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American Thoracic Society Documents Diagnosis and Initial Management of Nonmalignant Diseases Related to Asbestos This official statement of the American Thoracic Society was adopted by the ATS Board of Directors on December 12, 2003 CONTENTS Diagnostic Criteria and Guidelines for Documenting Them Asbestos as a Hazard Asbestos in Lung Tissue Clinical Evaluation and Indicators Symptoms Occupational and Environmental History Physical Examination Conventional Imaging Computed Tomography Bronchoalveolar Lavage Pulmonary Function Tests Nonmalignant Disease Outcomes Asbestosis Nonmalignant Pleural Abnormalities Associated with Asbestos Chronic Airway Obstruction Implications of Diagnosis for Patient Management Actions Required before Disease Is Apparent Actions Required after Diagnosis Conclusions Asbestos is a general term for a heterogeneous group of hydrated magnesium silicate minerals that have in common a tendency to separate into fibers (1). These fibers, inhaled and displaced by various means to lung tissue, can cause a spectrum of diseases including cancer and disorders related to inflammation and fi brosis. Asbestos has been the largest single cause of occupational cancer in the United States and a significant cause of disease and disability from nonmalignant disease. To this demonstrable burden of asbestos-related disease is added the burden of public concern and fear regarding risk after minimal exposure. This statement presents guidance for the diagnosis of nonmalignant asbestos-related disease. Nonmalignant asbestos-related disease refers to the following conditions: asbestosis, pleural thickening or asbestos-related pleural fibrosis (plaques or diffuse fibrosis), "benign" (nonmalignant) pleural effusion, and airflow obstruction. This document is intended to assist the clinician in making a diagnosis that will be the basis for individual manage ment of the patient. It therefore provides overarching criteria for the diagnosis, specific guidelines for satisfying these criteria, and descriptions of the clinical implications of the diagnosis, including the basic management plan that should be triggered by the diagnosis. It is understood that disease may be present Members of the Ad Hoc Statement Committee have disclosed any direct commer cial associations (financial relationships or legal obligations) related to the prepara tion of this statement. This information is kept on file at the ATS headquarters. Am J Respir Crit Care Med Vol 170. pp 691-715, 2004 DOI: 10.1164/rccm.200310-1436ST Internet address: www.atsjournals.org at a subclinical level and may not be sufficiently advanced to be apparent on histology, imaging, or functional studies. One of the most important implications of the diagnosis of nonmalignant asbestos-related disease is that there is a close correlation between the presence of nonmalignant disease and the risk of malignancy, which may arise from exposure levels required to produce nonmalignant disease or mechanisms shared with premalignant processes that lead to cancer. The major ma lignancies associated with asbestos are cancer of the lung (with a complex relationship to cigarette smoking) and mesothelioma (pleural or peritoneal), with excess risk also reported for other sites. There is a strong statistical association between asbestosrelated disease and malignancy, but the majority of patients with nonmalignant asbestos-related disease do not develop cancer. On the other hand, the risk of cancer may be elevated in a person exposed to asbestos without obvious signs of nonmalignant asbestos-related disease. However, a diagnosis of nonmalignant asbestos-related disease does imply a lifelong elevated risk for asbestos-related cancer. DIAGNOSTIC CRITERIA AND GUIDELINES FOR DOCUMENTING THEM People with past exposure to asbestos consult physicians for many relevant reasons: to be screened for asbestos-related dis ease, for evaluation of specific symptoms that may relate to past asbestos exposure (known or unsuspected), for treatment and advice, and for evaluation of impairment. In 1986, the American Thoracic Society convened a group of experts to review the literature and to present an authoritative consensus view of the current state of knowledge with respect to diagnosis of nonmalig nant disease related to asbestos (2). In 2001, a new group was convened to review and to update the 1986 criteria. This state ment constitutes that committee's report, completed in 2004. The criteria formulated in this statement are intended for the diagnosis of nonmalignant asbestos-related disease in an individ ual in a clinical setting for the purpose of managing that person's current condition and future health. These general criteria are slightly modified from those presented in 1986 (Table 1) (2): Evidence of structural pathology consistent with asbestosrelated disease as documented by imaging or histology Evidence of causation by asbestos as documented by the occupational and environmental history, markers of expo sure (usually pleural plaques), recovery of asbestos bodies, or other means Exclusion of alternative plausible causes for the findings The rest of this statement is largely devoted to presenting clinical guidelines required to document that each of these crite ria is met. Demonstration of functional impairment is not re quired for the diagnosis of a nonmalignant asbestos-related dis ease, but where present should be documented as part of the complete evaluation. Evaluation of impairment has been exten- 692 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 TABLE 1. CRITERIA FOR DIAGNOSIS OF NONMALIGNANT LUNG DISEASE RELATED TO ASBESTOS 1986 Guidelines Chest film (irregular opacities) Pathology (College of American Pathologists) Consistent time interval Occupational and environmental history Asbestos bodies or fibers in lung tissue 2004 Guidelines Evidence of structural change, as demonstrated by one or more of the following: Imaging methods Histology (College of American Pathologists) Evidence of plausible causation, as demonstrated by one or more of the following: Occupational and environmental history of exposure (with plausible latency) Markers of exposure (e.g., pleural plaques) Recovery of asbestos bodies Rule out other causes of interstitial fibrosis or obstructive disease Exclusion of alternative diagnoses "Evidence of abnormal test" Crackles, bilateral, not cleared by cough Restrictive disease Reduced diffusing capacity Evidence of functional impairment, as demonstrated by one or more of the following: Signs and symptoms (including crackles) Change in ventilatory function (restrictive, obstructive patterns in context or disease history) Impaired gas exchange (e.g., reduced diffusing capacity) Inflammation (e.g., by bronchoalveolar lavage) Exercise testing Comparison and Notes Demonstrates the existence of a structural lesion consistent with the effects of asbestos. The criteria outlined in the 1986 guidelines were most explicit for asbestosis Chest film, HRCT, and possibly future methods based on imaging. The 1986 guidelines specified ILO classification 1/1 Criteria for identifying asbestosis on microscopic examination of tissue are unchanged Evidence of plausible causation implies that the temporal relationship, including latency, is plausible The 2004 guidelines are not limited to lung tissue, consider the role of BAL to be established, and deemphasize fibers because they are difficult to detect and a systematic analysis for asbestos fibers is not generally available The 1986 guidelines primarily addressed asbestosis but mentioned smoking as a cause of obstructive disease. Implicit in the article, however, is that nonmalignant diseases presenting similarly to asbestos-related disease should also be ruled out Functional assessment is not required for diagnosis but is part of a complete evaluation. It contributes to diagnosis in defining the activity of disease and the resulting impairment Signs and symptoms are not specific for diagnosis but are valuable in assessing impairment The 1986 criteria admitted the possibility of obstructive disease; the 2004 criteria address this specifically The 1986 guidelines noted possible utility of bronchoalveolar lavage and gallium scanning but considered them to be experimental techniques. The 2004 guidelines exclude gallium scanning, suggest that additional indicators of active inflammation may become useful in future Definition of abbreviations: BAL = bronchoalveolar lavage; HRCT = high-resolution computed tomography; ILO = International Labour Organization. From References 64 and 65. sively reviewed elsewhere and is not repeated here (3). Func tional impairment may be demonstrated by evidence of symp toms or signs, ventilatory dysfunction, impaired gas exchange, and inflammation. Pulmonary function testing should be con ducted in conformity with standards already published by the American Thoracic Society (4, 5), including multiple trials to con firm reproducibility and documentation of all trials attempted. These guidelines are designed for clinical application, not for research, epidemiologic surveillance, screening, litigation, or adjudication. They balance the need to be as accurate as possible with protection of the patient's safety and the yield, cost, and accessibility of the diagnostic procedures available. These guide lines, if they err, err on the side of specificity rather than sensitiv ity. This is because nonmalignant asbestos-related disorders are difficult to detect in their earliest stages and because there is no early intervention that has been proven to alter the subsequent evolution of the disease. On the other hand, the documentation of causation by asbestos carries important implications for the patient and can be established with reasonable certainty, once the disease is identified. Asbestos as a Hazard The generic term "asbestos" is used to describe a group of minerals that, when crushed, break into fibers. As defined by the National Research Council (1), the term "asbestos" is a "commercial-industrial term rather than a mineralogical term. It refers to well-developed and hair-like long-fibered varieties of certain minerals that satisfy particular industrial needs." They are chemically heterogeneous hydrated silicates and each has chemical analogs with different structures that do not form fibers. Fibers have parallel sides with length three or more times greater than width. Asbestos fibers have great tensile strength, heat resistance, and acid resistance; varieties are also flexible. The six minerals that are traditionally defined as asbestos include chrysotile asbestos (the asbestiform variety of serpentine); the amphiboles, which include crocidolite (the asbestiform variety of riebeckite) and amosite (the asbestiformvariety of cummingtonite-grunerite); and the asbestiform varieties of the amphiboles, which include anthophyllite (anthophyllite asbestos), actinolite (actinolite asbestos), and tremolite (tremolite asbestos) (6). Just as all forms of asbestos, by the definition and classifica tion above, appear to cause malignancy, all may cause the nonmalignant diseases described. Issues of relative potency among the forms of asbestos, and particularly between chrysotile and the amphiboles, are primarily of concern with respect to the risk of malignancy and are not discussed in this document. Commercial-grade asbestos is made up of fiber bundles. These bundles, in turn, are composed of extremely long and thin fibers, often with splayed ends, that can easily be separated from American Thoracic Society Documents 695 been coated with an iron-rich, proteinaceous concretion (Figures 1 and 2). Amphibole asbestos forms the majority of asbestos bodies and is more persistent in lung tissue than chrysotile (25). Asbestos bodies are larger than asbestos fibers and can be identi fied and quantified by light microscopy. An iron stain is helpful to identify fibrous bodies coated by iron (hence the general name "ferruginous bodies"). Ferruginous bodies generally form on fibers at least 10 ^m in length, and more than 90% of all coated fibers have asbestos cores. Demonstration of an elevated body burden of asbestos confirms past exposure (19). Levels of at least one or two asbestos bodies per field of a tissue section on a slide under light microscopy are consistent with occupational exposure (19, 22, 24). Transbronchial biopsy. Transbronchial lung biopsies are usu ally too small to analyze for asbestos bodies. Bronchoalveolar lavage recovers more material and therefore provides a better indicator of tissue burden. Some experienced clinicians have found that identification of six or more bodies in bleach-digested samples from at least two biopsies is characteristic of patients with occupational exposure (26). However, the absence of ob servable asbestos bodies is not reliable in excluding significant exposure in transbronchial biopsy tissue (20). These indicators of fiber burden are sufficient but not neces sary to identify occupational exposure and to diagnose asbestosrelated disease. Beyond clinical research, the method has appli cations in litigation and exposure assessment for epidemiology. Bronchoalveolar lavage. Asbestos bodies and fibers can be identified and quantified in BAL specimens, as in Figure 2 (22). There is considerable variation among laboratories in these tests (18, 19, 22, 23). The count of asbestos bodies in BAL fluid appears to correlate with the presence or degree of fibrosis in some studies but not others (24, 27, 28). BAL in patients with asbestosis has demonstrated an alveolar macrophage alveolitis associated with a modest increase in neutro phils (12, 13). This neutrophilia correlates with the finding of crack les (rales) on physical examination and disturbances in oxygen ation (12, 27) and is apt to be more pronounced in patients with advanced disease (13). Clinically apparent asbestosis occurs only after a significant latent period. However, studies using BAL, computed tomography (CT) scanning, and gallium-67 scanning have demonstrated that inflammatory events occur well before the onset of clinical disease. Thus, it is likely that the initial exposure induces inflammation and injury that persist through the latent or subclinical phase and later develop into the clinical disease, which is typically diagnosed by chest imaging (13). CLINICAL EVALUATION AND INDICATORS The clinical evaluation of nonmalignant asbestos-related disease should consider subjective symptoms as well as objective findings on physical examination, pulmonary function tests, and chest radiographic studies. In the large majority of patients, the diag nosis of nonmalignant asbestos-related lung disease is based on the clinical findings discussed below, in the context of an appropriate history of exposure to asbestos and a documented latency period sufficient to place an individual at risk. Symptoms The insidious onset of dyspnea is the most common respiratory symptom associated with asbestosis, typically beginning with dyspnea on exertion. A nonproductive cough is commonly pres ent. The presence of wheeze or dyspnea (27), as reported on the ATS-DLD-78A respiratory questionnaire (5), is strongly associated with diminished ventilatory capacity in cross-sectional studies of asbestos-exposed workers, with an 11 to 17% reduction in ventilatory capacity (27, 29). A 2-8% reduction in ventilatory capacity has been observed for cough, phlegm, and symptoms of chronic bronchitis among asbestos-exposed workers (29). De velopment or progression of respiratory symptoms has been associated with accelerated loss of ventilatory capacity in a longi tudinal investigation of asbestos-exposed workers, with an excess 28-ml/year decline in FEV1 associated with development of dys pnea, and 67-ml/year excess decline in FVC associated with newly developed wheezing, relative to asymptomatic individuals (30). In a study of 64 patients, diffuse pleural thickening or fibrothorax was associated with dyspnea on exertion, usually mild, in 95%, chest pain in more than half, and restrictive defect in one-third. The chest pain was intermittent in most but constant in 9% (31). Rapidly progressive or severe chest pain should raise clinical suspicion of either malignancy or a nonmalignant pleuritis. Subjective symptoms are not easily interpreted in the absence of objective findings but provide important ancillary information. The persistence or new onset of respiratory symptoms is corre lated with accelerated loss of lung function in asbestos-exposed workers and therefore may predict future risk (30). Occupational and Environmental History It is essential to take a comprehensive occupational and environ mental history when asbestos-related disease is suspected (32). The occupational history should emphasize occupational and environmental opportunities for exposure that occurred about 15 years and more before presentation. The diagnosis of asbestosis is ideally based on an accurate exposure history, obtained whenever possible directly from the patient, that defines the duration, intensity, time of onset, and setting of exposure experienced by the patient. Patients may forget short periods of employment, during which intense expo sure is possible, or employment early in their lives. In such cases the characteristic radiographic signs of asbestos exposure may be enough to document exposure. The occupational title is not enough, as the names of many occupations and trades are uninformative, such as "millwright" or "fireman" (a misleading title that sometimes refers to furnace workers and stokers) or "mixer." Representative occupational exposures include, but are not limited to, manufacture of asbes tos products, asbestos mining and milling, construction trades (including insulators, sheet metal workers, electricians, plumb ers, pipefitters, and carpenters), power plant workers, boilermak ers, and shipyard workers. Asbestosis is commonly associated with prolonged exposure, usually over 10 to 20 years. However, short, intense exposures to asbestos, lasting from several months to 1 year or more, can be sufficient to cause asbestosis. For example, shipyard workers who applied or removed insulation in confined spaces have de veloped asbestosis after brief periods of heavy exposure. Insula tion workers have had similarly intense exposures during their apprenticeship when they unloaded asbestos-containing sacks into troughs for mixing asbestos cement. Such occupational ex posures are now rare but were common in the United States from the years after World War II until the 1970s. Adequate industrial hygiene controls were absent or not widely applied. Protective regulations were inadequate and only partially en forced during much of that period. Workers whose own jobs may not require handling asbestos may still be "bystanders" who worked in close proximity to other users, especially in the construction trades, where workers have experienced exposure from insulation being installed around them. Among sheet metal workers, for example, the prevalence of asbestos-related changes on chest film was 31% (19% pleural only, 7% parenchymal only, and 6% both). Among those who had been in the trade for 40 or more years, 41.5% had radio 696 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 graphic findings (33). These findings established that sheet metal workers, although not working directly with asbestos, had sub stantial exposure in the work environment. Measures taken to protect workers, or lapses in these mea sures, may be important in documenting exposure. Although exposure levels are generally low in developed countries today, lapses occur and were more frequent in the past. Some patients who have immigrated may have worked in countries where occu pational health regulations have been poorly enforced or where environmental exposure has occurred. Environmental sources of exposure, for example, tailings of asbestos mines or prolonged exposure in buildings with exposed sources of asbestos contamination, may be important in some cases. Passive exposure, for example, of children in the home when asbestos is brought into the house on the clothes of a worker, may cause disease (34). Undisturbed and nonfriable asbestos insulation in buildings, including schools, does not pres ent a hazard. The prevalence of asbestosis among asbestos workers in creases with the length of employment, as illustrated in an early report in which investigators analyzed chest films of 1,117 New York and New Jersey asbestos insulation workers. They found asbestosis in 10% of workers who had been employed for 10 to 19 years, 73% among those employed for 20 to 29 years, and in 92% of those employed for 40 or more years (35). A similar exposure-response relationship was found among asbestos ce ment workers (36). Differences in solubility among the various types of asbestos may affect fiber retention, body burden, and the risk of nonmalignant disease. The clinician is rarely in a position to evaluate this aspect of exposure and there is no validated means to adjust the occupational history to take this factor into account. Solubility is primarily of concern with respect to projecting future risk, particularly of malignant disease, given a history of exposure. It is irrelevant to diagnosis when disease is already present and other indicators of exposure are demonstrable. Physical Examination Physical findings in asbestosis include basilar rales, often charac terized by end-inspiratory crackles (rales) (36, 37); in some cases of advanced asbestosis, finger clubbing may be present. Physical findings of crackles, clubbing, or cyanosis are associated with increased risk for asbestos-related mortality (36). Although these physical signs are useful when present, their overall clinical utility is limited by low sensitivity. For example, in one study as many as 80% of individuals with radiographic asbestosis demonstrated crackles, a frequency that appears to be unusually high in the experience of other clinicians (27). Conventional Imaging The chest radiograph remains an extremely useful tool for the radiographic diagnosis of asbestosis and asbestos-related pleural disease, and is widely available internationally. The plain film has long been the basis for assessing asbestos-related disease of the lung and pleura. A standardized system for taking and classifying films for presence and profusion of opacities consis tent with pneumoconiosis and for pleural changes was developed in the 1950s and is now known as the International Classification ofRadiographs ofPneumoconiosis (or "ILO classification" after its sponsor, the International Labour Organization). The ILO classification has been revised (38). This system, which is the basis of the "B-reader" qualification for designating persons as competent in classifying pneumoconiosis films, was developed for grading the radiographic severity of pneumoconiosis in epide miologic studies but has been applied to clinical settings to main tain consistency in classifying chest films. The ILO classification requires conventional film-based posteroanterior (PA) chest films taken at prescribed specifications and classified with due regard for quality. Conventions for classifying digitized films and other advanced imaging systems have lagged behind the development of technology. The initial radiographic presentation of asbestosis is typically that of bilateral small primarily irregular parenchymal opacities in the lower lobes bilaterally. Over time, the distribution and density or "profusion" of opacities may spread through the mid dle and upper lung zones. Although irregular opacities are most common from asbestos exposure, mixed irregular and rounded opacities are often present. The ILO classification profusion score correlates strongly with mortality risk (36), reduced diffus ing capacity, and diminished ventilatory capacity (37, 39). A critical distinction is made between films that are suggestive but not presumptively diagnostic (0/1) and those that are presump tively diagnostic but not unequivocal (1/0). This dividing point is generally taken to separate films that are considered to be "positive" for asbestosis from those that are considered to be "negative." However, profusion itself is continuous (36, 38). Plain chest radiographs are limited with respect to sensitivity and specificity in cases of mild or early asbestosis. Among indi viduals with asbestosis confirmed by histopathologic findings, 15-20% had no radiographic evidence of parenchymal fibrosis in one study (40), similar to the proportion of other interstitial lung diseases that present with normal chest films (41). Pleural plaques are frequently documented on plain chest radiographs, but CT is more sensitive for their detection. Only 50 to 80% of cases of documented pleural thickening demon strated by autopsy, conventional CT, or high-resolution CT (HRCT) are detected by chest radiograph (42, 43). Plain chest radiographs are also limited by specificity in cases of mild pleural disease, which may be difficult to distinguish from extrapleural fat pads (39, 44). Oblique views can enhance both sensitivity and specificity of plain chest radiographs in clinical settings where HRCT is unavailable, but may also fail to distinguish plaques from fat pads (45). CT and HRCT are discussed in the next section. Computed Tomography A chest film clearly showing the characteristic signs of asbestosis in the presence of a compatible history of exposure is adequate for the diagnosis of the disease: further imaging procedures are not required. Conventional CT is superior to chest films in identi fying parenchymal lesions, rounded atelectasis, and pleural plaques (46). However, conventional CT has been displaced by HRCT for the evaluation of asbestos-exposed subjects because the latter is more sensitive for detecting parenchymal fibrosis. In subjects with low profusion categories of asbestosis, CT signs tend to be clustered as follows (47): Honeycombing and thickening of septa and interlobular fissures, suggesting interstitial fibrosis Diffuse pleural thickening, parenchymal bands, and rounded atelectasis, suggesting diffuse fibrosis involving the visceral pleura Pleural plaques HRCT has an important role when experienced readers disagree about the presence or absence of abnormalities on a highquality chest film, when chest radiographic findings are equivo cal, when diminished pulmonary function is identified in associa tion with otherwise normal plain chest radiographic findings, and when extensive overlying pleural abnormalities do not allow a clear interpretation of parenchymal markings. Because HRCT is more sensitive than other techniques for detecting parenchymal changes, it may reveal abnormalities with uncertain prognostic 698 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 Figure 3. H&E-stained section demonstrating asbestos bodies within alveolus of person with asbestosis. At center is a single large asbestos body within a multinucleated giant cell. Figure 4. H&E-stained section showing junction of terminal (membranous) bronchiole with a respiratory bronchiole from a person with asbestosis who was an ex-smoker. The walls of the bronchioles are thickened by collagen and show mild smooth muscle hyperplasia. There is a mild chronic inflam matory cell infiltrate in the wall. These features are consistent with asbestos-related small air way disease. American Thoracic Society Documents 699 Figure 5. Photomicrograph showing predominantly Grade III asbestosis, partially defined by diffuse interstitial fibrosis ex tending from acinus to acinus. The respiratory bronchiole at bottom left (*) could be classi fied as a Grade I lesion (see Table 2). Figure 6. H&E-stained section of lung showing Grade IV asbestosis with honeycombing. The overlying pleura (bottom right) is also thickened. American Thoracic Society Documents 701 Figure 8. Advanced asbestosis (details of case not available). Note char acteristic features: fibrotic bands superimposed on a background of widespread irregular opacities, shaggy heart border and septal thick ening, extensive pleural changes, and blunted costophrenic angles. diagnosis of asbestosis when a significant exposure history is obtained, lung biopsy may be warranted to exclude other, poten tially treatable diseases. Biopsy material may be helpful in identi fying the nature of a disease in an indeterminate case or one lacking an adequate exposure history. The presence of asbestos bodies in tissue sections should be Figure 7. Whole lung section of freeze-dried lung from a person who died of asbestosis. Note the peripheral honeycombing, which is most severe in the lower zones. terized physiologically by increased isoflow volume, and increased upstream resistance at low lung volumes (14,16). These obstruc tive findings may be due to asbestos-induced small airway dis ease. Thus, mixed restrictive and obstructive abnormalities do not rule out asbestosis or necessarily imply that asbestos has not caused an obstructive functional impairment (76). Asbestosis may remain static or progress; regression is rare (77). The factors that determine prognosis and evolution of the disease are poorly understood. Progression, after cessation of exposure or reduction to current permissible exposure levels, is considerably more common in persons who already have radio graphic abnormalities and appears to be associated with level and duration of exposure and therefore cumulative exposure (78). Differential diagnosis. Although not usually necessary for the 0 Figure 9. Early asbestosis, showing irregular opacities in lower lung fields that may be categorized as 0/1 or approaching 1/0 according to the ILO classification. Note pleural changes. 702 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 sufficient to differentiate asbestosis from other forms of intersti tial fibrosis. The chance of finding one asbestos body from back ground exposure alone has been shown to be about 1 per 1,000 (79). Conversely, the presence of interstitial fibrosis in the ab sence of asbestos bodies is most likely not asbestosis, although rare cases of pulmonary fibrosis with large numbers of uncoated asbestos fibers have been described (80-82). Idiopathic pulmo nary fibrosis (IPF in clinical terms or usual interstitial pneumoni tis in terms of pathology) has an acinar pattern of fibrosis differ ent from that of asbestosis and is not associated with asbestos bodies in tissue sections. On occasion, asbestosis is seen in con junction with an unrelated interstitial lung disease (such as sar coidosis) or in association with another pneumoconiosis, for example, silicosis. In the absence of fibrosis, asbestos bodies are an indication of exposure, not disease. Asbestosis resembles a variety of other diffuse interstitial inflammatory and fibrotic processes in the lung and must be distinguished from other pneumoconioses, IPF, hypersensitivity pneumonitis, sarcoidosis, and other diseases of this class. The clinical features of asbestosis, although characteristic, are not individually unique or pathognomonic, but the characteristic signs of the disease are highly suggestive when they occur to gether. The presence of pleural plaques provides useful corollary evidence that the parenchymal process is asbestos related. Diagnostic uncertainty is most likely in certain groups of patients. Patients may have a heavy cigarette-smoking history and concurrent emphysema (which also reduces the diffusing capacity). In such cases, one expects a history of asbestos expo sure commensurate with the degree of disease. On occasion, a patient with another interstitial lung disease, such as IPF, will have a history of asbestos exposure. Rapid progression, with a visible, year-to-year increase in symptoms, progression of radio graphic findings, and loss of pulmonary function in the absence of intense asbestos exposure, suggests the diagnosis of IPF rather than asbestosis. Patients may be exposed at various times in their working life to more than one dust, such as silica and asbestos, or to mixed exposures, such as dusts in combination with fumes and vapors in welding (83). These patients may have combined dis ease or the effects of one dust or other exposure may dominate. For example, predominantly upper lobe rounded opacities, hilar node enlargement, and progressive massive fibrosis are not fea tures of asbestosis and if present suggest other causes for the lung disease than asbestos, such as silicosis. On occasion, isolated fibrotic lesions associated with asbestos resemble solitary pulmonary nodules. These are sometimes called "asbestomas" and usually occur against a background of irregular opacities; they rarely appear in isolation. They normally require biopsy because they are not distinguishable from lung malignancies otherwise (84). Nonmalignant Pleural Abnormalities Associated with Asbestos Pleural abnormalities associated with asbestos exposure are the result of collagen deposition resulting in subpleural thickening, which may subsequently calcify, and which in the visceral pleura may be associated with parenchymal fibrosis in adjacent subpleural alveoli (Figures 10 and 11). Pleural thickening, as a marker of asbestos exposure, has continued to be a prominent feature of exposure to asbestos while other outcomes, such as asbestosis, have become less frequent due to declining exposure levels. The major determinant of pleural thickening is duration from first exposure (70). It is unclear whether the relative frequency of diffuse and circumscribed pleural thickening has changed. The International Classification of Radiographs of Pneumoconioses (38) provides a basis for recording and classifying both types of pleural thick ening, allowing correlation with indices of exposure and mea surements of lung function. Manifestations of disease of the lung and of the pleura have become less evident and less characteristic on plain films as exposures have decreased. However, CT scan (including high-resolution images) detects pleural thickening not evident on the plain film, and sometimes fails to confirm apparent pleural thickening read on the plain film. Schemes to quantify extent of pleural thickening on CT scan have been published (55, 85). Rarely, interlobar pleural thickening may mimic lung nodules on CT scan (86). Pleuritis: acute pleural effusion, chronic pleuritic pain. Asbes tos may cause an acute pleural effusion, often lasting several months, that is exudative and often hemorrhagic, with variable numbers of erythrocytes, neutrophils, lymphocytes, mesothelial cells, and often eosinophils (87-89). It may occur early (within 10 years, unlike other asbestos-related diseases) or late after the onset of asbestos exposure (90). It may be superimposed on long-standing pleural plaques (91). Although it is usually asymp tomatic, the acute pleural effusion due to asbestos may also be exuberant, with fever and severe pleuritic pain. It is sometimes detected only incidentally on a radiograph taken for another purpose (87, 88). The effusion may persist for months, present bilaterally, or recur on the same or the opposite side (87). A friction rub may be present (92,93). The traces of pleural effusion may be observed years later as a blunted costophrenic angle or as diffuse pleural thickening. Acute pleuritis is thought to underlie many cases of diffuse pleural thickening. Of 20 insulators with a past history of definite pleural effusion, diffuse pleural thickening was detected on radiograph in 16 (90). Dose-response relation ships or characteristic features of exposure associated with effu sion have not been described. Chronic severe pleuritic pain is rare in patients with asbestosrelated pleural disease (92, 93). Vague discomfort appears to be more frequent. Studies examining the frequency of atypical chest pain in asbestos-exposed patients have not been performed. In the few cases described, it was present for many years, disabling, and often bilateral. Radiographic evidence of pleural disease ranged from plaques to extensive diffuse and circumscribed pleu ral thickening; several cases followed pleural effusions. The diag nosis of acute asbestos-related pleural effusion is by exclusion of other causes of acute pleuritis, and most often is not arrived at until the pleural space is fully explored and biopsied, generally by thoracoscopy. Differentiation from Dressler's syndrome is difficult in asbestos-exposed patients who have undergone recent cardiac surgery. Differentiation from mesothelioma or pleural extension of a pulmonary malignancy is critical, and may be difficult on clinical grounds (including positive gallium and posi tron emission scan). Pleural fluid cytology is useful for distin guishing benign from malignant effusions. It is not unusual for nonspecific effusions to precede mesothelioma by several years. If a malignancy has not manifested itself within 3 years, the effusion is generally considered benign. The diagnosis of chronic pleuritis manifested by pleuritic pain is reached by excluding malignancies, because most other causes of acute pleuritis do not result in chronic pain. Malignancy is unlikely when pain persists for years with little or no clinical or radiographic change. Plaques: circumscribed pleural thickening. Pleural plaques are indicators of exposure to asbestos. They are clearly the most common manifestation of the inhalation, retention, and biologic effect of asbestos. Their prevalence is most directly related to duration from first exposure; they are rare within less than 20 years. Pleural plaques consistent with asbestos exposure appear in chest films of 2.3% of U.S. males, a percentage that has been 704 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 Figure 12. Gross appearance at autopsy of asbestos-associated pleural plaques overlying the lateral thoracic wall. remarkably stable both for the general population in the early 1970s and veterans in the 1990s (94, 95). Calcification is similarly related to duration. Smoking plays no role in the prevalence of pleural plaques (68). Pleural plaques are bilateral, but not symmetric, lesions of the parietal pleura. Characteristically, they are found following the ribs on the lower posterior thoracic wall (Figure 12) and over the central tendons of the diaphragm (Figure 13). They are raised, sharply circum scribed with a smooth or with a rounded knobby surface, and range in color from white to pale yellow. They generally spare the costophrenic angles and apices of the thoracic cavity. Micro scopically, they consist of mature collagen fibers arranged in an open basket-weave pattern and are covered by flattened or cuboidal mesothelial cells. They are relatively avascular and acellular and show minimal inflammation. They are sharply de marcated from subpleural tissues and central calcification is com mon. Asbestos bodies are not seen in or adjacent to the lesions (64). Isolated plaques may be associated with tuberculosis, trauma, and hemothorax; however, multiple lesions having the classic appearances described above are almost invariably associ ated with asbestos exposure. The conventional chest film is a sensitive and appropriate imaging method for plaques, although it may identify abnormali ties that resemble plaques but are not. In the PA radiograph, they are best seen in profile on the midlateral chest walls and on the diaphragm or face on, and show serrated borders. HRCT is not a practical screening method for demonstrating plaques because of the separation between sections, the high radiation exposure, and the lack of access to the test in some locations. HRCT is useful to identify questionable abnormalities and to resolve questions about structures that resemble plaques. Typical pleural plaques are easily identified on plain films by sharp, often foliate, borders (face on) and by a raised straight surface with clear, cut-off edges when seen face on (Figures 14-16) and as irregular margins (sometimes almost rectangular) when seen in profile on the chest wall or diaphragm. Apparent pleural thickening with gradually tapering or indistinct edges is often due to subpleural fat or superimposed soft tissue; fat pads below the parietal pleura typically occur in the midthoracic wall, Figure 13. Gross appearance of large asbestos-related pleural plaque over the dome of the diaphragm. American Thoracic Society Documents 707 Plaques are indicators of increased risk for the future develop ment of asbestosis (94). This may reflect greater exposure or retained body burden. An autopsy study has demonstrated more frequent peribronchiolar fibrosis when plaques are present (90). This finding, as well as derangements in gas exchange (114) and evidence from HRCT, indicate that subradiographic asbestosis may be present in some patients with only pleural plaques. The presence of plaques is therefore an indication to monitor the patient over time for interstitial fibrosis (115). Diffuse pleural thickening. Diffuse thickening of the visceral pleura is not sharply demarcated and is often associated with fibrous strands ("crow's feet") extending into the parenchyma. In large surveys of asbestos-exposed workers, diffuse pleural thickening has ranged from 9 to 22% of those with pleural disease. Both circumscribed and diffuse pleural thickening may be present in the same hemithorax. Diffuse pleural thickening superimposed on circumscribed plaques has been observed, of ten after pleural effusion (91). The frequency of diffuse pleural thickening increases with time from first exposure and is thought to be dose related (104). Diffuse pleural thickening has been observed after acute pleuritis (90). It may also be caused by extension of interstitial fibrosis to the visceral pleura, consistent with the pleural migration of asbestos fibers. The extent of diffuse pleural thickening seems to be more or less uniformly distributed, the different degrees being fairly equally often seen, however, in contradistinction to circumscribed pleural thickening, in which the lowest categories are more frequent (113). Lung burdens of asbestos in these cases are intermediate between asbestosis and pleural plaques (116-118). This condition affects the visceral pleural surface and is quite different in appearance from the parietal pleural plaque. It con sists of pale gray diffuse thickening that blends at the edges with the more normal pleura. It may be extensive and cover a whole lobe or whole lung and obliterate lobar fissures. It ranges in thickness from less than 1 mm up to 1 cm or more. Adhesions to the parietal pleura are common, particularly opposite to pleural plaques. The lesion may show a gradient with immature granula tion tissue and fibrin at the surface, progressing to mature colla gen adjacent to the lung. The fibrosis may extend for a few millimeters into the lung parenchyma and into the lobular septae. The latter features do not constitute asbestosis. Diffuse pleural thickening may have a significantly greater impact on pulmonary function than circumscribed plaques. A reduction of 270 ml of FVC has been associated with diffuse pleural thickening (76,119). Workers with diffuse pleural thick ening have a significantly greater decrement in FVC (by a factor of two or more) than those with circumscribed pleural thickening (76, 113). This effect is unrelated to the radiographic extent of pleural thickening; a similar reduction in FVC was seen with little more than costophrenic angle blunting as with extensive involvement (113). Decrements associated with diffuse pleural thickening reflect pulmonary restriction as a result of adhesions of the parietal with the visceral pleura. Restrictive impairment is characteristic, with relative preservation of diffusing capacity (pattern of entrapped lung). Diffuse pleural fibrosis extends continuously over a portion of the visceral pleura, often causing adhesions to the parietal pleura, involving the fissures and obliterating the costophrenic angle. The newly revised ILO classification (2003) recognizes pleural thickening as diffuse "only in the presence of and in continuity with, an obliterated costophrenic angle" (38). Local ized subpleural parenchymal fibrosis is often present without diffuse interstitial fibrosis (117). Calcification of the pleura occurs with the passage of time, and may involve fissures. A rare variant of visceral pleural fibrosis is progressive apical thickening associ ated with fibrosis of the upper lobe (120, 121). Pachypleuritis is extensive, often bilateral, pleural fibrosis with evidence of active inflammation histologically and by gal lium uptake. Extension of fibrosis into the lung is often evident radiographically as irregular pleural and pericardial borders, fi brous streaks, or "crow's feet" and bands. Ventilatory failure leading to CO2 retention, cor pulmonale, and death has been described in four patients with bilateral involvement and little or no parenchymal fibrosis, and in one patient with unilateral pleural thickening. Decortication may be beneficial (122). Rounded atelectasis. Rounded atelectasis (123, 124), also known as shrinking pleuritis, contracted pleurisy, pleuroma, Blesovsky's syndrome (125), or folded lung, presents radiographi cally as a mass and may be mistaken for a tumor (Figure 17). The condition may result from pleuritis of any cause. The lesion is thought to develop from infolding of thickened visceral pleura with collapse of the intervening lung parenchyma. Clinical expe rience suggests that it is more likely to occur today as a result of asbestos exposure than other causes. The classic "comet sign" is pathognomonic and is often more readily seen on an HRCT than on plain films. Clues to its identity are a band connecting the mass to an area of thickened pleura and a slower evolution than that of a lung cancer, so that previous films will show a similar finding. Histologic examination shows folded and fibrotic visceral pleura with atelectasis and variable amounts of chronic inflamma tion in the adjacent lung parenchyma. The sudden appearance of rounded atelectasis may follow acute pleuritis with effusion. Rounded atelectasis may be multiple and bilateral (124, 126). Rounded atelectasis is important for the diagnostic patholo gist to recognize as it is frequently removed surgically as a sus pected peripheral lung cancer. Asbestos bodies and/or evidence of asbestosis should be carefully sought. Differential diagnosis, including rounded atelectasis and apical thickening. Acute pleuritis of any cause can result in diffuse pleural thickening that is indistinguishable from that associated with asbestos, although such causes are usually unilateral. The most likely causes, empyema, tuberculosis, and trauma, including surgery, are likely to be identified in the medical history. Empy ema in childhood or an infected pleural effusion associated with pneumonia may not be. The major differential diagnostic consideration with diffuse pleural thickening is mesothelioma, which is progressive and more likely to be symptomatic at the time of detection. On occasion, when fibrosis and mesothelial proliferation are exuber ant, the distinction is difficult clinically, radiographically, and histologically. Apical thickening (120, 122) must also be distin- Figure 16. Extensive evaluation in 1983 of a 65-year-old business executive who, in the 1950s, had worked in shipyards for approximately 2 years and was exposed to high levels of asbestos. This case is unusual because both early asbestosis and a huge pleural plaque are unilateral. (A) PA film shows asbestosis and an extensive pleural plaque extending over three-quarters of the length of the hemothorax. Right costophrenic angle is blunted but would not satisfy strict criteria for this according to the ILO classification. (B) Lateral film, showing extensive calcified plaques over diaphragm, also visible on left in PA film. (C) Because of concern for possible mass in right lower lung lobe, PA film was repeated with nipple markers: mass not seen in this view. (D) Left anterior oblique, showing absence of other plaques on chest wall. (E) Right anterior oblique, showing detail of plaque. (F) CT scan, showing plaque. 708 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 170 2004 Figure 17. Rounded atelectasis in a 57-year-old sheet metal worker. (A) Presentation as a mass in the left chest. (B) CT scan showing pleural base and infolding of structures. guished from mesothelioma and tuberculosis, which may be sug gested by history and (previous) bacteriologic findings. Chronic Airway Obstruction Asbestos exposure has traditionally been considered to cause predominantly restrictive physiologic abnormalities. The role of asbestos as a cause of airway obstruction has been controversial. However, asbestos exposure has long been known to be associ ated with an obstructive physiological abnormality (127-129). This association might arise in one or more of several ways: Asbestos specifically causes obstructive abnormality. Asbestos causes obstructive abnormality nonspecifically (i.e., as do large burdens of most inorganic dusts) (83,130). Work leading to extensive asbestos exposure is frequently associated with exposure to other agents affecting airways. Confounding by tobacco smoking may lead to an associa tion. Anatomic and physiologic airway abnormalities develop as part of the pathophysiologic process of asbestosis and are not an independent entity. Asbestos-related chronic airway obstruction may result in reduction in the FEV1/FVC ratio associated with reduced FEV1 (29, 76, 113, 127). Epidemiologic studies have demonstrated a significant association between asbestos exposure or asbestosis category as defined radiographically and reduction in FEV1, FEV1/FVC ratio, and midexpiratory flow rates (111, 130-133). The relationship between surrogate measures of exposure and the FEV1 and FEV1/FVC ratio also occurs in subjects who do not have radiographic evidence of asbestosis (defined as an ILO score exceeding 1/0) (130, 133, 134). A small effect has been observed in lifelong nonsmokers (14, 113, 135, 136). This effect begins in small airways, consistent with the known pathology of bronchiolitis in early asbestosis (136, 137). Radiographically, airflow abnormalities may also be associated with emphysema (138). Histologically, inflammation and airway fibrosis characterize asbestos-related small airway disease. A major site of asbestos deposition is in the walls of membranous and respiratory bron chioles. In the walls of membranous bronchioles this leads to fibrosis and smooth muscle hyperplasia that are similar, but more severe, than that produced by cigarette smoking (128, 139) (Figures 4, 5, and 18). The respiratory bronchioles show fibrosis, which extends into the alveolated portions of the walls and alveolar ducts (Figure 19). In this regard, it differs from the lesion of cigarette smoking, which primarily involves the nonalveolated portions of the first generation of respiratory bronchioles (140). Asbestos bodies are not present in the walls of the membranous bronchioles, although inflammatory changes are present, but are commonly seen in the walls of the respiratory bronchioles and/ or adjacent alveoli. Some authorities consider it appropriate to describe these lesions as true asbestosis because the walls of respiratory bronchioles are largely alveolated and therefore within the gas exchange region of the lung (64). Others consider the small airway lesions as distinct from asbestosis and refer to the lesions of both membranous and respiratory bronchioles as asbestos-induced small airway disease (12). These small airway lesions are the likely anatomic basis for airflow limitation in asbestos-exposed individuals. In general, the magnitude of the asbestos effect on airway function is relatively small. This effect, by itself, is unlikely to result in functional impairment or the usual symptoms and signs of chronic obstructive pulmonary disease. However, if superim posed on another disease process, the additional loss of function due to the asbestos effect might contribute significantly to in creased functional impairment, especially in persons with low lung function. Asbestos exposure independently contributes to accelerated decline in airflow over time, whether or not exposure ceases (77, 129, 133, 134, 141). Dyspnea, cigarette smoking, diffuse pleural thickening, honeycombing observed on HRCT scan, and indica tors of active inflammation have been associated with worsening obstruction (142). Effects on measures of early small airway dysfunction (e.g., midexpiratory flow rates) in themselves are unlikely to produce clinically relevant impairment, but may indi cate an increased probability that disease will develop later (128, 129, 134, 143). Development or persistence of respiratory symp toms among asbestos-exposed workers is associated with acceler ated loss of lung function, both FVC and FEV1 (30). In patients with severe obstructive airway disease from another cause, the additional contribution of asbestos-related airflow obstruction might be functionally significant at low levels of lung function. Short duration and low cumulative exposure are less likely to produce significant obstructive abnormality (112, 134). American Thoracic Society Documents Assessment of functional impairment of clinical significance (3) should generally be based on the restrictive findings associ ated with asbestosis, as these are more likely to be disabling. However, the addition of obstructive disease adds to the level of functional impairment (144). Treating restriction and obstruc tion separately may underestimate their combined effect on im pairment. The normal indicator for restrictive impairment, total lung capacity, has proven to be insensitive to total impairment in subjects with both asbestosis and chronic obstructive lung disease. In such cases, diffusing capacity and alveolar-arterial oxygen difference may be more revealing (144). Some of the restrictive component may be contributed by air trapping rather than fibrosis (145). Chronic obstructive airway disease that is not due to asbestos (e.g., secondary to smoking) may complicate the recognition of asbestosis. For example, total lung capacity may be normal when both disorders are present, due to a restrictive process offsetting air trapping (143). Whereas the FEVi/FVC ratio may be reduced in asbestos-exposed persons with no or a low profusion of small, irregular opacities, this ratio may also be normal in more ad vanced asbestosis (i.e., with higher profusion and diminished FVC) because of a reduction in FVC (75). Effects on airflow begin before the development of asbestosis (129). In individuals who develop asbestosis, physiologic findings associated with airflow obstruction (e.g., reduction in the FEV1/ FVC ratio) become less prominent as asbestosis progresses; this may reflect increased pulmonary recoil. The dose and time course of asbestos-associated airway ab normalities have received limited attention. Many available stud- Figure 19. Photomicrograph of asbestos-related small airway disease, in this case a respiratory bronchiole, with extension of the fibrosis into the adjacent parenchyma (Grade II asbestosis; see Table 2). 709 Figure 18. Photomicrograph of asbestos-related small airway dis ease, showing thickened mem branous bronchiole. There is also fibrosis around the airway, and a mild chronic inflamma tory cell infiltrate in its wall. American Thoracic Society Documents 711 the interaction between smoking and asbestos exposure in en hancing the risk of lung cancer. Such persons who smoke may be more motivated to consider cessation when the connection between asbestos and the risk of respiratory impairment and of malignancy is brought up at this time (151). The risk conferred by other occupational and environmental carcinogens should also be emphasized at this time. The question of monitoring for asbestos-related disease is complicated by requirements for occupational surveillance, espe cially for those with minimal exposure. The Occupational Safety and Health Administration asbestos standard requires employ ers to monitor their asbestos-exposed workers during employ ment but makes no provision beyond the period of employment, despite the latency, and private insurance may or may not allow the expense thereafter (8). Persons with a history of exposure to asbestos but no manifest disease, and for whom the time since initial exposure is 10 years or more, may reasonably be monitored with chest films and pulmonary function studies every 3 to 5 years to identify the onset of asbestos-related disease. Persons with a history of exposure to asbestos are also at risk for asbestos-related malignancies. Periodic health surveillance for lung cancer or mesothelioma is not recommended. Screening for lung cancer using periodic (annual) chest films, low-dose computed tomography, or sputum cytology has not been shown to be effective in preventing mortality or improving quality of life in populations of smokers without known adverse occupational exposures (152,153). New technologies (e.g., low-dose spiral CT scanning) are being evaluated for use in high-risk groups (153). The risk of extrathoracic malignancies may also be increased in asbestos-exposed workers. Studies suggest that there may be an elevation in the risk of colon cancer (149, 150), although this remains controversial (154). Because colon cancer is often treat able and screening for colorectal cancer is recommended by the American Cancer Society for persons more than 50 years of age (155), it is reasonable on the basis of current evidence to screen for this condition. The risk of cancer of the larynx (156) and possibly gastrointestinal cancers other than colon, including pan creas, stomach, and esophagus (154), may also be increased with asbestos exposure, but the presence and magnitude of an associa tion with asbestos remain controversial for extrathoracic cancers (154). Routine screening for these cancers is in any case not practical at present. No prophylactic medication or treatment is currently avail able to prevent the development or progression of asbestosis or other asbestos-related diseases, once exposure has occurred. Actions Required after Diagnosis The diagnosis of asbestosis, in particular, imposes a duty to inform the patient that he or she has a disease that is workrelated, to report the disease, and to inform the patient that he or she may have legal or adjudication options for compensation. The role of the physician in this compensation process includes performing an objective evaluation of impairment consistent with the rules of the specific compensation system. Guidelines developed by the American Thoracic Society (3) may be of use and are incorporated into the AMA Guides to the Evaluation of Permanent Impairment (157). As in the management of any lung disorder, the physician should also manage the clinical mani festations of the disease and counsel the patient to protect re maining lung function. The patient with evidence of asbestosis should be considered to be at risk of progressive lung disease, whatever the level of impairment on first encounter. It seems logical that removal from further exposure to asbestos or other significant occupa tional and environmental exposures may avoid more rapid pro gression of lung disease, although specific evidence for this is lacking. However, if such exposures are minimal and are well within occupational guidelines, care must be taken not to deprive the patient of a livelihood for no clinical benefit. Immunization against pneumococcal pneumonia and annual influenza vaccine should be administered unless contraindicated for other reasons. Effective management of concurrent chronic obstructive pulmonary disease or asthma, if present, may reduce morbidity from mixed disease. Severe asbestosis is rare in the United States and other coun tries with generally effective occupational health regulation. Cor pulmonale, secondary polycythemia, and respiratory insufficiency and failure are all treated in the conventional manner in patients with asbestosis. In the spring of 2000, the Association of Occupational and Environmental Clinics adopted a resolution recommending nec essary standards for screening programs (158). This action was taken in response to the proliferation of screening programs undertaken to identify cases for possible legal actions in which counseling and education may be lacking (159), but the recom mendations also apply to those conducted for patient care and protection. Their recommendations were consistent with those given above and also emphasized timely physician disclosure of results to the patient, appropriate medical follow-up, and patient education. The National Institute of Occupational Safety and Health has outlined elements of an adequate screening program, with special reference to screening for asbestos-related disorders in currently employed mineworkers, in a white paper produced in 2002 that has received little attention (160). The National Institute for Occupational Safety and Health recommended that such programs should be under the direction of a "qualified physician or other qualified health care provider" knowledgeable in the field and competent to administer it, and documented with written reports to workers and employers (the latter provi sion that would not necessarily be applicable to workers who had separated from the employer). However, the National Insti tute for Occupational Safety and Health did not address the issue of counseling in that document or clinical interventions to reduce future risk. CONCLUSIONS The diagnosis of nonmalignant asbestos-related disease rests, as it did in 1986, on the essential criteria described: a compatible structural lesion, evidence of exposure, and exclusion of other plausible conditions, with an additional requirement for impair ment assessment if the other three criteria suggest asbestosrelated disease (2). Each criterion may be satisfied by one of a number of findings or tests. The 2004 criteria are open to future testing modalities if and when they are validated. For example, HRCT has greatly increased the sensitivity of detection and has become a standard method of imaging. Evidence for exposure still rests on the occupational history, the demonstration of asbes tos fibers or bodies, or pleural plaques. Impairment evaluation is largely unchanged from 1986 and remains an essential part of the clinical assessment. Potentially confounding conditions, such as idiopathic pulmonary fibrosis, are better understood and many, such as tuberculosis, are less common than in the past so that the clinical picture is less often confusing. These criteria and the guidelines that support them are com patible with the Helsinki criteria, developed by an expert group in 1997, which represents substantial consensus worldwide (147). 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