Document KJerDYv2zNmZvajd2LxOYOw7o

DISTRIBUTION C&P MEDICAL DIRECTORS c. F. Andrews B. H. Avashia R. Boone J. P. Gracie J. J. Higgs J. Hip-Flores W. R. Keene E. F. Kramer R. G. Rowe D. Teter D. Crowell Location Code Taft Institute Sisterville Canada Texas City Bound Brook Woodbine Port Lavaca Tech Center S. Charleston Danbury 519 512 380 440 515 312 581 510 511 514 E-3 Article/Source: "The Diagnosis of Nonmalignant Diseases Related to Asbestos" AM REV RESPIR DIS 1986: 134:363-368 HCI/?wi nsohn/tt 1076A 8-15-86 A 0243? UCC 017888 % A THE DIAGNOSIS OF NONMALIGNANT DISEASES RELATED TO ASBESTOS TklS OFFICIAL STATEMENT OF THE AMERICAN Thoracic Society was adopted by the ATS Board of Directors, March 1986. Objective The health effects of asbestos have become a cause of serious concern in recent years. It has been estimated that from 1940 to 1979, in the United States alone, 27,500,000 indi viduals were exposed to this mineral at work. Recognition of the diseases caused by asbestos exposure has led manufacturers to reduce ex posure in a variety of ways, such as by using alternative materials and by instituting im proved work practices. It has also led to wide spread public concern over the presence of asbestos in the environment, and fear on the part of persons with minimal exposure. This and projections of future asbestos related ill ness have posed important public policy questions -- whether to remove all asbestos in public buildings and what to do about the enormous estimated legal liability. In this con text, physicians are commonly asked for ad vice. Furthermore, they are also consulted re garding the diagnosis of an asbestos-related respiratory condition in an exposed in dividual. While abundant literature exists on the health effects of asbestos, there is much that is conflicting. Accordingly, this report has been prepared by a group of experts to' present an authoritative consensus view of the current state of knowledge while pointing out areas where additional information is neces sary. An attempt is made to summarize our present knowledge on the diagnosis of nonmalignant asbestos-related pulmonary disease and provide the sources on which the opin ion is based. Reprints may be requested from your state or t mii> AsMiriation Asbestos--the Mineral i.e., less than 5 microns (2-21). These are The generic term "asbestos" is used to describe a group of minerals which, when crushed, break into fibers rather than dust. They are hydrated fibrous silicates which have great ten sile strength, heat resistance, acid resistance, and some varieties are also flexible. This weavable rock has numerous important uses in an industrial society, and world production and use climbed steadily since its commercial in troduction in the late 19th century. Geology, mineralogy, and uses have been well described elsewhere (1,2). World production of asbestos has dropped markedly since the mid 1970's. poorly visible or invisible on light microscopy but have been demonstrated by phase micros copy and electron microscopy. Asbestos bod ies are commonly found in small numbers in lungs of city dwellers at routine autopsies in the absence of occupational exposure to as bestos and asbestos related illness. These are usually few in number and unassociated with pathologic abnormality in the parenchyma. This observation emphasizes the importance of developing standardized techniques to quantify the number and type of asbestos fibers in lung tissue (to be discussed below). The cumulative production of asbestos, how ever, continues to increase. There has been a good deal of debate about the mineralogic definitions of asbestos and asbestiform fibers. The most complete recent discussion on trends in asbestos production and now widely ac cepted mineralogic definitions are found in the NAS Report on asbestiform fibers (3). Benign Pleural Abnormalities Associated with Asbestos Asbestos causes pleural plaques, pleural thick ening and pleural effusion. Pleural plaques are discrete, elevated, opaque, shiny, rounded lesions. They characteristically occur on the posterolateral aspect of the lower parietal Asbestos in Lung Tissue pleura or diaphragm, but usually not on the visceral pleura, at the costophrenic angles, or Inhaled asbestos that is retained in the lung at the apices. Thin plaques are smooth and can become coated with a proteinaceous iron grayish-white. Thicker ones are ivory-colored staining material. The resulting asbestos or or gray and may have either a smooth surface ferruginous body is a most characteristic in or bosselated surface, or be coarsely nodular dex of asbestos exposure. It is usually recog with the consistency of cartilage. Plaques are nized by its beaded-necklace or drumstick ap of two types, diffuse or nodular, and elevated. pearance. The longer fibers are more likely They can vary in size and shape. On inspec to become coated (2-22). The core of asbestos, tion of gross specimens, calcification may be i.e., bodies found in human lungs, is more present but is not common. Microscopically, likely to be an amphibole fiber than to be plaques are seen to be laminated collagenous chrysotile, perhaps due to the greater ability connective tissue, acellular, with few inflam of the former to survive in lung tissue, while matory or fibrocytic nuclei; many are covered chrysotile tends to disappear over time. The by a thin layer of regular and well-differenti majority of the lung burden of asbestos, how ated mesothelial cells. Capillaries are rare (23, $*0 2*$'3ever, is uncoated and consists of Elast ic staining shows intact lamellae be- AM REV RESPIR DIS 1986 134 363-368 I UCC 017889 364 AMERICAN THORACIC SOCIETY neath the plaque in continuity with the sur rounding normal parietal pleural connective tissue, suggesting that plaques are extrapleural and develop between the latter and its cover ing layer of mesothelial cells (23). On micro scopic examination, calcium deposition is present in a large proportion of plaques, and occurs as deposits along the course of the col lagen fibers, ceasing abruptly where the con nective tissue changes into normal pleural tis sue (23). Well-differentiated cuboidal meso thelial cells are present on the surface and the edges of the plaque (23); metaplastic changes are uncommon (24, 25). Although coated asbestos fibers have not been reported in relation to pleural plaques in the extensive series of 172 sections exam ined by Meurman (23) using polarized light, the presence of many uncoated fibers may be noted when ashed tissue is studied (26, 27). Recent studies of the digestate of a small num ber of plaques has demonstrated the presence of submicroscopic fibers of both chrysotile and amosite fiber in these structures. It is of interest that these are more concentrated in the calcified zones than in the fibrous zones (28). The usual effect of asbestos on the visceral pleura is a focal or diffuse thickening. This varies from a thin, milky white discoloration, detectable only on gross visualization to a thick peel encasing the lung and easily seen on chest roentgenogram. In contrast to plaques, which are frequently diagnosed roentgenolog ically in asymptomatic persons, pleural fibro sis may cause symptoms and impair pulmo nary function. Pleural effusion may be caused by inhala tion of asbestos; this is an early manifesta tion and is usually an exudate. On rare occa sions it may persist for months or years. It may recur on the same or the opposite side after several years of exposure. In unusual cir cumstances it may be bilateral. Macroscopically, the fluid may be blood stained with vari able numbers of erythrocytes, macrophages, lymphocytes, and mesothelial cells (29). Pulmonary Asbestosis Definition The term asbestosis should be reserved for the interstitial fibrosis of the pulmonary pa renchyma in which asbestos bodies or fibers may be demonstrated. While pleural abnor malities are commonly associated with pa renchymal disease, they should be separately classified as there are differences between pleural and parenchymal fibrosis in epidemi ology, clinical features, and prognosis. Pathologic Features In lungs with minimal or moderate fibrosis, the changes may be subtle and difficult to demonstrate. On examination of gross speci mens, they appear as gray opaque areas de void of air spaces in an otherwise brown lung. The microscopic changes in pulmonary as bestosis vary from small areas of basal fibro sis to a diffuse, fine fibrosis of both lungs. In general, the more extensive the process the smaller the volume of the lungs. The cut sur face of the lung has a dark brown color with streaks of a fine, gray-colored fibrosis that generally appears to affect subpleural areas first and, frequently, in multiple and sepa rate areas. This fibrosis may accentuate lo bar and lobular septa and extends projections into the lung parenchyma. The parenchymal fibrosis, which has a linear and reticular ap pearance by X-ray, affects the lower lobes first, and extends upward with prolonged or heavy exposure (10, 30, 31). The fibrosis may take one of three forms. One is a diffuse fibrosis without air space enlargement; a second form is called honeycombing. This form may af fect the lower lobes and subpleural regions (31). The third form is a combination of both diffuse fibrosis and honeycombing. This lat ter form is the one most frequently observed. The honeycombing is characterized by en larged thick-walled air spaces ranging in size from 1 to 15 mm (32). The pleural surface adjacent to the fibrosis is invariably involved in the fibrotic process, either mildly with the appearance of a milky covering to the fibro sis, or with widespread fibrosis and symphy sis (30, 31). The hilar lymph nodes are only slightly enlarged and soft unless other dis ease coexists. While emphysema has been reported in the past, it is unusual, and may have been incorrectly labelled as honeycomb ing (10, 33). Microscopic Appearances There is little information on the early pathophysiology of asbestosis in humans. Current opinion is largely based on inferences from animal studies. Some evidence exists that release of lysosomal enzymes may result from the partial ingestion of the asbestos fibers and the incomplete fusions of the phagosome membrane, so allowing the release of enzymes into the medium from lysosomes which have fused with the phagosome. The cytotoxic ac tivity of asbestos exhibited by the release of lysosomal enzymes may result from the fibers penetrating intracellular structures, such as the nucleus and lysosomes, by preventing the movement of organelles within the cytoplasm, or by disrupting the cytoplasmic organization provided by microfilaments and microtubules (34). In any case, the initial reaction to as bestos fiber infoduced into the lung is the immediate exudation of neutrophils and mac rophages into the alveolar spaces in the locus of asbestos. This exudate varies with the age of the lesion. In the initial stages the exudate may be predominantly neutrophilic. Macro phages are the most common cells in the in filtrate. The inflammatory infiltrate soon is associated with varying degrees of organiza tion with fibrosis (35, 36). The process is be lieved to be concentrated initially in peribron chiolar regions (10, 30). The initial lesion af ter exposure by inhalation is in the region of the respiratory or terminal bronchioles. There is a macrophage exudate in the lumen associ ated with asbestos fibers and bodies. Metapla sia of the cuboidal epithelium to squamous type may occur. In the early stages, fibrosis may be minimal but, when present, is in the respiratory and terminal bronchiolar regions and in the alveoli arising from the most prox imal alveolar ducts. Alternatively, there may be coboidalization of the epithelial cells. Char acteristically, in early stages only an occa sional pulmonary subunit is involved. More advanced cases show a diffuse fibrosis, in volving the interstitium, frequently associated with areas of extensive fibrosis with oblitera tion of air spaces and condensation of the bronchovascular structures. Areas adjacent to the fibrosis may show accumulation of al veolar macrophages, some of which have in gested asbestos fibers or other fragments. Al veolar epithelial hyperplasia may also occur. When moderate or severe degrees of fibrosis are present, the small pulmonary arteries and arterioles are thickened and sclerotic (30). (The presence of uncoated asbestos fibers and asbestos bodies in the presence of interstitial fibrosis is mandatory for the pathologic di agnosis of asbestosis.) Before a pathologic diagnosis of asbesto sis can be made we must consider a number of problems, including the following: 1. There are numerous other causes of inter stitial fibrosis. 2. The distribution of interstitial fibrosis in asbestosis may be irregular, and therefore, adequate sampling of the lung must be done. The lingula and the right middle lobe are par ticularly prone to nonspecific fibrosis and sampling must take this into consideration. 3. While advanced asbestosis characteristi cally shows numerous asbestos bodies, they may not always be found because many fibers are cleared from the lungs and some, partic ularly chrysotile, may undergo dissolution and fragmentation with time (32). Thus, in un usual cases it may be difficult to demonstrate fibers or asbestos bodies in the histologic prep aration. When that is the case, 5 to 10 addi tional sections from the same block, and 5 to 10 additional new blocks from areas with fibrosis, should be prepared, stained, and sur veyed for asbestos bodies. If they are not found, the diagnosis of asbestosis is unlikely. 4. Even in the absence of a history of asbestos exposure, the presence of several or more as bestos bodies in areas of extensive interstitial fibrosis is sufficient evidence for a morpho logic diagnosis of asbestosis. 5. Not everyone who inhales an asbestos fi ber, or even a few fibers, develops even mi croscopic asbestosis. Normal lung defense mechanisms remove fibers via several welldescribed mechanisms. The Pneumoconiosis Committee of the American College of Pathologists and the Na tional Institute for Occupational Safety and Health dealt with these considerations when formulating the following statement with which we concur: "The criteria that permit the pathologist to es tablish the diagnosis of asbestosis have evolved during a review of many cases of the disease. F'resently, the minimal features that permit the UCC 017890 AMERICAN THORACIC SOCIETY 365 diagnosis are the demonstration of discrete foci ol fibrosis in the walls of respiratory bronchi oles associated with accumulations of asbestos bodies. These morphologic findings, although adequate to establish the diagnosis of asbestosis in an early evolutionary stage, have not been shown to result in functional and radiologic al terations. T he demonstration of asbestos bod ies in the absence of fibrosis is insufficient evi dence to justify the diagnosis of asbestosis. Con versely, a definite diagnosis of asbestosis cannot be made by the pathologist in cases that show characteristic fibrosis in the absence of asbestos bodies or other evidence of fibers. Because as bestos bodies are unevenly distributed in tis sue, an adequate number of samples should be examined thoroughly." (32) They further state that although the demon stration of asbestos fibers by the electron mi croscopic study of tissue digestates provides evidence of exposure, ultrastructural tech nique alone cannot be used to establish defini tively the etiologic role of asbestos in disease (32). This Committee has published guidelines for methods of assessing lung fiber concen tration and pathologic grading of asbestosis. The certainty of the cause and effect relation ship of asbestos to the fibrotic process in creases with increasing numbers of such par ticles and fibers visualized by light micros copy. Electron microscopy of digested Jung preparation from documented cases of as bestosis shows very large numbers of uncoated fiber fragments (37). Since asbestos bodies and fibers appear in lungs without evidence of asbestos-related dis ease, the question arises as to how many such bodies are necessary to infer a cause and ef fect relationship between asbestos particles and fibrosis. No precise answer exists, but ef forts to quantify the numbers of asbestos par ticles in known cases indicate that it is high. In the cases of asbestosis studied by Whitwell, the lungs nearly always showed three million light visible fibers per gram; control lungs gener ally show less than 20,000 fibers per gram (38). Electron microscopy is a more sensitive in dex of asbestos exposure than light micros copy. It will detect 10 to 100 times more fibers than seen by light microscopy. Fibers seen only by light or electron microscopy, in the absence of parenchymal fibrosis, indicates only that exposure to asbestos has occurred. Additional studies are required to define the number of fibers in the lungs of persons with a variety of occupational exposures, and with varying periods of exposure, as well as in nonoccupational populations. Investigations have demonstrated that as many as a million fibers per gram of dry tis sue of chrysotile may be present in the lungs from nonoccupational exposures in the general population. By contrast, lungs con taining a million fibers of amosite or crocidolite per gram are considered to reflect sub stantial occupational exposure to asbestos dust (39). An electron microscopic field of necessity represents a small sample of the lung and analysis of multiple fields is required to reflect the true asbestos lung burden. In our opinion, additional studies on the numbers and types of asbestos fibers in the lungs of control and exposed persons must be per formed to provide the informational bases for interpretation of quantitative data concern ing asbestos fibers in the lung and their rela tion to the presence of asbestosis or other as bestos related diseases. Exposure History Numerous studies have shown that asbesto sis has a relatively close association with both the magnitude and the duration of exposure to inhaled asbestos; the more intense and longer the exposure, the greater the numbers of affected workers and the greater the severity of their illness. There is no evidence that cas ual or indirect exposure, such as occurs in the general population, causes asbestosis. The major problem facing the clinician is to as sess whether an exposure has been sufficient to cause disease. Although dust levels have been measured in many industries for many years, they are not usually available to or eas ily interpreted by clinicians. Nevertheless, some general statements can be made. A care ful sequential history of all exposures to all potentially harmful substances is obviously important. Particular attention should be paid to occupations in which direct contact with asbestos has occurred. Consultation with phy sicians trained in occupational medicine or with industrial hygienists may be helpful in unclear cases. Evidence of asbestosis has been found many years after relatively brief but extremely heavy exposure. Such exposure often occurred in the asbestos textile industry over 50 years ago and has occurred more recently in work ers who have not used respiratory protection while spraying dry asbestos on steel beams. Fortunately, such exposure is rare at this time. With levels of exposure common in the past few decades, the latent period between the state of the exposure and the discovery of the manifestations of asbestosis is likely to be a minimum of 15 years, and more often con siderably longer. With exposures below the current recommended permissible exposure limit value, asbestosis is not likely to be found during the course of a working career. With proper engineering controls, work practice, and where necessary, personal respiratory pro tective devices, asbestosis should not occur. Clinical Diagnosis In the usual clinical setting, the diagnosis of asbestosis has to be made in the absence of histologic examination of lung tissue. Open lung biopsy is rarely indicated in the assess ment of workers for compensation purposes. The benefit of the doubt should be given whenever the clinical features and occupa tional exposure data are compatible with the diagnosis. In most instances, the clinician and epidemiologist must still rely on indirect methods of diagnosing asbestosis. These prin ciples of diagnosis are based on observations from pathologically proven cases. When bi opsy is done, careful attention must be paid to the sampling considerations mentioned above and the surgical technique employed (40). Assessment of lung dust burden in such biopsy material is desirable. Diagnosis of as bestosis does not mean that measurable im pairment of lung function or physical disa bility is necessarily present. Clinical Features In advanced stages, asbestosis is a restrictive lung disease associated with dyspnea, club bing of the fingers, basilar crackles and wide spread irregular opacifications on roentgeno grams. The latter are usually more prominent at the lung bases. Pleural thickening and cal cification may also be present as noted above. The vital capacity is usually reduced with pres ervation of the FEV,/FVC ratio and gas ex change impaired. Cor pulmonale may occur in advanced disease. When many or all of these features are present the diagnosis is made without difficulty. However, in the absence of the opportunity to examine lung tissue microscopically, the diagnosis is always in ferential. The certainty increases with increas ing numbers and severity of typical clinical abnormalities. The chest roentgenogram appears to be the most valuable examination in diagnosing as bestosis. A diffuse irregular interstitial pat tern coupled with evidence of pleural disease, e.g., plaques or extensive pleural thickening in a person with known exposure, presents little diagnostic difficulty. The difficulty with the use of the chest roentgenogram relates to the detection of lesser degrees of interstitial fibrosis. Efforts have been made to stan dardize the interpretation of roentgenograms in the pneumoconioses. The most widely ac cepted and extensively studied method for as sessing the degree of roentgenologic involve ment in the pneumoconioses was developed by the International Labour Office and is cur rently called the ILO-1980 Classification (41). This scheme evolved from studies of miners and focused initially on the detection of sili cosis. The X-ray appearance of silicosis is characterized initially by small rounded opacifications. The classification was later broadened to describe abnormalities which occur in asbestosis and do not have a rounded appearance. These are fine, medium and coarse, small irregular opacifications, and they are called s, t, and u, respectively. The classification, originally developed for describing radiologic changes in epidemio logic studies, has also been used in the clini cal context for case detection and/or diagno sis. In the latter instance, the information given in the chest radiograph is added to all other information about the individual in or der to arrive at a diagnosis. The number of these abnormalities in a given area of the chest film, whether rounded or irregular, is called their profusion. The pro fusion was initially graded as 0 for none, 1 for slight, 2 for moderate, and 3 for severe. AU243b UCC 017891 366 AMERICAN THORACIC SOCIETY It became apparent, however, that even expe rienced readers had difficulty in grading opacifications into these categories in a re producible fashion. However, if observers were asked to give two classifications, i.e., the one category they thought was most likely and another which they thought might also be con sidered, the observer reliability (i.e., in terms of reproducibility) was considerably im proved. This method of giving the observer two options (the one he thought most likely and next most likely) was called the expanded classification. It formed a 12-point scale that has proven to be very useful epidemiologically. It is likely that an individual who develops asbestosis moves more or less uniformly from the normal roentgenologic appearances (-/0, 0/0,0/1) to the abnormal (1/2,2/1,2/2, etc.). The problem is that the interpretation of the lesser degrees of abnormality on this scale is subjective and that numerous causes of such roentgenologic shadowing other than asbesto sis exist. In the presence of marked diffuse pleural thickening, it is difficult to diagnose or grade the severity of interstitial fibrosis. Accordingly, criteria other than roentgenographic ones have been sought. Dyspnea Asbestosis has been described as a monosymptomatic disease, dyspnea being the ma jor complaint of the affected individual (42). There is no doubt that shortness of breath is common and troublesome in individuals with clinically significant interstitial fibrosis. Dyspnea, however, is a nonspecific symptom, common in many other cardiopulmonary dis orders, and it is particularly subject to emo tional factors likely to be relevant in instances of suspected industrially-related disease. Ac cordingly, it is not adequate to use dyspnea as the only evidence on which to base a clini cal diagnosis of asbestosis in an individual at risk. Clubbing Clubbing of the fingers occurs more com monly in asbestos-exposed workers than in controls (43, 44, 45). The diagnostic useful ness of clubbing is limited, however, by two important considerations. There are many other causes of clubbing and clubbing, when present, is a late finding in pulmonary asbesto sis (46). Since the majority of persons with significant asbestosis do not have clubbing, and asbestos workers with clubbing may have it for reasons other than pulmonary fibrosis, the diagnostic usefulness of clubbing is limited. Basilar Crackles Crackles have been recognized as a feature )f asbestosis for over 50 years and are believed ?y many to be an early finding (47, 48, 49). They have been described as characteristic in CO their sound ("fine," "cellophane," "velcro," "close to the ear") and in their bilateral, basi lar distribution (50). They differ in quality and timing from the crackles of bronchitis which tend to be fewer in number and earlier in timing. Bronchitic crackling begins with the beginning of inspiration and usually dis continues prior to mid or late inspiration. Characteristically, the crackles of interstitial fibrosis are pan inspiratory or have an end inspiratory accentuation. They appear first at the bases in the mid-axillary lines and tend to spread toward the posterior bases. As the disease advances, the crackles become dis tributed at progressively high levels up from the bases (50). They are often difficult to dis tinguish from the crackles of congestive heart failure. Reported rates vary, but about half of the persons considered to have asbestosis on clinical grounds have crackles (47, 51, 52, 53); prevalences in exposed populations range from about 10-20%. Such prevalences depend on duration of exposure, the age of the popu lation, and prevalence of other diseases caus ing fine crackles. Observer variability exists in chest auscultation, but this can be reduced by training and waveform analysis (54, 55, 56). In summary, under carefully controlled circumstances crackles can be useful in diag nosing interstitial fibrosis. However, they are not also specific for the interstitial fibrosis related to asbestos. Pulmonary Function The characteristic features of pulmonary as bestosis are those of a restrictive lung disease, i.e., a reduction in lung volumes, with inspira tory capacity and vital capacity being primar ily affected, functional residual capacity be ing less affected, and residual volume even less. These changes are consistent with a de crease in pulmonary compliance. Hypoxemia may be present at rest or develop with exer cise. Diffusing capacity is also usually im paired, depending on the extent of the dis ease. By contrast, large airway function as reflected in the FEV,/FVC ratio is generally well preserved. Review of the prediction for mulas for pulmonary function tests reveals there is no one set applicable to all laborato ries and patient populations. Predicted nor mal values used in pulmonary function labor atories should be based on regression equa tions from studies whose testing equipment, methodologies and control populations most clearly resemble the patients under study. Numerous studies have shown that the effects of asbestos on lung function are dose related (57, 58, 59). There is convincing evidence that an as bestos related pulmonary abnormality can oc cur in the absence of definite radiologic change. These pathologic changes of early as bestosis have been demonstrated in biopsy material from asbestos-exposed individuals with minimal or no radiologic abnormality (60). Likewise, exposure response relation ships for certain pulmonary function abnor malities (including reduced lung compliance and impaired flow at low lung volumes) have been demonstrated in asbestos-exposed sub jects without radiologic abnormalities or reduction in vital capacity (58), and their oc currence subsequently confirmed in large an imal models with biopsy confirmation of the associated pathologic changes. The impair ment associated with such abnormality is usu ally modest. Diffusing Capacity Diffusing capacity or transfer factor has been the subject of numerous studies with some what conflicting results. In most studies of unexposed populations it is lower in asbestos exposed workers than in normal controls al though not always at a statistically signifi cant level (44, 45, 57, 62, 63). There is not always a clear relationship to dust exposure indices (58,64). It has, however, been shown to correlate with the severity of the histologic lesion in interstitial fibrosis (64), and its reduc tion can precede roentgenologic abnormali ties. At this time a reduction of the diffusing capacity in an asbestos worker, in the absence of other known causes for impaired gas ex change, would provide suggestive evidence for asbestosis, but further population studies are necessary to elucidate the precise role of this test. Other Studies Various other measurements have been em ployed for monitoring persons exposed to as bestos. A reduction in roentgenologic lung volume appears promising since it is applica ble to serial studies of patients, but it requires careful control of inspiration (66). This ap proach has not yet been taken in a large num ber of subjects exposed to asbestos. Inspiratory capacity was shown to be suita ble for surveillance of workers but is not likely to add much more than vital capacity (VC) as the two tests are highly correlated (59). This finding suggests that tests for small airways disease might in the future be applicable to early detection (67). In one study, neither clos ing volume nor closing capacity correlated with the duration of exposure or with the as bestos dust index (68). Gallium scanning, bronchoalveolar lavage, and transbronchial biopsy need further evaluation with respect to their usefulness in diagnosing asbestosis. CT scanning is of particular value in detect ing and quantitating pleural disease and aid ing in the differentiation of pleural from pa renchymal disease. The value of CT scanning in the detection of interstitial fibrosis also needs to be further evaluated. Thus, at this time, criteria other than crackles, restrictive lung functional abnormality, reduced diffus ing capacity of the lung (Dl), and roentgeno gram consistent with interstitial fibrosis of 1/1 or more are either impractical, of un proven value, or are not likely to yield addi tional information because of their high corre lation with one of these four. In our opinion, combinations of these abnormalities are more reliable in terms of specificity, relation to duration of exposure, consistency, and predictive value; however, little work has assessed combinations of ab normalities. Combinations Combinations of abnormal test results are not AU243 UCC 017892 AMf RICAN IHORACIC SOCIt T Y 367 11kcI\ lo punc moii' cl tcct i\c 111 detecting the kr (he relatively nonspecific finding of pleural ( ommitteeof the Scientific Assembh on 1 n- earliest changes m asbestosis. itmiiiively, one thickening, the demonstration of pleural vimnmental and Occupational Health in con test is likely to become abnormal first. It is plaques with or without calcification is bet junction with the American College of Chest likely that the I list ahnoi malits is not always ter evidence of asbestos exposure. Unfortu Physicians. The members of the Committee the same one (c.g., one worker may have only nately, the latter usually occurs only many were: an abnotmal I); |69], and another only crackles as the first manifestation). This has been demonstrated with respect to restrictive lung function pattern and reduced Dl. It is likely that observations will have to be made in large groups over long periods to delineate clearly the best single test for early diagnosis of ashestosis if, indeed, a single initial ab normality exists. Differential Diagnosis Streaky densities on chest films consistent years after the onset of the exposure, thus lim iting usefulness of early diagnosis. A major problem exists in the differential diagnosis when more than one disease is pres ent, whether it is congestive heart failure, COPD, or other chronic lung disease. There are diseases unrelated to asbestos exposure but with similar symptoms, and these may occur in some persons with asbestos exposure. However, given a clear history of exposure to asbestos, a diffuse interstitial fibrosis can be presumed to be due to the asbestos as other Raymond T. Murphy, M.D., Chairman Margaret R. Becklake, M.D. Stuart M. Brooks, M.D. Edward A. Gaensler, M.D. Bernard L. Gee, M.D. Allan M. Goldman, M.D. Jerome I. Kleinerman, M.D. Hilton C. Lewinsohn, M.D. Roger S. Mitchell, M.D. Mark J. Utell, M.D. Hans Weill, M.D. with a parenchymal disease have many causes. All alternative diagnoses must be considered before accepting the presumptive diagnosis of ashestosis. Occasionally, ashestosis is coexistent with chronic obstructive pulmonary disease. Evi dence is accumulating that obstruction may also be related to an individual's occupational exposure (70). The relative importance of cig arette smoking and asbestos in the develop ment of the combined problem of restrictive and obstructive disease may be difficult or even impossible to assess. Since a not uncommon feature of asbestos exposure is bilateral pleural thickening, the question arises as to the helpfulness of such thickening in indicating that a patient with pulmonary fibrosis has ashestosis. Indeed, as forms of interstitial fibrosis are relatively un common. The prevalence of lesser degrees of interstitial fibrosis is not well known and con siderable caution has to be exercised in at tributing all such phenomena to asbestos ex posure, either known or occult. Summary This document has focused on clinically de tectable interstitial fibrosis due to asbestos ex posure. While direct examination of lung tis sue is the most reliable method of diagnosis, as stated above, this is rarely indicated in the assessment of workers for compensation pur poses. Open lung biopsy is indicated in our opinion only when a clear health, rather than financial, benefit is likely to be provided. In the absence of pathologic examination of lung References 1. Hamilton A, Hardy H. Industrial toxicology. Ed. 3, Publishing Sciences Group Inc., Acton, M A, 1974; 421. 2. Gilson GC. Asbestos cancer: Past and future hazards. Proc R Soc Med 1973; 66: 395. 3. Zussman J. Asbestos: Nature and history. Rev. Ciba Geigy 1972; 2: 3. 4. Smither WJ. Asbestos and asbestosis. Ann Occup Hyg 1970; 13: 3. 5. Biological effects of asbestos. Selikoff IJ, Churg J. Co-chairmen, Proceedings of a conference held at the New York Academy of Sciences, Oct. 19-21, 1964. Ann N Y Acad Sci, 1965; 132:1-766. 6. Biological effects of asbestos. Anspach M, Chairman Deutsches Zentralinstitut fur Arbeitsmedizin: Gesellschaft fur Arbeitshygiene and Arbeitsschutz in der DDR. Dresden (April 22-25) 1968; bestos appears to be a rather potent stimulus tissue, the diagnosis of asbestosis is a judge 1- 312. for the development of pleural abnormalities. ment based on a careful consideration of all 7. Biological effects of asbestos. Bogovski P; Gil Selikoff found pleural fibrosis in 65% of per relevant clinical findings. In our opinion, it son JG; Timbrell V, Wagner JC, eds. Proceedings sons he studied 40 years from the onset of is necessary that there be: of a working conference at IARC, Lyon, October their initial exposure to asbestos. With pa tients with no known exposure to asbestos or 1. A reliable history of exposure. 2. An appropriate time interval between 2- 6,1972, IARC Scientific Publications No. 8, Lyon 1973; 1-341. other known hazardous materials (71), the exposure and detection (see pages 9-10) 8. Proceedings of the Pneumoconiosis Confer question arises as to whether an indirect or Furthermore, we regard the following clini ence. Johannesburg, South Africa, February 1959, occult exposure to asbestos might have caused cal criteria to be of recognized value: Orenstein AJ, ed, J and A Churchill Ltd., London the pleural thickening. Severe diffuse pleural 1. Chest roentgenographic evidence of I960; 1-629. thickening is not common even in asbestos exposure. It was present in only 2.5% of the asbestos workers studied by Selikoff. Since type "s," "t," "u," small irregular opacifi cations of a profusion of 1/1 or greater 2. A restrictive pattern of lung impairment 9. Pneumoconiosis. Shapiro HA, ed. Proceedings of the International Conference, Johannesburg, South Africa, 1969, Oxford University Press, Cape Town, 1970; 3-645. there were no controls in that study, it is dif ficult to be certain that asbestos was the cause with a forced vital capacity below the lower limit of normal 10. Parkes WR. Asbestos-related disorders. Brit J Dis Chest 1973; 67:261. of the pleural fibrosis in those subjects. In deed, Gilson reported in 1969 that pleural 3. A diffusing capacity below the lower limit of normal 11. Stell PM, McGill T. Asbestos and laryngeal carcinoma. Lancet 1973; 2: 416. thickening was found on 187 of 3,860(0.05%) 4. Bilateral late or pan inspiratory crackles 12. Newhouse ML, Berry G. Asbestos and laryn i routine roentgenograms of the chest in Great Britain (72). He conducted one of the few ob at the posterior lung bases not cleared by cough geal carcinoma. Lancet, 1973, 2, 615. 13. Libshitz HI, Wershba MS, AtkinsotV GW, jective studies of pleural thickening by com Of these, the findings on the chest roent Southard ME. Asbestos and carcinoma of the lar paring the asbestos exposure of 113 of the 187 genogram are the most important. When this ynx. JAMA 1974; 228: 1571. subjects with that of 113 age- and sex-matched criteria is not met, considerable caution is war 14. Guidotti TL, Abraham JL, DeNee PB. As controls. He found "a slight but unimpres ranted. The specificity of the above criteria bestos exposure and cancer of the larynx. West J fbc sive excess of positive histories of exposure increases with increasing numbers of positive Med 1975; 122: 75. to asbestos among the cases." Thus, it is not criteria. As in all clinical judgments, con 15. Graham J, Graham R. Ovarian cancer and as (^ necessary to assume an occult exposure to as founding variables, such as the presence of bestos. 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