Document R9NZLbbOYvxn1ZDo2rR5Vygn

to repeated Mantoux testing is nega quantity and long enough to produce tive.*1** It may be extremely difficult to disease occurs most commonly in miners. isolate tubercle bacilli during life in pa Industrial occupations that may be hazard tients with progressive massive fibrosis, ous include asbestos weaving or spinning despite subsequent postmortem demon and steam-pipe lagging. One report of the stration of active tuberculous infection.**17 development of asbestosis in a worker en gaged in automobile undercoating***3 indi Asbestosis cates the hazard of this occupation, although a survey of other workers in this field showed Asbestosis is the most important mem no other cases, perhaps because few ber of the group of pneumoconioses remain for long in this uncomfortable known as the silicatoses, in which salts of occupation. A. unique characteristic of silicic acid are the exciting agents. The asbestos is that it may produce pleuropul-' importance of asbestos lies not only in the monary disease in persons not directly hazard it presents to those involved in its involved in mining or processing but mining, but also, and perhaps more impor merely living in the oictmty of these ac tantly, because of its extensive use in a tivities;807- **** **** in fact, the disease can wide variety of occupations. In addition to develop in those who repeatedly handle asbestos, three other silicates can cause the clothes of asbestos workers.**'* pneumoconiosis --talc, kaolin (china-clay), Asbestos exists in several forms, and the and mica. manifestations of asbestosis may vary ac cording to the variety of asbestos to which Epidemiology an individual is exposed. This applies par ticularly in mining, since most commercial The use of asbestos in industry has in asbestos is & mixture of types. The ore creased enormously during the past half leaves the mine as crushed rock con century --world production has jumped taining a silicate of iron, magnesium, and from 500 tons in 1900 to 3 million tons in aluminum which, when refined, is 1968.**1* composed of fibers which can be spun, The prevalence of the mineral through woven, or carded. The most common form out the world and its potentially hazard is chrysotile (white asbestos), which is ous effects on man is indicated by the produced mainly in Quebec and consists large percentage of cases in which as of hydrated magnesium silicate extracted bestos bodies are found at routine from serpentine rock. This fiber appears to necropsy: this incidence ranges from 24.3 have less malignant properties than the per cent in London*8'* to 41 per cent in long blue fiber known as crocidolite which Pittsburgh*8*0 and 48 per cent in Mon is found largely in South Africa and con treal.*821 As has been pointed out by An- tains mostly iron rather than magnesium. jilvel and Thurlbeck,*8*' these reported The short-fibered amosite (brown asbes differences in incidence probably indicate tos) also is found largely in South .Africa only the different pathologic techniques and is predominantly iron-containing. by different observers. However, it is Anthophyllite and tremolite are mined noteworthy that these results were ob principally in Finland*8*7 and have a tained on unselected routine necropsy strong propensity to incite pleural reaction series --not on asbestos workers; similarly, in the form of plaques, not only in miners they represent the incidence of demon but also in persons living in the vicinity of strable asbestos bodies, not the mor the mines.807 phologic state characteristic of asbestosis. The asbestos fiber is inhaled and, de It also is of some importance that proof is spite its length (100/x or more), reaches the lacking that these "asbestos bodies" are, respiratory bronchioles and alveoli. This in fact, derived from asbestos. The finding remarkable tendency for such a long fiber of asbestos bodies in the lungs during to penetrate so deeply into the lung routine necropsies occurs more commonly parenchyma is probably explained by the in males and in urban residents; fibrosis, relationship between die falling speed of a usually of only minimal degree, is found fiber and its diameter:**** with a diameter in some of those with multiple asbestos of about 3/a, the asbestos fiber has a slow ( bodies.**** falling speed which allows it to escape Exposure to asbestos dust in sufficient deposition in the upper airways. 934 CHAPTER 12 INHALATION DISEASES OF THE LUNG Pathologic Characteristics Roentgenographic Manifestations As with other pneumoconioses, die development of pulmonary or pleural disease in asbestosis appears to depend on a combination of the degree and the length of exposure. Ghnracteristically. manifestations of the disease do not ap pear until 20 to 4U years atter the begin ning of exposure. The precise mechanism "by which the fibers produce pulmonary and pleural disease is not known, but mechanical irritation by the fiber and the slow liberation of silicic acid as it de composes may act individually or in com bination. As with silica particles the asbes tos fiber becomes coated with protein, and this gelatinous coat probably protects the pulmonary tissue to some extent It may be that the precipitated protein and subse quent fibrosis represent antigen-antibody formation and the effect of antibody on the tissues. The fiber is relatively soluble compared with quartz dust, which may explain die diffuse nature of the fibrosis and die relative paucity of asbestos bodies in advanced asbestosis.*01 In experimental asbestosis, the fibers are found first in bronchioles and respira tory bronchioles and within a few hours in alveoli: peribronchiolar edema and intraalveolar hemorrhage result Botham and Holt*7*0 have beautifully illustrated the formation of asbestos bodies: these are formed by the deposition of ferritin on the asbestos fibers within macrophages, first as a smooth coating and then in the form of beading as the macrophages shrink and rupture. Fibrosis first occurs in the peribronchiolar region and then in the interstitium. Varying degrees of fibrosis and distortion result, ranging from relative pres ervation of lung architecture to gross dis tortion with formation of microcysts and honeycombing (bronchiolectasis). Asbes tos fibers lie both in the interstitium and free in air spaces. Striking pleural thickening is usually present The pleural changes are thought to be due to penetration of the visceral pleura by the asbestos fiber, with irritation of the parietal pleura and subsequent fibrosis of this layer. Using a technique of incinera tion and phase-contrast microscopy, Hourihane and colleagues*010 detected asbestos fibers within pleural plaques, an observa tion which has led to the use of pleural biopsy to establish the diagnosis. The roentgenographic changes in the chest in asbestosis may be both pleural and parenchymal, but only recently was it recognized that the former are far more striking than the latter.*** **** The ac curacy with which the commonly accented roentgenographic signs mav be recognized Is rather poor; in their 1960 observer-error study. Willtarns and Hugh-Tones**0 showed wide disparity in the opinions registered by 11 experienced observers in assessing the roentgenograms ot patients with established asbestosis The roentgenographic changes in the lungs may be divided into three stages:** (1) a fine reticulation occupying pre dominantly the lower lung zones, asso ciated with a "ground-glass" appearance which has been attributed to pleural thickening although without absolute justi fication;**0 (2) a stage in which interstitial reticulation becomes more marked; a com bination of parenchymal and pleural changes leads to partial obscuration of the heart border--the so-called "shaggy-heart" sign--and of the diaphragm (Figure iz-idj; and (3) a late stage in which reticu lation becomes visible in the mid and upper lung zones and the cardiac and diaphragmatic contours become more ob scured.***' ** Hilar lymph-node enlarge ment is seldom if ever notable.*31 r The vlettral manifestations dominate the pjrhirp rrtpntc'pnngraPtlicallV:Jl,*` Ot cases described by Freundlich and Greening,**7 nw cent chewed pleural thickening alone. 41 per cent showed com bined pleural and narenchvmal manifesta tions,and only 11 per cent showwl parenchymal changes alone; the shaggy- heart sign was observed in 20 per cent A similar predominance of pleural over parenchyma] changes was reported by Anton:*30 of 40 patients with proved asbes tosis, only five had parenchymal changes in the lung bases, pleural plaques being the sole manifestation of the disease in the other 35. p, ie^lilraIl thickening pr_ pleural plaq^^1 usualiv (fifn.ra 10-Ifl) prominent in the lower half of the thorax, and tend to follow the rib contours.*10 The frequency of pleural calcification is variable; Anton*030 reportea finding caT cified and noncalcified plaques in roughly equal numbers of his 40 cases, whereas INHALATION DISEASES DUE TO INORGANIC DUST 935 Figure 12-10. Asbestosis. This 61- year-old man had been involved in asbestos mining for many years. A posteroanterior roentgenogram (A) re veals severe disorganization of lung architecture, most of the lungs being the site of a very coarse reticulation which in the right base has become confluent resulting in obliteration of die right hemidiaphragm. The central lung zones appear to show consider able emphysema. Marked pleural thickening is present over both lungs particularly in the apical and axillaryregions. A spontaneous pneumothorax is present on the left. Four months later, an anteroposterior roentgeno gram (B) reveals marked deterioration in the appearance of die chest; the lungs have undergone further loss of volume, and much of the reticulation, particularly that in the lower lung zones, has become confluent resulting in obliteration of the heart borders (the "shaggy heart" appearance) and dia phragm. On neither of these roentgen ograms is there evidence of hilar lymph-node enlargement or pleural calcification. BRG 1055 936 CHATTER 12 INHALATION DISEASES OF THE LUNC Freundlich and Greening observed calcifi cation in only 21 per cent of their 56 cases.,,,T In an American survey of 261 workers exposed to asbestos in industry, calcified pleura was found in none,7*37 whereas in Finland it is common,**7 a dif ference in incidence which probably re lates to die variety of asbestos concerned. Regardless of which figures are accepted. It is clear that noncalcined plaques occur often enough to be regarded as strongly suggesbvfi evidence ot asbestosis: in fact Anton-"" believes that the roentgenographic appearance of multiple pleural plaques is so specific that in the absence -ot an occupational history ot exposure to. die relAt&fl KiiBetkls,~Talc and mica, expoillteTfo Ubestos can be conduaea wnen the plaque! present. In contrast to the visceral pleural in volvement which gpaiactgnzefLJiifiyigus Remothorajnir^rngyemj^jhgjitaguesjrfybti!>lU!>ii> anse"fcrom the parietal pleura, most cfllhfflihly over die anterolateral chest wall and die central diaphragmatic domes.*0*-*07, **** It may be difficult to vis ualize uncalcified plaques, particularly en aryl tangential roentgenograms may alcifiedj>lagues_yary from ___ or circular snaHowTcommonTy situated over tne**c[iapKragmaEc^omesto complete encirclement_fljtie^Qai_Eprnons ot the luflgsJ^^Wnen calcification is minimal, a roentgenogram overexposed at maximal inspiration facilitates visi bility.7031 Clinical Manifestations Symptoms and Signs. It is probable that the great majority of patients with pleuropulmonary asbestosis have no symptoms.**,*7 Rarely, an acute pleural effu sion is considered to be precipitated by asbestos fibers, in which circumstances die patient experiences acute pleural pain.7*3* Symptoms, which seldom develop before at least 20 to 30 years* exposure,7*30,7837 include shortness ofbreath on exertion and cough, sometimes with mucopurulent sputum. Physical examina tion may reveal evidence of deformity of the thoracic cage, due to underlying pleural disease, even in symptom-free patients.*07 Basal crepitations may be present, and finger-clubbing occurs in many cases.7*37 Asbestos bodies are almost invariably found in the sputum of patients with roentgenographic evidence of the disease, even in the absence of symptoms.7*30 Pulmonary Function Studies. Cor relation is poor between the roentgeno- prraphic changes in asbestosis and the physiologic measurements of function. Function may be impaired despite a nor mal chest roentgenogram; on tne other "hand, roentgenographic changes may be Extensive with little evidence ot dysnihcnon.*J,1< f unction tests in paaents with parenchymal involvement show a decrease in VC and sometimes in RV, with rela tively well-preserved ventilatory capacity. Ventilation-perfusion inequality appears to occur early in the disease and is mirrored in a decrease in diffusing capacity and in crease in alveolar-arterial oxygen dif ference. Exercise may provoke hypoxemia, but the PcOj is normal or low; pulmonary compliance characteristically is greatly re duced.7810, 7037, 7030, 7840 Relationship to Neoplasia Of all non-neoplastic pulmonary dis eases, asbestosis undoubtedly has the hig_h_e__st* incidence--3 . F, nXTStSHTCTi -JOSS' pJ^iajesgeciaUyJnsyuJigggjjj^^ bronchioloalveolar carcinoma^and--paitic- {jflgg^ugggjJjg^Jps^**^^1^873-7877'>831- I*3S' xsii-iMi jn fact, Doll7840 concluded that can cer of the lung is a specific industrial hazard of certain asbestos workers and that the average risk ffr ^lllXIUDllIIinLfor ?P years or more is ten timeq thaLfaclhc-gen- CTal nomilaKrm Selilrnff and colleagues18*1 reported an incidence of bronchogenic car cinoma in patients with a history of long and heavy exposure to asbestos six to eight times that expected. Lung cancer is usually of oat-cell or anaplastic type, although squamous-cell carcinoma and adenocarcinoma also have been re ported.1874, 7840 A latent period of at least 20 years' expo sure is characteristic of those asbestos workers in whom pleuropulmonary malig nancy develops.780* Even when fibrosis is of only minimal degree, asbestos bodies are present in the lung parenchyma and in some cases in the neoplasm also.1874 Pa tients very heavily exposed to asbestos may die of asbestosis and cor pulmonale before sufficient time has elapsed for the development of neoplasia. In a follow-up INHALATION DISEASES DOE TO INORGANIC DUST 937 of 370 asbestos workers with heavy expo sure, Selikoff and colleagues101* found the incidence of death due to bronchogenic carcinoma, mesothelioma of the pleura and peritoneum, and gastrointestinal carcinoma to be significantly higher than expected. Their results indicated a synergistic car cinogenic effect of cigarette smoking and asbestos exposure: non-cigarette smokers did not die of bronchogenic carcinoma, although three succumbed to asbestosis and one to mesothelioma. The incidence of associated neoplasia appears to relate to the type of asbestos involved. The crocidolite variety is the most commonly implicated, particularly with mesothelioma, a relationship which was first described by Wagner and asso ciates'"* in crocidolite miners and in residents in the vicinity of the mines. Most authors report a similar although less-marked relationship between chrysotile exposure and mesothelioma.*"*' **43 In their study of chrysotile miners Elwood and colleagues'*4* found no increase in in cidence of mesothelioma but more deaths than expected from bronchogenic carci noma; an extensive study by Braun and Truan**** of asbestos workers in Quebec, the main source of chrysotile asbestos, revealed no evidence of a greater in cidence of bronchogenic carcinoma in these men than in the general population of Canada and the U.S.A. Hourihane**47 established criteria for differentiating mesothelioma from simple pleural fibrosis and concluded that diffuse mesothelioma could be diagnosed with reasonable accuracy from histologic exami nation of small pieces of tissue; conse quently, he considers that needle biopsy is usually sufficient to permit this differenti ation. The incidence of peritoneal mesothelio mas also is greater in patients with asbes tosis.**41'**4' Enticknap and Smither*'4* described 11 patients with peritoneal neoplasms, all of whom had worked in the same asbestos factory. Curiously, one group of observers10*1 found an unexpectedly large number of insulation workers exposed to asbestos who died from carcinoma of the stomach or rectum, despite a death rate for other cancers which was within the ex pected limit The reason for this incidence is not known. Talcosis This relatively uncommon variety of sil icatosis results from many years' exposure to high concentrations of fibrous or tremolite talc (magnesium silicate).***1, **** The disease has been described in miners, mill ers,**** rubber workers,***4 and soap-stone workers.**** Pathologic Characteristics In several cases necropsy has revealed diffuse and nodular fibrosis with scattered asbestos-like bodies and numerous bireftingent particles, resembling short needles, within the nodules.***4- **** Irreg ular areas of fibrosis surround bronchioles and small vessels, resulting in dilatation of the former.*7*4 Roentgenographic Manifestations The sheet-anchor in the roentgenologic diagnosis of talcosis is pleural plaque for mation. These are often diaphragmatic in position and may be massive, often bizarre in shape and extending over much of the surface of both lungs (see Figure 4-166, page 368)****'***7 and sometimes involving the pericardium. The incidence of pleural abnormality in talcosis is similar to that in asbestosis; in a study of 221 workers exposed to tremolite talc. Smith found pleural plaques in 14 (6.3 per cent).**3* Parenchymal involvement is said to be similar to that in asbestosis,***4' ***7, **** the roentgenographic pattern being one of gen eral haziness, nodulation, and reticula tion, with sparing of the apices and costophrenic sinuses.**** Some cases may show confluence of lesions, giving a tu mor-like appearance (Figure 12-11).**** Clinical Manifestations Symptoms are similar to those of any other disabling pneumoconiosis and in clude dyspnea and productive cough. De creased breath sounds (presumably due to pleural thickening), rales at the lung bases, limited chest expansion, and finger clubbing are. found on physical examina tion.***7, *** In a study of 110 men em ployed in the mining and processing of soap stone in Sweden, Ahlmark and asso- iBRG 1057 Figure 12-11. Pulmonary Talcosis. This 31-year-old woman had noted the onset of dyspnea on exertion several months previously and at the time of this roentgenographic examination could only climb ten stairs without stop ping; on occasion, she awoke at night gasping for breath and had to use two pillows to sleep. There was no cough or recent hemoptysis. A posteroanterior roentgenogram (A) reveals extensive involvement of both lungs by a rather coarse reticular pattern. In the upper axillary zone on the right and in the left mid-lung (B) are two areas of homogeneous consolidation possessing poorly-defined margins. Paratracheal lymph-node enlargement is pres ent bilaterally, more marked on the left. At thoracotomy, biopsies obtained from lung and lymph node revealed multiple fibrotic and hyalinized granulomata lying in close proximity to blood vessels and containing extremely numerous doubly-reffactile crystals. In view of these findings, the patient was questioned further regarding her habits and finally admitted (somewhat reluctantly) to an extraordinary history of excessive inhalation of lavenderscented talcum powder during a three-month-period when she was pregnant two years previously; the was in the habit of spreading the talcum powder liberally over her pillow and blankets at night and actually inhaled it in large amounts from her cupped hands! Subsequent assay of the doubly-refractile particles observed histologically proved them to be talc. FsJBRG 1058 INHALATION DISEASES DUE TO INORGANIC DUST 939 dates*'** found five cases with at least 20 years' exposure who showed minimal roentgenographic evidence of pneumoco niosis and no restriction of work capacity. Diffusing capacity is said to correlate with the extent of parenchyma] involvement seen roentgenographically. We studied one case, proved by biopsy, in which both VC and RV were moderately decreased and repeated measurement of the steadystate Dlco was less than 50 per cent of pre dicted normal. Kaolin (China-Clay) Pneumoconiosis This rare form of silicatosis is due to the inhalation of a mixture of sand, mica, and aluminum silicate. The initial process in the mining of china clay is wet, so that exposure to the dust does not occur until the material is dried iri kilns and subse quently placed in bags. The incidence of significant chest disease varies in reported series; in one study of 5130 workers in the kaolin industry,***1 it was concluded that their general state of health varied little from that of the regional general popula tion of corresponding age and race. By contrast, in a study of 553 Cornish chinaclay workers exposed to kaolin dust for periods exceeding five years, 48 (9 per cent) showed clinical and roentgeno graphic evidence of disease; findings were positive in 23 per cent of those exposed for more than 15 years.*"* The roentgenographic pattern varies widely: there may be no more than a gen eral increase in lung markings; with pro longed and severe exposure, a diffuse no dular and miliary mottling is present; and a late manifestation is bilateral progressive massive fibrosis identical to that in sili cosis, talcosis, and coal-worker's pneumo coniosis.*TS4- **'* Even after many years' exposure, most of the patients have no disability and show only slight increase in lung markings roentgenographically. Disabling pneumo coniosis is believed to develop in only a small proportion of these workers.***"1 Pneumoconiosis Due to Mica Mica is a complex silicate of potassium, aluminum, magnesium, calcium, and flu orine. Pneumoconiosis is a rare complica tion with roentgenographic and clinical manifestations virtually indistinguishable from those of related silicatoses, asbestosis, and talcosis.**'*1 ***** ***4 Coal-Workers' Pneumoconiosis Exposure to mixed dusts containing varying percentages of free silica in com bination with carbon or hematite can pro duce several different pneumoconioses which usually are known by the occupa tion with which they are associated--coalworkers' pneumoconiosis (anthracosis, anthracosilicosis), graphite-workers' pneu moconiosis, foundry-workers' lung, weld ers' siderosis (siderosilicosis), and the pneumoconiosis of hematite miners. The content of free silica in these dusts is small, usually less than 10 per cent Epidemiology Whereas in a small percentage of coal miners silicosis will develop as a result of high quartz content of certain coal seams, in the majority a pneumoconiosis develops which is entirely different and which is characterized by absence of symptoms in the early stages, a roentgenographic pattern which lacks the well-defined nodularity of silicosis and a morphologic picture quite distinct from that of pure silicosis. Al though a small amount of free silica is present in all coal dust and can be found in the ash ofcoal-workers' lungs at necropsy, it seems that the morphologic changes are due chiefly to the deposition within the lungs of large quantities of carbon. The finding of pathologic changes identical to those of coal-workers' pneumoconiosis in carbon-electrode workers,**** in whom the inhaled dust consists of coke and anthracite and almost no quartz, supports the conten tion that free silica plays little part in the lung disease of coal workers.***" Although the great majority of reports on coal-workers' pneumoconiosis originate in Great Britain and continental Europe, a disease with similar clinical, roentgeno graphic, and pulmonary function pat terns is recognized in the U.S.A. also.'"*'-*'** The incidence of coalworkers' pneumoconiosis varies from col liery to colliery, probably relating to dust ^ S^t /Glhj , /6 - JL^-fS BRG 1052