuated strain of tubercle bacilli, which produced the typical `primary complex' with definite tendencies to limitation and healing, and the usual primary involvement of regional lymph nodes. Groups of infected animals were dusted with quart/, granite, and carborundum dusts respectively. The dusting occurred at intervals when the healing process was started, well under way, or nearly completed. We are interested particularly in the effects of quartz dust, contain ing 99-M per cent SiO... In the first group, when dusting began fifty-four to eighty-seven days after infection and was continued eight hours per day, except Sundays, for variable periods, there teas a spread of the tuberculous process in all the animals. In those exposed to dust one hundred fifty-one / and one hundred seventy-seven days after infection, there was evidence of a spread in Go per cent. In the third group, in which dusting began two hundred six days after infection. per cent showed spread. This was usually most marked in those animals dusted for the longest period before killing. The spread developed by direct extension from the primary Foci with or without subsequent widespread bronchogenic dissemination. We are particularly interested in the question as to whether reactivation of tuberculous lesions can occur before it is pos sible for any demonstrable evidences of silicosis to become ap parent. Gardner's experiments would seem to prove that it can, but we must bear in mind that his quartz-dusted animals were exposed to an atmosphere containing 859 million par- 158 SILICOSIS AND ASBESTOSIS tides per cubic foot under 10 micra, of which 188 million were under 1.5 micra in size, which are very high silica dust counts for human industrical exposures. On the other hand, we must remember that the micro-organisms in the human subject are of much greater virulence than those used by Gardner. Let us approach the problem from the standpoint of reac tivation during a prefibrotic stage of silicosis. Gardner and many other investigators have shown us, and many of us have seen for ourselves, that dust cells will phagocyte very variable numbers of particles of different dusts, and that, in the case of silica, only as few as one to four particles will be incorporated, compared to enormous numbers of coal or carborundum par ticles. Probably, or at least, mainly for this reason, according to Gardner, quartz gives no limitations to locomotion and rapid removal to lymphoid tissue, nor does it interfere with physiological action in the sense of phagocytosis for the tubercle bacillus. It is also known that a reactivated tubercle has included in its structure great numbers of dust cells. Gardner states that it is uncertain just how the dust reactivates the quiescent tuberculous focus. It has been proved that in flammatory reactions, specific in the case of the frequent inci dence of Friedlander pneumonia, and nonspecific through the applications of irritants, are not the factors per se. Gardner 65 concedes that, in view of our present knowledge, or lack of it, the action must be chemical, either by silica or some other substance. He regards two general views as tena ble : ( 1 ) That silica may injure the tissues and produce an environment particularly suitable for the growth of the bacil lus through the elaboration of some substance by the action of silica on the body cells and better suited to the micro organism than its environment in the tubercle protected from body fields by a wall of hyaline fibrous tissue ; and ( 2 ) that in dilute solution, silica stimulates proliferation of the bacil- ROENTGEN-RAY DIAGNOSIS *59 I us, although we have as yet no accurate information as to such solubility in body fluids. The second aspect of the situation, in regard to the newly silica-saturated lung acting as a predisposing factor in the incidence and rapid progression of a tuberculous infection, is not so easily disposed of. The foregoing remarks on animal experimentation would certainly apply to the rapid progres sion of the infectious process when once it had been initiated. Predisposition under the circumstances imposed has not been prosed, but it is an issue which must lie met. We are inclined to regard it as a strong possibility as yet unproved. The type of case discussed under group 3 would lead one to suspect the possibility from both clinical and roentgenological stand points. As to the roentgenological appearances in such cases, whether the infection was reactivated or incidental through chance or predisposition, we might expect the usual rapid forms of adult tuberculosis or a rapidly progressing and spreading pneumonic process, such as were encountered in many instances in group three cases. The important deciding factor in predisposition for the incidence of infection or in the silica saturation's being the cause of reactivation and pro gression cannot be the roentgenological examination, because the latter does not show evidences of silicosis. The decision, for the present at least, must rest almost solely upon the actual and proved physical factors present in the individual's occupation, which must be beyond all shadow of doubt be fore condemning a man in this group or placing the responsi bility. 5 : The fifth group comprises those cases of obvious tuber culosis in which there is evidence of silicosis which could readily be a predisposing factor in the incidence of the in fection. This group embraces a large number of cases, and has received wide recognition. The peculiar feature of this l6o SILICOSIS AND ASBESTOSIS group is that the roentgenological evidences of the infection are usually out of all proportion to the clinical aspect of the cases. These eases are well reiugni/etl as one of tlie group ol silicotuberculosis. 1'he rapidity of progress of the infection is often, if not usually, commensurate with that of the sili cosis. In the more slowly developing cases of silicosis, the infection behaves differently from ordinary tuberculosis. As Gardner 06 states, the clinical study of human pneumoconiosis complicated by tuberculosis has shown that the disease tends to run a chronic course, and the symptoms of intoxication are not so pronounced as in undusted individuals. The slow prog ress is due to the fibrosis, which is usually intensified by the combination of the two conditions, as is generally recog nized. Gardner regards the lymphatic obstruction of the silicosis as sufficient explanation for the lack of toxic symp toms. Obviously the more rapid the progression of the sili cosis, the more likely is the infectious process to be influenced like the cases of groups three and four. 6 : The last group does not so much concern a definite group of silicotuberculous individuals as it does a pathologi cal problem. Frequently, when examining silicotic suspects, we encounter cases whose roentgenograms show very obvious calcifications in the pulmonary lymph nodes, with or without a calcified primary nodule, and the question arises as to the possible effects of childhood tuberculosis upon the progres sion of silicosis. In 1925, Gardner 66 stated that the lungs of individuals whose pulmonary lymph nodes were involved with healing or healed tuberculosis would more readily react to smaller amounts of dust, and that an obstructive fibrosis would occur in a shorter time. He intimated that this might account for the great irregularity in the time required for the development of demonstrable silicosis in industry. We believe this still remains a theoretical problem, but we feel that an individual with a homogeneous calcification of the 1 ROENTGEN-RAV DIAGNOSIS lymph nodes is a safe subject for employment in a dusty at mosphere, whereas the individual having calcified nodes that are punctate or mottled may not be. Tuberculosis is a very frequent complication of silicosis, and, as such, is almost certain to be the eventual cause of disability and is quite like!v to be the essential cause of death. It is to the interest of the employer, therefore, to make cer tain that hygienic surroundings under living, as well as under working, conditions are kept healthful. It is highly important that the worker in hazardous dusts does not contract tubercu losis from an outside source if it can be prevented. Naturally, the individual with active tuberculosis should not be entploved, and, with past evidence of an infection, employment should be considered with the utmost caution. ComI't.iCAnoss in Silicosis1"0 Primarx Bronchogenic Carcinoma. -- Primary broncho genic carcinoma is arousing much interest in connection with pneumoconiosis because of the possibility of the latter con dition's acting as a predisposing cause. ( Figure 26 ) The publicity of the historic and very obvious predisposition of the Schneeberg miners to lung cancer and the more recent knowl edge of a similar state of affairs among the Joachimstal under ground workers has led to a belief that pneumoconiosis mav plav a part in the etiology of bronchial carcinoma. W'e have studied a few such patients, yet we are not con vinced that there is ample justification at the present time for a belief that pneumoconiosis is a predisposing factor in the incidence of primary bronchogenic carcinoma ; and for the following reasons : 1. We have had the opportunity to study a large number of cases of pneumoconiosis from various industries and. in addi tion, have been so situated, in a medical center and in an institution well equipped with an active bronchoscopic clinic, Figure 26 Primary carcinoma of the right lower lobe in a worker. There is very little, if any, roentgen evidence of silicosis. The silicotic changes, however, were demonstrable in the post-mortem exami nation. t ROENTGEN-RAY DIAGNOSIS 163 as to have referred to us for examination or consultation many cases of primary lung cancer. Notwithstanding these facts, we have seen only three proved cases of bronchogenic carcinoma in association with pneumoconiosis. While Wel ler 67 states that other authors have reported cases among coal miners, sandstone workers, cigar makers, and in many other occupations, we cannot accept isolated reports as conclusive evidence, especially as every male patient with cancer of the lung has, presumably, had a job of some kind. 2. The Schneeberg and Joachimstal cases were obviously due to some factor different from the usual causes of pneu moconiosis, and radium emanation or arsenic would seem to have been the most likely of the unproved predisposing causes. 3. While animal experimentation, as carried out by Willis,M Willis and Brutsaert,69 Murphy and Sturm,70 and others, has suggested that certain cell hyperplasias, producible through the action of dusts, tar, and other irritants, may be precancerous conditions, there is no absolute proof that they are. More over, similar hyperplasias are noted bronchoscopically quite often in the human subject and are invariably reported histo logically as inflammatory in origin. The Jacksons 71 report that, on many occasions, they have removed tumor-like bodies obstructing a bronchus and the histologic examinations have shown nothing except chronic inflammatory tissue. These growths have been regarded as serious because of the result ing secondary effects of atelectasis, drowned lungs, suppura tion, abscess, and bronchiectasis. The etiologic factors have been regarded as stagnation of secretions, especially of a purulent character, and the specific granulomas -- tubercu losis, syphilis, and fungus infections. Any inflammatory process in the bronchi may be associated with a nodule that assumes tumor-like form, and mechanical contraction through elongation and shortening of the bronchi during respiration 164 SILICOSIS AND ASBESTOSIS f might mold protuberant inflammatory new formations into tumor-like form. Fried,72 like many others, is inclined to ascribe broncho genic carcinoma to infections and inflammatory conditions. Of the three types of cells found in the bronchial mucosa- 1r ciliated, goblet and basal' epithelial cells -- the last is con cerned in the regeneration of respiratory mucosa. Metaplasia of these cells occurs in numerous bronchopulmonary diseases, as influenzal pneumonia, measles, diphtheria, and whooping cough, and Fried regards this metaplasia as, in a sense, a pre- cancerous state. He believes that only the basal cells produce cancer. This opinion is not shared by others. Fox,7J for ex ample, found 3 cancers with mucous producing or goblet cells among 37 positive biopsies in 85 referred bronchoscopic tissues. A brief review of the Schneeberg and Joachimstal situa tions seems worth while for a better understanding of the relations between lung cancer and mining operations. 1- I Weller67 states that cancer among the Schneeberg miners 'is f ' probably the most extraordinary and at the same time the least understood of all associations which have been dis covered to exist between occupation and the incidence of neoplasm.' Literature on the subject of the high mortality among the underground workers of the Schneeberg cobalt mines in Saxony began as early as 1500. Weller refers to the report of Thiele, Rostoski, Saupe, and Schmorl74 of official investigations of 154 miners during a period of nearly four years, during which time 21 died, and 13 of these with a diagnosis of primary lung cancer made at autopsy. Tivo of these men had not worked in the mines for many years, which, we believe, makes the theory of radium emanation as the etiologic factor a debatable point, although it may not exclude it. Weller also refers to the investigation of the mines by Rostoski, Saupe, and Schmorl.75 There was much hard rock ROENTGEN-RAY DIAGNOSIS 165 drilling and a great amount of dust. The ore contained iron, bismuth, tin, zinc, lead, manganese, uranium, cobalt, and nickel, chiefly in combination with sulphur and arsenic. Be cause of the uranium content, and therefore radium also, the ore was radioactive, as was, also, the mine atmosphere up to as high as 50 mache units. The possible etiologic factors con sidered were silica, chemically active dusts, especially arsenic, and, in volatile form, radium emanation and the flora of the damp mines. Many of the men had demonstrable silicosis. The exact factor still remains uncertain. In regard to the radium emanation, Martland 76 states that the active deposit present after death of the individual would be entirely too small to be measured. At Joachimstal, in Bohemia, and 30 kilometers from Schneeberg, are the mines which have been famous as a source of radium, although originally they were worked for silver, cobalt, nickel, bismuth, and arsenic. The mining for uranium preceded the discoverv of radium. In 1929 and 1930, Pirchan and Sikl:r investigated these miners, who also had been known to have a high mortality rate for pulmonary diseases. During that period. 19 miners died, 10 recently active and 9 pensioners. 13 of these were examined post mortem, and primary lung cancer was found in 9. Tuber culosis, pneumonia, and trauma were the other causes of death. Unfortunately, careful studies were not made from the standpoint of the etiologx of the cancer. The atmosphere of the mines had approximately the same radioactivity as at Schneeberg. Unlike Schneeberg miners, these men presented no marked degree of silicosis. We cannot help but feel that radium emanation and arsenic must be strongly suspected as etiologic factors in both of these mines, although it would be most difficult to obtain positive proof for the implication of the former. - Cardiac Lesions. -- A few articles in the literature call at- i66 SILICOSIS AND ASBESTOSIS tendon to silicotic fibrosis as an etiologic factor in cardiac enlargement and break-down. While this may be true, it is very difficult to prove, and one raises the question as to whether there may not be some other etiologic factor opera tive coincidentally. If such were true, silicosis might be re garded as a major factor without sufficient evidence. The Erythrocyte Sedimentation Reaction in Silicosis There is some evidence 73 to show that the sedimentation rate in silicosis is increased. I have not had sufficient ex perience to allow me to state whether it is increased in in dividuals without active infection. Preliminary observations would seem to justify the following statement, however. In the absence of clinical or roentgen evidence of active infec tion, in workers showing roentgen evidence of silicosis or of silicosis with healed infection, I have rarely found an in creased sedimentation rate. If this observation is subsequently substantiated, the sedimentation rate will become an excel lent test to use in conjunction with other clinical studies to evaluate the activity or quiescence of a given lung lesion. Asbestosis The Asbestos Industry.49 -- This industry has grown ex tensively during the past twenty years. This has caused atten tion to be centered around it as a factor in industrial disease, mainly, however, because of some very unusual features found in the lungs of those exposed to the inhalation of the dust. The first important one is the fact that pneumoconiosis is produced in the workers apparently by silicates instead of directly by silica. This fact will, no doubt, lead to further interesting studies of industries in which silicates predomi nate in the dusts. There is some confusion in regard to the action of silicates in the production of pneumoconiosis, es- ROENTCEN-RAY DIAGNOSIS 167 pecially as certain o them, like clay and kaolin, are supposed by some authorities to retard the action of silica. In addition to these, talc, French chalk, soap stone, pumice, and many other silicate substances are extensively used in various in dustries. Another unusual feature of pneumoconiosis in as bestos workers is, lirst, the ante-mortem and autopsy finding in the lungs of some very interesting, unusual, and character istic mineral deposits, and still another is a progression of fibrosis and roentgenographic appearances differing from those of most injurious dust producing industries. Numerous articles have appeared on the subject during the past four years. The most comprehensive one has been that of Merewether and Price/9 supplemented by Merewether,80 in 1930, and again in 1934,31 in a general review of all phases of the asbestos industry in Great Britain and a resume of the results of their examinations of 363 asbestos workers. Prior to 1928, there were available records in medical literature of only 2 deaths among employees in the factories, but since then, a considerable number have been reported. The importance of the condition and its differences from other forms of pneumo coniosis seem to warrant a general acceptance of the term, `asbestosis.' Lynch and Smith,82-83 in their reports, have been the first in this country, at least in medical literature, to deal specifi cally with the subject. One of their cases, a negro, died as a result of a gunshot injury after working twenty-eight months in a mill during a period of three years. His lungs showed definite interlobular, perivascular, and peribronchial fibrosis, and also the various asbestosis bodies. The second case, also a negro, died of lobar pneumonia after four and a half years of continuous work in a mill. His lungs showed, everywhere, a definite increase of young fibrous tissue, in addition to the various asbestos bodies. In view of the meagre number of complete autopsy re- i / 168 SILICOSIS AND ASBESTOSIS ports in this country, the following report of Lynch and Smith83 is given in its entirety : A ulujtoy The body had been embalmed prior to tiie autopsy. There was marked subcutaneous edema, especially of the feet and legs to above the knees, and some of the hands and forearms. The toes and fingers were stubby, but there was no cyanosis, perhaps interfered with by the embalming. The sternum was flattened above and definitely depressed over the epigastrium. The pericardium and heart were definitely displaced to the left, the apex well outside the nipple line at about the fifth interspace. The heart weighed 343 gm. empty, was definitely broadened but not lengthened, the right heart furnishing the breadth, the left, not enlarged. The right cavities were well enlarged and open, the left ventricle closed. The right myocardium measured 8 to 10 mm. in thickness well up from the apex toward the pulmonary ori fice. Microscopically the muscle fibres were not of uniform size, and there was generally a distinct enlargement of those of the right. They were of indistinct outlines and striations, and those of the right ventricle were frequently vacuolated. There was an increase of stroma, and the veins, particularly of the right, were definitely distended with blood. The aorta was the seat of a minor atheroma, and the whole vascular system, outside the heart, was in good condition. Both pleural sacs were completely obliterated by old ad hesions, usually very dense, especially over the whole right lung and the upper and lower left. The diaphragm was up to about the fourth rib on the left but was low on the right. The left lung was retracted well over to the outer wall and high, occupying about one-half to two-thirds of the usual space. The pleura generally was thick and cartilage-like, especially over the apex and base. The lung was coarse, ROENTGEN-RAY DIAGNOSIS 169 leathery, nodular and lumpy over the upper half and the base, the middle being more spongy- and air-bearing. The vessels and bronchi were very prominent emphysematous bullae in the parenchyma especially in the apex where there was a group or chain of honey-combed sacs. The interlobar pleura was obliterated. The bronchi appeared congested. The hilum lymph nodes were inconspicuous, did not appear en larged, and were smoky black. There was no evidence of tuberculosis. The right lung was large, filling the whole right chest and encroaching some toward the left. Its whole pleura was very thick and cartilage-like. The interlobar pleura was se.- ed outwardly, but was open, a clean membrane presenting, be tween the adjacent lobes. The lung was very much like its fellow generally, the upper lobe densely fibrous and lumpy, vessels and bronchi prominent, and a mass of emphysema tous bullae in the apex. The middle lobe was not so fi brous, nodular or lumpy, and had prominent bronchi and air bullae. Both lungs, especially the right, bore much frothy fluid, which, expressed and examined, revealed numerous asbestosis bodies, free, in sheaves or clumps, and ingested by giant cells. The two ends were often engulfed by different giant cells. There were also a few dust cells, with fine black granular pigment, and masses of a yellowish amorphous sub stance, of the color of the asbestosis bodies, in cellular debris. Microscopically there was an extreme grade of hvalinizing fibrosis of the lungs, universally but irregularly distributed. The pleura was thick and fibrous, and there was marked in terlobular fibrosis. Scattered here and there were irregularly rounded areas of hyaline fibrous tissue, in somewhat lami nated form, within which were masses of greenish-black granular substance. Here were also areas of liquefaction and calcification in the centre of these hyaline nodules. A large part of the alveoli were obliterated or virtually so. Some 170 SILICOSIS AND ASBESTOSIS lobules remained open, the sacs having thick fibrous walls. In these open alveoli, the epithelium was sometimes cuboidal and there were fairly numerous large round phagocytes, some with a group of nuclei, some mononuclear. These mac rophages contained black or greenish-black or brownish granular pigment and an occasional asbestosis body. Where the lung was less fibrous, there were young connective-tissue cells and lymphocytic accumulations. The bronchioles were dilated and their walls thick and fibrous. In some areas, the lobules of alveoli showed marked emphysema, large empty sacs with thin walls. Asbestosis bodies in typical forms, with a variety of architectural figures, yellowish-brown, clubbed, dumb-bell and rod forms, were to be found widespread, singly or in groups within giant cells in the alveoli of less fibrous areas, singly in the alveolar walls and interlobular tissues showing the younger fibrosis. Associated with them was much granular substance of the same color, as if from disintegrated asbestosis bodies. Besides these pigments, there was much ordinary black anthracotic material around the vessels of the interlobular tissues. The interlobar pleura was especially thick. The large bronchi were practically normal. The peribronchial lymph nodes were the seat of marked fi brosis, edema, atrophy of follicles, and accumulation of masses of black and yellowish-brown granular pigment, of the same order as that in the lung. The liver was grossly and microscopically in a state of e\treme chronic passive congestion, which state, in lesser de gree, was conspicuous in spleen, kidneys, and other viscera. More and more data of this type are becoming available as recorded in the more recent contributions of Merewether,81 Lanza, et al.,84 Lanza,85 and Shull.86 Symptomatology. -- The symptom-complex of pulmonary asbestosis may be of interest to roentgenologists, especially because the condition is a rather new one in the group of 1 ROENTGEN-RAY DIAGNOSIS 171 pneumoconioses, or, rather, an old one come to light and extensively studied. We have made a composite grouping of symptoms assembled from the reports of Wood,"7 of his 13 cases, Haddow,*'* Stewart and Haddow,39 Soper,90 and Wood and Glovne,91 including 22 cases additional to those reported by Wood, as follows : ( 1 1 On<rt. This is variable and depends upon the exact occupation .uid the quantity of dust inhaled. Both are im portant, for the individual may not be engaged in a very dustv duty, but may be working in a room made very dusty by another procedure in the manufacturing process. Wood states that symptoms may appear comparatively early and gives, as the time limits, one and fourteen years. Haddow places the average period at about five years, and states that die condition is usually recognized first during or after an attack of influenza or winter cold. Cases are usually better in summer. (2 ) Cough. This is a very variable symptom, sometimes nearly or entirely absent and seldom excessive. (3) Expectoration. This is moderate when present, but is usually lacking except during bronchitic attacks. (4) Anorexia. This is a rather constant late symptom. Haddow regards it as an indication to stop work. Individuals may then live for several years, but become progressively weaker, more emaciated, and exhausted, until pneumonia or bronchitis brings death. (5 ) Dyspnea. This is the most striking symptom and practically the most important one. It is progressive as in other forms of pneumoconiosis, whether the individual stops work or not. Wood and Glovne speak of it as `a terrible tightness of the chest,' which is very expressive. While dys pnea is due primarily to inelasticity of the lungs, which is always beautifully demonstrated by roentgenoscopic observa tions of the diaphragmatic excursion, it is also, in a measure, 172 SILICOSIS AND ASBESTOSIS a result o interference with blood supply. Therefore, it is slow and insidious in its development, until, finally, the lungs are able to accomplish no more than just sufficient oxygenation of the blood to sustain life. (6) Cyanosis. This is a very frequent late manifestation. (7) Weight Loss and Emaciation. These manifestations are very striking in the late stages. They are out of all pro portion to the physical signs, and thus differ from tubercu losis alone. All of these symptoms are more or less those found in other forms of pneumoconiosis, and a symptomatology largely applicable to all forms is placed here for emphasis on this particular one. The last three symptoms are to be emphasized in connection with the same pulverizing industry. There is an interesting skin lesion found in connection with the asbestos industry known as the asbestos corn. It has been mentioned particularly by Gloyne and by Soper, among the writers on pulmonary asbestosis. The fine asbestos fibers penetrate the superficial layers of the epiderm like thistle thorns and produce small corns or hypertrophies of the epiderm around them. No asbestosis bodies have ever been found in these lesions. Roentgenologic Considerations.49-- Comparatively few of the report on pulmonary asbestosis contain roentgenographic findings, and in many of those which do, the descriptions are not so scientifically made as to permit of easy comprehension or interpretation. Most writers who describe the appearances or mention them casually seem to regard them as most un usual or characteristic of the occupation, notably Wood,87 Wood and Gloyne,91 and Merewether.80 It is true that they are unusual, but we would hardly regard them as character istic for the reason that other conditions induce quite similar roentgenographic appearances. In all industrial pneumo conioses in which the roentgenographic appearances deviate ROENTGEN-RAY DIAGNOSIS >73 from the stereotyped description first given to those of the hard rock miners, one must become familiar with those of . the industry and correlate them with diaphragmatic excur sion, clinical findings and degree of disability represented before being able to interpret the findings for that particular industry. For example, from the roentgenograms of 17 as bestos factory employees, examined by Pancoast in 1917 and reported by us in lgaG,9-' the appearances were not regarded as of any particular moment, but simply as minor changes such as are frequently found in connection with slowly fi brosing dusts. On reviewing these roentgenograms with Dr. J.Y.Sparks,95 who made the roentgenological studies of Wood's cases, referring to our records of the diaphragmatic measurements, and with a knowledge of the peculiarities of the asbestos industry, particularly from the standpoint of roentgenographic appearances, we at once realized that our first interpretations were based upon an entirely erroneous conception. It is questionable whether anyone viewing a number of roentgenograms of atypical pneumoconiosis rep resenting several industries, could pick out the ones of as- bestosis subjects alone. All of the cases represented in the series just mentioned were only moderately advanced. In some roentgenograms of asbestos factory workers seen with Dr.Lanza,94 we noted that there was a direct progression into a terminal diffuse fibrosis without any nodular pre dominance. This terminal state seemed to have been reached in about twenty years, on an average. Nevertheless, in some instances, the nodular fibrosis was quite evident. Wood 8* has given a very excellent description of the roent genographic findings in the ly cases examined, and this has been corroborated by Soper 90 in 1 case, by Oliver95 and by Wood and Gloyne.91 Our interpretation of these findings was that there had been a rather predominant early interstitial ~r fibrosis, with, later on, an associated soft nodular fibrosis. 174 SILICOSIS AND ASBESTOSIS The transition to the third stage, if we should adhere to that term, or at least to the terminal stage, would seem to have -been mainly through a continuance of the interstitial pre dominance with very little prominence of nodular fibrosis. The early interstitial predominance was described as resem bling a ground glass appearance. On reviewing our own roentgenograms with Dr.Sparks and comparing them with the excellent roentgenograms of some of Wood's cases, we found a great similarity in the appearances. The early evidence of the condition was a faint homogeneous haze in the lower part of the mid-lung field which seemed to correspond to the appearance we have pre viously suggested as an early predominance of interstitial fibrosis. This haze spreads through the lower one-half or two-thirds of the lung field and may almost obscure the domes of the diaphragm later on, with very little evidence of nodular fibrosis. With it, there is a very decided restriction in movement of the domes of the diaphragm without the appearance of pleural adhesions, which seems to be proof of the general fibrotic nature of the process. Thickened pleura does exist, of course, as in any fairly well advanced case of pneumoconiosis. The most unusual feature of the condition seemed to us to be the fact that, in both sets of roentgenograms, the appearance seemed to begin more often on the left side than the right, and progressed more on that side. This is the reverse of all other occupations that we have studied. Merewether30 states that it begins on the right side, as one would expect, and the cases we observed may have been examples of the exceptions which are occasionally ob served in any industrial pneumoconiosis. 'We noted the same tendency to obliteration of the left cardiac border as men tioned by "Wood, because of the diffuse fibrosis and the promi nent trunk shadows. Wood states that the late stage may or may not show consolidations. "Wood and Gloyne 91 state that 1 ROENTGEN-RAY DIAGNOSIS l75 the ground glass appearance in late cases, on careful analysis, resolves itself into a fine mottling and linear shadows which, toward the base, may look like cobwebs. It is evident that the nature of these changes in the lungs requires the best type of roentgenograms for their portrayal. Also, the seriousness of what may seem to be minor changes to the uninitiated requires a roentgenoscopic study of dia phragmatic movements to make one realize the actual state of disability present. It is evident also, as Merewether states/" that an opinion as to the degree and intensity of an asbes- tosis fibrosis, based upon a comparison of roentgenographic changes with those shown in standard silicosis films, will be an underestimate. More recently, Merewether 31 and Shull36 have not em phasized on which side the process is most evident in the beginning or late in the disease. This coincides with my more recent experience. The disease process may be diffuse, bi lateral, or unilateral, but is practically always limited to the lower half or lower two-thirds of the lung field. Of the 363 cases examined by Merewether and Price. 133 had roentgenographic studies. Of these, 52 were said to have presented appearances of diffuse fibrosis and 22 were sus picious. Merewether31 says that approximately seven years must elapse between the commencement of exposure and the production of a serious degree of asbestosis. This space of time includes not only the trapping period of the fibrosis- producing dose of dust, but also the maturation period of the fibrosis, which periods, of course, overlap. The existence of this fibrosis-producing period accounts for the fact that no appreciable number of asbestosis cases are discovered until the second five years of employment. Relatively few cases mature in this minimum period of seven years; many, even in the more dusty processes, require eleven years. When 176 SILICOSIS AND ASBESTOSIS fibrosis of serious import has matured, the worker is unduly short of breath on any extra exertion, has a slight cyanosis of the lips, and a little dry cough, mostly in the mornings. He still, however, is quite able to work, and, usually, is not concerned about his state of health. Many workers, in fact, will not admit symptoms of any kind at this stage. Discussion of the Nature of the Roentgenologic Appear ances seen in Asbestosis. -- From my experience, the roent genologic findings in asbestosis are largely limited to the lower half or lower two-thirds of the lung fields, whereas in silicosis, the opposite obtains. In asbestosis, the lesion may be bilateral or largely unilateral. Emphysema, blebs, or bullae always accompany well established changes in asbes tosis and occur in the upper portions of the lung fields ; whereas, in silicosis, the lower lung fields, to a large extent, are the site of these changes. I have found it extremely difficult to determine the early manifestations of asbestosis. I believe an explanation for this would include the lack of an adequate pre-employment ex amination, in which a careful fluoroscopic study of the re spiratory and cardiac movements is made. It seems to me that fluoroscopy, directing special attention to costal and dia phragmatic expansion, is essential in the determination of early changes in asbestosis. If one can assume that the pathological process is due to changes secondary to the lodgment of asbestos fibers in the smaller bronchioles, the roentgen findings might be ex plained as follows. Disturbance in the roentgen appearance would not be seen except following the lodgment of the fiber in the smaller bronchioles. Sufficient time would have to elapse until a definite collar of fibrosis had become mani fest so extensively that it would limit the ingress and egress of air into the lung areas distal to the point of obstruction. Figure 27 Asbestosis, early manifestations indicated by the beginning ob literation of the costophrenic sulcus. Moderate hypoventilation of the lower lung fields due to thickening of the parietal pleura and slight thickening of the interlobar pleura. 178 SILICOSIS AND ASBESTOSIS In such damaged bronchioles, it is justifiable to anticipate that the lack o ventilation and drainage, distal to the point of obstruction, might become an ideal site for the develop ment of infection or atelectasis. The infection, in turn, would increase the amount of serum protein in the tissues and as sist, or stimulate, a pre-existing tendency for fibrosis. The fibrosis, itself, might limit the amount of normal lymph flow and, in succession, the infection would extend to and in volve neighboring areas. When a sufficient amount of tissue had become involved, one might be able to demonstrate beginning changes in the roentgenogram, such as beginning obliteration of the costophrenic sulcus and fluoroscopically, some limitation of costal and diaphragmatic expansion. ( Fig ure 27) I should assume, when such an appearance is ob served in the loentgenogram, that the process might be re garded as moderately advanced. The next step in the pathological process would seem to include an extension of the affection to the periphery. With involvement of the periphery, there is a definite limitation in the respiratory movements, which would be extremely slight in the early case of asbestosis but marked in the more advanced degrees of the disease. (Figures 28 and 29) The ribs are somewhat fixed and in thin individuals, they are de pendent. In fat persons, they change very little. The inter spaces may become quite narrow. In the consideration of the healthy chest above, I called attention to the importance of the respiratory movements in lymph flow, and also to the fact that any restriction of these movements would tend to limit the flow of lymph. Any limitation of the flow of lymph increases the development of pre-existing pathologic changes. It was, likewise, empha sized above, that thickening of the pleura occurs to a greater extent in the lower thoracic region than it does in the upper, the explanation for this being the powerful costal and dia- ROENTGEN-RAY DIAGNOSIS !79 v-ftj 4 Fit.I RL 28 Man aged 41 ; silk wea\er for twenty years, asbestos weaver for five years. The rocmgcnngraphic findings are within the limits of a healthy chest. phragmatic movements in the lower chest and the relative fixation of the upper chest. Almost every autopsy protocol has called attention to the ST Figure 29 Asbestosis moderately advanced. Same individual as illustrated in Fig. 28. Examination made five years after that illustrated in Fig. 28. Note the relatively marked changes in the right lower lobe, which include thickening of the parietal and diaphrag matic pleura, obliteration of the costophrenic sulcus, slight thick ening of the interlobar pleura, some narrowing of the interspaces and enlargement of the cardiac silhouette. There is evidence of hyperventilation in the upper lung fields. ROENTGEN-RAY DIAGNOSIS l8l marked thickening of tiie pleura and occasional thickening of the pleuropevicardinm. It is my feeling that these definite changes in the pleura tan be adequately explained upon the basis of an underhing infection of the lung, extending to the pleura with subsequent thickening of the structure, due to the powerful respiratory movements and cardiac pul sations. ( Figures 30 and 31 ) The haziness of the lung fields, called attention to by al most every writer, can be explained by pleural thickening and a lack of ventilation. One should be careful in distin guishing between the shadow caused by pleural thickening and that resulting from the subcostal muscles. This has been discussed under tire healthy chest. I have been forced to place less and less importance upon observations concerning the trunk or vascular markings. These shadows are so changeable with variations in phases of respiration and cardiac pulsations that, unless one is re examining patients and employing critical technics, such as making exposures during forced inspiration and during the systolic or diastolic phase of the cardiac cycle, one is abso lutely confounded with changes in the size of the shadows, entirely within physiologic limits. However, when changes develop sufficiently, one can see disturbance in the movements of the domes of the diaphragm and of the ribs, and obliteration of the costophrenic sulci. From this point on, the pathologic process in the lungs seems to advance fairly rapidly, exactly as one would expect it to do. This can readily be demonstrated by comparing the vertical diameter of the thorax in serial examinations of an individual who has a well developed asbestosis. If a period of at least five years is allowed to elapse, the vertical dimension is ma terially reduced. This observation corresponds to the limi tation of the movement of the domes of the diaphragm, and, in a rough way, indicates the ability of the individual to / i I Figure 30 Asbestosis moderately advanced. Close-up of the right lower lung field in the individual illustrated in Fig. 29. Figure 31 Asbestosis moderately advanced. Note die position of the ribs, the hypoventilation of the lung fields and thickening of the pa rietal pleura, which, in turn, are responsible for the ground-glass appearance of the lung fields. The interlobar pleura between the upper and lower lobes is thickened. From its position, one can readily see the extent of scar contraction already existent in the right lower lobe. The vascular trunk shadows have largely lost 'their identity. 184 SILICOSIS AND ASBESTOSIS ventilate the lung fields. The shadows are more pronounced in the liases and diminish as they approach the upper third of tiie lung field. Figure 32 Asbestosis markedly advanced. The lesion occupies the lower lung fields and there is hyperventilation in the upper lung fields. Note the indistinct outline of the cardiac silhouette. This is prob ably due to thickening of the pleuropericardium and superim posed shadows in the lung fields. Note the dependent position of the ribs. ROENTGEN-RAY DIAGNOSIS 185 My comments thus far have been limited entirely to the lungs and pleura. The heart and pericardium also suffer in asbestosis, much more so in this occupational disease, in fact, than in any dust hazard with which I am acquainted. With a moderately advanced degree of asbestosis, the shadow of the cardiac outline is obscured by the shadows of super imposed lung structures and involvement of the pleuropericardium. (Figure 32 ) One rarely sees the cardiac shadow sharply demarcated, as observed in ordinary roentgenograms. The pleuropericarclium becomes thickened and, in some in stances, markedly so, for the same reason that the pleura over the lower lung fields and the domes of die diaphragm become thickened. Pulsations of the heart and infections e\tending to the pleura in this region play a major role, I believe, in producing the marked thickening of the pleuropericardium. These changes and those of the lung probably account for the right-sided hypertrophy and ultimate de compensation of the heart. In some instances, the cardiac silhouette is quite enlarged. Realizing, therefore, that ven tilation of the lungs is seriously interfered with and that cardiac action is impaired, one can readily understand why these patients are embarrassed with dyspnea, weakness, and cyanosis. In my present state of knowledge, if I were called upon to make a classification of asbestosis from a roentgenographic standpoint, I should include only two stages ; asbestosis mod erately advanced, and asbestosis markedly advanced ; or as bestosis, first and second degree. I feel quite certain that the roentgenologic diagnosis of the clinically early stage of asbes tosis is not entirely reliable. ( Figure 33 ) Prognosis. -- It seems to be the rather general opinion that the prognosis in pulmonary asbestosis among factory workers is to be regarded as grave without adequate protec tion, in a large number of cases, among those who work 186 SILICOSIS AND ASBESTOSIS Figure 33 Asbestosis, an unusual type. This may be due to the fact that the individual has had some silica exposure. The shadows in the middle third of the right lung field are not typically nodular. where there is great concentration of dust. The condition is apparently progressive, even after cessation of occupation. Merewether and Price 79 state that, with continued exposure to high concentration dust, fibrosis may be fully developed ROENTGEN-RAY DIAGNOSIS 187 in from seven to nine years, and that death may result in about thirteen years. With less concentration, fibrosis may not be fully developed for fifteen, twenty, or twenty-five vears. Inhalation of dust in high concentration results in a more marked degree of fibrosis in a shorter time than when the concentration is lower. There is no disease among the industrial hazards in which it is more important to have serial examinations than in the asbestos industry. Almost every investigator has been ham pered by either no pre-employment roentgenologic examina tions of the chest or relatively few opportunities for re examinations of the individual exposed to asbestos dust. Shull3S states that it would seem that improvement could be expected in the early cases, but that, as the disease pro gresses, improvement is less likely. Sparks ,c feels that it is too early in the study of this disease to say very much on the subject. Lanza 33 believes that it is by no means certain that asbestosis progresses as does silicosis after withdrawal from dust exposure, nor that infection seems to be so closely and intimately associated with asbestosis as with silicosis. My experience in this condition is also limited, but I feel quite certain that, tvhen asbestosis can be diagnosed by roent genologic examination, the condition is likely to become progressive, due to the important role exerted by fixation of the lung structures secondary to the pleural involvement. This can be readily demonstrated in serial roentgenograms, even in the absence of fine lung detail. The striking feature is the reduction of the perpendicular diameter of the chest. Predisposition to Tuberculosis.--The cond. on of pul monary asbestosis being a new child in the pneumoconiosis family, a great amount of interest centers around the inci dence of tuberculosis. Among the early case reports referred to in the beginning of this occupational section, pulmonary tuberculosis was reported as an accompanying condition in a i88 SILICOSIS AND ASBESTOSIS few instances. Cooke's case had advanced tuberculosis. Simson reported 1 case which died with tuberculosis and 1 with out evidences of the infection. He thought that we could not as yet formulate any definite opinion as to the frequency of the predisposition. Simson quoted Hoffman 97 as reporting 13 deaths among asbestos workers, 3 of whom had tubercu losis. He also quoted Collis98 as reporting 5 deaths from tuberculosis among less than 40 workers at a factory. Wood and Gloyne91 referred to 3 cases showing evidences of tu berculosis at autopsy. Haddow88 observed many asbestosis cases, among whom 4 died. He did not believe that the con dition predisposed to the infection, at least not as a rule. Merewether and Price 79 stated that asbestosis differed from silicosis in the distribution of the fibrous tissue, in more rapid development, in roentgenographic features, and, pos sibly, in a lessened susceptibility to tuberculosis. Mere wether 80-81 states that, out of 374 cases examined, evidence of active tuberculosis was found in 3. He thinks that, while there is no outstanding susceptibility proved, the question has not been fully settled as yet. I believe, however, that when tuberculosis does complicate asbestosis, that one can readily suspect or diagnose the tuberculous lesion with a fair degree of accuracy, due to the fact that the tuberculous proc ess often occurs in the upper lobes, where there is usually very little evidence of asbestosis. If a basal tuberculous process were superimposed upon asbestosis, it would be very difficult, if not impossible, to diagnose it. ( Figure 34) Differential Diagnosis. -- Passive Congestion of the Lungs as a Result of Cardiac Decompensation. -- In this condition, the enlargement of the heart shadow, the abnormalities of the cardiac silhouette, especially in cases of mitral stenosis, and the clinical picture serve to establish the presence or ^absence of passive congestion. If asbestosis is absent, the appearances are likely to disappear with restoration of com- Figure 34 Asbestosis with a complicating tuberculous lesion in the right upper lobe. It is entirely possible that tuberculosis may account for the entire appearance found in this individual, but it was subsequently shown that this individual not only had tuberculosis but also haci asbestosis in the lower lung fields. igo SILICOSIS AND ASBESTOSIS pensation, but not altogether in long-standing cases. Marked emphysema is usually associated with asbestosis and is apt to cause a certain amount of rotation of the heart, so that the sagittal roentgenogram does not convey a direct impres sion of cardiac size or shape. The lateral view is always nec essary to clear up the diagnosis. Any phase of asbestosis is likely to have its roentgenographic appearance greatly ac centuated by passive congestion. Advanced Bilateral Bronchiectasis. -- The dilated bronchi, retained secretions and associated tracheobronchitis charac teristic of this condition will produce the appearance of greatly accentuated trunk shadows, which may simulate tl.tit of the moderately advanced phase of asbestosis. Other conditions that simulate asbestosis include poly cythemia or erythremia and infiltrating malignant metastases, especially those extending from the mediastinum. BIBLIOGRAPHY 1. Pendergrass,E.P., and Hodes.P.J. The healthy chest, Atn.J. Roentgenol., 38:15, 1937. 2. Sxarby.H.G. 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McPhedran.F.M., and Weyl,C.N. Clinical and physiologic deductions from synchronized roentgen-rav exposures, A111.J. M.Sc., 173:313* 19*729. Miller,W.S. Pulmonary lymphoid tissue in old age. Am. Rcv.Tubcrc., 9:519, 1924. 30. Drinker,C.K., and Fiei.d.M.E. Lymphatics, Lymph and Tis sue Fluid, Williams 8: Wilkins Co., Baltimore, 1933. 31. Henry,C.G. Studies on the lymphatic vessels and on the movement of lymph in the ear of the rabbit, Anat.Rcc., 57:263, 1933. 32. Miller,W.S. A study of the factors underlying the forma tion of alveolar pores in pneumonia, J.Exper.Med., 38:707, 192S33. Macklin.C.C. Alveolar pores and their significance in the human lung, Arch.Path., 21:202, 1936. 34. Dolley.F.S., and Wiese,E.R. Effects of a large closed bi lateral pneumothorax on thoracic lymph flow, Arch.Surg., 18:542, 1929. 35. Macklin.C.C. X-ray studies on bronchial movements, Am.J. Anat., 35:303, 1925, 36. Macklin.C.C. Dynamic bronchial tree, Am.Rev.Tuberc., 25:393* ^S237. Weyl,C., Warren,S.R.,Jr., and O'Neill,D.B. Survey of chest roentgenographic technique, Am.J.Roentgenol., 35: 526, 1936. 38. Weyl,C., Warren,S.R.,Jr., and O'Neill,D.B. Choice of certain technical factors for chest roentgenography, Am.J. Roentgenol., 35:534, 1936. 39. Lanza,A.J., and Childs,S.B. Roentgen-ray Findings in Min- ROENTGEN-RAY DIAGNOSIS 193 ers' Consumption, Based upon a Study of 150 Cases, U.S. Pub.Hcalth Bull.X0.83. 1917. 40. Wait.A.H.. Irvine.I..G.. Johnson.J.P.. and Stewart,W. Silicosis (miners' phthisis) in the W'itwatcrsrand, Appendix X'0.6 of the Miners' Phthisis Prevention Committee of South Africa, Pretoria. 1916. j 1. Jarvis.D.C. A roentgen study of dust inhalation in the granite industry. Am.J.Roentgenol.. 8:244. 1921. 12. Jarvis.D.C. Dunham's fans in roentgen-ray study of granite dust inhalation, Am. [.Roentgenol., 8:500. 1921. 43. Jarvis.D.C. A conception of chest x-ray densities based on a study of granite dust inhalation, Am.J.Roentgenol., 9:226, 1922. 44. WATKixs-PiTCHroRn.M'. The silicosis of the South African gold mines, and the changes produced in it by legislative and administrative efforts. J.Imlust.Hvg., 19:109, 1927. 45. Ci.t ver.E.H. The International Silicosis Conference, J.Mcd. .Ass. South Africa, September, 1930. 46. Miller.W.S. Some essential points in the anatomy of the lung, Am. J.Roentgenol., 4:269. 1917. 47. Miller.W.S. Key points in lung structure, Radiology, 4:173. 1925- 48. Gardxer,L.U. Appendix on Pathological Studies. U.S.Pub. Health Bull.N0.187. U.S.Gov.Printing Office, Washington, July, 1929. 49. Pancoast.H.K., and Pendergrass,E.P. A review of pneumo coniosis : Further roentgenological and pathological studies, Am.J.Roentgenol., 26:556, 1931. 50. Pancoast.H.K., and Pl.ndercrass.E.P. The roentgenological aspects of pneumoconiosis and its medicolegal importance, J.Indust.Hyg., 15:117, 1933. 51. Pancoast.H.K., Pendergrass,E.P., Riddell,A.R., Lanza, A.J., McConnell,W.J., Sayers,R.R., Sampson,H.L., and Gardner,L.U. Roentgenological appearances in silicosis and the underlying pathological lesions, U.S.Pub.Health Report, vol.50, N0.31, August 1935. 94 SILICOSIS AND ASBESTOSIS 52. Fawcett,R. BritJ.Rad., 9:172, 1936. Also: Brit.J.Rad., 9:354, i93<>53. Arricom.A. The pneumoconiosis of barium. Clinical, radio logical and experimental observations. La Med.d.Lavoro, 24:461, 1933. 54. Yatf.r,W.M., and Constam,G.R. Pulmonary arteriosclerosis, M.Clin.North America, 12:1689, 1929. 55. Rosenthal,S.R. Sclerosis of the pulmonary artery and arteri oles, Arch.Path., 10:717, 1930. 56. Moschowit7,E. The cause of arteriosclerosis, Ain.J.M.Sc., 178:244, 1929. 57. Wood.F.C. Personal communication. 58. Cooxe.W.E. Silico-anthracosis, Practitioner, 129:483, 1932. 59. Cummins,S.L. Effects of coal dust upon the silcotic lung, J.Path.8: Bacteriol., 30:615, 1927 Go. Middleton,E.L. A study of pulmonary silicosis, J.Indust. Hyg., 2:433, 1920-1921. 61. Mavrocordato.A. Studies in experimental silicosis and other pneumoconioses. Pub. of South African Institute for Med.Research, X0.15, March 1922. 62. Mavrocordato.A. A contribution to the study of miners' phthisis, Ibid., December 1926. 63. Hefferxan.P. Some notes on the biophysics of silica and the etiology of silicosis, Brit.M.J., 2:489, 1929. 64. Hefferxan.P.. and Green,A.T. The method of action of silica dust in the lungs, J.Indust.Hyg., 10:272, 1928. 65. Garoner.L.L\ Studies on experimental pneumonoconiosis. V. The rcacmation of healing tubercles in the lung by the inhalation of quartz, granite and carborundum dusts, Am. Rev.Tuberc.. 20:833, 1929. 66. Gardner.L.L'. Tuberculous infection and tuberculosis as modified by experimental pneumonoconiosis, Tubercle, 6:336, 1925. 67. Weller.C.V. The pathology of primary carcinoma of the lung, Arch.Path., 7:478, 68. Willis,H.S. The pulmonary effects of over three years' ex- ROENTGEN-RAY DIAGNOSIS lQr, postirc of guinea pigs to silica dust. Am.Rev.Tuberc., 17:233, 1928. (3y. Wil.us.H.S.. and Brusaert.P. Tumor-like structures in the lungs of guinea j>i"s .artificially exposed to silica dust, Am.Rev.Tuberc., 17:268, 1928. 70. Mt ri'HY.J.B.. and Sturm.E. Primary lung tumors in mice following the cutaneous application of coal tar, T.Exper. Med.. 42:693, 1923. 71. Jackson.C., and J ackson.C.L. Benign tumors of the trachea and bronchi, with special reference to tumor-like forma tions of inflammatory origin. J.A.M.A., 99:1747, 1932. 72. Frif.d.B.M. Primary carcinoma of the lungs : III. Histogene sis and metaplasia of bronchial epithelium, Arch.Path., 8:46, I92973. Fox.H. Personal communication. 7 t. Thiele. Rostoski, Salpe. and ScuwoRt. Leber den Schncc- berger Litngenkrebs, Mucnchen, medAVchnschr., 71:24. '924. 73. Rostoski. .Salpe, and Schmorl. Die Pergkrankheit der E12beigleute in Schneeberg in Sachsen, Ztschr.f.Krcbsforsch., 23:360, 1926. 76. Martland.H.S. The occurrence of malignancy in radio active persons, Am.J.Cancer, 15:2435, 1931. 77. Pirchan.A., and Sikl.H. Cancer of the lung in the miners of Jachyraov (Joachimstal) : Report of cases observed in 1929-1930, Am.J.Cancer, 16:681, 1932. 78. Robins.A.R. The erythrocyte sedimentation reaction in chronic pulmonary disease, Am.Rev.Tuberc., 35:763, 1937. 79. Merewether,E.R.A., and Price,C.W. Report on effects of asbestos dust on the lungs and dust suppression in the as bestos industry, H.M.Stationery Office, London, 1930. So. Merewether.E.R.A. The occurrence of pulmonary fibrosis and other pulmonary affections in asbestos workers, J.Indust. Hyg., 12:198 and 239. 1930. 81. Merewether.E.R.A. A memorandum on asbestosis, Tuber cle, Xovember-Dccember, 1933, January, 1934. pages 69-81, 109-118, 152-159. J 196 SILICOSIS AND ASBESTOSIS 82. Lynch,K.M., and Smith,W.A. Asbestosis bodies in sputum and lung. J.A.M.A., 93:659, 1930. 83. Lynch,K.M., and Smith.W.A. Pulmonary Asbestosis II. Ain. Rev.Tulierc., 23:643, 1931. 84. Lanza,A.J., McConnell,W.J., and FehnelJ.W. Effects o the inhalation of asbestos dust on the lungs o asbestos workers. U.S.Pub.Health Repts., 50:1, 1935. 85. Lanza,A.J. .Asbestosis. J.A.M.A., 106:368, 1936. 86. ShlllJ.R. Asbestosis : A roentgenologic review o seventy- one cases. Radiologs-, 27:279, 1936. 87. Wood.W.B. Pulmonary asbestosis; radiographic appear ances in skiagrams of the chests of workers in asbestos. Tubercle, 10:353, 1929. 88. Haddow,A.C. Clinical aspects of pulmonary asbestosis. Brit. M.J., 2:580, 1929. 89. Stewart,M.J., and Haddow.A.C. Demonstration of the pe culiar bodies of pulmonary asbestosis (`asbestos bodies') in material obtained by lung puncture and in the sputum. J.Path.fc Bacteriol., 32:172, 1929. 90. Soper,W.B. Pulmonary asbestosis ; a report of a case and a review. Am.Rev.Tuberc., 22:571, 1930. 91. Wood,W.B., and Gloyne,S.R. Pulmonary asbestosis. Lancet, i:445- !9392. Pancoast,H.K., and Pendergrass,E.P. Pneumoconiosis (Sil icosis ). A Roentgenological Study with Notes on Pathology. Paul B.Hoeber, Inc, New York, 1926. 93. Sparks,J.V. Personal Communication. 94. Lanza,A.J. Personal Communication. 95. Oliver,T. Pulmonary asbestosis: a sociomedical study. Arch.F.Gewerbepathol.u.Gewerbehyg., 1:67, 1930. 96. Sparks,J.V. Pulmonary asbestosis. Radiology, 17:1249, 1931. 97. Hoffman,F.L. Mortality from respiratory disease in dusty trades. U.S.Bur.of Lab.Stat.Bull.231, 1918. (Quoted by Sirason) 98. Collis.E.L. Annual Report Chief Inspector of Factories and Work Shops for England and Wales, 1910. (Quoted by Simson) ROENTGEN-RAY DIAGNOSIS 197 99. Pancoast,H.K., and Pendergrvss.E.P. Roentgenological As pects of simple silicosis and silicotuberculosis. Am.Rev. Tuberc., 29:43, 1934. 100. ' Pancoast, H.K., and Pendergrass.E.P. Roentgenologic As pects of pneumoconiosis and its differential diagnosis. J.A.M.A. 101:387, 1933. to 1. Pancoast,H.K., and Pendercrass,E.P. Pneumoconiosis : The importance of accuracy in roentgenological interpreta tion. New Eng.J.Mecl.. 209:423. 1933. 102. Lanza,A.J., Gardner.L.U., Haythorn.S.R., Hazlett.T.L., Jones,R.R., Pendercrass.E.P., Sander,O.A., and Sayers,R.R. Silicosis and Allied Disorders. Medical Series, Bulletin No. 1. Air Hygiene Foundation of American, Inc., Pittsburgh, Pa., 1937. The author has drawn rather freely from a number of the writ ings in which he has collaborated, in view of the fact that their observations largely represent his present views. When present opinions have differed, a discussion of the reasons for the change is included in the text. : ) IV. PATHOLOGY S. Roodhouse Gloyne, M.D.,D.P.H. : ' pathologist, pathological laboratories and research INSTITUTE, THE LONDON CHEST HOSPITAL INTRODUCTION Definitions The term silicosis trill be used in this chapter to denote the changes which take place in the body tissues as a result of the inhalation of dust containing silicon dioxide, generally referred to in this connection as "free silica." The Interna tional Conference held at Johannesburg1 in 1930 proposed in interpreting this term that the following conditions be | . satisfied, viz., that the silica must reach the lungs ( a) in a . . chemically uncombined condition, although it might be i mixed with other dusts ; ( b ) in fine particles of the order 1; of less than 10 microns in diameter; (c) in sufficient ij | amount, and over a certain period of time. Ijji;1 For some years pathologists regarded free silica as the only ' siliceous dust likely to produce the disease, but recently "combined silica" or various mineral silicates found in in dustrial dusts have been included in the indictment and a new term, silicatosis, has come into use to denote the types of disease thus produced. The chief example of this new group of diseases has al ready become sufficiently important to receive a special des ignation, asbestosis, a disease resulting from the inhalation of the dust of asbestos, which contains the silicates of iron and magnesium. - As the diseases caused by these various substances differ 198 PATHOLOGY 199 in cheir pathology, it will be necessary to describe them sep arately, but before doing so certain general considerations from a pathologist's point of view require discussion. Just as a chronic infective disease such as tuberculosis is regarded From the three-fold point of view of the organism, the portals of entry and the tissue reaction, so in the study of a pul monary dust disease the nature of the dust, the conditions of its entry into the body, and the tissue reaction which ensues all need separate consideration. .Vatu re of the Dust. Mavrogordato - ( 1930) has classified die dusts which enter the lung into four types : ( 1 ) Dust that is harmless 1(2) dust that is usually harmless but which mav contribute to the lung mischief tv hen inhaled in asso ciation with a harmful dust ; ( 3 ) dust that is usually harm less and may actually have a prophylactic value when inhaled in association with a harmful dust; (4 ) dust that is harm ful. The first group does not concern us here. In the second group may be placed such dusts as iron ore and coal dust in association with silica. The third group is a doubtful one. At the moment one would not feel justified in placing any dust in this category with certainty, for the pneumoconioses take many years to develop and surprises are not uncommon. The fourth and last group must include notvadays not only free but also combined silica. Free silica occurs mostly in the form of mineral quartz. In the British Silicosis Compensation Scheme of 1928 it is referred to as silica rock, quartzose sand or `any dry deposit or dry residue of silica.' Combined silica includes a large number of silicates which tend to increase with industry. The commonest of those in use which are under suspicion as possible producers of pul monary changes are enumerated by Middleton ( 1936) .20 The size of the dust particle is important. Only very small particles reach the lung tissues. Probably the majority, as soo SILICOSIS AND ASBESTOSIS Mavrogordato suggests, are about the size of the common pathogenic micro-organisms. -- The shape of the particle has also a bearing on the re sultant lesion. Broadly speaking there are 3 morphological types : ( O Small particles with irregular surfaces and sharp edges and diameters approximately equal. This is the com mon shape for quartz particles. ( 2 ) Long fibres of asbestos, which may extend up to too microns in length. Even if we regard the particle as inert, size and shape are of great im portance because they determine the penetrating power of the particle. The long needle-like asbestos fibre readily "en gages" in the respiratory bronchiole and easily comes to rest athwart the lumen of any narrow passage it may enter, whereas the small silica particle whose diameters do not dif fer greatly can readily penetrate to the peribronchial lymph spaces and the mediastinal glands. (3) Minute needles of fibrous sericite -- a hydrous silicate of aluminium and potas sium. These vary from 2 to 5 microns in length and have been described by W.R. Jones3 (1933) in silicotic lungs as occurring in `piled-up bundles of needles,' hundreds of which are present, he states, for every grain of quartz that can be recognised. Although sericite had been previously described, it was not regarded as of great importance until the work of Jones. He regarded it, rather than the uncom bined silica or quartz, as the important causative factor in silicosis. At the present moment the matter must still be regarded as sub judice. Obviously a series of carefully con trolled pathological observations is needed in workers who have been exposed to the dust of quartz particles alone and sericite particles alone, but according to Drinker and Hatch 4 ( 1936) quartz free fibrous sericite is difficult to obtain. Middleton has pointed out, however, that in Britain workers exposed to sericite without uncombined silica are found in i PATHOLOGY 201 the china clay industry and that so far there has been no high incidence of silicosis in this industry. The experimental evidence in laboratory animals falls out side the scope of this chapter. Xon-siliceous particles are found in practically all cases of silicosis and may cause confusion. Carbon, for example, is generally present in the shape of very fine amorphous par ticles. but coal dust may occur as elongated sharp jagged particles often up to 10 microns in length. In the course of recent investigations on dust sampling, Briscoe, Matthews, Holt and Sanderson 5 ( 1937 ) noted that dust which had been exposed for some time to the moist atmosphere of mines iost an unusually large amount of water on ignition, in striking contrast with the relatively small loss of weight on drying at 100 C, indicating that the dust had taken into firm combination a relatively large amount of water. In other words the comminution of the minerals had exposed fractured surfaces on which, at numerous points, there existed free and unsatisfied valency forces whereby water was attracted and held as water of constitution in the hydrated particle. Hydration of this nature can apparently liberate bases held in the crystal lattice. The writers found for instance that alkali was liberated in amounts equivalent to about one-sixth of the total alkalis present in the minerals. Obviously important new possibilities are opened up by these researches. Freshly formed dangerous dusts yield to water both alkali and soluble silica in larger amounts than do 'dead dusts' -- i.e., dusts which have been exposed to air for some time. The Portal of Entry. Probably only a small fraction of the inhaled dust reaches the pulmonary alveoli. The greater portion is deposited in various parts of the respiratory tract and expelled therefrom. In the case of asbestos workers, for 208 SILICOSIS AND ASBESTOSIS instance, the fibres can be found in the nose and throat and even occasionally in the conjunctival sac. The histological examination of the nails of the larynx, trachea and large bronchi in cases coming to autopsy usually reveals no lesions of asbestosis. Probably the same is true of silicosis though the writer knows of no investigations on the point. It may be assumed, therefore, that mechanical forces come into play to drive out the invading dust. Such are the muscular move ments of the eyelids, the cleansing effect of the lachrymal secretion, the action of cilia and the outward flow of mucus in trachea and bronchi. In the case of cilia these protective phenomena have been demonstrated by Leonard Hill6 ( 1928 ). Using the trachea of horse, ox and sheep, he found that a suspension oE lamp black in Ringer's solution was carried along the mucous membrane by the cilia at a rate which might be as fast as 3 centimeters in one minute and that fine particles such as those of iron and aluminium filings were readily passed along the trachea in this way. If a small area of ciliated epithelium was damaged by injury, cautery, or various chemicals (including chemical fumes) the trans port of suspended particles was greatly reduced or even in hibited altogether. Irvine 7 ( 1930) has suggested that re peated inhalation of silica dust may lead in the course of time to a dry bronchitis and bronchiolitis with denudation of epithelium. In this case the portal of entry is opened wide, as it were, and the penetrating dust will meet with little or no resistance. No doubt, too, some types of particles may be more readily expelled than others. These various factors may explain why different dusts seem to have a predilection for different parts of the lung. The Tissue Reaction. Obviously the tissue reaction must, to some extent, be dependent on a variety of factors, viz., the duration or intermittent nature of the dust exposure, the size of the dose, the admixture of dusts, the age and sex PATHOLOGY 203 of the worker, and the condition of the respiratory passages prior to exposure. These factors take long years to observe in conjunction with employment histories and post-mortem findings and in many industries the necessary data for assess ment are not yet available. Meanwhile the interaction of the dust particle and the tissues may be briefly and tentatively summarised as follows : -- ( 1) Many dust particles are doubtless expelled en route, but if a particle reaches the end of the journey in the distant parts of the portal of entry it "stays put." It does not multiply or become bacterioiysed like a micro-organism but remains as a more or less insoluble and irremovable irritant particle. ( 2 ) The end of the journey for the silica particle is die peribronchial lymphoid tissue, but in the case of the asbestos fibre it is the respiratory bronchiole and the alveolus ; hence the difference in the pathological picture. ( 3 ) Although bacteria may be found mixed with the dust, they are for the most part non-pathogenic organisms ; the dust particle can therefore be regarded as a non-infective irritant, and the tissue reaction is fibroblastic, ending in the production of the collagenous fibre. (4) The amount of plasma exudation is minimal. The exudative reaction in the lung is characteristic of the bac terial diseases. (5 ) Although we speak of the silica particle and the asbestosis fibre as being practically insoluble, many investi gators believe that a colloidal silicic acid is actually formed by a slow disintegration of the particles in the lung and that the morbid processes are the result of a toxic action. There is indeed experimental evidence in the work of Gye and Purdy 8 (1922 ) in favour of such a view in the case of silica sol. Asbestos fibres are known to persist in the lungs of per sons who have not been exposed to the dust for more than twenty years and any disintegrating action must therefore 204 SILICOSIS AND ASBESTOSIS be extremely slow. Sundius, Bygden and Bruce,9 ( 1936) indeed, consider that this chemical theory of slow disintegra tion of dust particles is still an open question. (6) It follows that if the dust particle is practically in soluble or only very slowly soluble, the lung must in the course of time become choked with irremovable foreign mat ter. This dust accumulates chiefly in the lymphatic drainage system. (7 ) The process of phagocytosis, so prominent a part of the tissue reaction to bacterial diseases of the lung is much modified. Many of the panicles, notably the asbestos fibre, are too large to be engulfed by a single phagocyte and a group of these cells can often be seen surrounding but not engulfing the meal which is obviously too large for them. Again, the particle even iE engulfed cannot be digested and disposed of in the same way as the more soluble protoplasmic bacterium. This may be one reason why the phagocyte ap pears to remain so long in situ in the silicotic tissue in ex perimental animals. Lastly the phagocyte is for the most part a large mononuclear macrophage and not the small poly morphonuclear leucocyte from the blood stream. The latter is the phagocyte, par excellence, of pyogenic cocci in the lung. (8) Lymphoid hyperplasia. This is one of the striking features of the tissue reaction. Small collections of lymphoid tissue are normally situated on the outside of the trails of the small bronchi but they are so small as generally to escape notice. These minute lymphoid aggregations absorb much carbon pigment and are a striking feature in the lungs of all persons exposed to the dust of large towns irrespective of sili cosis. They should be distinguished from true lymphatic glands. They become markedly hypertrophied as the result of the drift of the silicotic particles into them. In the course PATHOLOGY 205 of time collagenous fibres are laid down and constitute the first simple silicotic nodules. SILICOSIS Macroscopical Appearances As a rule the body of the silicotic is not markedly wasted unless tuberculosis has supervened. Cyanosis may be present. Defoi.nity of the chest wall is rare, whereas in the fibroid disease of the lung of non-industrial origin which begins generally in childhood, flattening and deformity are com mon. Lungs and Pleurae. On opening the thorax the lungs as a rule do not collapse. They are heavier than normal and fre quently bulky. Pigment is variable in amount. In the British cases it is generally pronounced owing to the carbonaceous dust of the industrial towns and may indeed be extreme in amount. Emphysema is almost the rule, bullae at the apices being especially common, whilst all the free borders may be affected. The essential feature of the silicotic lung, however, is the nodular fibrosis. This begins with small raised hard nodules or islets of fibrosis immediately beneath the pleura and in the peribronchial regions of the lung. The former can be felt by running the fingers lightly over the pleura and are less pigmented than those in the lung. At first the nodules are no bigger than miliary tubercles but as the disease progresses adjacent nodules coalesce into composite nodules or small irregularly shaped masses which look rather like pieces of hard black rubber embedded in the lung. They can be de tected by the touch as the knife cuts through the lung sub stance and they stand out prominently on the cut surface as the crepitant lung tissue collapses, but a true `gritty' feel is 206 SILICOSIS AND ASBESTOSIS only imparted to the knife, as a rule, by extreme cases such as the stone mason's lung. In this case small particles of quartz can actually be dug out of the nodule with the point of the knife. The nodules are usually more plentiful in the upper lobes where they readily tend to run together into masses of large size. As the presence of the nodule is the essential feature for diagnosis, attempts have been made to arrive at a classifica tion in terms of distribution and severity of the lesion. Simson and Strachan 10 ( 1930) in describing simple silicosis as it exists in the South African mines give the following classi fication which is used by the Miners Phthisis Bureau : ( 1 ) Slight -- lesions small and moderately numerous, or medium-sized to large but sparse; ( 2 ) Moderate -- lesions numerous and small or moderately numerous and large ; ( 3) Well marked -- lesions numerous and large. ( 4 ) Very well marked -- lesions very numerous and large. These authors state that in estimating the degree of nodulation present the whole lung substance has to be considered for the obvious reason that the distribution may be limited or unequal. The term small is used for islets of fibrosis with diameters up to 2 millimetres, medium from 2 to 4 milli metres, and large from 5 millimetres up to a centimetre. The term sparse is used to describe the distribution of nodules on the cut surface of the lung of the order of one nodule in a square with a side of 5 centimetres ; modeiately numerous signifies one nodule per square with a 3 centimetres side, nu merous when the square has a side of 2 centimetres and very numerous when the square has a side of less than 2 centi metres. The nodule must be distinguished from calcified deposits and from the small fibrotic patches of obsolescent tubercu- PATHOLOGY 207 losis. As noted above, the silicotic nodule in the British cases is usually darkly pigmented, whereas calcified deposits and patches of obsolescent tuberculosis are much less so. In long standing cases the aerated lung tissue between the nodules collapses, thus causing the groups of composite nod ules to run together into the large hard, dark pigmented masses already described. These masses are commonest in the upper lobes; they may be wedge shaped with the ape\ of the wedge towards the hilum like deposits of caseous tubercu losis ; they are frequently subpleural, and beneath the apical pleura are associated with emphysematous bullae, and even tually they may occupy the greater part or even the whole of the lobe. ( Figures 1 and 2 ) In addition to this characteristic fibrotic nodule the pleura generally shows evidence of old pleurisy in the shape of thickening, usually patchy, with obliteration of the inter lobar fissures, and the production of sessile adhesions closing portions or the whole of the pleural sac. A layer of soft plastic fibrin, the result of a recent terminal pleurisy is often found at the autopsy, covering the old thickened pleura. Pleural effusion is rare. In the lung the most important change apart from the fibrotic nodule, is the presence of emphysema. This is so common as to form almost an integral part of the picture. It occurs in the shape of bullae beneath the apical pleura, and along the thin anterior margins of the lungs, similar to the emphysematous lesion in other lung diseases. But it is seen also in another characteristic form, viz., a compensatory emphysema of the deeper portions of the lung tissue giving rise to an irregular honeycomb appearance. The later stages of the disease are often characterized by a septic bronchitis with muco-pus plugging the bronchi, and a terminal reddening of the lower lobes from congestion Figure i Silicotic lung showing massive noclules best marked in upper lobe. PATHOLOGY 20Q Figure a Silicotic lung showing extensive nodulation especially in lower lobes. which may go on to a true red hepatization. These terminal conditions will be referred to again under the complications and sequelae of the silicotic lung. In uncomplicated cases little of importance may be found in the other organs. Myocardial degeneration is not uncom mon and is considered by some pathologists to be due to the obstruction in the pulmonarv circulation as a result of the fi brosis, but it must be remembered that, as a rule, silicosis as seen in the autopsy room is a disease of the elderly industrial worker whose heart is likely to show signs of wear and tear in 210 SILICOSIS AND ASBESTOSIS any case. Although silicosis is believed to show a biochemical aspect there is as a rule no obvious toxic effect on distant or gans in man, such as one finds in gout for instance, though lesions in the kidneys and other organs have been obtained by Gye and Purdy 8 ( 1922 ) and others in experimental ani mals. Chronic interstitial nephritis may be found in silicosis but there are generally other reasons for its presence, (e.g. atheroma) and one cannot with any confidence claim that such lesions are simply the result of a silicotic toxin. Microscopical Appearances The Silicotic Nodule. The silicotic nodule is best studied when small and discrete and for this purpose the earlier the nodule is obtained the better. The key to the situation is to be found in the minute aggregations of l>mphoid tissue which are normally located, in the lungs of man, in relation to the bronchioles, saccular ducts, small branches of the blood vessels and pleura. These aggregations of lymphoid tissue have been carefully described by W.Snow Miller 11 ( 1937 ) and should be distinguished from the lymph nodes which are found in intimate relation with the cartilaginous bronchi. These small collections of lymphoid tissue are simply minute aggregates of lymph corpuscles without the organised struc ture of supporting framework and capsule of connective tis sue which a true lymph node of the cartilaginous bronchus possesses. In relation to the bronchioles they are found lying between them and the accompanying branch of the pulmo nary artery. They are also to be seen along the course of the pulmonary artery and the pulmonary vein, in the interlobu lar septa and beneath the pleura, probably in this case in association with minute radicles of the pulmonary veins but not necessarily so. Miller has examined the lungs of elderly persons in order to determine the distribution of this lymph oid tissue in relation to the usual carbon pigment which PATHOLOGY 211 accumulates in the lung with age. The masses of lymphoid tissue around the bronchioles and the branches of the pulmo nary artery were found to be hypertrophied into a common mass, whilst those associated with the pulmonary veins and the venous trunks in the interlobular septa were also hyper trophied. He further noted that these masses were usually found where alveoli were in the direct line of the air cur rent against the septa. The lymphoid masses beneath the pleura are similarly hypertrophied. These small masses of lymphoid tissue, therefore, are the sites of the formation of the silicotic nodule, a point which has been well stressed by Strachan and Simson 10 ( 1930) . Pathologists get very few opportunities of examining the nod ule in its very early stages in man and the picture tends to be obscured by subsequent events, especially b\ the presence of pigment, but probably the sequence of events is as follows. Amorphous particles of silica together with carbon pig ment reach the saccular ducts and alveoli. Here they are taken up by large macrophages, generally designated by the unscientikc but expressive term dust cells,' and reach the masses of lymphoid tissue described above. At this site these `dust cells' come to rest and are surrounded by fibroblasts. In the course of time they degenerate and disappear leaving behind them the insoluble particles of silica and carbon pig ment. Meanwhile the fibroblasts have given place to collage nous fibres and one or two minute capillaries may be formed from neighbouring \essels. The early nodule is now complete. When suitably stained it resembles a small round wicker basket in which the interwoven wicker work may be taken to represent strands of collagenous fibres. ( Figure 3 ) In the centre are a few small capillaries, and lying between the fibres are particles of silica and carbon pigment. Surrounding the whole, ness- fibroblasts are formed producing in their turn `more collagenous fibres. By this process the older fibres in the 212 SILICOSIS AND ASBESTOSIS Figure 3 . .Discrete silicotic nodules, a early stage (x 80) ; b intermediate .stage (x 40 ) ; c late stage ( x 40 ). inner parts of the nodule are compressed and come to lie closer together and have a hyaline appearance when stained. The capillaries too are compressed and may ultimately disap pear. The picture is now less like a wicker basket and more like a large onion with tightly packed concentric layers. A circle of capillaries can often be found around the nodule in this stage, especially when the nodules are subpleural. In this PATHOLOGY 213 late stage the South African writers have also described both a fatty degeneration and a pre-calcification phase. In the course of time discrete nodules come into juxta-position by reason of the collapse of intervening alveoli. They then form an ir regular composite nodule. As a rule the individual nodules forming this composite mass can still be recognised and around it there may be small areas of emphysema. ( Figure 4) Ficcre 4 Composite nodules of silicosis ( x 60). The remaining portions of the lung show collections of macrophages in the alveoli, whilst desquamation of lining epithelium of the small bronchi is common. Hypertrophy of the aggregations of lymphoid tissue is the rule. 4 si4 SILICOSIS AND ASBESTOSIS The Complications and Sequelae of Silicosis The following are the chief complications and sequelae noted in the post-mortem room. Emphysema. This has already been referred to as an almost constant finding. Occasionally an emphysematous area may become sufficiently large to form a cavity filled with mucopus and inhaled pigment from neighbouring bronchi. Such a cavity may be mistaken for a tuberculous or bronchiectatic cavity but as a rule it does not possess the well defined wall oE either of these. The Heart. The patient often dies with all the symptoms of cardiac failure. But this is a notoriously unsatisfactoryterm, and at the autopsy there is usually nothing to be found except a pale, soft, flabby heart muscle with some dilatation of the chambers. There are no valvular lesions, and histologi cally there is little to be made out. Septic Bronchitis and Pneumonia. Secondary infection with one or other of the organisms associated with bron chitis and pneumonia is common, the streptococcus being the organism most frequently found. On section of the lung muco-pus exudes from the bronchi around which are areas of broncho-pneumonia. The combination of a septic broncho-pneumonia and the nodular fibrosis of silicosis may be confused with chronic fibro-caseous tuberculosis ; it is never safe to pass over the condition without microscopical investigation. Histologically the lesions resemble those of septic bron chitis and pneumonia in general, but mention must be made of the hypertrophy of the minute aggregations of lymphoid tissue in the bronchial wall which may be confused with early microscopic lesions of tuberculosis. Bronchiectasis. Dilatation of bronchi may supervene as a secondary result of the silicotic fibrosis. It is not very com- PATHOLOGY 215 mon and as a rule does not reach the stage of a fully devel oped foul smelling purulent bronchiectasis. Tuberculosis. Next to septic bronchitis and pneumonia, tuberculosis is the commonest sequela of silicosis. Indeed, so common and so intimate a part of the pathological picture is it that some miters have declined to admit that such a disease as simple silicosis exists, and have attributed the whole condition to a chronic form of tuberculosis. Silicosis accompanied by tuberculosis is often referred to as 'infective silicosis.' This form of the disease will therefore be treated separately. Carcinoma. Bridge and Henry 12 [ 1928 ] have proposed that cancer, in order to be classified as of industrial origin, should fulfil the following conditions : ( 1 ) The rate of in cidence in titer occupation under review should exceed that in the general population to a significant extent, and ( 2 ) in the occupation concerned there should be sufficient as sociation of the worker with a substance proved experi mentally to have carcinogenic properties. Suggestions have been made from time to time, notably in the case of the Schneeberg miners in Germany (Rostoski13 [1928] Schmorl14 [ 1928 ]) and again recently by Dible 15 [ 1934 ] in England that carcinoma of the lung is likely to supervene upon pneumoconiosis of long standing. The data we possess at the moment however are not sufficient to satisfy Bridge and Henry's postulates and we cannot do more than regard the association of silicosis and carcinoma ( and of asbestosis and carcinoma) with suspicion. The varieties of cancer found in association with silicosis are those found in intrathoracic malignant neoplasms in general (Gloyne16 [ 1930 ]) They are : ( 1 ) growths involving the mediastinal glands ( 2 ) growths involving the bronchi. The primary growth involving the mediastinal glands is a rapidly growing white tumour situated in the neighbour 2l6 SILICOSIS AND ASBESTOSIS hood of the bifurcation of the trachea and along the course of the two main bronchi. The glands become adherent to each other as they enlarge and coalesce into an irregular collar of growth surrounding the lower end of the trachea, the wo main bronchi, and the great vessels. For many years this type of growth was described histologically as a lymphosarcoma, but it is now generally regarded as a carcinoma, an oat cell carcinoma, by reason of its characteristic oval cells, though it is not clear from what part of the respiratory tract it arises. The deep layer of cells of the epithelial lining of the main bronchi has been suggested. The other type of malignant growth is more clearly bron chial in origin. It may arise in large or small bronchi and may be single or multiple. It needs to be carefully distin guished from the type of grotvth described above which has a predilection for the mediastinal glands. These primary bronchial growths extend along the bronchial wall pushing their way through the silicotic tissue as they grow. Ulcera tion and necrosis with cavity formation is common. This last point is important because the growth cavity may easily be confused with a pyogenic abscess or bronchiectatic cavity. Microscopic sections, therefore, should never be neglected. Histologically they are, for the most part, squamous cell car cinomata possessing the usual characteristics with prickle cell arrangement, keratinisation, and cell nest formation. The precise relationship of these tumours to the silicosis in the matter of causation is of course impossible to define. This subject will be referred to again under the heading of asbestosis and carcinoma where the pathological relationship has been worked out further. Silicosis and Tuberculosis If, when silicosis is accompanied by tuberculosis, the two pathological processes were always found side by side as they PATHOLOGY 217 are in silicosis and pneumonia, there would be little diffi culty in differentiating between the two diseases. Unfortu nately, this is not always so. The two are often intimately asso ciated in such a way as to produce what is tantamount to a separate disease. In theory, there are three possibilities in the inodes of onset and of progress : ( 1 ) the tubercle bacillus is already implanted in the lung before the silica exposure be gins, the tuberculous focus being either ( a) quiescent or (b) active; (2) the tubercle bacillus reaches the site as a secondary infection in a lung which has already become silicotic, the silica exposure (a) having ceased or ( b) be ing still in operation ; ( 3 ) the tubercle bacillus and the silica particles reach the healthy lung more or less simul taneously. This third possibility must be rare. The legal mind is very much alive to these possibilities and questions relative to them are frequently asked of medical witnesses in court. Unfortunately Nature does not always paint her patho logical pictures with an eye to these fine distinctions and we must be careful to distinguish between the post-mortem ap pearances actually found and the inferences drawn from them as to the mode of onset. For descriptive purposes we may classify the various findings of the post-mortem room into three main groups, though it will be realized that in ac tual practice the picture is not always so well defined: ( 1 ) silicosis with obsolescent tuberculosis ; (2 ) silicosis with open tuberculosis ; ( 3 ) tuberculo-silicosis. Silicosis with Obsolescent Tuberculosis. Three cardinal signs of obsolescent tuberculosis are generally recognisable : ( 1 ) dense pleural adhesions, especially in the upper part of the pleural sac tethering the apex of the lung to the apical pleura ; ( 2 ) fibrotic contraction and scarring of the visceral pleura and subjacent lung tissue without adhesions, again especially well marked at the apices ; ( 3 ) calcified nodules. In the presence of a chronic fibrotic disease of the lung such 4 2l8 SILICOSIS AND ASBESTOSIS as silicosis these signs are often difficult to interpret. Calcifica tion is probably the most reliable, but the South African pathologists have described small deposits of calcium in the silicotic nodule, and of course, calcification of non tubercu lous origin may take place in a vessel wall or around a foreign body. A calcified nodule beneath the pleura, or attached to the wall of a small bronchus, or in a mediastinal gland gener ally means obsolescent tuberculosis. If calcified deposits are found in the mesenteric glands, this fact may be taken as cor roborative evidence. Generally speaking, however, silicosis found in the presence of obsolescent tuberculosis does not present any unusual features. Silicosis with Manifest Tuberculosis. Frank active tuber culosis when it occurs is most commonly a terminal e\cnt. The following varieties are to be found : ( 1 ) pleural ef fusion, tuberculous empyema, or pyopneumothorax ; ( 2 ) old cavities, often multilocular, with fibrotic walls having silicotic nodules adjacent thereto or actually forming part of the wall; ( 3) rounded foci of caseous tuberculosis with a sharply defined black rim of compressed pigmented lung tis sue surrounding the foci; ( 4 ) miliary spread from an older tuberculous focus ; ( 5 ) tuberculous broncho-pneumonia ( which cannot always be distinguished from that due to other organisms without microscopic examination ). We have here a composite picture resulting from the invasion of the pulmonary tissues by two very different types of invaders. The one is an insoluble particle which reaches the distal parts of the bronchial tree but does not reproduce, the other is a parasite with a capacity for multiplication and for being lysed by the tissues. The former remains strictly bronchogenic in its spread, the latter soon reaches the blood stream and is dis seminated widely. This applies also to the next group, but to a less marked degree. - Tuberculo-Silicosis. It is convenient if not essential to have PATHOLOGY 219 a special term by means of which to designate a form of silicosis accompanied by tuberculosis in which the one disease is modified in association with the other. The term tuberculosilicosis is used in this chapter in this sense only. The modification is generally in favour of the tuberculosis, which is frequently of such a chronic fibroid type that it can not be recognised until histological examination is made. The first and essential feature is the excessive fibrosis. The second characteristic is the closely interwoven texture of the two disease processes, tuberculosis and silicosis, in contradis tinction to the picture seen in silicosis with manifest tubercu losis. The third is the tendency to calcification. Tuberculo-silicotic nodules vary a good deal in appearance as a result of the distribution of pigment, the silicotic portion being as a rule darkly pigmented and the tuberculous portions free from pigment. The result is that at least four different types of nodules may be recognized : ( 1 ) a nodule with a soft gray tuberculous centre and a pigmented silicotic periphery ( 2 ) a nodule with a darkly pigmented silicotic centre and a gray tuberculous periphery ( 3) a pigmented silicotic centre surrounded by a ring of small gray satellite tubercles ( 4) tuberculous and silicotic nodules side by side, the one compressing the other. These various types of nodules may result in the affected portions of the lung having a mottled or marbled gray-black appearance. ( Figure 5 ) Histologically the tuberculo-silicotic nodule has the fol lowing characteristics : ( 1 ) a tendency to be more irregular in shape than the simple silicotic discrete nodule, the foci running together more readily into composite nodules ( 2 ) collagenous fibres form only part of the nodule, the rest being caseous material (3) minute deposits of calcium are not uncommon (4 ) giant cells are few and generally lie just out side the nodule ( 5 ) tubercle bacilli are variable, the more caseous looking the nodule the greater is the likelihood of 220 SILICOSIS AND ASBESTOSIS Figure 5 Tuberculo-silicocic nodulation, the upper half of the photo micrograph showing caseous nodules, the lower a tuberculo-silicotic nodule with a caseating centre (x 80). finding them ; they should be searched for in the neighbour hood of the giant cell ( 6 ) lastly, small branches of the pulmonary artery may exhibit an obliterative thromboarteritis which may be mistaken for silicotic nodules. Of course, not all nodules found in a case of tuberculosilicosis exhibit these characteristics ; simple silicotic nodules and uncomplicated fibro-caseous tuberculous nodules occur. Kettle and Archer 17 [ 1933 ] have investigated some of the problems encountered in this disease, which are par ticularly difficult in Great Britain, where a low-grade tuber culosis with excessive fibrosis is common apart from dust hazards. They believe that the differential histological diag nosis depends upon the amount and distribution of collagen PATHOLOGY 22 1 in the tissue reaction. This is a matter of degree and they cannot define any delimiting standards. They suggest, how ever, that a chemical analysis for silica will often help when taken in conjunction with the other findings. In their ex perience an `ordinary dried lung- (amongst which may be in cluded uncomplicated tuberculosis) does not contain more than about 0.2 per cent of silica whereas in the tuberculosilicotic lungs they investigated, analyses up to 2.7 per cent were obtained. It goes without saying that a number of dif ferent portions of lung should be selected for analysis. ( Fig ure G ) Some Unusual Pathological Varieties of Silicosis The range of industries whose workers encounter free silica is a wide one and it is not surprising that certain forms of the disease should, from the pathologist's point of view, appear unusual. At least three of these call for special descrip tions. Silicosis in Coal Miners. This condition is occasionally re ferred to as anthraco-silicosis and is met with in a variety of forms in those parts of the coal field which show a silica risk. A great deal has been written on this subject and a distinction is not always made between pure anthracosis and anthracosis with silicosis. One of the best recent accounts is that of Cum mins and Sladden 18 ( 1930) dealing with miners in the Welsh coal field in the hard headings' of which silica dust is present. The outstanding feature of their cases was a lung showing deep black to dark gray consolidated areas on a background of chocolate coloured or gray aerated lung sub stance. The consolidated areas usually varied from small `maculae' in the lower lobes to large confluent areas in the upper. Histologically the characteristic appearances were a diffuse fibrous hyperplasia of the lung with massive dust "accumulation in the alveoli and lymphatics together with 222 SILICOSIS AND ASBESTOSIS Figure 6 Quartz particles from sumc-masnn's lung. Photographed with dark, ground illumination (xtaoo). ( Courtesy of Tubercle ) the occurrence of fibrous nodules, some of which showed little or no lamination while others were markedly laminated or whorled. Silicosis in Hematite Miners. Stewart and Faulds19 ( 1934 ) have described a set ies of cases in which both hematite and silica dust were present in large amounts in the lungs ( sidero-silicosis ) . The hematite found teas a ferric oxide producing a fine dry dust and gave to the affected parts of the lungs a bright red colour. The condition appeared to resemble closely the coal miner's lung in its histology, a diffuse or massive fibrosis with much dust accumulation and a few discrete rounded nodules of the usual silicotic type.' PATHOLOGY 223 In the one case the fibrotic areas appeared as bright red areas on a dark brown aerated lung background, in the other, the librotic areas were almost coal black on a background of chocolate coloured or gray aerated lung. Both these types of disease are of much interest to the pathologist and doubtless other similar conditions will in the course of time be de scribed. Broadly speaking there are two large groups of cases ( 1 ) one in w hich the free silica dust is preceded or accompanied by massive accumulation of a fine non-siliceous, non-toxic dust which acts chiefly in choking up the alveoli and the whole lymphatic drainage system of the lung, ( 2 ) a group in which the free silica is accompanied by a silicate which may have toxic and lethal properties of its own. (In this connec tion the writer is indebted to Dr.E.R.A.Merewether for a lung which shows the effects of exposure to free silica and asbestos.) Acute Silicosis. Of recent years a number of cases of socalled `acute silicosis' have been described, characterized gen erally by a short exposure to a siliceous dust and a rapidly fatal issue. The records have been collected and reviewed by Middleton-6 ( 1936) who gives the employment history of the largest group so far reported. In most instances there has been something unusual in the kind of dust to which the worker has been exposed. Often it has been a highly siliceous one mixed with an alkali or powdered soap for the manu facture of abrasive soap powders, and the suggestion has been made that a silica sol may be quickly formed in the presence of alkalis which is responsible for the rapid course of the disease. Descriptions of the pathology are still very meagre. The first autopsy record w'as that of MacDonald 21 ( 1930) and colleagues. They described the lower lobes of the lung as being solid, greenish-gray in colour somewhat resembling 2 24 SILICOSIS AND ASBESTOSIS marble, with innumerable tiny pinhead nodules of a lighter gray colour, whilst the upper lobes were still aerated but contained similar nodules. Microscopically there were large fibrotic patches which were practically acellular and were surrounded by small-celled infiltration. They found no histo logical evidence of tuberculosis and no tubercle bacilli. Kettle -- ( 1932 ) after examination of material from cases of acute silicosis considered that the sections showed `acute tuberculosis enhanced, no doubt, by the silica present.' Stuart McDonald21 (1932) recorded an example in which post-mortem examination revealed minute silicotic nodules in the lung not unlike miliary tubercles and strongn resembling the lesions of experimental silicosis in animals. Chapman 24 ( 1932 ) described a case in which the lungs, at autopsy, were about half the normal size, the middle twothirds being shrunken, fibrotic, and almost as hard as stone. Histologically the fibrotic nodules were found to have hyaline centres. Obviously the scanty nature of the pathological material available at present prevents our constructing a satisfactory picture of the pathology of the disease, and there is a danger of confusing the issue, as Kettle pointed out, with cases which are primarily acute tuberculosis. A distinction should be drawn between ( 1 ) workers who have had a very short but intensive exposure to siliceous dust but whose lungs, at au topsy, contain large and even massive patches of fibrosis re sembling those of the ordinary' chronic form of silicosis and ( 2 ) those with an equally short exposure but with miliary silicotic nodules resembling those of the experimental animal, as in Stuart McDonald's case. ( The natural life of the labora tory animal is short and therefore more strictly comparable with an acute than a chronic silicosis in man.) It might be best, at the moment, to confine the term acute silicosis to this I PATHOLOGY 225 second group. In any case it is inadvisable to include in the definition cases showing any evidence of tuberculosis, which can play such queer tricks in association with silicosis. ASBESTOSIS The word asbestosis was introduced into medical literature by Cooke25 (1927) and Stuart McDonald-6 (1927) to designate that type of pneumoconiosis induced by the inhala tion of asbestos dust. Several varieties of the mineral are used in industry, including chrysotile (white) crocidolite ( blue) and amosite, the first named being the commonest. A good account of the geology of the mineral is given in a monograph by Hall 27 ( 1930 ) . Naked-Eye Appearances In an uncomplicated case the pathological signs seen at autopsy are chiefly confined to the thoracic cavity, as follows. Pleurae. Old dense adhesions are common, and are nearly always sessile, producing in the end complete symphysis of the pleura ; the long pedunculated bands so frequently seen in tuberculosis are rare. Apical adhesions, however, occur and the interlobar fissures mar be completely closed. In the least affected portions the pleura retains its trans parency but as the disease ads ances it assumes a tvpical groundglass appearance and cscntuallv exhibiting stiff, yellosv and horn-like plaques some 2 to 3 inches in diameter. ( The older writers on non-industiial fibroid lung were conversant with this type of thickening and likened it to cartilage.) At the apices there may be definite scarring, but whether this is to be regarded as an insatiable sign of healed tuberculosis is doubtful. Here and there, generally near the apices also, the pleura may be thin over emphysematous bullae protruding from the lung. Lastly, covering and obscuring these signs of 226 SILICOSIS AND ASBESTOSIS old pleurisy are seen evidences of recent inflammation in the shape of reddish patches of lymph arranged in thin flat gauze like layers or as small shaggy processes. Occasionally little patches of recent haemorrhage may be seen, such patches be coming browner and darker with age. Displacement of the mediastinum is unusual. The changes seen in the parietal pleura are similar to those found in the visceral pleura, but less marked and the horn-like plaques are absent. Pleural effusion is rare, owing to the obliterative character of the disease. Lungs. The asbestos worker is generally a town dweller and therefore the pathological picture, like that of silicosis, is superimposed upon a certain amount of anthracosis which forms a background. This confusion between the two is how ever greater than in silicosis. The asbestosis lung is generally large and of increased weight, though as the disease progresses it may become con tracted from excessive formation of fibrous tissue. It does not collapse when the thorax is opened, and like fibroid lungs in general, is firm, tough, and dense. ( Figure 7 ) On section blue-black patches of irregularly polygonal shape about 14 to 14 inches across are seen ; they are hard and rough to the touch and are surrounded by a gray framework of thickened interlobular septa. This forms the typical unit of the asbestotic lung, corresponding to the silicotic nodule. In the upper lobe these polygonal areas are usually discrete with unaffected lobules lying between them. In the lower lobe they tend to run together and become confluent. En gorgement of the lung or an actual bronchopneumonia fre quently provides a deep red background for the blue-black polygonal areas. Much pigment and the blue-black polygonal patches of asbestosis are found in excess in the peripheral - portions of the lung immediately beneath the visceral pleura, Figure 7 The asbestosis lung. 4 228 SILICOSIS AND ASBESTOSIS exemplifying the `pleural drift' of the dust so common in pneumoconiosis. The interbronchial and other lymph glands of the middle mediastinal group which drain the lung, are intensely pigmented and fibrotic. The pigmented polygonal areas of asbestosis are roughly coincident in size and shape with pulmonary lobules, and if examined with a hand lens the cut ends of small bronchi, sometimes dilated, can be seen. The fibrotic nature of the lung is better appreciated when the specimen has been fixed. The pulmonary vessels and bronchi now show thickened walls and the cut ends stand widely open, but the writer has not seen a typical extensive purulent bronchiectasis such as is sometimes described in chronic fibroid lung of non-industrial origin. Occasionally the cut surface of the lung shows a honeycomb appearance due to the breaking down of alveolar structure analogous to the spongy emphysema described by Cummins and Sladden 18 in anthracosis. This is commoner in asbestosis than in silicosis. Cavitation without tuberculosis, such as is described by Cummins and Sladden in anthracosis, has not been found in these areas. Mediastinal Glands. The absorption of asbestos fibres into the mediastinal glands, is a much more difficult task for the lung than is the absorption of carbon or even small particles of free silica; but in the course of time the glands become small and hard with a thick fibrous envelope, and trabeculae are seen as white lines traversing them. When bronchopneu monia supervenes, they become secondarily enlarged and red dened. Other Organs. Apart from the complications and sequelae to be dealt with later, there are few naked-eye changes in other organs. As in silicosis the heart muscle may be thin, pale, and flabby, and the spleen hard and fibrotic, but there is little else of importance. l'ATHOLOGV 229 Microscopical Appearancfs The Asbestos Fibre find the Asbestosis Budx. The ns bestode lung is essentially n dusty lung. It contains in addition to the asbestos fibres and the bodies formed 1mm them, carbon pigment common to all town dwellers, jagged carbonaceous particles such as are present in coal miners' lungs, blood pigment, and metallic impurities of the asbestos dust which tend to accumulate in the neighbourhood of the asbestosis bodies. These various structures are apt to obscure the real causative factor, the asbestos fibre. If asbestos dust he ex amined with dark-ground illumination, it will be seen r. Figure 8 .\sbestotic lung showing the respirators bronchioles packed with asbestosis bodies, fibres and pigment ( x 360 ) . *3 SILICOSIS AND ASBESTOSIS Figure 9 Asbestotic lung showing reticular fibrosis of the ahoolar walls (x 150). consist of fibres of varying length mixed up with particulate matter of irregular shape and often of reddish colour, repre senting various mineral impurities. The fibres themselves are straight and highly refractive, and of course, vary in length according to the thoroughness with which the crude material has been broken up. They may extend across the whole field of the microscope or they may be no longer than an anthrax bacillus. They can even be broken up sufficiently small .0 make a suspension which can be inoculated intravenously into the blood stream of the rabbit without producing emboli. In the raw material the fibres are held together in thick, straight bundles which, when crushed, are split up into PATHOLOGY 231 smaller ancl smaller bundles, until eventually very fine fibres are obtained. Xo branching has been observed. Under darkground illumination the fibres appear to be brightly illumi nated like the filament in an electric bulb, and when verv thin base a bluish luminosity. They are readily distinguish able from the irregularly shaped silica particles of the silicosis lung. ! Figures S, 9 and io 1 The asbestos fibre is of a highly resistant nature, hence its use in industry. It will withstand heat, and is not clestroved In mineral acids. It has been stated that with high-powei magnification minute |x>res can be perceived in the fibre which render it capable of absorbing, to a certain extent, dyes Figure io Asbestos fibres (crocidolite). Photographed with dark ground illumination ( x 1200 ). 2J2 SILICOSIS AND ASBESTOSIS such as methylene blue. The writer has not been able to confirm this. The fibres are found in large numbers in the lungs. Their detection is readily achieved by destroying the surrounding lung tissue with concentrated sulphuric acid, but in ordinary stained sections the presence of these fibres is often obscured by other foreign particles. In the lung of man two types of tissue reaction take place. The one is the thickening of the fibre, as a result of deposition of iron-containing material along its course, to form the asbestosis body. The other is the cellular reaction to the fibre. The asbestosis body has had a curious history. In 1914 Fahr,-* demonstrating to the Medical Society of Hamburg specimens and photomicrographs of the lungs from a case of pneumoconiosis occurring in an asbestos worker, observed the presence in the lung of a large number of crystals and stated that similar structures had been seen in 1906 by Marchand and Riesel, who had speculated as to whether they were due to the inhalation of asbestos dust or were a haemoglobin derivative. No pictures are given in Fahr's communication, but it is probable that what Marchand and Riesel and Fainsaw was the asbestosis body. However, these descriptions at tracted little attention at the time and seem to have been for gotten. The next step came in 1927 when Cooke and Hill and Stuart McDonald:6 described certain `curious bodies' found in the lungs of an asbestos worker who had died in 1924. Cooke had previously recorded the case in 1924 but had not at that time mentioned these bodies. Cooke and Hill wrote of them as follows : 'They are yellowish-brown in colour and do not stain with the usual stains, but give the Prussian blue reaction. There is a uniformity in appearance, group distribu tion. and fructating heads that make one think of a fungus. The hyphae are verruciform and discoid, and definite spores PATHOLOGY 23:1 are seen.' Pathologists to whom the material was submitted suggested various possibilities, v h.. diatomaceae. casts of small cavities, particles of asbestos fibre that had become coated with colloidal matter, fungoid bodies. Later m the same year. Stuart McDonald, to whom post mortem material had been submitted from the same case bv C'.ookc. gave a fuller description of the bodies. He regarded them as foreign bodies associated with tiie asbestos and was satisfied that thev were neither vegetable nor animal in origin, and quoted another case of an asbestos worker in whose lungs he had found similar bodies. The lust illustrations were given by Cooke and Hill in their original description. Subsequently thev were depicted by Simson ( 192S') in autopsies of South African cases. His paper also included a micropiiotograph of the bodies pro duced experimentally in the lung of the guinea-pig bv Mav- logordato. the first occasion on which the bodies had been so produced. At this stage Stewart and Haddow 31 ( 19291 made the suggestion that tiie bodies should be called `asbestosis bodies.' a term which has now been generally adopted. Finally Gloyne J- ( 1929 ) showed in the following experi ment that the body consisted of an asbestos fibre coated with a substance soluble in a strong acid. A wet preparation of the bodies was placed on die stage of the dark-ground illumination microscope, and the position of a readily recognisable group of these bodies noted. Concen trated sulphuric acid was then run very gently under the cover slip, the bodies being kept under observation all the time. They began slowly to dissolve, and in the middle of the structure of each appeared a tvpical asbestos fibre. At the end of half an hour practically all the material of which the I>oclies were composed had disappeared. leaving only faint ghost-like 'outlines with refrnctile asbestos fibres within them. 2 34 SILICOSIS AND ASBESTOSIS The diversity in shape of the bodies makes it difficult to write a satisfactory description of them. The following sum mary comprises the chief points : ( 1 ) Marked variation in length ( 24 to Go microns ) and breadth ( 12 to 24 microns ). Gardner and Cummings ii record them as long as 27,0 microns in experimental animals. The short forms are sometimes in gested by phagocytes. ( 2 ) Golden-yellow colour. Gardner and Cummings have pointed out the resemblance in colour to haemosiderin deposits in tissue in which haemorrhage lias occurred. ( 3 ) Homogeneous structure. { 4 ) The central fibre. This can lie best seen by reducing the illumination. The fibre may sometimes be detected projecting beyond the body. (5) Xo differentiation with polarised light (Cooke and Stuart McDonald). ( 6 ) Tendency to be arranged in ir regular clumps and clusters. ( 7) Very early forms unseg mented ( 'sausage shaped' ) . ( 8 ) Later forms crenated. seg mented, or resembling a series of oval discs or beads strung together in necklace form. (9) Bulbous or pointed ex tremities ( or one bulbous and one pointed suggesting heads and tails'). ( 10) Generally quite straight, occasionally curved, very rarely S-shaped. When examined in a wet prep aration slight pressure on the cover slip will sometimes cause them to bend owing to the elasticity of the central fibre. (11) Forms seen `end-on' look like knobs or door-handles. Small secondary knobs and bosses sometimes seen thereon. The bodies do not stain with the ordinary aniline dyes, but according to Gardner and Cummings, Wright's blood stain gives them a `creenish cast.' They will also retain neutral red slightly, but these partial reactions cannot be called true staining reactions. Cooke and Hill and Stuart McDonald, in their original descriptions, noted that the bodies could be stained by means of the Prussian blue reaction, and Gloyne has shown that they become black on treatment with am- "momum sulphide. Haematoxylin, which also has an affinity I'ATHOLOGY 233 For iron, can be made to colour them to some extent, but it is more a deposit o[ stain than a true staining reaction. "With regard to their Formation, no such bodies have been found in crude asbestos or in asbestos dust, and it seems practically certain that they are only produced when the fibres gain access to thing tissues and remain there For a consider able period oF time. Gardner and Cummings showed that the golden-vellow material which covers the fibre contained iron, whilst Simson and Strachan put Forward the view that the iron-containing substance was of cellular origin. From a study of a large number of different forms of as' bestosis bodies, the present writer has endeavoured to build up a complete picture oF Formation from the original inhaled fibre. Figures n, to ii:i show deposition of some material on the fibres to a varying extent. When completely covered the body thus built up has a sausage-like form without any differentiation From end to end ( Figure 114) . These thick ened Forms next begin to show definite fissures ( Figures 11. to 117 ) . giving the appearance of incomplete segmentation at irregular intervals. In Figure it* this segmentation has advanced a stage further, the fissures now extending almost to the mid-line of the body and occurring at irregular intervals along its length. These fissures produce the appearance of a head or knobs at the ends ( Figures u,, and nlft) . As they become deeper and more numerous a completely but ir regularly segmented body results (Figure nu). When the fissures reach the straight central fibre they appear as ( a ) a small number of long segments as in Figures u,., to nls, or ( b ) a large number of short segments as in Figures 1 i!n to 1134. These short segments may be regular in sue and shape resembling beads on a necklace (Figures 11 n._, to nS4), or the segmentation may be complete at one end of the body and incomplete at the other. 3* # Jfc38 40 Ficlre 11 Stages of formation of the asbestosis bodies. ( Courtesy of Tubercle ) A V ! PATHOLOGY 2.i7 In this filial stage some of the segments op even small poitions break awa\ leaving bare lengths of lihve between the remaining segments i figures iu- to u;17;. Vers occasion ally these broken fragments can be actualh seen in the process of breaking away. This is well shown in Figures uSi and' ii;;. Bodies viewed end-on or obliquely are seen in Figures 1to 1 i4l. The asbestosis body would appear, therefore, to be formed I Krni the original fibre by a process of ( i ) deposition of some material around the fibre so as to thicken it; (2) fissure of this material giv ing rise to the appearance of seg ments ; and ( 3 } fragmentation or the separating off from the asbestosis body of fractured portions of the deposited ma terial. The central fibre having been satisfactorily demonstrated, the question arises, of what does the golden material consist which forms the segmented coating ? Iron certainly enters into its composition, for, as far as we know, all asbestosis bodies give an iron reaction. This metal is present in crude asbestos in varying amounts, but it is also present in haemoglobin. On the whole, the ev idence is in favour of the iron being de rived from the tissues -- probably from blood pigment -- but the point has not been conclusively settled, and it seems probable that the golden yellow substance is the product of a colloidal reaction between the fibre and blood protein. Asbestosis bodies have considerable power of resisting the ferments of the gastro-intestinal tract when swallowed with sputum and have been found in the faeces. They also resist heat. The effect of acids varies a good deal. In sections of lung tissue they resist decalcifying fluid, which contains -t\/n per cent of nitric acid, for several weeks. Concentrated sulphuric acid leaves only a mere semblance of a ghost-like body with a central fibre. Hydrochloric acid has the effect of bleaching the bodies ; the yellow colour is taken out almost immediately 238 SILICOSIS AND ASBESTOSIS leaving a colourless skeleton of the bodv, suggestive of a minute hyaline urinary cast. Nitric add has less effect and glacial acetic acid none. The bodies will resist 20 per cent caustic soda for twenty-four hours without losing their goldenyellow colour. They become black when digested with trvpsin. The inference from these reactions would appear to be that die asbestosis body consists of at least two portions sur rounding the fibre -- viz., an acid resistant material which forms a framework and gives the body the characteristic shape, and a golden-yellow pigment contained therein which is not acid resistant. The question now arises, what inference can be drawn from the presence of the asbestosis body ? Since these struc tures have not been found in any other disease, their presence is an indication of exposure to asbestos dust, whilst the fact that the bodies ha\e not been found in asbestos dust itself implies that their formation takes place in the body -- prob ably as a result of a colloidal reaction with the blood proteins in which the iron plays an important part. They have been found in the guinea-pig by different observers from seventy days to six months after exposure to dust. Simson has recorded the bodies in a human lung with a history of only two months' exposure. Lastly, can it be inferred from the presence of the asbestosis body that fibrosis necessarily exists in the lung ? The presence of the asbestosis body implies a tissue reaction to the fibre, but it does not necessarily follow that this reaction runs parri passu with the production of pulmonary fibrosis. On one occasion the writer found fine collagenous fibres in the tissues of a guinea-pig as early as twelve days after subcutaneous in oculation of asbestos fibres, but the amount was very minute. A heavy dose of fibres may be needed -- and even then years may elapse -- before pulmonary fibrosis is sufficient to be detected by physical signs or roentgenogram during life. It PATHOLOGY 239 would lie unsafe, therefore, to accept the presence of the ashestnsis body as undeniable evidence of librnsis ; all we can say at present is that the ashestnsis body is an expression of a tissue reaction to a foreign body acting as a benign irritant, and that fibrosis of an appreciable extent may or may not be a part of that tissue reaction. There is some e\ idence that asbestosis bodies are not formed with the same facility in all the tissues of the body. Thus they have not yet been described in the skin warts to which the workers are liable. The writer has examined with out success sections of a wart which teas known to have been present for many weeks, and has failed also to find them in r'. e skin of a guinea-pig seven months alter the asbestos fibres had been introduced into the cutaneous tissues. Dewirtz also does not make any mention of asbestosis bodies in sections of warts he examined from the skin of Moscow factory workers. Furthermore, even the lung varies in its reaction to asbestos in different animals. Gardner and CummingsJi (1931) record that the lung of the rabbit apparently offers a much less favourable environment for the production of the bodies than does the lung of man and of the guinea-pig. The rat also does not produce bodies readily, whilst Schuster( 1931 ) failed to find them in the lungs of a dog which had been kept on factory premises lor the purpose of ratting for several years, though fibrosis of the lungs was present. The Lungs. The tissue leaction to the asbestos fibre in the lungs depends parth on the non-absorbable character of the particle and patth on its silicate content. There is little leucocytic reaction, the cells chiefly concerned being the lin ing epithelium of the respiratory bronchioles and the large macrophage which is the striking feature of the cellular re action in many of the non-pyogenic pulmonary diseases. The bronchial epithelial cells do not phagocyte the asl>estos fibre. They are simply desquamated into the lumen of the tube as 24O SILICOSIS AND ASBESTOSIS a mechanical result of the irritant action of the fibre. The macrophages are identical with the so-called 'dust cells' of the lung and surround the fibre in an attempt to engulf it. Fre quently the fibre is too long to be completely engulfed and looks as though it was sticking into the cell with one end protruding, like a pin in a pincushion. Whether this is in all cases a true statement of facts is not quite certain owing to the liability of the long asbestos fibre to lie obliquelv rather than in one plane. ( Figure 12) In addition to these tissue phagocytes, asbestosis giant cells and fibroblasts are seen. The former are foreign body giant cells probable resulting from partial degeneration of small collections of the above-described large phagocytes which have Figure 12 .Asbestosis bodies (low power) in unstained section of lung (x 520) (Reproduced from article by W.Burton Wood and D.S.Page) (Courtesy of Tubercle) PATHOLOGY 241 lost all their envelopes. In early lesions, e.g. in the guinea-pig, the cytoplasm has a pigmented stippled appearance in con tradistinction to the almost structureless look of the tuber culosis giant cell. Sometimes the I'aint outlines of the de generated individual cells which form this composite 'cell' can he seen. The cell also varies considerable in si;e according to the number of phagocytes composing it. Finally, the nuclei of the asbestosis giant cell are large ancl less numerous than those of the tuberculosis giant cell and have not the same tendency to be arranged round the periphery. The fibroblast does not appear to differ in appearance in asbestosis from the fibroblast of other varieties of pneumoconiosis. It is found around bron chioles .and alveoli, in interlobular septa and in the subpleural connective tissue. ( Figure 13 j The trachea and main bronchi are little affected in asbes tosis. The bodies can be seen on the surface of the epithelium, having been carried there In bronchial secretion, and occasionallv they may be seen in the mucous or fibrous layer of the wall of the main bronchus surrounded by phagocytes and free pigment. The writer has not yet seen them actually in the tissues of the trachea. In the intra-pulmonary bronchi, from the point where they enter the lung to the point where they terminate in respiratory bronchioles, the most marked change is the desquamation of the epithelium, and lying amongst the desquamated epithelial cells asbestosis bodies, fibres and loose pigment are frequently to be found, often plugging the lumen. The basement membrane is thickened and the fibromuscular coat surrounded by a ring of collagenous fibres. The elastic fibres generally remain intact, but in some places they are found to be contracted together as though defi .ely increased and when ulceration takes place they may he found in the sputum. Asbestosis bodies may be found in any part of the wall. Gardner and Cummings :-'1 ( 1931 ) have shown by animal 242 SILICOSIS AND ASBESTOSIS Figure 13 The asbestosis giant cell showing phagocytcd asbestosis bodies and fibres (x 1200) (Courtesy of Tubercle) inoculation experiments, however, that the chief site of as bestos dust localisation is the respiratory bronchiole. In man. asbestos fibres, pigment, cellular debris, phagocytes and asbes tosis bodies -- the latter frequently in radially arranged clumps -- are all to be found choking the lumina of these tracts, blocking the narrow alveolar ducts, and filling the air sacs and alveoli. Lastly, around these distal portions of the bronchial tree and of the alveoli a fine network of collagenous fibres is formed, ultimately producing a generalised reticular fibrosis which is a distinguishing feature of the disease. When this diffuse fibrosis has reached an advanced stage all alveoli in the area may be compressed out of recognition. Whorled nod- PATHOLOGY 243 ules sudi as those of silicosis are rare but are occasionally found in these areas of advanced fibrosis. Asbestosis bodies are occasionally present in the proximal parts of the plexus of Umphatics around the smaller bronchi, and become more numerous towards the respiratory bronchioles and are plenti ful at the level of aheolar duc ts. The lvmphatics accompanving the branches of the pulmonary artery less frequently show asbestosis bodies or pigment. In the small lymph-nodes drain ing the 1 ung tissue asbestosis bodies as a rule are not plentiful owing to the difficulty the fibres encounter in entering the afferent ducts. The aggregations of lymphoid tissue in the walls of the small bronchi are hypertrophied. Changes in the vascular system are relatively unimportant, presumably because the toxicitv of asbestos is not marked. There may be an increase of collagenous fibres around branches of the pulmonary artery and asbestosis bodies may also be seen lying in the connective tissue between the artery and the wall of the bronc hiole. The capillaries are of course involved in the reticular fibrosis of the alveoli wall of which they are the chief constituents and may be compressed almost to the point of occlusion. The pulmonary venules are also in volved in this fibrosis. Lynch and Smith ( 1930) have re|>orted asbestosis bodies in the thrombi of veins. The Pleura. The surface of the visceral pleura is generally extensively denuded of epithelium, with patches of fibrin containing a few desquamated endothelial cells lying on the denuded surface. The subendothelial portion is much thick ened by the formation of collagenous fibres with many fibroblasts, and new formed blood-capillaries are numerous, especiallv in the deeper layers. Asbestosis bodies are scanty and tend to be short and stumpy -- probably the larger fibres do not penetrate so far -- and usually lie surrounded by con nective tissue in small groups. Fibres are also occasionally seen, singly or in sheafs. The elastic layer is generally intact. *' ! 1 / hi I 244 SILICOSIS AND ASBESTOSIS The interlobular septa may show ashestosis bodies, fibres and pigment with or without collagenous thickening. In two cases whorls of connective tissue resembling discrete silicotic nodules were found by the writer near the point where the septum joined the pleura -- which is the point at which the pulmonary deep lymph-vessels in the septum anastomose with the subpleural lymph-vessels. Histology of other Organs. H.L.Stewart, Butcher and Cole man 35 ( 1931 ) bas e found asbestosis bodies in the spleen. The present writer lias failed to find them in anv of the abdominal organs, even in the walls of the stomach nd in testines where swallowed sputum might conceivably carry the bodies. To summarise, the typical histological lesions of asbes tosis are three : (. 1 ) The pouring out of large macrophages into the most distal portions of the bronchial tree and of the alveoli to surround and as far as possible phagocyte the invad ing fibres ; ( 2 ) the formation of the asbestosis giant cell ; ( 3 ) a generalised reticular fibrosis surrounding the bronchi oles, alveolar ducts, alveoli and air sacs, capillaries and ven ules, the interlobular septa and pleura, ultimately resulting in a complete obliteration of all lung structure. Complications and Sequelae The chief complications and sequelae of pulmonary asbes tosis are as follows : -- ( a) Purulent bronchitis. ( b) Bronchopneumonia, which is best seen in the parts of the lung least affected with the asbestosis. This point is prob ably of importance because it explains why bronchopneu monia is such a fatal disease in asbestosis -- it puts out of action the last remaining functioning portions of the lung, (c) Pulmonary tuberculosis. In a series of 100 cases pub lished by Burton Wood36 (1934) and the writer, active I PATHOLOGY 243 tuberculosis was found in 21. The cases coming to autopsv ?_have been of the acute caseous type ( in one case with a gen eralised miliary spread), with few Langhans giant cells and no obvious sign of healing. Asbestos fibres, asbestosis bodies and tubercle bacilli have been found King side bv side in the caseous centres, but there is evidence in animal experi ments 1 Gardner and Cummings) that asbestosis nodies dis appear in caseous areas. I11 the series quoted above there was one case of pyopneumothorax with lardaceous disease follow ing treatment by collapse therapv. A number of cases of healed and obsolescent tuberculosis have also been found at autopsv. These are probably not more numerous than in post mortem work in general, but they indicate that the superven tion of asbestosis does not necessarily mean the lighting up of quiescent tuberculosis. ( d ) Empyema. In the series mentioned above there teas one case of tuberculous empyema. (e) Bronchiectasis. Dilated bronchi are occasionallv met with, but bronchiectasis with fusiform or cavity-like dilata tions containing foul pus have not been encountered bv the writer. ( f) Carcinoma has been found in 6 cases examined by the writer at autopsy. Until more statistics are available it is im possible to draw any very definite conclusions as to the rela tion of the two diseases. The points noted up to the present are (1)5 out of the G cases of carcinoma have been of the squamous variety, the sixth being an oat cell carcinoma ; ( 2 ) 4 out of the 6 have been associated with asbestosis which was fairly advanced and of long standing; ( 3 'i in. 4 cases the carcinoma consisted of an isolated nodule only : (4) the nodules were in the portions of the lung most affected by the asbestosis -- i.c. basal or peripheral : ( rt) 2 only showed ^ secondary growths, one in pericardium, thoracic wall, liver and kidney, the other in thoracic vertebrae ; (6 ) histologi- 246 SILICOSIS AND ASBESTOSIS cally the squamous carcinoma appeared to advance along the mucosa of the small bronchi, pushing aside the pigment, asbestos fibres and asbestosis bodies as it grew, whilst in the 1 case of oat cell carcinoma observed, the tumour grew out wards from a centre in a compact mass without any tendency to confine itself to prolongation along and infiltration of the bronchial mucosa ; (7) death occurred in 4 of the cases whilst the growth was still small (i.e. not more than 1 to 114 inches in diameter.) Clinical Pathology and Post-Mortem Examination Laboratory investigations of silicosis and asbestosis have been few. The following is a brief summary, and the reader is referred to text books on biochemistry for the more detailed account of silica estimations. Sputum. Patients usually produce very little sputum until the late stages of the disease when the material expectorated is often the product of intercurrent bronchitis and, owing to the excess of mucus, may be of small value. The sputum of asbestosis is more likely to yield helpful information than that of silicosis by reason of the asbestosis body. Asbestosis. The sputum is generally thick and mucoid -- frequently so thick that it resembles semi-coagulated egg albumin. In the latest stages small nummules of pus appear. The asbestosis body may occasionally be found by examina tion of a direct smear, but as a rule a concentration method is necessary for its detection. The one in general use is that originally devised by Stewart and Haddow J1 ( 1929). It is carried out as follows : -- About half an ounce of sputum is dissolved in an equal quantity of undiluted formalin, cen trifuged, the deposit washed and examined microscopically. This may be done by drying and fixing a direct smear of the deposit ( which need not be stained ) or by mounting a small PATHOLOCY 247 quantity under a cover glass as in examining a urine deposit. Stewartjr ( 1934) suggests that the occurrence of asbestosis bodies in clusters is indicative of tissue destruction in the lung sufficient to liberate the clusters from the small bron chioles in which they have been formed. Stewart and Haddow ( 1929) have also obtained the bodies by direct lung puncture, whilst the present writer has obtained them in faeces in a case in which it was believed that the sputum was being swallowed. Silicosis. Here there is no distinctive structure to fall back upon and the detection of particles of free silica by direct illumination and the ordinary microscopic technique is im possible. Burke '* ( 1933 ) has described a technique which unfortunately requires a larger amount of sputum for its per formance than is available in the great majority of instances. A large quantity of sputum ( 100 cc or more) is gently heated in a beaker until most of the water is evajxarated ; 30 cc of agua regia is then added and the mixture left at room tem perature for twenty-four hours with occasional shaking. It is then centrifuged at high speed for one hour, the deposit smeared on chemically clean slides and incinerated to a white or pale grey ash. This deposit is examined by polarised light for doubly refractile particles which are generally angular or needle-shaped and vary in size from 1 to 5 microns. These particles can be further identified as quartz by mounting in immersion fluids of known refractive indices. Blood. Schlomka and Nolte 39 ( 1933) have made blood counts and sedimentation rate estimations on a series of pa tients with silicosis. Their results indicate that this method of approach may be helpful in marking the onset of tuber culosis. They found that in various types of silicosis accom panied by tuberculosis the blood sedimentation rate was in creased, the total leucocyte count was higher and the propor- 248 SILICOSIS AND ASBESTOSIS tion of polymorphonuclear cells in the differential count was increased, when compared with the figures obtained in simple silicosis. King and Stautial 40 ( 1933 ) recoi'd methods of estimating the silica in the blood by a micro-determination technique of analysis developed from those used by chemists in estimatingsmall quantities of silicic acid in various natural waters. Briefly this consists in the reduction of a yellow silicomolvbdit acid complex to give a blue colour with aminonaphtholsulphonic acid, a blue colour being more accurately matched with a colorimeter than a yellow. The methods are too long and complicated for abstraction here and the original papers should be consulted. Both soluble and total silica are ex amined, the former with 2 cc and the latter with 5 cc blood. The authors state that there appears to be an absence of any insoluble particulate silica and of any organic compound of silicon in the bh. d so that the figures for soluble and total silica are approximately equal. Urine. King and Stantial40 have also applied the above methods to the estimation of silica in small quantities of urine, viz., 5 cc. Silica is a natural constituent of animal tissues and the de ductions which can safely be made in cases of silicosis call for a good deal of experience. King and Dolan 41 ( 1934) found that silica which was absorbed from the lung or other parts of the body into the blood stream was rapidly excreted in the urine. The elimination of silica in the sputum was higher than in persons having no silica exposure. Attempts made to influence the absorption of silica from the lungs by the administration of alkali were inconclusive. Comparing the blood silica content of non-silicotic and silicotic ]iersous (all of whom had tuberculosis ) King and Dolan were un able to detect any significant differences. The results obtained by these workers accord with those obtained with numerous PATHOLOGY 249 oilier biochemical substances in disease. There appeal's to lie a `tissue threshold' uhiili enables the hnd\ to maintain the constituents ol'tlie blood on a laiiIs even keel until the last stages of disease. Biochemical investigations. therefore, in the present stage of our knowledge do not help the clinician verv greatlv in assessing the functional capacitv of the silicotic or n.sbestotic lung, though thev are invaluable in all research nork oil the subject. Autopsies. The following details in the making of post mortem examinations in these cases have, in the writer's prac tice, been found worth attention. The lungs should be opened in such a manner that thev can be compared with the roentgenogram and the chest dia gram of physical signs made by the physician during life. It makes things unnecessarily difficult for those who have to assess compensation claims to find that the lungs have been cut to ribbons in all directions. The writer's practice is to place the lungs, with trachea and bronchi attached, on the operating table with their posterior surfaces uppermost and then to make serial horizontal slices, which can be replaced, from the mid-line of the mediastinum outwards to the pleura. If this operation can be postponed until the lungs have been hardened in formalin, so much the better. The natural tendency of the pathologist is to reserve the most diseased portion of the lung for histological examina tion. Whilst this is in general sound practice, the portion thus selected is often so altered by fibrosis or tuberculosis that satisfactory study is difficult. The portion of lung which, naked eye, looks least affected by the disease is often the best for microscopy. Here the silicotic nodules may be found lying in the midst of relatively healthy tissue and can be examined readilv. In cases of doubt a portion of interbronchial lymph gland should also be selected : if there are silicotic nodules anywhere in the specimen they are most likely to be found 25O SILICOSIS AND ASBESTOSIS here. A minimum o three sections should therefore be chosen, ( i) the most typical portion of advanced disease ; ( 2 ) the healthiest looking piece of lung, and ( 3 ) an interbronchial lymph gland. If possible ( 1) and ( 2 ) should in clude pleura, whilst portions of lung representing inter mediate stages are also selected as inquired in difficult cases. The writer uses a chest diagram similar to those employed by physicians and marks thereon the position of all portions of lung selected for histological study. Histology. In silicosis where the demonstration of the whorled nodule is all important, a good stain for the col lagenous fibre is essential. Xo doubt pathologists will differ on this point, but the writer has a strong preference for Van Gieson's stain. Reliance on a simple routine haematoxylin stain is liable to lead one astray, especially in tuberculosilicosis. The only safe rule is to stain three sections from each block of tissue with ( 1 ) haematoxylin and a good counter stain for cellular structure, ( 2 ) a collagenous fibre stain such as Van Gieson or Mallory and ( 3 ) Ziehl Neelson for tubercle bacilli. These rules apply with less force to asbestosis. A warning may be given, however, with regard to the resistance prop erties of the asbestosis body. In studying the microscopical picture of the different organs one error must be guarded against, viz., the assumption that the asbestosis ImkIv has been actually formed at the site in which it is found. Although these bodies probably do not easily migrate far. if at all. during life from the position in which they are formed, they are easily moved in dead tissues by various manipulations. Moreover, they are highly resistant to cleansing, and glassware should be carefully cleansed by concentrated sulphuric acid. In forming an opinion as to whether an asbestosis body has been actually formed where cit is found lying in the tissues the following points are help- PATHOLOGY 25 1 ful : (a) the presence of amorphous brown pigment, phagocytes and fibrous tissue around : ( b ) its relation to surrounding struc tures ( bronchiole, capillary, etc.) The car dinal point in die histology is tire liahilitv of the asbestos libre to be held up at the distal end of die respiratory bronchiole. Silica particles cannot be detected satisfactorily in ordinary sections mounted in Canada balsam and viewed with trans mitted light. With a mounting Huid of high specific gravity sudi as bromoben/ene, particles are more readily detected, but it is only by the use of crossed nicols in a petrological microscope that silica particles can be demonstrated with any certainty. Viewed in this wav the quartz particles stand out c learly on a dark background. For tire actual technique of tire petrological microscope the reader is referred to special min- eralogical textbooks. Irwin4-' ( 1934) has devised a simple method of micro incineration which enables the observer to detect silica par ticles in sit i in silica nodules in sections. After removal of the paraffin from the section ( which should not be more than j microns thick ) in the usual way. the slide is heated to 550- (ioo C. After cooling the incinerated section is mounted in concentrated hydrochloric acid covered with a coverslip and examined by direct illumination for quartz particles. A small furnace is needed for the incineration. The microscope slides vary a good deal in their resistance to the necessary heat and in the writer's experience there are a good many casualties in the way of cracked slides. The ash pattern obtained with silicotic nodules by this method is characteristic. A somewhat similar technique has been used by Schutz and Braun ( quoted by Siegmund and Kbppenhofer 1935 ). Dark ground illumination also has its uses. It may be em ployed with advantage to detect the characteristic asbestos fibres in wet or dried fibres of sputum and in sections. Sieg mund and Kbppenhofer have also used it in silicosis (quoting *5* SILICOSIS AND ASBESTOSIS it as the method of Timms ) but the present writer lias found so many pitfalls that lie has discontinued it. Extraction of Asbestos and Silica Particles from Lung. The extraction of asbestos fibres and asbestosis bodies from the cut surface of the lung is usually a simple matter. A direct smear on to a slide or a film from the centrifuged deposit of a little tissue fluid which has been expressed from the organ is usu ally sufficient. In the old stone-mason's lung, also, quartz par ticles can sometimes be obtained readily by removing a sub- pleural nodule with the point of a scalpel and compressing it between two slides. But in most instances silica particles are much more diffi cult to isolate. The best technique is that devised by Jones J ( 1933 ) for the isolation of sericite fibres and termed by him sliming.' Portions of the lung freed from preservative by preliminary washing are treated by gradual disintegration with strong nitric acid over a period of several days. The slime thus obtained is diluted about ten times with hot water and the mixture filtered through Xo. 54 Whatman's filter paper ( this is important, since from the ash of many filter papers minute fibres of cellulose which may cause confusion under the petrological microscope are detached). After repeated washings the residue is carefully dried (the fumes given off are inflammable) and the material ignited in the usual way. The light ash is removed with a mixture of bromoform and benzene in a Sollas separator and the minerals which sink to the bottom are washed with benzene, then alcohol, dried, and mounted on slides in Canada balsam. A petrological micro scope is necessary for the identification of particles. Chemical Analysis of the Lung. This is done by chemical assay of the wet or dry ash of the lung. In both cases it is necessary to remove the organic matter first. Jones recom mends the method of wet ashing (as described above for the ^examination of silica particles ) on the ground that a dry ash PATHOLOGY 2 o3 may contain a high percentage of constituents such as phos phoric oxide. sodium oxide. etc., which are removed by his wet ash technique. The majority of analyses have, however, been carried out by dry ashing. This consists in mincing up large slices of lung, drying at too until friable, powdering in a coffee mill, mixing and drying again at no', ashing a small portion ( e.g. to gms) in crucible, weighing ash and assaying it ( e.g. by gravimetric method of fusion with alkaline carbonates, precipitation oE silica by repeated treatment with hvdrochloric acid, ashing the precipitate and determining the true silica content of this ash by treatment with hydrofluoric acid ) ( Kettle and Archer 17 [ 1933 ]). King and Stantial fn ( 1933 ) have devised a micro-deter mination technique bv means of which small quantities ol tissue can be analysed ( about 1 gram fresh tissue or 0.29 grams pulverised dried tissue ) as in the case of blood and urine mentioned above. The advantages of using such a method are obvious in that they afford an opportunity of comparing areas of diseased lung by chemical and histological methods which the ashing of a large slice of lung does not. No hard and fast line can be drawn between the percentage of silica in the dried lung in silicotic and non-silicotic per sons, but probably it would be safe to put the upper limit for the non-silicotic lung at about 0.2 per cent. Silicotic lungs often yield analyses of 1 to 2 per cent. MM.IOGRAPHY 1. Silicosis. Records ol International Conference, Johannes burg. Aug. 13-27. 1930. 2. Mavrocordato.A.L. Silicosis. Records of International Con ference, Johannesburg. Aug.. 1930. 3. Jones,W'.R. Silicotic Lungs : The Minerals They Contain. ` J-Hyg.. 33:37- 193^- 254 SILICOSIS AND ASBESTOSIS 4. Drinker.P. and Hatch,T. Industrial Dust. McGraw Hill Book Co., New York. 1936. 5. Briscoe.H.V.A., Matthews.S.W.. Holt.P.F.. and Sanderson, P.M. Memorandum o Institution of Mining and Metallurgy, London, 1937. 6. Hill,L. The Ciliary Movement of the Trachea Studied in Vitro. Lancet, 2:802, 1928. 7. Irvine.L.G. Silicosis. Records of the International Con ference, Johannesburg, Aug.. 1930. 8. Gye.W.E. and PcRnv.W'.J. The Poisonous Properties of Col loidal Silica. Brit.J.Expcr.Path.3:75, 1922. Gye.W.F.. and Kettle.E.H. Silicosis and Miners' Phthisis. Brit.J.E\per.Path.3:24i, 1932. Kettle.E.H. The Interstitial Reactions Caused by Various Dusts and Their Influence on Tuberculous Infections. J.Path. Bact., 33:393. 1932. 9. Scndil'S.N., Bycden.A., and Brcc.e.T. Trans.Ceramic.Soc.. 35:167, 1936. to. Simsos.F.W. Silicosis in South Africa. Johannesburg, Oct.. 1930. Strachan,A.S. Silicosis in South Africa. Johannesburg, Oct.. 1930. Strachan,A.S. anti Simson.F.W. Silicosis. Records of Inter national Conference, Johannesburg, Aug., 1930. 11. Miller.W.S. The Lung. Balliere, Tindall fc Cox, London. l93712. Bridge,S.C. and FIenry.S.A. Report of the International Con ference on Cancer, London, 1928. John Wright and Sons, Bristol, 1928. 13. Rostoski.O. Report of the International Conference on Cancer, London, 1928. John Wright and Sons. Bristol. 1928. 14. Schmorl.A. Report of the International Conference on Can cer, London, 1928. John Wright and Sons, Bristol, 1928. 15. DibleJ.H. Silicosis and Malignant Disease. Lancet, 2:982, '93416. Gloyne.S.R. The Morbid Anatomy of Malignant Disease of PATHOLOGY Mediastinal Glands, Lungs and Pleurae. Tubercle, 12:54, 17. Kkiti.f.E.H. and Archi.r.H.E. Proc.Roy.Soc.Mcd.. Sect.Path., 2r,:i.V '93318. Ct mmins.S.L. and Sladoen.A.F. Coal Miner's Lung: Investi gation into Anthracotic Lungs of Coal Miners in South Wales. J.Path. Pact.. 33:1093. 1930. ig. srtwART.M.J. and Fallon.J.S. The Pulmonary Fibrosis of Haematite Miners. J.Path.Bact.39:233. 193}. 20. Midm.hon.E.L. Industrial Pulmonary Disease Due to the Inhalation of Dust. Lancet 2:1. 193G. 21. MacDonai u.C.. Piggott.A.P.. and Gildkr.F.W. Acute Silicosis with Suggested Theory of Causation : Two Cases. Lancet. 2:84b. 1930. 22. Ki:tti.f.E.H. The Pneumoconioses. Lancet. 2:344. 1932. 23. Mt:Dov\t.o..S. Distussion at Section on Pathology, Meeting of Brit.Med.Assoc. Lancet. 2:34(1. 1932. 24. CHAr.\rA\.E.N. Acute Silicosis. J.Amer.Med.Assoc., 98:1439, '932. 23. CIookk.W.E. Pulmonary Asbestosis. Brit.Med.J., 2:102}. 1927. 2(>. McDonai.i>.S. Histology of Pulmonary Asbestosis. Brit.Med. J.. 2:1023, 1927. 27. Hai.l.A.L. Asbestosis in the Union of South Africa. Pretoria Govt. Printer. 1930. 28. Fahr.T. A.sbestosis-Pneumoconiosis. Munch Mcd.Woch., 61: 625. 1914. 29. Cooke.W.E. and Hii.l, C.F. Pncumokoniosis Due to Asbestos Dust. J.Roy.Micr.Soc., 47:232, 1927. 30. Simson.F.W. Pulmonary Asbestosis in South Africa. Brit. Mcd.J., 1:883, '928. 31. Stewart.M.J. and Haddow.A.C. Demonstration of the Pe culiar Bodies of Pulmonary Asbestosis (Asbestosis Bodies) in Material Obtained by Lung Puncture and in the Sputum. Jf.Path.Bact.32:172, 1929. 32. Gloyne,S.R. Presence of Asbestosis Fibre in Lesions of As bestos Workers. Tubercle. 10:404. 1929. [i 256 SILICOSIS AND ASBESTOSIS 33. Gardner,L-U. and Cummisgs.D.E. Studies on Experimental Pneumoconiosis; VI. Inhalation of Asbestos Dust; Its Effect upon Primary Tuberculous Infection. J.Ind.Hyg.. 13:63 & 97' 193134. Shlster.N.H. Pulmonary Asbestosis in a Dog. J.Path.Bact., 34:75- '93133. Stewart.H.L.. Bi tcher.C.J.. and Coleman.E.H. Asbestosis; Two Cases. Arch.Path., 12:909, 1931. 36. WoodAV.B. and Gloyxe.S.R. Pulmonary Asbestosis : A Re view of One Hundred Cases. Lancet, 2:1383. 1934. 37. Stewart.M.J. Concentration Method for the Demonstra tion of Asbestos Bodies in the Sputum. J.Tech.Methods, 3:7' *93438. Burke,H.E. The Detection of Mineral Panicles in the Spu tum in Silicosis. J.Ind.Hyg., 17:27, 1933. 39. Suhlomka.G. and Nalte,F.A. Hematological Studies of In dustrial Silicosis. Klin.Woch., 14:987, 1935. 40. Kinc.E.J. and Stantial.H. The Biochemistry of Silicic Acid. I. Micro-determination of Silica. Biochem.J., 27:990.1933. 41. Kinc.E.J. and Dolan,M. Silicosis and the Metabolism of Silica. Canad.Med.Assoc.J., 31:21, 1934. 42. Irwin,D.A. Micro-incineration as an Aid in the Diagnosis of Silicosis. Canad.Med.Assoc.J., 31:140, 1934. 43. Siecmcnd.H. and K6ppenhofer,G.F. Studies in the Patho genesis of Silicotic Tissue Changes. Parts I, II, and III. Arch. Y4 ' f.Gewerbepath.u.Gewerbehyg.6:1, 18, and 38, 1935. I { V. KXPFR1MKNTAL PATHOLOGY Leroy L'. Gardner. M.l). DIRECTOR. SARANAC LABORATORY FOR THE STL DY OF Tl BERCI LOSIS F. X P E RIM F. NTAI. PX F. V M OC.O NIC) S ES It was once maintained that silicosis, the best known form of pneumoconiosis, could not be studied by experimental methods for it was a chronic disease which took years to evolve and was commonly complicated by the most chronic manifestations of an infection like tuberculosis. However, experience has demonstrated the fallacy of this contention. With pure silica it has been possible not oniy to rtj loduce tissue changes that simulate the lesions of human silicosis in several short-lived species but to demonstrate that such changes alter native susceptibility to tuberculous infection. It has been necessary to curtail the essential factor of time but this has been largely compensated by exaggerating the reciprocal factor of dosage. While this necessary adjustment may have produced some distortion of die resultant lesions so that they are not always identical with those in human sili cosis, the same kinds of cells participate in the reaction and the type of tissue change is the same. ( Figure i, a k b) All of these effects are specific and cannot be produced with nonsiliceous materials. On the other hand, the mixed dusts, com posed of silica and other minerals, which apparently cause silicosis in different industries have not uniformly excited comparable reactions in animals. In searching for an explana tion for his apparent failures, the experimentor is beginning to discover principles which may be much more important than his successful reproduction of silicosis with pure silica. It would now appear that the non-siliceous components of a mixed dust are not merely inert diluents of the silica but 257 FlGl'RE 1 a. Vertical section lungs of white rat. Inhaled pure chalcedony 9 months, then normal atmosphere 5 months. 1>. Detail of above. Note marked swelling of collagen. EXPERIMENTAL PATHOLOGY 259 that they exert specific effects upon the silica either in the atmosphere or after it has been inhaled. Evidence is accumu lating from various sources to indicate that some types of mineral particles may accelerate the action of silica on the tissues ; others may retard it or perhaps prevent its inhalation from the atmosphere. The conditions governing such modi fications ha\e not been defined but the experimental methods now developed offer a means of attack.. Certainly a silicosis that develops with unusual rapidity should be capable of experimental reproduction. The limitations imposed by the span of life in small animals may preclude a complete evalu ation of inhibitory effects. Nevertheless experiments should point out principles which govern reaction to various com binations of dusts and they may disclose the manner in which silica injures the tissues. Other forms of pneumoconiosis have not been studied so thoroughly. The lack of significant degrees of reaction to non- siliceous clusts has been sufficiently well established to assert with a reasonable degree of certainty that the pneumoconi oses of this class are essentially pigmentations with little or no effect upon respiratory function. Finally, there is the group oE conditions caused by silicates, which Badham designated as `silicatoses.' Only one of these, asbestosis, which may be produced by several of the fibrous silicates, is generally recognized as a disease. Its early manifestations have been reproduced in animals but the evolution of its more advanced phases still awaits demonstration. The evi- lence of other forms of silicatosis is largely roentgeno- graphic. Experimental studies with this group of minerals have thus far yielded nothing to support a belief in their capacity to provoke progressive fibrosis. The basic facts that have already been discovered in an intensive study of man in various dusty environments and tire reliable methods of procedure now in possession of the 2fa> SILICOSIS AND ASBESTOSES experimentor offer hope that in time lie may be able to answer tiie perplexing questions that still enshroud the re action to all kinds of inhaled dusts. With these general considerations in mind the achieve ments of the experimental pathologist can now be examined. Much of his work remains to be done ; some of it will have to be repeated because of the discovery of certain pitfalls of which he was not aware in his earlier efforts. But many of his observations are undoubtedly sound and can be used as the basis for further investigation. Experimental Methods The experimentalist has a variety of methods at his com mand. Obviously the most satisfactory way to study the effect of inhaled dust is to make animals inhale it. This procedure is expensive, time-consuming and requires very special equip ment but it constitutes the only means by which the effect upon the lungs of atmospheric suspensions of dusts or mix tures of dusts can be determined. It permits investigation of the physical properties of such dusts as they exist in the atmosphere. It allows the protective mechanisms of the upper respiratory tract to come into play and to admit or exclude the different components of a dust from the lungs. It per mits the foreign particles to accumulate slowly and without gross trauma to the tissues and it does not interfere with the natural mechanisms of elimination. In fact the inhalation method is die only one to demonstrate decisively whether a given kind of dust suspended in the atmosphere will injure the lungs. All other methods merely indicate whether particles of a certain composition are capable of producing reaction in the tissues. They are most useful in eliminating the substances which are not irritating and which consequently do not need 'further investigation. Based upon the injection of aqueous EXPERIMENTAL PATHOLOGY 201 or saline suspensions of particles, tiiey have the advantage ol being easy to perform, ol requiring no special apparatus and of producing results in relati\cl\ short periods ol time. All of them are subject to the one fundamental objection that they test the action ol an aqueous rather than an air-borne suspension of pat: lies and it is note known that the prop erties of such suspensions are no., necessarily identical. With proper precautions this objection may not he particular!;, serious as long as pure substances are being tested. In dealing with mixtures of harmful and benign minerals exclusive re liance upon injection techniques may lead to false conclu sions. Many of the proposed procedures are also unsatisfac tory because such ovi-whelming doses of the substance under investigation arc injected that confusing non-specific infiatummorv reactions are produced. This is particularly true when the particles are introduced iirectly into the organ where their effects arc to he observed. In most instances the test organ is not the lung but this is probably of no moment for experience has demonstrated that free silica and all noilsiliceous minerals in {mrticuliUe form have the same effect upon connective tissues regardless of the organ in which they are located. Apparent exceptions are the fibrous sili cates known collectively as asbestos, which seem to exert their specific action only in the lungs. In spite of these ob jections. injection methods Inve their place and the ones which are technically satisfactory have contributed materially to the solution of the pneumoconiosis problem. One injection test. (Gardner and Cummings' 1933) 1 in the writer's opinion obviates the non-specific effects that have been mentioned and results in localization of particles by physiological mechanisms. It is based upon repeated in travenous injections of small fractional doses of particles suspended in physiologic salt solution. Full grown rabbits are injected by ear vein with one gram of particles, 1 to 3