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FILE NAME: Talc (TALC) DATE: 1960 DOC#: TALC221 DOCUMENT DESCRIPTION: Book Excerpt - Talks from Symposium on Industrial Pulmonary Diseases in 1957&1958 INDUSTRIAL PULMONARY DISEASES A Symposium held at The Postgraduate M edical School o f London 18th-20th September, 1957 and 25th-27th March, 1958 EDITED BY E. J. KING, M.A., D.Sc., F.R.I.C. Postgraduate Medical School o f London and C. M. FLETCHER, C.B.E., M.D.(Cantab.), F.R.C.P. Postgraduate Medical School of London W ith 98 Illustrations LITTLE, BROWN AND COMPANY BOSTON t Library W rW feSiW <ap c a u f o h # *# day A ll R ights R eserved This book is protected under the Berne Con vention. It may not be reproduced by any means, in whole or in part without permission. Applica tion with regard to reproduction should be addressed to the Publishers. J- & A. Churchill Ltd., 1960 Printed in Great Britain CONTENTS i IIAI'TER PAGE 1 Industrial Pulmonary Diseases in Great Britain--A. Meiklejohn 1 2 The Pathology of the Pneumoconioses-- J. Gough and A. G, Heppleston 23 Reaction of the L ung to D ust--E. J. King and C. V. Harrison 37 I Deposition of Dust in the Lungs: a Physical Process-- C. N. Davies 44 T A Review o f Theories o f Silicosis-- G. Nagelschmidt 59 (< Problems in Taking and Reading Chest R adiographs-- G. Simon 69 / Radiological D iagnosis o f Pneumoconiosis-- C. M . Fletcher 72 a Radiography in the Field--P. J. Chapman 78 '> Normal Lung F unction and its M easurem ent--P. Hugh-Jones 94 in I he D isturbance of Pulm onary Function in Industrial Pulm onary Disease--J. C. Gilson 110 II The Use of Pulm onary Function Tests in Epidemiological W ork-- C. B. McKerrow 127 I,' Pneumoconiosis in Cornw all--L . W. Hale 139 I * Iron and O ther R adio-O paque D usts--A. I. G. M cLaughlin 146 l l Pneumoconiosis due to Tin Oxide--A. John Robertson 168 Iv The Epidemiology of Byssinosis--R. S. F. Schilling 185 I(>, An A pproach to the Problem o f Bronchitis in In d u stry : Studies in Agricultural, Mining and Foundry Communities-- /. T. T. Higgins 195 l /. O ccupational Lung Cancer--Richard Doll 208 I v Epidemiology of Coalw orkers' Pneumoconiosis--A. L. Cochrane 221 Vili CONTENTS CHAPTER 19. R heum atoid Disease and Pneum oconiosis-- Anthony Caplan PAGE 232 20. The N atural History and M anagement of Coalworkers' Pneum oconiosis--J. Donald Ball 241 21. T he Prevention o f Silicosis-- Donald Hunter 255 Index 271 V 1 Nl I hi h In" I M. ,11 Hi l l . Jli II 11II I . I 1 |.|( ir.r ill |H tMI 'lH Wfl li.ihMull I III' lIlM'IIM |i i l m M u n c H nlilllrli. i rul l i V III in i iipnii< hi S iiHimm ir il. Irsciil .lini pallini piii'iimiiiiia il l*l'A* olii hIIh I'i Io IH' 111 >ih i r i li itimi minili ai i indili).' Ila- llill)!`i, lively dilli ni hai s I lpai lumini h pa l i i ` !il`> dn i o 11a M a n i ai i ai l i n K CHAPTER 2 THE PATHOLOGY OF THE PNEUMOCONIOSES By J. Gough and A. G. Heppleston Department o f Pathology, Welsh National School o f Medicine, Cardiff K discussing the pathology of the pneumoconioses it is essential to dr,imguish asbestosis, a variety which is caused by minerals with a libious structure, from those varieties due to particulate, non11Imms minerals, such as silica, coal and haematite. Numerically dii second group is the more important and will be considered first, hiking as types classical silicosis and coalworkers' pneumoconiosis, . ,n h of which assumes a simple and a massive form. Simple Pneumoconiosis By simple pneumoconiosis is meant the pulmonary reaction to dir,i uncomplicated by any other factor and the term thus refers to dir essential manifestation of the disease. Characteristically it takes iln form of numerous, small, focal lesions composed basically of dir.i and fibrous tissue in various proportions. These lesions are discrete and measure up to about 5 mm. in diameter; they are more a less evenly scattered throughout the lung substance, but may be "inewhat larger and more numerous in the upper than in the lower p Mis. To appreciate the mode of development of dust lesions i, In cnee must be made to the normal anatomy of the respiratory I'.hlion of the bronchiolar tree. The terminal bronchiole, that is the lo .i order of nonrespiratory bronchiole, gives rise to three successive oid, is of respiratory bronchiole (i.e. those bearing alveoli) before iln ingle order of alveolar duct is reached; the alveolar ducts then l, id lo atria and alveolar sacs (Heppleston, 1953). Dust deposited in du .dveoli is ingested by phagocytes which attempt to eliminate the die.i up the bronchiolar tree or to transport it to the lymphatic .iiiii. Dust may also move along airways and into the interstices ,'i die lung as free particles, but evidence of this is not easily lii.lined. Small accumulations of dust are found in relation to the 24 J. GOUGH AND A. G. HEPPLESTON intrapulmonary lymphoid tissue, situated along the peribronchial, periarterial and perivenous lymphatic channels, but a considerable concentration of dust occurs in the hilar lymph glands. It is some times contended that dust accumulation, with its associated fibrosis, in the hilar glands causes lymph stasis and thus leads to retrograde parenchymal accumulation of dust, but the evidence from both man (Simson, Strachan and Irvine, 1931) and animals (Heppleston, 1954b, 1958) contradicts this view. The typical dust foci, however, are situated in relation to respiratory air passages and they develop, both in man and in animals, because there are too many phagocytes to be evicted by the bronchial route and they therefore become trapped in the alveoli opening into and surrounding respiratory bronchioles (Heppleston, 1954a, 1954b). A physiological block evidently exists where respiratory bronchioles, i.e. alveolated air passages, join the nonrespiratory bronchiole. The subsequent course of events is determined by the nature of the dust, those containing a high proportion of free silica leading to the development of a specific lesion, the classical silicotic nodule, and dusts which contain little free silica, such as coal, to the formation of a quite distinct but equally characteristic dust lesion. Simple Silicosis The simple silicotic nodule develops in relation to the respiratory bronchioles. At an early stage a fibroblastic reaction appears in the dust cell aggregates and eventually progresses to the formation of one or more islets of acellular fibrous tissue, which is often hyaline and arranged in a whorled fashion. In the fully developed classical silicotic nodule, these islets are enclosed by a zone of concentrically arranged and rather cellular fibrous tissue, around which there is an external zone of irregularly disposed connective tissue (Simson, 1935; Belt, 1939). Incinerated preparations, seen by dark-field illumina tion, show a typical ash pattern. The central islets contain a variable amount of finely dispersed dust, but the concentric zone is totally or largely devoid of particles, while a distinctive halo of dust lies in the external zone (Belt, 1939). Increasing exposure to siliceous dust results in the enlargement of existing nodules and the development of new ones. Thus, in the simple silicotic nodule the amount of dust is overshadowed by the large amount of fibrous tissue, which possesses a characteristic disposition. It is important to note that the air spaces surrounding the fully developed nodule are often of THE PATHOLOGY OF THE PNEUMOCONIOSES 25 normal size (Heppleston, 1947, 1951). The question of emphysema in simple silicosis is discussed later. The proximate mechanism by which free silica induces fibrosis is still undecided, though some surface property is probably involved. For many years the silica solubility theory has been in vogue, but the idea that solution of silica in body fluids mediated the fibrosis was called in question by Gardner over twenty years ago when he pointed out that certain silicates, though more soluble than quartz, were not so fibrogenic (Gardner, 1934). King, Zaidi and Nagelschmidt (1956) have lately drawn attention to the inconsistencies of the silica solubility theory with the pathogenesis of silicosis. Once silicotic fibrosis has developed, hyalinization often follows and for this secondary process of hyalinization an immunological mechanism has been suggested. Pernis has demonstrated that silicotic hyaline tissue differs in its chemical constitution from other hyaline connective tissues o f physiological or pathological origin. These true hyaline connective tissues are composed of approximately 80% collagen and 20% globulin, whereas silicotic hyaline contains only 40% collagen, the remaining protein being a globulin with a position between the serum /?- and y-globulins. Silicotic hyaline also con tains more carbohydrate and much more lipid than ordinary hyaline connective tissue. In all these respects silicotic hyaline resembles amyloid (Vigliani and Pernis, 1958). There is presumptive evidence of an immunological mechanism in the genesis of amyloid (Vazquez and Dixon, 1956), and Pernis etal. (1957) have now demonstrated immunologically the presence of a serum globulin lying in the fi-y zone in the hyaline tissue of silicosis. These observations emphasise the role of the host in the genesis of silicosis and raise the possibility of a relationship to the so-called collagen diseases. Simple Pneumoconiosis in Coalworkers The simple dust lesion of coalworkers has three distinguishing features, a large amount of dust, a small amount of irregularly disposed fibrous tissue and frequently the presence of enlarged air spaces in and around the dust foci, that is focal emphysema (Gough, 1940, 1947; Heppleston, 1947, 1951). In all these regards the dust lesion of coalworkers contrasts with the silicotic nodule. To under stand the precise structural changes in coalworkers' simple pneumo coniosis recourse must be made to serial sections. These clearly show (a) that the lesion is in effect a fairly wide sleeve of vesicular 26 J. GOUGH AND A. G. HEPPLESTON tissue consolidated by dust and a little fibrosis disposed around the respiratory bronchioles, especially those of the second order, and (b) that it is these same respiratory bronchioles which dilate to pro duce the state known as focal emphysema (Heppleston, 1953). The appearance of these dust lesions in random histological preparations varies according to the plane of section. When this is transverse the lesion has a typically stellate outline with dilated air passages running through and surrounding the dust, whereas in longitudinal section the respiratory bronchioles are outlined in their tree-like form. By cinephotography of serial sections it is possible to trace the continuity of air passages in transverse, oblique and longitudinal planes, so reconciling the different appearances as manifestations of the same fundamental structure (Heppleston, 1955). The degree of focal emphysema varies widely from case to case and is sometimes so severe that alveolar ducts and sacs are compressed by the grossly dilated respiratory bronchioles. It is, however, important to recognize that the radiological features of simple pneumoconiosis in coalworkers are due to the dust itself plus the small amount of fibrous tissue and that chest X-rays reveal neither the existence nor the degree of focal emphysema (Gough, James and Wentworth, 1949). The composition of the dust generated in the various opera tions entailed in mining coal must vary considerably. Hicks and Nagelschmidt (1943), for instance, found that in the rock strata adjacent to and sometimes dividing the coal seams in certain Welsh collieries the quartz content varied from 8% to 46% of the total minerals, yet in our experience all coal-face workers develop the same focal type of lesion. Moreover, simple pneumoconiosis in coalworkers shows identical features irrespective of (a) the rank of coal worked, whether anthracite, carbonaceous or bituminous and (.b) the coalfield, whether British or American (Heppleston, 1947, 1951). Because airborne coal dust contains a little free silica, with a mean value less than 2% in South Wales (Nagelschmidt, 1943), this fraction has been regarded as the essential cause. If this were so the pure dust lesion of coalworkers would be expected to show some morphological resemblance to the classical silicotic nodule, that is the specific lesion caused by free silica. But, as already indicated, no such resemblance exists and we therefore believe that the simple dust lesion of coalworkers is a nonspecific reaction to the major fraction of the dust which is devoid of free silica and whatever the THE PATHOLOGY OF THE PNEUMOCONIOSES 27 isssr silica contributes is inconspicuous and non-specific (Heppleston, SI J. Crucial evidence supporting this conclusion was provided by a nom an exposed for five years to carbon black, a highly purified of carbon, and a man employed for 18 years in the manufacture j carbon electrodes. The simple dust lesions in these two individuals m no way differed from those in coalworkers, as Rrittner, Bovet and itafttermaur (1952) also found in the case of a graphite miller, who had been exposed to a dust with the remarkably low ash content of iMB50 and whose lung ash contained no quartz. From this it may ' he concluded that free silica is not necessary for the development of the pure dust lesion in coalworkers and that this form of pneumo coniosis represents the effects of simple mechanical accumulation of i sufficient amount of dust irrespective of its nature. The mechanics of focal emphysema is most easily interpreted on (Sae basis of imbalance between the forces of inspiration and expira tion (Heppleston, 1954a). As already shown, the simple dust lesion r f coalworkers is in effect a fairly wide cylinder of vesicular tissue consolidated by dust and a little fibrous tissue, disposed around the respiratory bronchioles. Dust consolidation prevents expansion of this vesicular tissue under the traction of inspiration and the tension normally expended on these alveoli is evidently transmitted to the respiratory bronchioles as an addition to the inspiratory force to hich they are normally subjected. A more important consequence of dust consolidation appears to be atrophy of the bronchiolar smooth muscle upon which expiratory contraction and shortening of respiratory bronchioles depend. These movements will therefore be diminished or abolished. Such interferences with the bronchiolar movements, both inspiratory and expiratory, will combine to produce die same effect, namely permanent dilatation, that is focal emphy sema. The simple silicotic nodule, although it develops in the same situation as the focal dust lesion of coalworkers, does not lead to focal emphysema as defined above because it is a progressively expanding lesion, which indents and actually narrows respiratory bronchioles and at the same time counteracts the increased inspira tory traction produced by simple consolidation of vesicular tissue around respiratory bronchioles. Sometimes, however, the air spaces around silicotic nodules are emphysematous, but this enlargement is distinct from focal emphysema in that it affects any air space adjacent to the nodule and not particular segments of the airway. Emphysema with this irregular distribution may be attributed to 28 J. GOUGH AND A. G. HEPPLESTON fibrous retraction after growth of the nodule ceases, which may not be for years after cessation of exposure to siliceous dust. Lesions fundamentally similar to those occurring in coalworkers are found in haematite miners, coke workers, graphite workers (Gloyne, Marshall and Hoyle, 1949) and boiler scalers (Harding and Massie, 1951). In all these occupations the dust, like coal, has a low free silica content and it is therefore reasonable to conclude that they share a common pathogenesis. Comparable lesions also occur in some foundry workers (McLaughlin, 1950). Massive Pneumoconiosis Massive lesions in coalworkers (Gough, 1940, 1947; Heppleston, 1951) consist of dust irregularly mingled with bundles of coarse, hyaline collagen fibres and tend to occur mainly in the upper parts of the lung. Blood vessels and air passages are inconspicuous, but the previous existence of arteries and arterioles in massive lesions is shown by the persistence of internal elastic lamellae after the lumina have been partially or totally obliterated by an invasion of fibrous tissue accompanied by dust-laden cells. The massive lesions of silicosis are distinguished by the typically nodular arrangement of the connective tissue, numerous nodules being matted together by fibrosis. Caseous areas may be found in massive fibrosis but they do not always show conclusive histological evidence of tuberculosis. A tuberculous element is often recognized to participate in the production of silicotic massive fibrosis (Simson and Strachan, 1935; Gardner, 1940; Strachan, 1947) but the aetiology of massive lesions in coalworkers has long formed a matter for dispute. It has been maintained that dust alone is sufficient for this purpose but James (1954) adduced several reasons which render this view most unlikely. Simple pneumoconiosis is symmetrical and, if massive fibrosis was due only to dust, both lungs should be equally affected, but this is often not the case. Numerous, large dust foci may occur without massive disease, which, on the other hand, is sometimes seen in young men with short dust exposures and relatively little dust in the non-fibrosed parts of the lung. Furthermore, coal-dust acting alone is inadequate to account for the excessive fibrosis. For this same reason collapse with coalescence of simple dust lesions is also an inadequate explanation for the genesis of massive fibrosis, quite apart from the fact that no evidence for collapse can be made out. In the genesis of massive fibrosis, therefore, a factor additional to the THE PATHOLOGY OF THE PNEUMOCONIOSES 29 m m must operate and for well over 100 years tuberculosis has iRepeatedly been advanced as the complicating element. This concept tnws thoroughly tested by James (1954), who found bacteriological or cfetstoiogical evidence of tuberculosis in 40 % of massive lesions from South Wales coalworkers. Although the remaining 60% of 11ese massive lesions showed no clear evidence of tuberculosis, they a y well represent healed lesions, since the general pathological features of massive fibrosis are always similar. James' analysis supports this interpretation, since 88 % of massive lesions from men - aider 40 showed tuberculosis, which was evident in only 29 % o f lesions from men of 60 or over. We therefore interpret these ladings as indicating the tuberculous origin of massive fibrosis and fcdieve that with increasing age the infection dies out. It is difficult to conceive of tubercle bacilli penetrating into existing massive teions. Tubercle bacilli only appear in the sputum when tuberculous jfcci communicate with bronchi, many of which however are obliserated in massive lesions. This probably explains why during life tubercle bacilli are present in the sputum of less than 2 % of men with massive fibrosis (Cochrane et al., 1952; Carpenter et al., 1956). A tuberculous element therefore exists in the massive fibrosis of coalworkers just as in classical silicosis, but in coalworkers it is torgely concealed, except in the younger men, many of whom are flew ers and getters. Why tuberculosis should be less apparent in coalworkers than in silicotics is not clear, but Cummins and his collaborators (1931,1938) showed that coal-dust adsorbed tuberculin and abolished the Mantoux reaction, but quartz did not do so. Coaldust might therefore alter the reaction of the tissues to the toxin of thse tubercle bacillus so as to restrict the extent and the progression of the disease. The tuberculous element clearly occurs in a modified form and the pathological features also suggest that it is limited in a s extension and retarded in its rate of progression. The epidemio logical observations of Mann (1951) and Cochrane (1954) accord with this view. The study of human material has provided no satis factory alternative to the view that tuberculosis is the complicating factor in the production of massive fibrosis. Those who do not accept the tuberculous origin of all cases of massive fibrosis may suggest that bronchial infection is the cause, but such infections have the reverse effect and cause dust to be discharged from the smg and not accumulated in it (Gough, 1957). Moreover, animal experiments show that tuberculous infection of the lungs combined 30 J. GOUGH AND A. G. HEPPLESTON with the inhalation or intratracheal injection of various dusts, including free silica (Gardner, 1937,1938) and coal (Zaidi et al., 1955), can induce extensive fibrosis, but non-tuberculous infection of the lungs of silicotic rabbits failed to do so (Vorwald, Delahant and Dworski, 1940). Massive fibrosis in coalworkers often leads to death, sometimes from overt pulmonary tuberculosis but much more frequently from pulmonary heart disease due to vascular obliteration and emphysema (Gough and Heppleston, 1955), whereas the reverse obtained in classical silicosis (Strachan, 1947). On the basis of the above evi dence, it can, however, be said that indirectly tuberculosis plays a large part in the mortality of coalworkers. Cavitation is frequently seen in the massive lesions of coalworkers and it develops as the consequence of two distinct pathological processes, ischaemia and tuberculosis (Kilpatrick, Heppleston and Fletcher, 1954). Vascular occlusion leads to colliquative necrosis and, if a patent bronchus is involved, to cavitation. Cavitation also results when softening occurs in areas of caseous tuberculosis enclosed by massive fibrosis and a bronchus is eroded. Closely similar types of cavitation are recognized in silicotic massive fibrosis (Vorwald, 1941). `Rheumatoid' Pneumoconiosis A condition recently recognized by Caplan (1953) is the so-called rheumatoid pneumoconiosis. Caplan drew attention to the greatly increased prevalence of massive fibrosis in Welsh coal-miners with rheumatoid arthritis and to the fact that about a quarter of these men also had peculiar, rounded opacities in their lung radiographs. These discrete opacities are now known to represent rheumatoid nodules, which may coalesce into massive lesions. Characteristically, the nodules appear in crops and develop much more rapidly than the areas of massive fibrosis in non-arthritic miners. The radiological severity of the lung changes does not necessarily parallel the degree of arthritis. Pulmonary lesions usually develop contemporaneously with the arthritis but either manifestation may precede the other by several years (Miall et al., 1953). Rheumatoid nodules are usually bigger than silicotic nodules and when fully developed show wide concentric bands of necrotic collagen separated by lines of dust. In addition rheumatoid nodules show peripheral zones of active inflammation in relation to necrotic collagen and this feature occurs in some nodules from which tubercle THE PATHOLOGY OF THE PNEUMOCONIOSES 31 bacilli cannot be recovered by culture or guinea pig inoculation. Rheumatoid disease is regarded by Kellgren (1952) as being essenazlly an inflammatory reaction to necrosis of normal or pathologi cally produced collagen. It is therefore suggested that coalworkers with rheumatoid disease react abnormally to the collagen produced a infective pneumoconiosis and the inflammatory reaction, occur ring in the absence of tubercle bacilli, is believed to be the rheuma toid component of these peculiar nodules (Gough et al., 1955). The subsequent Gourse of rheumatoid nodules varies. Sometimes 3he central necrosis involves an air passage and the necrotic material is expectorated so leaving one or more thin-walled cavities. In some such cases the sputum has been free from tubercle bacilli. Other rheumatoid nodules calcify and still others enter a stationary or quiescent stage. Asbestosis The term asbestos derives from the Greek meaning `unquenchable,' in the sense of being indestructible, and refers to certain fibrous silicates, which have been in use for over 2,000 years. These silicates belong to two groups of minerals, serpentine and amphibole, the fetter also being known as hornblende. The serpentine group is represented by the particular mineral chrysotile or white asbestos, which is a hydrated magnesium silicate containing a small amount of iron. The amphibole group includes crocidolite or blue asbestos and amosite, both of which are iron silicates, together with tremolite, a magnesium calcium silicate. These minerals occur in Canada, Italy and South Africa, crocidolite coming almost exclusively from South Africa. They are mined by blasting and quarrying and then processed by crushing, carding and spinning for use in the manu facture of textiles, paper and board, brake linings, asbestos cement and as fillers in paint and plaster. It is in mining and processing that fibres are produced and many of them are of a size that can penetrate the depths of the respiratory tract. In Britain asbestos is processed for industrial use but, since the introduction of the Asbestos Industry Regulations in 1931, the risks attending exposure to the inhalation of asbestos fibres have greatly diminished. Despite its ancient usage, the recognition of asbestos as a cause of industrial pulmonary disease is relatively recent and it was only 31 years ago that Cooke (1927) and McDonald (1927) first designated the condition as asbestosis. The pathological reaction in asbestosis has three main features. 32 J. GOUGH AND A. G. HEPPLESTON 1. Formation of asbestosis bodies. These are found only within the host and, judging by their rate of appearance in the sputum, they develop fairly rapidly after exposure. The body is composed of a central fibre, which is encased by a deposition of protein, evidently derived from tissue fluids. The protein sheath possesses a brown colour due to the presence of iron and often assumes a beaded or segmented appearance with bulbous extremities, which may also show cleavages. These fissures evidently represent a process of disintegration (Gloyne, 1938) and in long-standing or severe cases of asbestosis, the proportion of smaller bodies increases (Gloyne, 1951; Knox and Beattie, 1954a, 1954b). Histological preparations show that asbestosis bodies lie in the respiratory portion of the bronchial tree and occur singly or in groups. Their presence means only that a tissue reaction to the fibre has occurred. The formation of asbestosis bodies appears to render them innocuous, since bodies extracted from human lungs are unable to induce fibrosis in the guinea pig lung, whereas asbestos fibres themselves are active (Vorwald et al., 1951). Thus the reaction to the fibre does not necessarily parallel the production of pulmonary fibrosis. 2. Macrophage reaction. The presence in the lung parenchyma of asbestos fibres leads to a pronounced proliferation of macrophages which surround and attempt to engulf the fibres in the air spaces. Not infrequently foreign-body giant cells are formed, but even these are sometimes too small to ingest the longest fibres completely. 3. Fibrosis. In man several forms of fibrosis are seen and tend to affect the lower parts of the lung predominantly. A widespread fine fibrosis is common around respiratory bronchioles, alveolar ducts and sacs, that is in relation to the sites where asbestos fibres lodge. Fibrosis also occurs in the pleura, where it may be pronounced, and in the lung septa. In consequence of these changes the lung structure tends to be obliterated, but it is most likely that the massive fibrosis of human asbestosis is the result of secondary infection. Gardner (1938) failed to produce massive fibrosis in guinea pigs by exposure to asbestos alone but fibrous foci were formed after tuberculous or nontuberculous infection in animals with asbestosis. If, in human disease, the fibrosis has a patchy distribution, cystic change may develop in adjacent non-fibrosed areas of lung, so giving rise to a honeycomb appearance in a manner analogous to that seen in other pulmonary conditions (Heppleston, 1956). Complications. Hyperplasia of bronchiolar epithelium, which may 11 THE PATHOLOGY OF THE PNEUMOCONIOSES 33 also show squamous metaplasia, is not uncommonly associated with she fibrotic or fibrocystic changes of asbestosis, and the epithelial proliferation may progress to frank malignancy. When pulmonary carcinoma supervenes in asbestosis, it is usually of squamous type and, in contrast to the general population, predominantly arises in the lower lobes, which are also the site of maximum involvement by asbestosis. Isselbacher et al. (1953) summarized the published evidence and concluded that the association of bronchogenic carcinoma with asbestosis was more than coincidence. Doll (1955) siated that lung cancer was a specific industrial hazard of certain asbestos workers, and that the average risk among employees exposed for 20 or more years has been of the order of ten times that experienced by the general population. This risk has, however, progressively diminished since the working environment was improved by the introduction of the 1931 regulations. Endothelioma may develop in the greatly thickened pleura of asbestosis. In contrast to asbestosis, there is no evidence that silicosis (Irvine, 1935-38; Vorwald and Karr, 1938) or coalworkers' pneumoconiosis James, 1955) is associated with an increased liability to carcinoma o f the lung. Although it is possible that an increased risk of developing pulmonary tuberculosis exists in asbestosis, the evidence is too fragmentary to be dogmatic. The figures, though small, do suggest a lesser incidence of tuberculosis in asbestos workers than in silicotics '"Merewether, 1933-34). In guinea pigs, asbestos inhalation causes i restricted and temporary spread of pulmonary tuberculosis (Vorald et al., 1951). /Etiology. Two views have been expressed. The chemicalh ypothesis assumes that on disintegration of the fibres, the asbestos minerals are liberated and dissolve in the body fluids, so leading to fibrosis (Gloyne, 1951; Knox and Beattie, 1954a, 1954b). Because chrysotile and hornblende occurred in the dusts to which workers 'ere exposed but only hornblende in the lung residues, Kuhn (1941) drought that chrysotile was broken down to produce the lung changes faereas hornblende persisted and led to the formation of asbestosis bodies. The experimental evidence cited by Vorwald et al, (1951) is, however, opposed to the chemical hypothesis. Brucite (Mg(OH)2) fibres, containing very little silica, cause a similar fibrotic reaction to asbestos on intratracheal injection. The potency of free silica increases with diminishing particle sizes, but asbestos fibres less than 34 J. GOUGH AND A. G. HEPPLESTON 10-20 fi long are practically innocuous. Aluminium hydroxide neutralizes the effect of quartz but not asbestos. Nonfibrous serpen tine is inert in the tissues, but has the same chemical composition as the active fibrous chrysotile. Although the minerals causing asbes toses vary widely in their chemical composition they are all fibrous in form and hence the hypothesis of mechanical irritation is now favoured. The fibres, it seems, must be both long and flexible, since, according to Vorwald et ah, a minimum length of 20-50 ,u is required to produce fibrosis in the guinea pig and the inflexible fibres of glass wool are non-fibrogenic. Furthermore, the flexible fibres only appear to act in the lung and the peritoneum, that is in sites normally subjected to regular movement. It is clear from these considerations that the pathogenesis of asbestosis cannot be regarded as settled. Talc Pneumoconiosis Pure talc is a hydrated magnesium silicate, which occurs in foliated or compact masses or as plates, but commercial talc may also contain minerals of the serpentine and amphibole groups. Talc is mined in North America, Europe, Scandinavia, Egypt, India and China. The ore is first milled and then separated by air for industrial use as a filler, dusting powder and absorbent. Relatively few cases of talc pneumoconiosis have come to autopsy, but more have been diagnosed clinically. According to the accounts given by Porro et al. (1942), McLaughlin et al. (1949), di Biasi (1951), Schepers and Durkan (1955) and by Hunt (1956) talc pneumoconiosis is characterized by diffuse and nodular fibrosis, but the pattern does not suggest silicosis. The nodules contain numerous birfringent particles resembling short needles and scattered asbestosis-like bodies are also present. X-ray analysis of the lung ash from the case of McLaughlin et al. (1949) showed that there was probably less than 0-06 % of free silica in the dried lung, whilst in di Biasi's case no quartz was present in the lung on chemical or X-ray diffraction analysis. The X-ray diffrac tion pattern of the lung residues in Hunt's case indicated less than 0-5% quartz. There is a certain histological similarity between asbestosis and talc pneumoconiosis, which may depend on the similar physical form or chemical constitution of the minerals responsible. The resemblance is strengthened by the occurrence of asbestosis-like bodies in both conditions. THE PATHOLOGY OF THE PNEUMOCONIOSES 35 REFERENCES Belt, T. H. (1939). / . Path. Bad., 49, 39. Biasi, W. di (1951). Virchow's Arch., 319, 505. C aplan, A. (1953). Thorax, 8, 29. C arpenter, R. G., Cochrane, A. L., M iall, W. E., Jarman, T. F. andHocKADAY, G. (1956). Tubercle, 37, 225. Cochrane, A. L. (1954). Brit. J. Tuberc., 48, 274. Cochrane, A. L., Cox, J. G. and Jarman, T. F. (1952). Brit, rrted. J., 2, 843. Cooke, W. E. (1927). Brit. med. J., 2, 1024. C ummins, S. L., Weatherall, C. and Waters, E. T. (1931). J. Hyg. (Camb.), 31, 464. C ummins, S. L. and Williams, E. M. (1938). J. Hyg. (Camb.), 38, 638. 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V., K ing, E. J. and M itchison, D. A. (1955). Brit. J. exper. Path., 36, 553. CHAPTER 3 REACTION OF THE LUNG TO DUST By E. J. King and C. V. Harrison Postgraduate Medical School o f London The following account attempts to show by description and photo micrograph how the lung reacts to different dusts under the simplified circumstances of animal experiment before going on to consider the reactions of the human lung under the more complicated conditions that obtain during a worker's lifetime. The dusts we have studied most are coal and quartz, and in most of our experiments the dust has been given as a single intratracheal injection. This is a rather artificial method, but it has the advantage of allowing us to observe the reactions at known time intervals after the application of the dust. The Reaction of the Lung to Coal In this experiment rats were given a single intratracheal injection of 100 mg. of finely powdered coal-mine dust in the same range of particle size as respirable dust. (Nearly all the particles were less than 5 q and 20 % were less than 2 /< diameter.) The dust reaches the alveoli over a wide area of lung, but at first lies free. Within 30 days (Fig. la) it is nearly all picked up by alveolar phagocytes and these begin to collect into clusters, mainly around the vessels and respiratory bronchioles. A proportion of these dust cells migrate to the hilar lymph nodes. The residual dust cells remain in situ and in due course are surrounded by a minimal network of fine reticulin fibres (Fig \b). In a word this dust occupies space within the lung, but does not excite fibrosis. The Reaction of the Lung to Quartz With a fibrogenic dust like quartz the effects are quite different. The dust is given in the same way as coal, but the dose was only 50 mg. per rat. It is rapidly phagocytosed and the dust cells collect into clusters. This occurs rather more quickly than with coal; 37