Document 2J7QdX8Og9X16X9p6xGjO3b9p

Editorial Asbestos-related Diseases of the Lungs and Pleura Current Clinical issues1 PLAINTIFF'S EXHIBIT Asbestosis, or fibrosis of the lungs, oc curring in those with exposure to asbes tos, had been recognized by the early years of this century (1) and was the subject of careful investigation and report in the United Kingdom in 1930 and in the United States in 1938 (2, 3). This was followed by legislation on en vironmental control measures and health examinations in the United Kingdom, and recommendations on Threshold Limit Values in the United States, measures that it was hoped would result in disease control (1). However, by the 1960s it was apparent that this hope had been premature. Factors such as wartime stringencies, which had allowed increased useage with lax controls, postwar demolition of old buildings, including their asbes tos lagging, and the construction of high-rise buildings requiring spray-on insulation, had resulted in the reemer gence of asbestos-related disease as a major health hazard (1). Furthermore, new risks associated with exposure, such as cancer of the lung and pleura, had now become recognized; its role in the production of other cancers was also suspected (1). In addition, more acute parenchymal and pieurai reac tions, such as desquamative interstitial pneumonia and acute pleural effu sions, had been described (1). Over the last 20 yr the relationship of asbestos and disease has been the sub ject of intense study by scientists of many disciplines (4). Scientific investi gation has been accompanied by close attention from increasingly concerned work forces and manufacturers, from an increasingly informed public, and from governments sensitive to the health implications of the issues and concerned as to the role they should play. Nevertheless, the application of current scientific knowledge to person al health issues must inevitably remain in the hands of the individual physician dealing with his or her patient. This editorial addresses some current clinical issues from the perspective of the practicing physician and in light of present knowledge. Developments since an earlier clinical review in this Journal (5) will be emphasized. Public health issues have recently been re viewed elsewhere (6-9). Most physicians (and many members of the public) are now aware that there are several varieties of asbestos. The main commercial fiber is chrysotile, ac counting for approximately 95 wo of world use, with the commercial amphiboles--crocidoiite in the United King dom and amosite in the United States -- accounting for most of the rest (10). Anthophyllite has a small commercial use and exposure to tremolite occurs because it contaminates other exploited materials, e.g., chrysotile in Quebec, talc in New York state, or agricultural land, as in certain areas of Europe and the Middle East (10). In the earlier review (5) it was noted that exposure response relationships were demonstrable for the major as bestos-associated diseases despite the fact that all measurements of exposure developed could be regarded as no more than a poor reflection of dose de livered to the target organs. The ques tion of whether fibers differed in their disease potential was also reviewed; at the time there was already evidence of a fiber gradient for mesothelioma, less evidence of a gradient for lung cancer, and least for fibrosis (5). For meso thelioma, exposure to crocidoiite ap peared to carry the greatest risk, ex posure to chrysotile, a lesser risk, with amosite probably in between (11). An thophyllite, though recognized as car rying a lung cancer risk, had not been associated with mesothelioma produc tion (11). In addition, the mesotheli oma risk, at least for amosite and chry sotile, was thought to be higher in manufacturing than in mining and mil ling (11). A review of relevant present knowl edge is obviously beyond the scope of an editorial. However, the task is made easier by recent reviews (1,7-9) and the published proceedings of two recent in ternational conferences (12, 13). Con tributions to knowledge have come mainly from (/) epidemiologic studies in exposed populations addressing for the main part etiologic issues (14), (2) the quantitative as well as qualitative analyses of lung dust content (15), and (5) studies focused on the cell and its response to exposure (16). Lung Dust Assessments Lung dust burden may be assessed quantitatively, using fiber counts of ashed lung material, and qualitatively, by fiber identification. A conference in 1964 drew attention to three important points. First, lung dust content of asbestosis cases was much lower than that of silicosis cases and did not in crease with increasing degrees of fibro sis. The explanation offered was that asbestos fibers were dissolved in the lung over time and, on the basis of the physiochemical properties of the dif ferent fibers, it was suggested that chrysotile would be the most easily at tacked, amosite the least, with crocidolite in between (17). Second, using elec tromicroscopy it was shown that the buik of lung dust in laboratory animals and in humans consisted in small parti cles less than 1 pnm in length (18). Third, the widespread prevalence of coated fibers (asbestos bodies) in rou tine autopsy material (19) raised two issues, the apparent indestructibility of fibers in the lung and the universal nature of exposure clearly involving the general public. The latter issue was {Received for publication March 20, 19$2) 1 Supported by a grant for Studies in Working Environment and Health from Conseit de Recherche en Same du Quebec. 187 'mmifrmnnrmwrim 188 EDITORIAL if particular concern in view of the relatively recent (at that time) recogni tion of the mesothelioma risk, includ ing its association not only with occu- ional but also with nonoccupational ,josure such as domestic contact. 3y 1972, there had been impressive developments in the qualitative assess ment of individual fibers (20), and by 1978, there was ample confirmation that the bulk of the lung dust burden was in short fibers less than 5 /mm, and that fibers over 25 /mm were rarely seen. In addition the dimensional cha racteristics of lung dust were shown to vary with fiber type, chrysotile fibers appearing as the shortest and finest, amosite as the longest and coarsest, and crocidolite fibers being of an inter mediate range (21). Subsequent studies have shown that only the longer fibers are likely to undergo the process of coating (22), hence it follows that coated fiber counts in human lungs tend to reflect the amphiboie load and uncoated fiber counts the chrysetiie load (23-25). Subsequent studies have also strengthened the evidence that fibers dissolve out of the lungs over time, the loss occurring preferentially in chryso' ibers. Thus, though chrysotile ac- 'unts for the bulk of commercial use [ hence human exposure, it is the amphiboles that constitute the core of the majority of asbestos bodies found in human lungs, even in those known to have had occupational exposure to chrysotile (23, 24, 25). In addition, stupes of lung dust residues in Quebec chrysotile miners have shown the presence of almost as much tremolite, even though the latter fiber is a con taminant occurring only in small amounts in the chysotile deposits worked (IS). Finally, the results from two mesothelioma case control studies, one in the United Kingdom and one in the United States, reported in prelimi nary form in 1980 (14) (one was subse quently reported in full (27)), also sug gest the preferential loss of chrysotile. Thus, both studies showed the quanti ties of chrysotile in cases and their con trols to be comparable (chrysotile also accounted for most of the lung dust burden); however, there was an excess of - ">cidoIite in the United Kingdom and of amosite in North Ameri"ases in relation to their respective ci ols. All these findings strengthen the evidence that chrysotile is cleared more readily from the lungs than other fibers and may explain, in part at least, the fiber gradient in health effects (28). Quantitative and qualitative assess ment of lung dust residues provide (with obvious caveats as to degradation and clearance) a much closer measure of dose delivered to the target organ than indexes of exposure available to date for epidemiologic research. Often these have been no more than duration of employment since first exposure (5). Even a more complicated index such as cumulative exposure has to be based on incomplete past information obtained usually from area (not personal) sampling (7). More important, no in dex can in fact take account of any let alone the many factors, environmental and personal, that must determine whether or not inspired material will be retained and if so for how long (6). Asbestos-related Diseases of the Lungs and Pleura Acute pulmonary reactions to asbestos exposure. Appreciation of the prompt ness and character of these reactions, ir. particular those in the short-term (within days or weeks), comes from re search on animal models (29), from in vitro cell studies (16), and from obser vations on bronchoalveolar lavage material in animals (29) and in humans (30, 31). Thus exposure is followed by a reaction sequence that includes macrophage activation and release of chemotactic factors for neutrophils, as well as a protein factor that disturbs coiiagen balance; this sequence of events is thought to "cause chronic irri tation in the sense of intrinsic activity depending on the kind of fiber and its geometry" (16). Indeed, it is now diffi cult to accept that any airborne dust inhaled into the lung is truly inert, in cluding dusts not generally believed to be fiorogenic or oncogenic. However, the link between reactions at the cellu lar level and at the organ level remains to be established. An important ques tion is whether any components of the exposure reaction are reversible in humans, as is suggested by animal work (32). For instance, in one 7-yr prospective study in humans, certain clinical abnormalities such as basal rales, particularly if present on their own at the time of the first examina tion, were often not present on the next examination, a finding consistent with the possibility of regression of certain components of the human response (33). Parenchymal fibrosis. The clinical indicators of parenchymal fibrosis in clude breathlessness, basal rales, pul monary function changes, and small, mainly irregular, opacities on the chest radiograph (33). A relationship be tween exposure and prevalence of all these indicators, either individually and/or in combination, has been shown in most sectors of the asbestos industry, including mining and manu facturing, as well as in the application and use of asbestos materials (5). Ex perimental evidence suggests that ef fects are proportional to the number and dimensions of fibers rather than their dose by weight (16). Direct measurements of lung dust recently reviewed (34) tend to confirm the dose relationship between lung dust burden and fibrotic changes. However, it is not clear what determines progression from the initial cellular reaction men tioned above to what has graphically been described by Turner-Warwick and coworkers (31) as the "perpetuat ing circuits of fibroblastic proliferation or collagen condensation no longer dependent on the primary agent." Im plicated are certain changes in the im mune system (35, 36) but probably not genetic factors (37). Epidemiologic data showing that radiologic progres sion is only poorly related to exposure (38-41) also point to the importance of individual characteristics in determin ing a subject's response to exposure. In addition, after withdrawal from expo sure, not only may existing abnormal ities progress, but in a not unimportant number of cases, as much as 10ro in one study (38), new changes may ap pear. As regards between-fiber differ ences in fibrogenic potential, the evi dence is only very modest in contrast to that for between-fiber differences in oncogenic potential (7), which is con siderably stronger (see subsequently). Cancer of the lung. The first case of death from lung cancer in a man with asbestosis was reported in 1935; some 60 cases were reported over the next 20 yr (42). The first study to test the causal hypothesis was reported in 1955, and since then some 16 or more major cohort studies have been carried out and all showed an excess of lung cancer in relation to exposure (42). All major commercial types of asbestos have been implicated (7, 43, 44), though all probably do not carry the same risk (7, 14). In addition there is some evidence that risks may be greater when expo EDITO^Al 189 sure occurs in the manufacture of as bestos products and their use and ap plication than when exposure occurs in mining (7). The lag-time between first exposure and the development of lung cancer is long, seldom less than 10 and usually over 20 yr <7,14). Today's cases are thus the result of the exposures of yesteryear; cases will no doubt con tinue to appear but should, it is hoped, eventually level off in view of the gen eral improvement in working environ ments. It is still not clear whether the distri bution of cell types in asbestos-related lung cancers differs from that seen in nonexposed persons (35). Some asbes tos-related lung cancers appear to be scar cancers, i.e., a complication of asbestosis, as in other forms of pulmo nary fibrosis such as scleroderma. Their cell type (adenocarcinoma), as well as their location (peripheral, usually lower lobe) and origin (often multicentric), are consistent with this suggestion. Others, usually squamous cell types, occur often in association with only minimal fibrosis, are central ly located, and are usually seen in workers who smoke. Similarly, in epidemiologic studies, parenchymal radiographic abnormality, and by im plication pulmonary fibrosis, predates the appearance of cancer in some but not all subjects who later died of can cer (45). These findings are also not in consistent with the possibility of more than one etiologic mechanism operat ing in the production of asbestosrelated lung cancers. The role of ciga rette smoking, more than additive to the exposure risk in some epidemio logic studies, and multiplicative in others (14), cannot be assessed with certainty in the individual case. Lung cancer risk is related to expo sure, and most studies suggest that the relationship is linear and almost cer tainly without a threshold below which there is no risk (7, 44). Risk differs from work force to work force, differ ences that do not appear entirely ex plained by quantitative differences in exposure (7, 46). In addition a recent report on Australian crocidolite miners (47) serves to strengthen the existing evidence for a fiber gradient in lung cancer production, the risk being greater for crocidolite than for chrysotile (14). Industrial exposures also appear to carry a higher risk than mining and milling (7). Malignant mesotheiial tumors. An association between mesotheiial tu al pleura (usually occurring as part of mors and asbestos exposure was first parenchymal fibrosis) and parietal reported in 1959 (10). By 1963, it was pleural plaques had been recognized as recognized that most commercial fibers being associated with nonoccupational were implicated, and a fiber gradient as well as occupational exposure prior was suggested (48). By 1979, informa to 1964 (55) and likely influenced by fi tion on mesothelioma rates for work ber type. Exudative pleurisy (pleural forces exposed to Australian crocido effusion) and progressive pleural fi lite at source (47), as well as in its use in brosis were described later (5, 54). the manufacture of wartime gas masks In 1979 attention was drawn to the (49, 50), together with information on high prevalence of pleural changes in the differences in the recovery rate of workers in certain parts of the indus the various fiber types from the lung try, including mining (56), construc (see above), had greatly strengthened tion (54), and, in particular, shipyard the evidence for a fiber gradient. The occupations (57, 58) where the preval amphibole fibers (crocidolite in the ence of these changes may exceed that United Kingdom and amosite in North of parenchymal disease. In one study America) are more strongly implicated smoking appeared to influence the pre than chrysotile (14). Experimental evi valence of pleural reactions (57). There dence shows that the carcinogenic po is underdetection of pleural plaques by tential of fibers, given access to the the chest radiograph (59) and their ef cell, is primarily determined by particle fects on lung function are modest com size (10, 51). Exposure to tremolite pared with those of the pleural thicken may be associated with mesotheliomas ing and fibrosis that not infrequently if the particles are in the oncogenic size follows active pleural reactions (60). range, less than 2.5 pnm in diameter Thev rr.av, however, predict mortality and greater than 9 pnm in length (10). (45). Evidence for a dose relationship to Pleural plaques had been dubbed the exposure for this malignancy is still visiting cards of asbestos, a term modest. What is available supports the implying minimal health effects and in concept of increasing risk with increas line with the views expressed in 1972 ing dose without a threshold (7, 44), (61). However, it was clear from subse but with age at first exposure an impor quent reports that some pleural reac tant determinant (46). Cigarette smok tions, such as those associated with ing is not apparently related to its de dockyard exposures (57, 58), may be velopment. The long lag time, the less innocent than originally believed; often low levels of exposure in the workers with these changes are more remote past, and the occasional history likely to develop progressive parenchy of domestic and/or environmental ex mal fibrosis than those without (57), posure (accounting for as much as 10 and may have an increased risk of (52i and 15*0 (6) of cases, respectively) developing mesothelioma (62). remain the most disturbing aspects of Pleural plaques and/or calcification this tumor. Concern was increased by (detected by radiologic methods) have the recent report of what can reason been reported in rural populations in a ably be termed an epidemic of meso number of countries, including theliomas in rural Turkey (53). The Czechoslovakia, Bulgaria, Finland cases duster in certain villages (pleural (10), and recently in Greece (63), as mesotheliomas dominating in some well as in Turkey as discussed above. areas, peritoneal in others), while high These pleural reactions are attributed rates for other types of pleural reaction to exposure to fibers and/or other including plaques and calcification are materials found in the soil, the fibers seen in yet other areas. The soil and implicated being mainly tremolite and rocks in some regions contain not anthophyllite, but unlike the situation asbestos but zeolite minerals in fibrous in Turkey, these exposures do not ap form (erionite), with dimensions in the pear to evoke malignant pleural reac range believed to have oncogenic tions (10). capacity (see above), and these materi Airway responses. Evidence that oc als are frequently used in stucco ap cupational exposures to respirable par plied to the local buildings (10). ticles play a role in the development of Nonmalignant pleural disease. Non- bronchitic symptoms (in particular, in malignant pleural disease associated creased cough and sputum) has led to with asbestos exposure may take sever the acceptance of the term industrial al forms (54). Thickening of the viscer bronchitis (64). The relationships be- 190 f tween occupational exposure and ciga rette smoking on the one hand, and bronchitic symptoms and airflow limi, "''ion on the other hand, have been .died in some detail in coal miners in iom the deposition of the larger innaled particles in the major airways is believed to be responsible for the mucous hypersecretion; these airways are also thought to be the site for air flow limitation if it occurs (64). In con trast, small airway limitation in coal miners is believed to be more closely linked to smoking (64). The same spectrum of airway re sponses (mucous hypersecretion and/or airflow limitation in large and/or small airways) has been reported in asbestos workers (65-72) with the evidence link ing these changes to occupational ex posure being more or less strong. Thus studies in a general population have shown an increased prevalence of bronchitic symptoms, such as wheez ing, in workers exposed in a variety of occupations, Including those with as bestos exposure (65). Studies of asbes tos-exposed work forces have also shown an increase in bronchitic symp toms in relation to exposure consistent h the presence of an industrial bron .ris; this occurs not only in the min . sector (66), where the environmen tal pollution usually includes a certain amount if nc: a lot of rock dust, but also in the manufacturing section (67) where the environmental pollution is usually primarily in the form of fibers with or without other contaminants. Function profiles suggesting large airway obstruction are not infrequently seen in subjects with asbestosis in whom a restrictive pulmonary function profile would be anticipated on clinical grounds (68). Where such changes can not be attributed to smoking, it is not difficult to make a case for a role, con tributory or even causal, of the occupa tional exposure; such a role may also be as important even in the presence of a smoking history, though further re search is required to clarify the rela tionships of exposure, smoking, and airflow limitation in appropriate work forces. In addition, small airway ab normality has been shown to relate to exoosure in subjects who have no ologic abnormality (69); such *' -rnges may therefore reflect the ience of peribronchiolar fibrosis, which on the basis of both animal (32) and human (73) studies is believed to be the characteristic early lesion of asbestosis. Finally, documentation in animal studies of the promptness of the lung cellular reactions (see above) to asbes tos fibers and their nature (16, 74) has suggested potential mechanisms that might evoke parenchymal reactions to fiber inhalation other than fibrogenesis; for instance, endogenous elastase release leading to lung tissue destruc tion. Indeed, there appears to be good reason to review the role of all dusts, including asbestos dust, in evoking not only airway responses but also their possible role in the causation of airflow limitation. Research in this area is indi cated, however difficult, and is in line with the hope expressed in a recent task force report (75) that it might be pos sible to "lessen the contribution of workplace (exposures) to disorders that are highly prevalent, such as chronic bronchitis." Exposure-Response Relationships Epidemiologic studies have in general confirmed the relationship of respira tory abnormality and/or disease to ex posure in most industrial settings (5), so that the physician can reasonably assume this to be the case for most plants even if the plant or industry from which the patient comes has not been directly examined. 'Nevertheless, as pointed out above, there is consider able variation between subjects in response to what appear to be compar able doses, so that at high exposure levels there are those who do not re spond (5), and at low exposure levels there are those who do. This may be due merely to imprecision in the measurements of exposure (as the use of personal rather than area sampling seems to suggest (76)) or to imprecision in the measurements of response or to both. Alternatively, they may be due to real modifiers of response by individ ual characteristics that make up a sub ject's "susceptibility"- to react to expo sure. Indeed, as exposure levels fall (and they have been doing so in many workplaces over the last 20 yr (77-79)), individual characteristics may well assume a greater importance in deter mining not only the actual amount of material delivered to the target site and retained there, but also the nature of the response. Environmental Control Limits Control limits have in general been based on assessments of the risk of developing pulmonary fibrosis. For in stance, the 1968 recommendations of EOiTORIAL the British Occupational Health Socie ty for chrysotile, 2 fibers per cm3 averaged over 3 months (80), would allow, it was hoped, no more than a l<7o risk of developing asbestosis, as evidenced by basal crepitations, in a 50-yr working lifetime. The study underlying these proposals had been carried out in an asbestos textile plant. Subsequent 10-yr follow-up measure ments in the same plant showed higher prevalence rates of basal crepitations at all exposure levels, and in the investiga tors* opinion "left no room for compla cency," although they felt at that time that it was "impossible to state definite ly that the standard is inadequate" (77). In 1979 an advisory committee in the United Kingdom recommended that the control levels be reduced to 1 fiber per cm5 (78). The increasing impor tance of lung cancer as a cause of death in asbestos workers was emphasized in the medical review of the ill effects of asbestos on health prepared for this committee (7). For crocidolite, a con trol level of 0.2 fiber per cm3 was recommended (78). In a recent Review, Finkelstein (79) reports asbestosis rates in workers in an Ontario asbestos cement factory in relation to exposure, and compares his findings with those reported by Berry and associates (77) in the British textile factory referred to above. Finkelstein (79) used certification by the compen sation authorities as his diagnostic criterion for asbestosis, and estimated that the risk of developing asbestosis would reach l7o after a cumulative ex posure of only 10 fiber-yr/cm3. This value is considerably lower than the figure of 43 fiber-yr/cm (95^ confi dence limits, 34 to 52) estimated by Berry and associates (77) for reaching a l<7o risk of developing, not certifiable asbestosis but only one clinical indica tor of this disease, basal crepitations. For possible and certified asbestosis the figures were 55 and 72 fiberyr/cm3, respectively. The studies are not of course directly comparable for a number of reasons. Workers seeking compensation are more likely to be symptomatic than those who do not seek such assess ments, and their assessors are less like ly to give awards for short exposure. In consequence. Finkeistein's study may even have underestimated the overall risk to workers in the plant while exag gerating the slope of the overall expo sure response relationship (76). Both studies assume the absence of any clini- 5 t 3 EDITORIAL cal indicators of asbestosis (i.e., breath lessness on exercise, rales, parenchy mal opacities, and pulmonary function abnormality) in the absence of expo sure, whereas all have also been shown to occur with cigarette usage (33, 81, 82). In addition, in both studies the fiber levels used in the calculation of exposure indexes of the older men and covering the earlier years of operation of the plants are based on estimates, not measurements, of fibers in the en vironment, because at that time in both plants only particle counts were carried out. The indexes used, therefore, inevitably incorporate ail the inac curacies attendant on such extrapola tion (76), and though they are appro priate for within-plam comparisons, they are much less likely to be valid for between-plant comparisons. Indeed, the character of the environmental pol lution in a British texrile mill is unlikely to be directly comparable to that in an Ontario plant manufacturing other as bestos products. These uncertainties serve to under line the difficulties of extrapolating the health experience from one working environment to another. In addition, they underline the difficulties for scien tists in attempting to supply quantita tive information on exposure-response relationships and for legislators in us ing such information to set control limits (76). As a consequence, such lim its should be regarded as no more than estimates based on the best available information of levels that will protect human health within the limits stated. As for any other estimate, they have to be updated in light of new informa tion. Physicians need to appreciate the nature of such standards, if for no other reason than to avoid the mistake of excluding asbestos exposure as the relevant agent in a particular case be cause it is claimed that the environmen tal levels to which the patient was ex posed were "in compliance with control levels." Cases that appear to have de veloped under such circumstances should always serve to direct attention back to the environment and its careful reevaluation. Some Unresolved Issues .Among the important unresolved is sues is the risk associated with low level exposure. The issue is pertinent because even the latest engineering technology is capable of controlling fiber emissions to indeterminably low levels only in certain operations; others continue to remain dusty. Further dient in biologic effects between differ more, many, many tons of asbestos ent fibers and/or different types of ex materials are incorporated in buildings posure. The best explanation remains round the world where it will continue that of Timbrel! (90), namely, that bio both to delay the fire hazard on the one logic activity relates to the degree of hand, and on the other hand, to pose a penetration and deposition of inhaled health risk if friable or if removed asbestos particles (which primarily de without appropriate care. Further pends on their physical characteristics); more, some fibers will be released into however, in light of the current know the work environment as long as asbes ledge, biologic response is likely to be tos is mined and processed. Current modified by how long these particles knowledge on the risks associated with survive in lung tissue (which probably low level exposure depends on back depends on their chemical character ward extrapolation of the findings istics). Research throwing light on any associated with high exposure. With of these issues may, by providing ex the lower levels of exposure for most planatory information, also have use current work forces, lag time may be ful practical implications. longer and, perhaps, responses less ag gressive, factors that will tend to make Clinical Issues the research approaches used with suc The clinical issues have for the most cess to date (e.g., cohort studies'with part remained the same over the last mortality as the end point) less useful decade (5) and are concerned with (/) in the future. To address the issue of establishing the presence and nature of low level exposure, new approaches to the disease, (2) assessing impairment the measurement of exposure (76, 83), and disability (91), (5) assessing cause including exploiting external counting and'or helping to establish attributa- methods such as magnetopneumometry biiity (92), and (4) recommending for directly assessing lung dust burden measures to protect or improve health. ($4, 85), as well as new methods of Only for the last two issues does the ap measuring response (86) and new meth proach differ if the disease diagnosed ods in design and analysis (87, 88), (reactive, fibrotic, or neoplastic) is should be sought. Likewise, the sugges known or suspected of being linked to tion made in another context (89) to asbestos exposure. concentrate on what protects one per Attributability (in the medical sense) son 2nd not another, given comparable depends largely on establishing expo exposure to a risk factor (in this in sure, which can be done by history, by stance, asbestos exposure), might pay an environmental enquiry conducted at dividends. the work site, or by recovery of Fibers A second issue, related to the first, is from biologic fluids or other material. the evaluation ofthe impact of the con A good exposure history, carefully trol measures that have been intro taken, remains the most powerful of duced over the last 15 to 20 yr; it would the chest physician's tools (34). It be unforgivable not to learn from the should cover (J) ail occupations ever experiences of the 1930s. Here, appro held, including short-term and summer priate studies should exploit to the jobs and military or other service (with fullest the techniques of evaluation re sian and stop dates, job titles, job de search that have been developed in re scriptions including process anc cent years (87). agem(s) used, as well as plant healtl A number of etiologic issues have services and worker health experience) also been raised in this editorial. These (2) occupations of ail household mem include the following: the relationship bers, including their exposures, an- between fibrogenesis and carcinogene whether clothes were brought home fc sis in the pleura as well as in the lung laundering; (2) residence history, wit parenchyma; what modifies exposure particular reference to potenti; favorably and unfavorably for the in sources of neighborhood pollutio dividual and what personal characteris (e.g., mines, plants). Although it tics collectively determine "susceptibil usual clinical practice to pursue the e: ity" to respond unfavorably to expo posure history in face of a diagnosis < sure; whether the concept of an inert parenchymal fibrosis, it is less usual dust can be sustained, not only as far do so in face of a diagnosis of lu: as the lung parenchyma is concerned, cancer, unless there are specific indie but also, and particularly, as far as the tions. However, failure to do so in t airways are concerned. Finally, there is 19S0s may well be deemed negligent the question of what causes the gra viesv of the increasing number 192 EDITORIAL recognized human carcinogens (43), many of which are released into the , working environment. The vigor with which attempts to , -entify asbestos in biologic material is jrsued will vary with the clinical con text. For instance, in a case of pulmo nary fibrosis with long exposure in a plant with a known risk, it would hard ly be necessary for the purposes of clin ical diagnosis (or indeed for establish ing legal attributability) to seek further evidence. However, when the exposure history is inconclusive, particularly if it was short in duration and remote in time, identification and/or counting of fibers in biologic material, including sputum (93), bronchoalveolar lavage fluid (94), and biopsy or autopsy speci mens, may provide evidence of past ex posure (95). Coated fibers are readily seen under the light microscope with out special expertise; their presence in dicates exposure, often but not always recent, and usually to a heavy dust cloud containing long fibers. But their absence in no way excludes past expo sure, particularly if this has been to fine fibers (34). Coarse, uncoated fi bers can also be seen with phase con- t microscopy; for identification of ~->e fibers less than 0.2 pnm in diame\ , which constitute the bulk of the lung dust burde? (see above), the elec tron microscope is required. Qualita tive identification of fiber type by energy dispersive X-ray analysis is rare ly necessary in the clinical context, though it may obviously provide useful additional information. The application of qualitative and quantitative lung dust assessment to clinical derisions of diagnosis and etiol ogy is attractive (96). However, such measurements should clearly be used with caution until more information on unexposed subjects, as well as more in formation on exposure-response rela tionships, becomes available u*4). In addition, techniques will need to be standardized to reduce between-laboratory differences (97), and simplified (98). At present, to count ail the fibers, coated and uncoated, in 3 to 4 samples from one lung represents approximate ly 1 wk of work for a trained techni cs In light of the evidence that chryl -c is leached from the lung, it is ob- s that although high counts of any i ,r indicate important exposure, low counts by no means rule it out. Given evidence of exposure and dis ease, it is reasonable in the clinical con text to attribute the second to the first. The issue of attributability in law is be yond the scope of this editorial; it is, however, always the physician's job to bring the case to the attention of the appropriate health authorities. This is not only for purpose of possible com pensation but, more important, to be certain that appropriate protection of others exposed in the same workplace is carried out, particularly if the work place is one not previously recognized to be hazardous. Undoubtedly, the most important issue in case management is whether or not the individual patient should be ad vised against further exposure; it is also one of the most difficult. The advice given should depend on the stage of the disease (within the physician's exper tise) and on the current workplace en vironment (often outside the physician^ expertise). These issues have been dis cussed in greater detail elsewhere (34). Ir. many workplaces current environ mental levels are low or asbestos usage has been discontinued. Cleariy, it would be immoral not to recommend withdrawal if the workplace environ ment counts were not in conformity with current control levels. On the other hand, withdrawal from exposure is no certain protection against progression of already existing disease or development of new disease (33-41). Nor is it realistic to underesti mate what the loss or change of a job may mean to a person for both eco nomic and social reasons, particularly if he or she is without symptoms and believes himself or herself to be in good health. Nevertheless, few would dis agree with the view expressed by Weill in his summing up at the most recent Lyon conference (99) that "radiograph ic evidence of fibrosis should lead to the prudent course of avoiding further exposure." However, it is uncertain whether this course of action should also be recommended for workers who exhibit limited benign pleural abnor malities only (99). Nor is it known whether removal from exposure will also influence favorably future risk for developing lung cancer; nevertheless, because it seems to be cumulative dose that is relevant and, though withdraw ing from exposure may not diminish this risk, continuing exposure must surely increase it. For subjects who smoke there is good evidence (100) that quitting will favorably influence their cancer risk, as it would if they were en gaged in an occupation without asbes tos exposure. As always, it is up to the individual to make the final decision, and it is the physician's role to provide him or her with the medical facts as far as they are known. Margaret R. Becklake2'4 Departments of Epidemiology and Health, and of Medicine McGill University Montreal, Quebec, Canada * Career Investigator, Medical Research Council of Canada. 5 Requests for reprints should be addressed to Margaret R. Becklake, M.D., Department of Epidemiology and Health, McGill University, 3775 University Street, Montreal, Queber^ Canada H3A 2B4. * The writer acknowledges with much appre ciation critical comment on the text by Drs. F.D.K. Lidded. J.C. McDonald, and R. Oseasohn for. ir. particular, its epidemiologic content, and by Drs. P. Ernst and Judith Leech for, in particular, its clinical content. 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