Pneumoconioses caused by asbestos and by other siliceous and nonsiliceous dusts

Pneumoconioses Caused by Asbestos and Siliceous and Nonsiliceous Dusts

by Other

By LEONARD J. BRISTOL, M.D.

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HE TERM PNEUMOCONIOSIS, as defined by Gardner,]” means any change in the lungs induced by prolonged inhalation of dust particles. Two well-known pneumoconioses are silicosis, caused by the pulmonary deposition of free crystalline silica, and coal workers’ pneumoconiosis, produced by the inhalation of certain types of coal dust. These two will not be discussed in this presentation. Pulmonary fibrogenic reactions are also caused by diatomaceous earth, which is an amorphous form of free silica, and by other substances, including the silicates. The most prominent of these substances is asbestos, to which a greater part of this paper is devoted However, talc and kaolin as well as two nonsiliceous fibrous materials-bagasse and cotton-have been reported to cause varying degrees of pulmonary fibrosis. It should be stressed that not all silicates-and there are many-are pathogenic for pulmonary fibrosis, since both animal experiments and clinical experience have shown that some are inert. ASBESTOSIS

Asbestosis is a form of pneumoconiosis caused by the prolonged inhalation of asbestos fibers. Asbestos is the generic name applied to a group of fibrous minerals composed of long flexible fibers that can be subdivided longtitudinally into filaments of very small diameter.3 The asbestos minerals are silicates and they belong either to the serpentine or to the amphibole group of minerals3 The most important variety is chrysotile (white asbestos), a member of the serpentine group. Other important forms are amosite (brown) and crocidolite (blue), both of which belong to the amphibole group. Additional varieties of asbestos, though less important commercially, are anthophyllite, actinolite, and tremolite. The asbestos minerals differ in chemical composition: chrysotile is a magnesium silicate, amosite an iron magnesium silicate, and crocidolite an iron sodium silicate. The value of asbesto? depends upon its incombustible character and resistance to acid, its insulating properties, and its fibrous nature. Some varieties of the mineral can be split into long flexible filaments that can be woven or spun into yam. Other varieties, composed of shorter fibers, are used in a wide range of asbestos products. In the United States, which is the worlds largest user of asbestos, the principal commercial variety is chrysotile. Most of the chrysotile comes from Quebec, though smaller amounts are produced in Vermont, Arizona and California. Africa is the source of all of the amosite and most of the crocidolite. Australia LEONARD J. BRISTOL, M.D.: Saranac Lake, N. Y.

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and Bolivia also supply a small amount of crocidolite. Of the total world production of asbestos, estimated to be about 3 to 3.5 million tons per year, probably more than 90 per cent is chrysotile. In this country, only relatively small amounts of the other varieties of asbestos are used: about 22,000 tons per year of amosite and 17,000 tons per year of crocido1ite.l” Among the major products in which asbestos is used are asbestos textiles, asbestos cement materials, friction materials, gaskets, asbestos paper, floor tile, roof coatings, paint and plastics. Such a wide range of prchcts as safety clothing, curtains, brake linings, pipe coverings, and shingles are composed to a great extent of asbestos.3,19 The applications of this magic mineral are diverse and are constantly expanding, Experience has shown that the prolonged inhalation of significant amounts of asbestos fiber over an extended period of time may produce a fibrotic change within the lung. This pulmonary reaction may range from sparsely scattered small foci of fibrosis with intervening areas of normal lung to a dense fibrosis affecting most areas of the parenchyma. The pleura also may react to the fibrogenie substance by exhibmiting various degrees of thickening and calcification. Although the use of asbestos goes back some 4000 years”” and the disease asbestosis was presumably described by Herodotus in 450 B.C.,‘” one of the first cases of pulmonary asbestosis to be recorded was observed in Great Britain in. 1990. According to HunteF and McVittie,32 the postmortem findings on this case were described by Murray 7 years later. In his description of the morbid anatomy of the lungs, Murray referred not only to the presence of extensive diffuse pulmonary fibrosis, but also to spicules of asbestos in the lungs. The 34 year old man, who had been exposed to asbestos for 14 years as a carding machine operator, was the last survivor of 10 men who had worked in that particular room. The other 9 had died from lung disease at about the age of 30. Inasmuch as the entity of asbestosis had not then been established, a diagnosis of typical fibroid phthisis had been made. A number of years passed before a relationship between asbestos fiber and pulmonary fibrosis was demonstrated. During this hiatus most investigators in the field of occupational medicine were concentrating their efforts on studies of the ill effects that occur from the pulmonary deposition of free crystalline silica, and gave little attention to asbestos. It was not until 1924, when Cooke8 reported a case of a 33 year old woman who began to work in an asbestos factory at 13 years of age and continued working there until two years before her death, that serious consideration was given to the disease.ZR,44He called attention to a peculiar type of pulmonary fibrosis and to the presence of particles of asbestos fibers in the lung. However, it was a report by SeileF in 1928, which indicated a relationship between the asbestos fiber and pulmonary fibrosis, that provided the impetus for numerous investigative studies during the early 1930’s. Since that time, however, scientific knowledge concerning asbestosis has not progressed as rapidly as has our understanding of many other pathologic entities. Much of the information pertaining to the health hazard of the inhaled asbestos fiber is relatively recent. This may be one reason why certain unanswered questions confront us in this most interesting and serious problem. It would seem logical to suggest that all information derived by the various disciplines involved in the study of

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asbestosis should be readily and easily exchanged. If we are to achieve suecess in resolving the problems associated with human exposure to asbestos, international cooperation and well-planned epidemiological investigations in man are mandatory. Epidemiology

and Pathogenesis

In asbestos mines and in factories making asbestos products, the atmosphere at the breathing level contains asbestos fibers of different lengths and in various concentrations. Some of these fibers may be inhaled by exposed workers and reach the terminal respiratory units of the lung. Since the kind of dust to which an individual is exposed depends upon the environment in which he works, it is necessary to know not only the mineralogical variety of asbestos but also the contaminants present. The final site of lodgment of the inhaled asbestos fiber is in the alveoli arising directly from the respiratory bronchioles.“’ Until lately, it has not been fully understood how an asbestos fiber of 100 microns or even longer could gain access to the pulmonary alveoli of man or of the experimental animal. Recently, TimbreP’ has found that there is a relationship between the falling speed of a fiber and its diameter. If a fiber has a sufficiently small diameter, the falling speed can be slow enough for the fiber to escape deposition in the upper part of the respiratory tract, and deep penetration to the distal air space is then possible. The straighter a fiber, provided it has a diameter less than 3.5 microns, the greater its chance of penetrating into the lower respiratory tract. The places where respiratory bronchioles branch are preferred deposition sites for long fibers. The asbestos fibers and phagocytes accumulate in the alveoli and respiratory bronchioles and are probably held there by the development of a network of reticulin fibers. Several theories to explain the pathogenesis of this disease have been proposed. In the original hypothesis, it was assumed that the presence of asbestos fibers in the terminal air spaces caused irritation and damage to the walls of the alveoli and respiratory bronchioles, leading to fibrosis. It has also been postulated that fibrosis is due to the effects of silicic acid and metal ions leached out from the asbestos fibers. This is referred to as the solubility theory. Evidence of the relative solubility of asbestos fiber in the lungs as compared with free crystalline silica and coal has been demonstrated by animal inhalation experiments. The fact that only small amounts of asbestos are the found in the lungs in cases of asbestosis in man also helps to support solubility theory. More recently, the autoimmune theory has been advocated. This hypothesis proposes that the presence of asbestos fibers in the lungs and their interaction with fibroblasts or phagocytes either produce or localize abnormal globulin. Another aspect of the autoimmune theory is the effect of the fiber on the pulmonary phagocytes. Lysis of the phagocyte in or near the respiratory bronchioles releases a substance that is not accepted by the tissue as “self.” The stagnation of phagocytes theory assumes that the trapped phagocytes disintegrate in situ and, in doing so, release sclerosing agents which are probably lipids or lipoproteins.1”~‘“,S2 Quantitative inhalation experiments in animals have been carried out by

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WagneP in Johannesburg. These tests have shown that chrysotile (white asbestos) produces less fibrosis than amosite (brown asbestos) or crocidolite (blue asbestos) with the same dose by inhalation, and this appears to be due to the much more rapid elimination of the chrysotile fiber. The reason for the more rapid elimination is not yet clear but it may be related to solubility. Pathology Asbestosis is found most frequently in the lower parts of the lungs but does involve the midzones and the upper lobes. When the upper lobe involvement is predominant it is sometimes referred to as inverse distribution. Asbestosis is diagnosed histologically by the association of asbestos bodies and asbestos fibers with the diffuse fibrosis, T’he fibrosis alone is not diagnostic because histologically it is similar to that of other diseases. It frequently occurs as a diffuse interstitial fibrosis which may be associated with dilatation of some of the bronchioles and bronchi. It may also occur as solid fibrosis and be confused with other pneumoconioses and even carcin0ma.l” Thickening of the visceral and parietal pleurae is a usual finding in cases of asbestosis. The amount of thickening does not necessarily parallel the degree of parenchymal fibrosis. The pleural involvement may vary from a very slight and localized reaction to complete symphysis and extensive thickening of both pleural layers. In the latter case, the pleura has a cartilaginous-like covering, which may be as much as a few centimeters thick over the entire lung surface. Discrete pleural thickening may also occur. It is usually multiple and may be present on an otherwise normal pleura. 7 Some investigators have reported, from their human autopsy material, the occasional presence of calcification of the parietal pleura. A common site for these calcified pleura plaques is the diaphragmatic surface; however, no portion of the pleura is immune. Histologically, the lesions of early asbestosis are localized to the respiratory bronchioles.52 The walls of these tubular structures become thickened and occasional asbestos bodies and fragments of fibers can be seen intramurally. Many fibers and asbestos bodies are present in the lumens of the respiratory bronchioles, some lying within phagocytes and others lying free. As the disease advances, the fibrotic changes are seen to extend and involve the alveolar ducts and atria of the respiratory bronchioles. Eventually there develops a generalized interstitial fibrosis with thickening of the septa. The fibrosis tends to distort and obliterate the pulmonary architecture. In typical cases of asbestotic lung, asbestos bodies are usually well embedded in dense zones of proliferated connective tissue and mature fibrosis.7J1 Vorwald et a15” observed that the asbestos body is a golden yellow, beaded or haustrated rod, which may be either straight or curved. Most investigators agree that these curious bodies are a specific concomitant of asbestosis. Apparently asbestos bodies are inhaled fibers on which iron pigment and protein have been deposited. The bodies vary greatly in length, and dimensions exceeding 200 microns have been reported. Many osf these structures have a dumbbell shape.25,2i,33 Without an environmental history of adequate exposure to asbestos fibers, a clinical or radiological diagnosis of pulmonary asbestosis should not be made.5 The atmospheric concentration of asbestos fibers and the duration of exposure

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to those fibers required to induce pulmonary asbestosis have not been established. The world literature contains conflicting reports and data. However, it is know that certain factors, such as the mineralogic variety of the fiber, the presence of other substances in the air-suspended dust, and individual susceptibility to the disease can influence the development and extent of pulmonary invo1vement.52 For the present, it can be stated in more or less general terms that the pulmonary deposition of a sufficient amount of asbestos may cause a crippling form of pulmonary fibrosis. Clinical

Findings

Breathlessness, and especially exertional dyspnea, is usually the original symptom. The most universal physical signs are rales and crepitations at the lung bases and clubbing of the fingers.j4 Cough and wheezing occur in relatively few cases.37+ Cyanosis upon exercise is present in some advanced cases and car pulmonale can be a frequent sequela. It should be emphasized that the presence of asbestos bodies in the sputum simply indicates that the individual has inhaled asbestos fibers; it is not prima facie evidence that fibrosis is presenr.25,33,46,52,58 The primary physiologic abnormality in asbestosis is a reduced diffusing capacity of the lungs.55 This is also referred to as alveolar-capillary block and is the result of interstitial fibrosis involving the alveolar-capillary membrane with consequent impairment of diffusion of oxygen from the lung into the blood. This particular functional defect is not only present in asbestosis but occurs in a whole group of pulmonary disorders which are characterized by interstitial fibrosis.‘,j5 Williams and Hugh-JoneP conclude that the abnormal pulmonary physiologic findings of asbestosis parallel those of other interstitial fibroses and consist of a lowered diffusing capacity, a reduced inspiratory capacity, and hyperventilation on exertion with no evidence of airflow obstruction except in cases complicated by asthma or emphysema. Roentgen Findings Several studies indicate that there is a very poor correlation between those physiological changes and the appearance of the chest roentgenogram.54 It has also been shown that changes in pulmonary function, particularly impairment of diffusion of oxygen into the blood, may precede the clinical or radiological signs. Some cases of pulmonary asbestosis have shown marked physiological defects in the absence of any clearly recognizable abnormality in the chest roentgenogram. Conversely, there have been patients with asbestosis in whom the disturbance of function was very slight despite the presence, on the chest film, of changes which were compatible with the roentgen diagnosis of pulmonary asbestosis.“. As early as 1936, ShulP indicated that asbestosis should be classified as a pneumoconiosis which was characterized roentgenologically by an early interstitial fibrosis with progression into a terminal diffuse fibrosis. The fibrous reaction, as reflected in the chest roentgenogram, began in the bases of both lungs and, as the disease progressed, there developed a haziness of the lungs which he referred to as a “ground-glass” appearance. He also noted that the

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Fig. l.-This 71 year old man, living and well, was employed in the asbestos industry for 3 years, where he received a relatively light exposure to chrysotile fiber. There are extensive diffuse calcified plaques overlying the surface of the lung and also localized to the right diaphragmatic pleura.

right side of the heart was frequently enlarged in moderately advanced cases. Following a review of the chest roentgenograms of 71 men who had been employed in asbestos plants, it was apparent to Shull that the one constant roentgen finding in all the cases was the diffuse fibrosis. With this knowledge, he developed a roentgen classification of this disease which seemed adequate and proved useful for many years. The radiologic extent of fibrosis was the main feature of the classification, which grouped cases of asbestosis into slight, moderately advanced, and markedly advanced categories. Other signs, such as pericardial and pleural thickening, “shaggy” outline to the cardiac contour, and right-sided cardiac enlargement, were incorporated in the classification. A few years later, WegeliuP points out, Saupe of Germany described a similar roentgen classification, employing four categories, namely, an anteprimary stage of asbestosis and asbestosis I, II, and III. The radiologic diagnosis of pulmonary asbestosis is dependent on a positive occupational history of a sufficient exposure to asbestos fiber and abnormal findings of the lungs as manifested in the chest film.” Generally, the latter consist of pulmonary fibrosis, pleural thickening and calcified pleural plaques. A wide variety of conditions can cause fibrosis and pleural reaction. Calcified

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Fig. Z.-This man worked for 46 years in the asbestos industry, of which 26 years were considered to be heavy exposure. He died at 59 of a myocardial condition. At autopsy there were very extensive calcified plaques of the visceral and parietal pleurae, especially over the diaphragm. The lungs revealed moderately advanced interstitial fiorosis. The chest film shows a predominantly basal involvement, a “shaggy” heart, and severe emphysema.

pleural plaques (Figs. 1 and 2) when preslent, are often a reliable roentgenologic index of the presence of asbestosis. The differential diagnosis of calcified pleural plaques includes talc pneumoconiosis, old tuberculosis of the pleura, and calcified hemothorax. 34An adequate history of exposure to asbestos fiber is, of course, essential for confirming the diagnosis. The earliest roentgen changes generally occur at the bases of both lungs (Fig. 3). This usually presents as an extremely fine network of increased densities radiating from the cardiophrenic angles toward the costophrenic sulci. There may or may not be a superimposed granular pattern. The involved lung has a hazy appearance, sometimes described as “ground-glass.” As the pathologic process progresses, the middle thirds of the lungs may also become affected; the roentgen pattern becomes more dense and one may recognize small nodular opacities (Figs, 4 and 5). These may occupy a small portion of the lung or be distributed rather widely (Fig. 6). It should be stressed that the upper thirds of the lungs are not spared but involvement in that area usually indicates that the disease has been present for a considerable length of time (Fig. 7).

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Fig. 3-This 68 year old man worked for 47 years in an asbestos mill. He had no respiratory or cardiac symptoms. There is slight diffuse clouding at both lung bases. Kerley’s lines are present in the lower third of the left lung and there are calcified plaques along the left diaphragm and left cardiac border.

There are other parenchymal changes which may be reflected in the chest roentgenogram. In some cases, multiple small radiolucencies up to 1 cm. in diameter and of any geometric pattern, most of which are surrounded by a fine line of increased density, lie adjacent to each other. These may occupy a small or large portion of the lung. This finding is designated as a “honeycomb” appearance. Large opacities with a diameter exceeding 1 cm. are occasionally seen in pulmonary asbestosis. However, when they are present, an attempt must be made to exclude such other conditions as silicosis, tuberculosis and neoplasm (Fig. 8). Another roentgen manifestation involves a diffuse, hazy, ill defined pattern difficult to describe but peculiar to many cases of this disease. It has been tentatively designated “alpha” in a classification now being formulated4* (Figs. 8, 9 and 10). Occasionally it is difficult or impossible to outline the cardiac silhouette against the densities within the lung parenchyma and an irregular heart border ensues-the so-called shaggy hecut This merely is a manifestation of the silhouette sign (Figs. 2 and 4).

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Fig. 4.-A 54 year old man with a 27 year occupational chrysotile fiber. Diffuse shadows involve the middle and lower of both costophrenic sulci due to thickened pleura.

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history of exposure to pure lung fields. There is blunting

Calcified pleural plaque formation (Figs. 1, 2, 3, and 10) is alsO present in the chest film of some asbestos workers and is frequently located on the diaphragmatic pleural surface. The cause of the deposition of calcium in the pleura is not known.34 In our experience, the incidence of noncalcified pleural thickening is considerably higher than that of calcified pleural plaques, At present there are two schemes in use for codifying the chest roentgen appearance of silicosis and coal workers’ pneumoconiosis.35~36 The International Labour Office (I.L.O.) Classification is used exclusively outside the United States, while the United States Public Health Service (U.S.P.H.S.) scheme has been accepted in America. There is, however, no satisfactory roentgenologic classification of asbestosis as yet. The Occupational Medicine Section of the U.S.P.H.S. has recently convened an asbestos roentgenologic panel to study this problem.48 The primary objective of this group is to develop a standardized classification of the roentgen appearance of pulmonary asbestosis. A tentative classification which employs, insofar as possible, the U.S.P.H.S. modification of the I.L.O. classification for small and large opacities is being evaluated. In addition, other qualitative types of abnormality are being recorded, such as pleural thickening and calcification and abnormalities of the lung pattern other than small and large opacities. The “alpha” designation alluded to above is also being evaluated. These separate qualitative deviations from normal are also being estimated semiquantitatively. An amazing fact about this disease is that asbestos-exposed workers in dif-

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Fig. 5.-A 54 year old man with a 30 year exposure to asbestos. The middle and lower thirds of both lungs show very small nodules. The upper third of the lungs is relatively clear. Thickened pleura is present at both bases.

ferent countries apparently have different roentgen patterns of abnormality. Reports from one country stress small or large opacities, while investigators from another geographical location indicate the prevalence of pleural thickening, but without calcification. Kiviluoto *4 has indicated that in Finland calcified pleural plaques are the usual feature. It is probable that the type and severity of alterations of these roentgenologic changes vary with the mineralogic content of the fiber. Exposure to mixed dust is not uncommon in industry, and this factor may and often does modify the known roentgen pattern of a single type of exposure. Relationship

of Asbestosis to Cancer

Gloyne,17 reviewing Bridge and Henry’s work, infers that in order to classify cancer as industrial in origin, two criteria must be present: (1) the incidence rate of malignancy in the occupation under question should be significantly greater than that in the general population, and (2) in the environment under review, the worker should have a sufficient exposure to a material, indigenous to that occupation, which has been proved experimentally to be carcinogenic. One of the first cases to appear in the literature which suggested a possible relationship between asbestosis and pulmonary carcinoma was described by Lynch and Smithz9 in 193.5 Since that time there have been numerous conflicting reports concerning the association of asbestosis and pulmonary malignancy. Isselbacher et alz2 in 1953 and Dutra et a1.l” in 1965 state unequivocally that

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Fig. 6.-An asbestos worker with many years of exposure. The roentgenogram demonstrates small opacities scattered throughout the lower two-thirds of both lungs. There are localized thickened areas in the pleura of the lateral portion of the left upper thorax.

the chronic mechanical irritation by the asbestos fiber in some cases acts as a carcinogen. Homburgerzo considered it very doubtful that asbestosis predisposes to pulmonary carcinoma because of the lack of metaplasia occurring in the bronchial mucosa of individuals who have been exposed to asbestos fiber. Braun and Truan4 in 1958 carried out an epidemiological study of lung cancer in asbestos miners in the Province of Quebec and concluded that there was strong evidence against the carcinogenicity of asbestos. Elwood et a1.,12in a followup study of 1,261 workers from an asbestos factory, of whom 144 had died, did not find any deaths due to abdominal neoplasm, but one man was found to have died from mesothelioma of the pleura and 11 had died from carcinoma of the lung or bronchus. In the factory studied, only chrysotile from Africa and Canada had been used since 1935. AS a result of this study, the authors suggested that chrysotile fiber is probably not an etiological factor as far as mesothelioma or abdominal tumors are concerned. However, they indicated that there is some evidence osf an excess in the number of deaths from carcinoma of the lung and bronchus. The smoking habits of those who died were unknown. The conviction that asbestosis predisposes to pulmonary, pleural and even abdominal malignancies is gaining momlentum among workers in this area on

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Fig. ‘I.-This man had less exposure than the worker in Fig. 3. He died at age 59 following 30 years as a manual bagger of chrysotile fiber. He worked for 8 years with roentgen signs of advanced asbestosis and finally developed car pulmonale and severe dyspnea. The pathologic process involves all portions of the lung and thickened pleura is seen at both bases.

the basis of recent statistical experience. It would seem that a comprehensive epidemiological study of the entire environment located in and about an industrial asbestos installation-whether it be mining, manufacturing or shipping -should be done without delay so that more complete information can be obtained and this important and complex problem resolved. In addition to the true asbestos minerals, some attention should be given to other silicates which may produce a somewhat similar tissue reaction. TALC

My experience with talc miners and millers is limited to the type of talc which is mined in northern New York State. It is of the fibrous variety known as asbestine and contains varying amounts of tremolite and anthophyllite, the latter two being members of the amphibole group. These three minerals are silicates. The mined product usually is made up of coarse crystalline granules but some of the talc is capable of being subdivided into long, thin, flexible fibers which are incombustible and resistant to acid. Schepers and Durkan38 have suggested that the fibrous amphiboles of talc might cause the same pulmonary fibrosis as asbestos.

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Fig. 8.-This man died at age 60 after 33 years in the asbestos industry with 26 years of heavy exposure as a manual bagger. Postmortem findings included advanced asbestosis, car puhnonale, and oat cell carcinoma. The roentgenogram demonstrates haziness (“alpha” pattern) in both midlung fields and a large opacity in the left upper lobe, the site of the carcinoma.

Histologically, the response to the pulmonary deposition of these substances consists chiefly of irregular areas of diffuse fibrosis which are perivascular and peribronchiolar in location. There is distension of bronchioles and smaller bronchi. Elongated and club-shaped bodies similar to those seen in asbestosis are found mainly within the alveoli. Schepers and Durkan have referred to these as talc bodies, which are not distinguishable from asbestos bodies. The earliest and most constant roentgenographic change in pneumoconiosis due to talc is a diffuse haziness. Nodules, similar to but less dense and not as discrete as those of simple silicosis, may be present. This tends to give credence to the work of some investigator.? who believe that, in most individuals exposed to talc, quartz modifies the essential reaction to talc. The nodules are of varied size and may coalesce. As in asbestosis, the major portion of the roentgen change is usually in the lower half of both lungs. However, the upper lung fields are not spared and dense conglomerate shadows in these anatomical areas indicate long-standing and far advanced disease. In some cases plaques

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Fig. S.-This man, who died as a result of an acute myocardial infarction a 42 year history in the asbestos industry. The roentgen changes indicate advanced asbestosis, with an “alpha” pattern and thickened pleura.

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at age 67, had the presence of

of calcium density may be found on the pleural surface, not infrequently localized to the diaphragmatic regions. These are identical to those encountered in asbestosis. In size and shape, they vary from short straight lines to large irregular densitie?* overlying most of one or both lungs. As in asbestosis, these plaques are not necessarily associated with other pulmonary pathology and the underlying pulmonary tissue may or may not portray a fibrotic change. The thickened pleura described in asbestosis usually is not seen in cases which show a pulmonary reaction due to talc. KAOLIN

Another silicate employed in industry is kaolin. It is almost a pure aluminum silicate and has been used in pottery making for nearly 3030 years. The vast majority of kaolin which is mined in the United States comes from Georgia and South Carolina. Its employment in industry is well described by Edenfield.ll Perhaps its most extensive use is in the paper industry as a coating to produce “slick paper,” a product often preferred by the better magazines. Kaolin is also used in many other industries: plastics, paint, ceramics, rubber, adhesives, insecticides, and fertilizers. Its use in the treatment of diarrhea and dysentery has a long history in medical annals. According to Lynch and McIver, 30 kaolin is a kind of clay obtained by disintegration of an aluminous mineral, such as feldspar or mica. This alteration occurs in nature usually by hydrothermal processes or by surface weatheringsz3 In the commercial operation, the clay is removed from the ground in huge

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Fig. IO.-This man worked for 20 years in an asbestos industry, became disabled, and died 13 years later at age 50 of car pulmonale. There is a calcified pleural plaque at the right diaphragm and pulmonary fibrosis involving both mid- and lower lung fields. An “alpha” pattern is seen in the right midlung. The cardiac silhouette is enlarged.

moist clumps and at this stage presents no environmental problem. The exposure to the kaolinite mineral occurs in processing plants that use a dry method of preparation. The industry has replaced this method by the so-called “wet process;” however, the bagging and loading division of the industry still causes some degree of dust hazard and, unless adequate industrial hygiene measures are instituted, is a source of alarm. The mineral kaolinite, according to King et a1.,23does not appear to produce a significant fibrotic lesion in rats following intratracheal insufflation into the lungs. Other investigators11.30 have described pulmonary lesioas in human beings who had had a long exposure to kaolin dust. The basic finding is a chronic fibrotic reaction involving the lung. Briefly, the microscopic pathology consists of nodular areas of whorled collagen. Some alveoli are dilated and their walls are thickened by the fibrous reaction. Perivascular fibrosis may also be present. The pleura is thickened. Edenfield states that such lesions have not been associated with clinical evidence of impaired pulmonary function and have shown little if any evidence of progression. Conversely, Lynch and McIver feel that sufficient exposure to the inhalation of kaolin dust will cause in some individuals a chronic fibrotic reaction in the lungs that may be disabling and even prove fatal. The chief roentgen change caused by pulmonary deposi-

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tion of kaolin is a generalized and discrete nodulation. The nodules have the ability to coalesce. If the pulmonary lesion progresses, conglomerate shadows develop and closely resemble the progressive massive fibrosis of silicosis. BYSSINOSIS

Byssinosis is a form of pneumoconiosis due to the pulmonary deposition of cotton dust. The term byssinosis is derived from the Greek, meaning flax or cotton. Irritation usually occurs after the worker has been exposed to cotton dust for 6 to 10 years, when tightness of the chest is noted. Characteristically, it affects the individual after the weekend break; hence it has been called “Monday fever,” and is associated with dyspnea, fatigue, and cough.3s These symptoms may be present until the individual terminates his employment in the cotton industry, when all complaints disappear and, as far as is known, there is no impairment of pulmonary function. If exposure to cotton dust continues, the patient’s complaints increase and the symptoms of dyspnea and tightness of the chest become more severe. The pertinent pathological lesions of byssinosis, if it is progressive, are emphysema and chronic bronchitis. The emphysematous changes are generalized and, in addition to chronic inflammation of the bronchi, there may be metaplasia of the epithelium. There is little or no pulmonary fibrosis. Roentgen signs are not present in the early cases and usually the respiratory impairment is only temporary. In the later stages of byssinosis, the symptoms mimic chronic obstructive lung disease and the chest roentgenogram still may not demonstrate any definite abnormality. However, multiple small infiltrates may appear and roentgen signs o’f diffuse emphysema may develop. Arnoldson et al.’ believe that the latent pulmonary impairment is the result of bronchospasm, edema of the bronchial mucosa, bronchial secretions, or any combination of these factors. BAGASSOSIS

Bagassosis is a respiratory occupational disease caused by the pulmonary deposition of bagasse fiber. The latter is the residue after the sugar has been extracted from sugar cane. Bagasse is used in the manufacturing of paper, insulating materials, and wall board. Little is known about the pathology of bagassosis but a report of Buechner, 6 based upon lung biopsies, reveals that pulmonary fibrosis has been found in several patients in whom the clinical diagnosis of bagassosis had been made. The chest roentgen appearance of this disease does not appear to be specific. It varies from small localized nodules to diffuse fine nodulation. There may also be faint to medium linear areas of increased densities. Localized pneumonic foci are sometimes dispersed throughout the lungs. SodemarP has raised the question as to whether this condition should be classified as a pneumoconiosis. He indicates that the process may resolve and, as such, is unlike other pneumoconioses. There is evidence that during the acute phase of the illness, abnormal pulmonary ventilator-y changes are present. However, if the clinical picture improves, then the physiologic pulmonary function reverts to normal6

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DIATOMACEOUS EARTH

Diatomaceous earth, a nonmetallic mineral which is composed of siliceous skeletons of unicellular aquatic plants ,g has many industrial uses. It has application in the manufacturing of filters, adsorbants, insulators, and fine abrasive powder used in polishing compounds. It is also referred to as diatomite. Basically, diatomaceous earth is a hydrated form of amorphous silica and is classified as an opal. In the manufacturing process, three types of powder are made: natural, calcined, and flux-calcined. The calcined and flux-calcined products are obtained by heating the natural powder to temperatures of approximately 1800°F. This process causes the formation of cristobalite, a type of free crystalline silica. The cristobalite content may vary from an insignificant quantity in the calcined product to a substantial amount in the flux-calcined material.45 Adequate industrial hygiene measures are sufficient to maintain satisfactory working conditions. The silicates formed in the flux-calcined procedure, which are calcium silicate or magnesium silicate, have little if any pulmonary fibrogenic potential.18 The unit pathological lesion is a generalized perivascular thickening which also involves the alveolar walls and the peribronchial spaces. This finding is the result of increased cellularity and the deposition of delicate collagenous fibers.45 The alveolar spaces contain phagocytes with ingested dust fragments. According to Vorwald et al., 49the lack of discrete hyalinized nodules differentiates it from uncomplicated silicosis. Also the diffuse diatomaceous earth lesion remains essentially cellular with a relatively slight deposition of collagen. With progression of the pathologic reaction, areas of coalescence develop. These lesions, which consist of hyaline fibrous tissue interspersed with some areas of necrosis, vary in size. There is also obliteration of the lumen of the vascular channels. Again, in this advanced stage of pulmonary reaction, the lesion can be distinguished from the conglomerate phase caused by quartz. The hyaline collagen is not whorled and necrosis is more evident. It should be mentioned that the pulmonary reaction to the natural diatomaceous earth is far less severe than that to the flux-calcined product and is relatively benign. Cooper and Cralley,g in their monograph on diatomaceous earth, point out that Oechsli, Jacobson, Brodeur, and Kordan, who comprised a U.S.P.H.S. radiologic panel, have designed a roentgenologic classification for this disease. The densities are class&d semiquantitatively as either linear-nodular or confluent opacities. The work of this panel indicates that the nodules are small and not as dense or discrete as those of silicosis caused by quartz. These lesions do not appear to become larger in their cross-sectional diameter if the disease progresses; rather, the degree of profusion and concentration increases. At times the nodules coalesce and massive shadows develop. The conglomerate shadows vary in size and are usually con&red to the middle and upper third of either lung. In almost every case of confluency, an underlying pattern of linear-nodular change is present ( Figs. I1 and 12). SHAVER'S DISEASE

(BAUXITE

PNEUMOCONIOSIS)

Shaver’s disease, named for Dr. Cecil G. Shaver of Ontario, Canada, who first reported it,j7 is bauxite pneumoconiosis. Various aspects of the disease

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Fig. 11. Diatomaceous earth pneumoconiosis. The chest roentgenogram of this 41 year old man demonstrates generalized diffuse linear-nodular densities with commencing coalescence in the outer portions of both upper lung fields.

were discussed at the Sixth Saranac Symposium, which was held in 1947. The proceedings of that symposium were later published as a book.“” Shaver’s disease is a remarkable disorder which has a high incidence among a relatively small group of workers engaged in the processing of bauxite. Calcined bauxite, which contains from 80 to 85 per cent A&O, and from 4.5 to 7 per cent SiOs, is the chief raw material employed in the manufacture of corundum for abrasives. The manufacturing process, conducted in special electric furnaces, consists of the high temperature fusion of bauxite, to which are added small quantities of coke and iron scrap. During this fusion, or when the coke or iron is added, a dense white fume evolves. The lung changes occur only among those bauxite workers exposed to the fume. Chemical analysis of the fume reveals 40-62 per cent Al,O, and 28-44 per cent SiO,. Even though the fume is rich in alumina and silica, the specific agent in the fume responsible for the pulmonary changes has not been positively identified. The basic microscopic pathology of this disease is a diffuse pulmonary fibrosis which obliterates normal lung architecture and is hyaline in character. The development of secondary pulmonary emphysema and pleural blebs is quite common. According to the late Dr. Leroy U. Gardner,5G the pattern is not that of any of the well-known pneumoconioses that are associated with fibrosis. The absence of nodules, characteristic of silicosis, would appear to exclude that con-

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Fig. 12. Diatomaceous earth pneumoconiosis. This 46 year old man had a moderately severe exposure. The roentgenogram demonstrates contracting conglomerate lesions in both upper lung fields and linear-nodular lesions in the middle and lower zones of both lungs, some of which are coalescing.

dition; the absence of characteristic asb,estos bodies as well as th’e lack of occupational exposure to asbestos fiber eliminates the possibility of asbestosis. Early in the disease, the chest roentgenogram demonstrates a slight departure from normal, characterized by a fine, delicate fibrotic reaction of a nonnodular type. Eater, extensive fibrosis and emphysematous blebs of varised size are apparent. The blebs often rupture, causing spontaneous pneumothorax. A special feature of the advanced cases is that the pneumothorax is often bilateral. The hilar structures are prominent and, coupled with increased vascular markings, may mimic chronic passive congestion of the lungs. Pleural thickening of varying degree is usually present ( Fig. 13 ) . SUMMARY

END

CONCLUSIONS

In the United States, which is the worlds largest user of asbestos, chrysotile is the main commercial variety and only very small amounts of the amosite and crocidolite forms are used. The pulmonary deposition of asbestos fiber in

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Fig. 13. Shaver’s disease (bauxite). A 33 year old man employed as a furnace operator in the processing of bauxite for a period of six years. A partial pneumothorax is present in the peripheral portion of the left upper lung. A marked pleural reaction is seen at both bases. The interstitial fibrosis is characterized by the diffuse ill defined conglomerate areas of increased density scattered throughout both lungs.

sufficient concentration may precipitate a disabling pulmonary fibrotic reaction. Histologically, the diagnosis is made by identifying asbestos bodies and fibers which are enmeshed in a diffuse pulmonary fibrosis. Radiologically, the disease manifests itself in peculiar changes of the lung parenchyma and pleura. The parenchymal changes are not consiste,nt or uniform. They have been described as small opacities involving small to large areas of either or both lungs, less frequently large opacities, a de&i&e but usually localized ‘Xoneycomb” pattern, and ill-defined areas of increased densities. The pleura may show various degrees of thickening and calcification. There may be obliteration of the usual sharp outline of the cardiac silhouette. An acceptable roentgenologic classification for this pneumoconiosis has not yet been formulated. Well-planned epidemiologic studies are mandatory in order to determine with absolute certainty whether or not there is a relationship between asbestosis and malignant neoplasms. Talc and kaolin are two other silicates which may produce a similar pulmonary tissue reaction. In some talc cases, pleural plaques containing calcium may be present. These are identical with the plaques described in asbestosis. The thickened pleura noted in asbestosis usually is not seen with talc. The greater portion of the chest roentgen change is usually in the lower half of the

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lungs. The upper lung fields are not spared and dense conglomerate shadows here suggest long-standing and far advanced reaction to talc. The chief roentgen change caused by pulmonary deposition of kaolin is generalized and discrete nodulation; as in coal workers’ pneumoconiosis and silicosis, the nodules may coalesce to form conglomerate shadows. The dusts from the vegetable residue of sugar cane after the sugar has been extracted-bagasse-and from cotton fibers are considered to be non-pathogenic. The reaction caused by the former-bagassosis-does not exhibit typical roentgen changes. During the acute phase of the illness focal areas of increased densities compatible with the roentgen diagnosis of bronchopneumonia may be present. The more chronic form of bagassosis resembles chronic asthmatic bronchitis and emphysema. Byssinosis, caused by prolonged exposure to heavy concentrations of cotton fiber dust, does not produce chest roentgen changes in the early cases. In advanced cases the findings are those of emphysema and sometimes local infiltrates. Flux-calcined diatomaceous earth, which contains considerable cristobalite, is capable of producing diffuse pulmonary fibrosis. The abnormal densities in the chest film have been classified semiquantitatively as either linear-nodular or confluent opacities. Bauxite, too, produces diffuse fibrosis. Bullous emphysema, often resulting in pneumothorax, is a feature of the disease. To establish a correct diagnosis when changes in the lung are manifested on the chest roentgenogram or on histologic section, an accurate occupational history is essential. Often an individual exposed to more than one dust will have chest roentgen findings which do not conform to any known pneumo coniosis. Cases of this kind are usually referred to as having mixed pneumoconioses, and the roentgen and pathologic patterns may be modified by the presence in the environment of more than one substance, either toxic or inert. There is poor correlation of the roentgenographic and pulmonary functional studies in pulmonary asbestosis and in pneumoconiosis caused by cristobalite ( diatomaceous earth). ACKNOWLEDGMENTS The author wishes to express his gratitude to Dr. Paul Cartier, Thetford, Quebec, for making available some of the roentgenograms used in this article. He also wishes to thank Mr. Thomas M. Durkan and Mrs. Lillian R. Blinn for their tireless assistance in the prepsation of the manuscript and Mr. Francis T. Creedon for preparing the illustrations.

REFERENCES 1. Amoldsson, H., Bouhuys, A., and Lindell, S. E.: Byssinosis. Acta Med. Stand. 173:761-768, 1963. 2. Bader, M. E., Bader, R. A., and Selikoff, I. J.: pulmonary function in asbestosis of the lung. An alveolar-capillary block syndrome. Amer. J. Med. 30:235-242, 1961. 3. Bowles, 0.: Asbestos. A chapter from Mineral Facts and Problems. Bureau of Mines Bulletin 556. Superintendent of Doc-

uments, Washington, D. C., 1955. 4. Braun, D. C. and Truan, D. T.: An epidemiological study of lung cancer in asbestos miners. Arch. Indust. Health 17:634653, 1958. 5. Bristol, L. J.: Roentgenologic aspects of silicosis and asbestosis. Arch Indust. Health 11: 189-195, 1955. 6. Buechner, H. A.: Bagassosis.A true pneumoconiosis. Indust. Med. and Surg. 31:

304 311-314, 1962. 7. Caplan, A., Gilson, J. C., Hinson, K. F. W., McVittie, J. C., and Wagner, J. C.: II. A preliminary study of observer variation in the classification of radiographs of asbestos-exposed workers and the relation of pathology and x-ray appearances. Ann. N. Y. Acad. Sci. 132:379-386, 1965. 8. Cooke, W. E.: Fibrosis of the lungs due to the inhalation of asbestos dust. Brit. Med. J. 2:147, 1924. 9. Cooper, W. C., and Cralley, L. J.: Pneumoconiosis in diatomite mining and prccessing. Public Health Service Publication 601. Superintendent of Documents, Washington, D. C., 1958. 10. Dutra, F. R., and Carney, J. D.: Ashestosis and pulmonary carcinoma. Arch. Environ. Health 10:416-423, 1965. 11. Edenfield, R. W.: A clinical and roentgenological study of kaolin workers. Arch. Environ. Health 1: 392-403, 1960. 12. Elwood, P. C., Cochrane, A. L., Benjamin, I. T., and Seys-Prosser, D.: A followup study of workers from an ashesto:; factory. Brit. J. Indust. Med. 21:304-307, 1964. 13. Gardner, L. U., and Cummings, D. E. : Studies on experimental pneumonokoniosis. VI Inhalation of asbestos dust: Its effect upon primary tuberculous infection. J. Indust. Hyg. 13:97-114, 1931. 14. Gardner, L. U.: The pathology and roentgenographic manifestations of pneumoconiosis. J.A.M.A. 114:535-545, 1940. 15. Gardner, L. U.: Elements of diagnosis and prognosis in pneumoconiosis. Rocky Mountain Med. J. 41:385-391, 1944. 16. Gough, J.: Differential diagnosis in the pathology of asbestosis. Ann. N. Y. Acad. Sci. 132:368-371, 1965. 17. Gloyne, R. S.: Two cases of squamous carcinoma of the lung occurring in asbestosis. Tubercle 17:5-10, 1935. 18. Gross, P., Westrick, 11. L., McNerney, J. M., Schrenk, H. H., and Srsic, R. P.: The pulmonary effects of synthetic silicates derived from diatomaceous earth. Arch Indust. Health 16:317-325, 1937. 19. Hendry, N. W.: The geology, cccmrences, and major uses of asbestos. Ann. N. k-. Acad. Sci. 132:12-21, 1933. 20. Hornburger, F.: The c:lincidence of primary carcinoma of the lungs and pulmonary asbestosis. Amer. J. Path. 19:797805, 1943.

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21. Hunter, D.: The Diseases of Occupation. Boston, Little, Erown and Co., 1955. 22. Isselbacher, K. J., Klaus, H., and Hardy, H. L.: Asbestosis and bronchogenic carcinoma. Report of one autopsied case and review of the available literature. Amer. J. Med. 15:721-732, 1953. 23. King, E. J., Harrison, C. U., and Nagelschmidt, G.: The effects of kaolin on the lungs of rats. J. Path. Bact. 60:435-440, 1948. 24. Kiviluoto, R.: Pleural plaques and asbestos: Further observations on endemic and other nonoccupational asbestosis. Ann. N. Y. Acad. Sci. 132:235-239, 1965. 25. Lanza, A. J.: Silicosis and Asbestosis. New York, Oxford University Press, 1938. 26. Lanza, A. J.: Asbestosis. Paper read before the Fourth Conference of McIntyre Research Foundation on Silicosis. 1952. 27. Lynch, K. M., and Smith, W. A.: Asbestcsis bodies in sputum and lung. J.A.M.A. 95:659-661, 193G. 28. Lynch, K. M., and Smith, W. A.: Pulmonary asbestosis. 11. Including the report of a pure case. Amer. Rev. Tuberc. 23:643-659, 1931. 29. Lynch, K. M., and Smith, W. A.: Pulmonary asbestosis. III. Carcinoma of lung in asbesto-silicosis. Amer. J. Cancer 24: 56-64, 1935. 30. Lynch, K. M., and McIver, F. A.: Pneum3coniosis from exposure to kaolin dust: Kaolinosis. Amer. J. Path. 30:11171127, 1954. 31. Lynch, K. M.: Pathology of asbestosis. Arch Indust. Health 11:185-188, 1955. 32. McVittie, J. C.: Asbestosis in Great Britain. Ann. N. Y. Acad. Sci. 132:128-138, 1965. 33. hlerewether, E. R. A., and Price, C. W.: Report on effects of asbestos dust on the lungs and dust suppression in the asbestos industry. H. M. Stationery Office, London, 1930. 34. Oosthuizen, S. F., Theron, C. P., and Sluis-Cremer, G. K.: Calcified pleural plaques in asbestosis. Medical Proceedings. Published under the auspices of the Miners’ .\lcdical Bureau, Department of Mines, Joh:mnesburg, 1964. 35. Pendergrass, E. P., Felson, B., Jacobscn, G., Flinn, R. H., and Lainhart, \V. S.: U.,e cf ths IL0 classification in the study o$ silicosis. The international classification of roentgenograms ( 1958) with slight modifi-

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cations. Arch. Environ. Health 10:776-785, 1965. 36. Radiologic classification of the pneumoconioses. An Anglo-American radiograph reading exercise and study of the lnternational Labour Office ( 1958) classification of the pneumoconioses. Arch. Environ. Health 12:314-330, 1966. 37. Sanders, 0.: Silicosis and asbestosis. Amer. J. Surg. 90:115-119, 1955. 38. Schepers, G. W. H., and Durkan, T. M.: The effects of inhaled talc-mining dust on the human lung. Arch. Indust. Health 12: 182-197, 1955. 39. Schilling, R. S. F.: Byssinosis. Brit. Med. Bull. 7:52-56, 1950. 40. Seiler, H. E.: A case of pneumoconiosis. Result of the inhalation of asbestos dust. Brit. Med. J. 2:982, 1928. 41. Shull, R. J.: Asbestosis: A roentgenologic review of 71 cases. Radiology 27:279292, 1936. 42. Siegal, W., Smith, A. R., and Greenburg, L.: The dust hazard in tremolite talc mining, including roentgenological findings in talc workers. Amer. J. Roentg. 49:11-29, 1943. 43. Sodeman, W. A.: Bagasse disease of the lungs. Dis. Chest. 15:162-167, 1949. 44. Soper, W. B.: Pulmonary asbestosis. Amer. Rev. Tuberc. 22:571-584, 1930. 54. Smart, R. H., and Anderson, W. M.: Clinical and x-ray aspects of pneumoconiosis due to diatomaceous earth. Paper read before the Fourth Conference of McIntyre Research Foundation on Silicosis, 1952. 46. Sparks, J. V.: Pulmonary asbestosis. Radiology 17: 1249-1257, 1931. 47. Timbrell, V.: The inhalation of fibrous dust. Ann. N.Y. Acad. Sci. 132:255-273,

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1965. 48. U.S.P.H.S. Asbestosis Roentgenologic Panel (Bristol, L. J., Felson, B., Jacobson, G., and Pendergrass, E. P. ) 1967. Personal communication. 49. Vorwald, A. J., Durkan, T. M., Pratt, P. C., and Delahant, A. B.: Diatomaceous earth pneumoconiosis. Proceedings of the Ninth International Congress on Industrial Medicine, Bristol, John Wright & Sons Ltd., 1949. 50. Vorwald, A. J., Durkan, T. M., and Pratt, P. C.: Experimental Studies of Asbestosjs. Arch. Indust. Hyg. & Occup. Med. 3:1-43, 1951. 51. Wagner, J. C.: Asbestosis in experimental animals. Brit. J. Industr. Med. 20:112, 1963. 52. Wagner, J. C.: The sequelae of exposure to asbestos dust. Ann. N.Y. Acad. Sci. 132:691-695, 1965. 53. Wegelius, C.: Changes in the lungs in 126 cases of asbestosis observed in Finland. Acta Radiol. 28: 139-152, 1947. 54. Williams, R., and Hugh-Jones, P.: The significance of lung function changes in asbestosis. Thorax 15: 109-119, 1960. 55. Wright, G. W.: Symposium on occupational diseases of lungs; functional abnormalities of industrial pulmonary fibrosis. Arch. Indust. Health 11:196-203, 1955. 56. Gardner, L. U.: Unpublished records at the Saranac Laboratory. 57. Shaver, C. G., and Riddell, A. R.: Lung changes associated with the manufacture of alumina abrasives. J. Indust. Hyg. & Toxicol. 29:145-157, 1947. 58. Vorwald, A. J.: PneumoconiosisBeryllium, Bauxite Fumes, Compensation. New York, Paul B. Hoeber, Inc., 1950.