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Council Report ,ydx2<?/yci' "tF/^L PLAINTIFF'S EXHIBIT A Physician's Guide to Asbestos-Related Diseases Council on Scientific Affairs IN RECENT years, public concern provided for the reader who requires milling of the ore, (2) the manufac over the health effects of asbestos has more comprehensive knowledge. ture and use of asbestos-containing sharply escalated. According to Walk \ er et al (J Occup Med 1983^5:409), as INTRODUCTION products, and (3) the repair and dem olition of structures containing asbes many as 65,000 industrial workers in The term asbestos refers to a family tos. Insulators and other construction this country may now have clinically of naturally occurring silicate miner workers, such as painters and electri diagnosable asbestosis, and mesothe als with a fibrous structure. Endowed cians, are particularly at risk. Count lioma may develop in 19,000 before with unique properties of heat and less industrial and consumer products the end of this century. Asbestos also corrosion resistance, asbestos has (eg, electrical appliances and equip increases the occurrence of bronch.- long played a prominent role in our ment; brake and clutch linings; fire genic carcinoma among exposed industrial society. Chrysotile is the proof paper and textiles; water pipes; workers. Disease frequency of this most important commercial type of siding and insulation materials; floor magnitude consequent to a common asbestos, accounting for more than and ceiling tiles; and spackling, environmental pollutant is unprece 90% of the asbestos consumed in the patching, and taping compounds) dented and of critical public health United States today. Two other types, have asbestos incorporated in their importance. crocidolite and amosite, were used manufacture. In May 1982, the Council on Scien extensively in the past. In the 1940s Recently, the US Environmental tific Affairs commissioned a select and 1950s, worldwide consumption of Protection Agency (EPA) has di panel of experts to prepare a report asbestos increased dramatically. In rected special attention to the inte- on the diseases attributed to asbestos recent years it has declined, in large exposure. There are already a number part because of concerns about the of excellent reviews on the subject for adverse effects of asbestos on health. specialists in the fields of radiology, pathology, pulmonary medicine, and oncology. This report is organized as a series of answers to some of the Medical knowledge regarding the outcome of exposure to the mineral has expanded greatly since the first published report of asbestos-associ Member* of the Council on Scientific Affairs include the following: John R. Beljan, MO, Oeyton, Ohio; Theodore Cooper, MO, Kalamazoo, Mich; WtLUm 0. Dofan, MO, Chairmen, Arlington, Va; Ira R. Friedlander, more common questions asked of or ated lung disease in 1924. But only in by physicians regarding asbestos and the past few years has the general health. A selected list of references is public become aware of the extent to which asbestos exposure can cause From th, Council on SdonUfie Attilr,, {XvUlon o< disease. The long latency before the '* Personal and Public Kutth Policy, American Medical Aaaocialkm, Chicago. appearance of clinical manifestations Report F of the Coond on Scientific Affaire, delayed the emergence of a signifi adopted by the House of Delegates of the American Medical Association at the 1883 Interim Meeting. This report is not sitended to serve as a standard cant number of new cases until the 1960s and 1970s. At the same time, of medical care; standards ol medical care that are the media has publicized a burgeon determined locally and are constantly subject to change are established on the basis of al the several fects of the Individual case. ing number of damage claims filed by persons alleging disease and disabili Reprint requests to Division of Personal and Public Health Policy. Council on Scientific Affairs, American Medical Association. 635 N Dearborn St, ty from asbestos exposure. Occupational exposure to asbestos Chicago, 0.60610 (Robert H. Wheatar). may occur during (1) mining and MO, Chicago, Resident Physician; Ray W. Gifford, Jr, MO, Cleveland, Vice-Chairman; Michael 8. Kaatan, St Louie, Medical Stu dent; John H. Moxley 01, MO, 8#verty HtUe, Calif; Richard T. F. Schmidt, MO, Cincinnati; Joseph H. Skom, MD, Chicago; Rogers J. Smith, MO, Portland, Ore. Pest Chairman; James 8. Snow, Jr, MO. Philadelphia; C. John Tupper, MO, Davis, Calif; and Richard J. Jones, MO, Chicago, Secretary. Members of the panel who prepared this report Include the following: William R. Bar* day, MO; John E. Craighead, MO (Chair* man); David W. Cogetf, MO; Wtftiam D. Dolan, MO; Richard J. Jones, MO (CouncS on Scientific Affaire Secretary); Elliott Kagan, MO, Michael B. Shimkin, MO; Joeeph P. TomaehefakJ, MO; Robert K. Wheatar, MS (Panel Secretary). JAMA, Nov 9, 1984--Vol 252, No. 18 Asbestos-Related Diseases--Council on Scientific Affaire 2593 A- I I riors of schools and other public buildings that could contain friable asbestos. In 1982, the EPA mandated that all elementary and secondary schools be inspected and the informa* tion be provided to school employees and parent-teacher associations. As bestos is ubiquitous in the urban environment; it can be detected in the dust on streets and in public buildings. Thus, the general public is invariably exposed to small amounts of material. The asbestos-related pulmonary diseases progress insidiously. Many years elapse from first exposure to the appearance of symptoms. The pathological sequelae of asbestos exposure are irreversible and can progress after exposure ceases. At present, there is no satisfactory treat ment; prevention is the only practical way to avoid the disease. QUESTIONS AND ANSWERS What An the Major Pathological Responses to Asbestos Exposure? Interstitial pulmonary fibrosis (asbestosis) is one of the major adverse health consequences of asbestos expo sure. Pleural fibrosis and `'plaques" often accompany but.may occur inde pendently of the parenchymal dis ease. They serve as markers of expo sure. Malignant mesotheliomas of the pleural and peritoneal cavities and bronchogenic carcinoma are linked to asbestos inhalation. In some studies, carcinomas of the larynx and gastro intestinal tract (ie, the buccal cavity, oropharynx, esophagus, stomach, and colon) and lymphoplasmocytic malig nant conditions have been associated with asbestos exposure. How Does Asbestosls Differ From ' Other Forms of Pulmonary Fibrosis? Pulmonary fibrosis has many causes, but in all cases' asbestos should be considered a possible causal factor. Asbestosis has distinctive his tological features, particularly during its early stages. The lesion begins in the respiratory bronchioles; fibrosis then progresses to adjacent pulmo nary units until the lungs are exten sively involved. Typically, the lower lobes are more severely affected, and fibrous thickening of the visceral pleura frequently is found. A small proportion of fibers in the lung become encapsulated with an iron- protein coat and are referred to as "asbestos bodies." Large numbers of uncoated asbestos fibers are com monly found in lung tissue of those who are occupationally exposed to asbestos. Fibers are also present in the lungs of the general population, although industrially exposed persons tend to have higher concentrations. Quantitative counts of fibers in lung tissue cannot be used as a measure of disease. What Are tha Clinical Features of Asbestosle? The diagnosis of asbestosis is facili tated if there is a history of exposure. The patient's lifetime employment should be reviewed, with special attention to the individual tasks per formed by the patient in the remote past. The early stages of the disease usually are asymptomatic. As it pro gresses, complaints generally include the usual respiratory symptoms of dyspnea and cough, with or without sputum production, as well as fatigue, weight loss, and chest pain. In the advanced stages, expansion of the thorax is limited, and there are inspi ratory crackles on auscultation of the chest, clubbing of the digits, and cyanosis of the extremities. Chest roentgenograms at this stage show fibrosis of the lungs, particularly of the lower lobes. Pulmonary function tests do not differentiate between asbestosis and other forms of pulmo nary fibrosis. Cigarette smoking of ten complicates interpretation of the results of pulmonary function tests. The major adverse effects of cigarette smoking on lung function is expirato ry airflow obstruction, whereas re duced lung volumes and impaired gas diffusion are found in patients with asbestosis. What Exposure Is Required for the Development of Asbestosis? Brief exposure to a high concentra tion of the fiber in ambient air occa sionally results in disease. Generally, however, one must inhale relatively large amounts of asbestos for an extended period. Fibrotic lesions usu ally are not roentgenographically evi dent until at least five years after the onset of exposure; much longer peri ods usually are required. Workers handling insulation or other asbestoscontaining products and others in the immediate area are particularly at risk. Casual and sporadic exposures to relatively small amounts of the fibers do not generally produce pulmonary fibrosis; however, contamination of the household environment through work clothes has resulted in asbesto sis among family members. Konfriable products, which do not release fibers into the air, are not danger ous. Is Thar* Any Relationship Between Fiber Size and the Development of Asbestos-Related Disease? Asbestos fibers vary considerably in length and diameter. The bulk of evidence indicates that long fibers (equal to or greater than 8 pm) play an important pathogenic role in asbestosis and mesothelioma. Most fibers in commercial products are relatively short; their importance as a cause of disease is controversial. The techniques currently used to monitor the environment ignore fibers less than 5 ftm in length. The current Occupational Safety and Health Ad ministration standards do not require monitoring of the short fibers. Does Asbestosis Develop In All Those Who Are Heavily Exposed - for Extended Periods? Humans appear to differ markedly in their response to asbeBtos fibers, which suggests that host factors may be important determinants in "resist ance" to the development of pulmo nary fibrosis. Various immunologic abnormalities are noted in persons with asbestosis; hence, immune mech anisms might be involved in the path ogenesis. Inasmuch as genetic mecha nisms have been shown to play a role in immunologic responsiveness, it is conceivable that heritable traits in fluence susceptibility to the patholog ical effects of asbestos. What Effect Does Asbestos Have on the Immune .System? A variety of immunologic abnor malities have been demonstrated in subjects with asbestosis. Cell-me diated immunity is impaired, as evi denced by cutaneous anergy for certain recall and de novo antigens. Further more, decreased numbers of circulat ing suppressor T cells and an increase in the ratio of T-helper to T-suppressor cells has been found in some 2594 JAMA, Nov 9, 1984--Vol 252, No. 18 Asbestos-Relafed Diseases--Council oft Seentlfic Affairs ' patients with asbestosis. Patients often have elevated serum and secre tory immunoglobulin levels, serum rheumatoid factors, and antinuclear antibodies. Although immunologic re actions might play a role in asbesto sis, the evidence is circumstantial. What la tha Rola of Pulmonary Biopsy in tha Diagnosis of Asbastosls? In most cases, persons with a pro longed exposure to asbestos will have physical findings and roentgenographic evidence that are sufficient to establish the diagnosis. However, many workers are exposed to a varie ty of inhalants, and often the history of exposure is either unknown or vague. Thus, when the nature of the lesion is obscure or when there is a suggestion of other complicating, treatable conditions, pulmonary biop sy is indicated. Under these circum stances, histologic examination of a specimen of lung tissue can help to establish the diagnosis. The lesions of asbestos often have a spotty distribu tion when the disease is either mild or moderately serve. Adequate sampling of the lung parenchyma is critical, and open lung biopsy is recom mended. Transthoracic needle aspira tion and transbronchial biopsies usu ally do not yield sufficient tissue to permit a diagnosis. What Features In the Pulmonary Biopsy Permit the Specific Diagnosis of Asbestosis? Discrete foci of fibrosis in the walls of respiratory bronchioles associated with accumulations of asbestos bodies are the minimal pathological features that permit the diagnosis of asbesto sis. Although these early morphologi cal findings are adequate to establish the pathological diagnosis, they do not necessarily result in functional and roentgenographically apparent alterations. The demonstration of asbestos bodies in the absence of fibrosis is insufficient evidence to justify the diagnosis of asbestosis. Conversely, a definitive diagnosis of asbestosis cannot be made in cases that show characteristic fibrosis in the absence of asbestos bodies, even in a patient with a history of expo sure. Some investigators believe that asbestos bodies occasionally are not demonstrable in lungs with fibrosis caused by asbestos, but this claim has not been substantiated by systematic pathological studies. Can tha Diagnosis Ba Established by Sputum Cytotogical Tests? No. Asbestos bodies in sputum are evidence of asbestos exposure, but they are not diagnostic of asbestosis. Similarly, asbestos bodies in broncho pulmonary lavage specimens are not diagnostic. On the other hand, rela tively large numbers of asbestos bod ies often are found in the pulmonary secretions of patients with asbestosis. Thus, asbestos bodieB in sputum strongly suggest past exposure to asbestos and reflect the presence of a significant asbestos burden in the lungs. What It the Traatmtnt for Asbestosis? The asbestos-related pulmonary diseases progress insidiously. There is a long latent period of many years from first exposure to the appearance of symptoms. The pathological se quelae of asbestos exposure are irre versible and can progress after expo sure ceases. At present, there is no specific treatment; prevention of ex posure to friable asbestos is the only practical way to control the disease, and general measures for the man agement of any pneumoconiosis should be pursued. Is It Advisable to Change Jobs When Evidence of Asbestosis Develops? Persons with asbestosis should eliminate further exposure to asbes tos. This might require changing jobs, but improved hygienic standards in the workplace and the use of personal protective equipment, such as an approved face mask or a respirator, can make a change of occupation unnecessary. Doss the Disease Become More Severe After Exposure Ceases? Roentgenographic changes in the lung parenchyma have been shown to progress in some persons after asbes tos exposure ceases. This has been attributed to asbestosis, but progres sive chronic bronchitis and decreas ing pulmonary function may also relate to other factors, such as ciga rette smoking and the natural decline in pulmonary reserve that occurs with aging. What Change* In the Pleura Are Observed After Asbestos Exposure? Asbestos is unique in its ability to produce isolated lesions of the pleura; these include effusion, fibrosis, plaques, and mesothelioma (Figure). The effusions generally are bilateral and can develop many years after cessation of asbestos exposure. They can be asymptomatic, but often they are associated with chest pain. Fre quently, the fluid is blood stained and the protein content exceeds 3 g/dL. Many months may pass before spon taneous resolution of the lesions occurs, but recurrences are unusual. Asbestos bodies are seldom found in the pleura. Pleural plaques are localized fibrotic lesions that originate just below the surface of the parietal pleura. They commonly occur on the lateral aspects of the rib cage and on the dome of the diaphragm. Calcification often is found in plaques of long duration. Adhesions between the vis ceral and parietal pleurae are sel dom present. Roentgenographically, plaques appear as bilaterally sym metrical, localized areas of pleural thickening. They have characteristic pathological features. Diffuse pleural thickening, often involving the costophrenic angles, can develop with or without localized plaques. Postmor tem studies show that pleural changes occur more frequently than is apparent in chest roentgenograms. Pleural thickening is highly sug gestive of asbestos exposure when other possible causes, such as trauma, surgery, and infection, are excluded. Pleural mesotheliomas invariably produce chest pain, usually before the appearance of other symptoms. Even tually, either large nodular or lobulated opacities appear at the lung margin. Roentgenographic evidence of pulmonary fibrosis is often not present and is not required to estab lish the diagnosis. There is no satisfactory treatment How I* the Diagnosis of Mesothelioma Established? Cytopathological evaluation of cells in pleural fluid is difficult, and the technique is not recommended for the definitive diagnosis of mesothelioma. JAMA. Nov 9, 1984--Vol 252, No. 18 . Asbestos-Relaled Diseases--Council on Scientific Affairs 2595 I "I n r' a o n r\ 11= m nn-ior^-^-r 'Incisional biopsies of a mass in the pleural and peritoneal cavities usual ly provide adequate material for pathological study. The hiatopathological diagnosis of mesothelioma can be difficult, since other neoplasms can mimic these tumors. In addition, these lesionB exhibit a wide range of morphological features. Thus, the diagnosis must be one of exclusion. Special histochemical, immunochemi cal, and electron microscopic tech niques occasionally are useful in the pathological evaluation of mesothe lioma. Panels of pathologists have been established to assist in the diag nosis of mesothelioma. Do Pleural Plaques Develop Into Malignant Mesotheliomas? Persons in whom malignant pleural or peritoneal mesotheliomas develop frequently have coexistent pleural plaques. On the other hand, the majority of persons with pleural plaques do not experience the devel opment of malignant mesotheliomas. Pleural plaques are not believed to be premalignant lesions. Can Masothaliomas Develop After Either Transient or Casual Exposure to Asbestos? Mesotheliomas are a rare form of cancer. They have been reported in persons with only limited exposure to asbestos in nonoccupational settings. For example, on rare occasions these tumors have developed in household contacts of asbestos workers and in persons who have visited or resided near asbestos mines, mills, factories, and waste dumps. Although it is conceivable that asbestos exposure was brief in these cases, it may have been heavy. The development of mesothelioma is not associated with cigarette abuse. Most, but not all, cases of malignant mesothelioma are asbestos related. Nevertheless, in a published series of cases, from 11% to 16% of patients with mesothelioma do not have a history of exposure. Are All Commercial Types of Asbestos Equally Hazardous to Humans? It is generally accepted that the three major commercial types of asbestos (chrysotile, amosite, and crocidolite) are capable of causing pleu ral plaques and interstitial pulmo- 60 SO uEi 40 30 3 20 j-- ft 10 - Asbestos Effusion Pulmonary Fibrosis. Pleural Ptsques Ptetxel Calcification n ol-- 30-39 40-49 Years Since First Exposure Clinical occurrence of various asbestos-associated lesions among industrial workers chronical ly exposed to airborne mineral fibers. Data are based on physical examinations and roentgenograms obtained systematically during 60-year period (from Epler at at"). Age-Standardized Lung Cancer Death Rates for Cigarette Smoking and/or Occupational Exposure to Asbestos Dust Compared With No Smoking and No Occupational Exposure to Asbestos Dust* Group Control ; _ AfbSftMJtrsrk#/* Control Asbsstos workers Exposure to Asbestos , History ot Ciaarstts - Smoking No No ' .;.. >YM Ml J L No NP-mCv Yes Yes Yes .Oeath' Mortality * Rate '' Difference 11 0 123 ill 602 600 Mortality ` Ratio ; > 1.0 10.9 - 63.2 *R*ts per 100,000 man-years atandarized for age on the distnbution of the man-years of all the asbestos workers. Number of lung cancer deaths baaed on death canificate information. Table reproduced with permission from the Ann*I* ot the New Yotk Academy ol Sciences.1* nary fibrosis. There is, however, considerable debate regarding the relative carcinogenic potential of the different asbestos fiber types. The controversy stems from the fact that all commercial varieties of asbestos induce mesotheliomas in experimen tal animals, yet the carcinogenic risk appears to be much greater for crocidolite than for chrysotile, with the risk for amosite being intermediate in severity. Does Cigarette Smoking Influence the Development of Asbestos-Related Disease? There is no evidence that smoking predisposes a person to either the development or the progression of pulmonary fibrosis and mesothelio ma. However, smoking can decrease pulmonary function and compromise overall health. The synergistic effect of cigarette smoke and asbestos exposure greatly increases the risk of bronchogenic carcinoma, as evidenced by a compar ison of the mortality ratios in the Table. Whereas the lung cancer death rate for the nonsmoking asbestos worker is five times that of the controls, the asbestos worker who smokes is subject to a 53-fold increase. A carcinogen in its own right, asbestos appears to act as a cocarcinogen with cigarette smoke in the pathogenesis of bronchogenic car cinoma. The effects of asbestosrelated diseases and cigarette smok ing are synergistic or multiplicative rather than additive. Patients with asbestos exposure must be counseled on the risks of continued smoking. What Is the Likelihood That Bronchogenic Carcinoma Will Develop In a Patient With Asbestosls? Most epidemiologic studies of work ers exposed to asbestos (Table) have failed to relate the occurrence of bronchogenic carcinoma specifically to the presence and severity of asbes- 2596 JAMA, Nov 9, 1984--Vol 252, No. 18 , Asbestos-Related Diseases--Council on Scientific Affairs II 1 CAPCO JEN 0012538 toii. Recent investigation* in the United States and Great Britain have shown that about 20% to 40% of patients with asbestosis will die of cancer of the lung. As might be expected, the majority of these per sons are smokers. In most case stud ies, there is an increased prevalence of adenocarcinoma in those with asbestosis. What Risks Aro Associated With Drinking Water Containing Asbestos? Asbestoslike mineral fibers com monly are found in drinking water sources throughout the United States. The material comes from rock out crops in watersheds and, to a variable extent, from refuse dumps and asbes tos-containing water pipes. There is no evidence to indicate that ingested fibers are responsible for disease in man. How Effective Are the Current Engineering Controls and Personal Protsctlve Devices In Reducing the Risk of Contracting an Asbestos-Related Disease? Attention to engineering controls such as ventilation and remote han dling of asbestos as well as improved housekeeping in the workplace have made the federal standards for air borne fiber concentrations attainable. These approaches should be the pri mary means of control. Pace masks and respirators ap proved by the National Institute for Occupational Safety and Health re duce the risk of inhaling asbestos fibers if they are fitted and used properly. Too often the worker--and his supervisor--is unmindful of the importance of a good fit to the face and of the need to keep the interior of the mask clean. When masks and respirators are not used properly, they create a false sense of security. Personal protective devices are essen tial when all other measures either fail or are impractical They should not be used as the first line of defense. Aro the Current Standards for Airborne Concentrations of Asbeatoa Fibers In the Workplace Sufficient to Prevent the Development of Asbestosis and Asbestos-Associated Neoplasms? Health standards do not represent criteria for the absolute elimination of risk or the prevention of disease. There appears to be a rough doseresponse relationship between asbes tos exposure and the development of disease. It is likely that today's regu lations protect the worker from asbestosis. The existing standards of the feder al and state regulatory agencies seek only to establish guidelines for a "reasonably safe" level of exposure that is not likely to produce disease during the lifetime of a worker. The basis for any standard is the avail able medical and scientific evidence and a consideration of the societal and economic impact of the stan dards. Technological feasibility of control measures and the availability of analytic procedures are other important considerations. ' What Can the Physician and the General Public Do When They Become Aware - of a Potentially Hazardous Source of Asbestos Exposure? Workers should be advised of their rights under the Occupational Safety and Health Act of 1970. They, or their representatives, are entitled to re quest a hazard evaluation review by the National Institute for Occupa tional Safety and Health and an inspection of the work site by a federal or state compliance officer. Under the law, the person who ini tiates the report cannot be penalized by his employer for doing so. The general public can seek assist ance through the EPA, the Consumer Product Safety Commission, and the local or state public health depart ment Do the Commonly Used Asbestos Substitutes, Such as Fibrous Glass and Mineral Wool, Cause Diseases Similar to or Different From Those Associated With Asbestos? To date, there is no reason to believe that fibers of glass or mineral wool cause chronic pulmonary dis ease. The effects of inhaling these fibers are reversible. Since their introduction in I960, ultrafine fibers (<5 pm in diameter) have gradually replaced those having a larger diame ter (6 to 8 pm) and are now the standard of the fiberglass industry. Suggested Reading 1, Boeklake HR: Asbestos-related diseases of the lunge and pleura. Am Rev Respir Die 1983;126:187-194. 2. Craighead JE, Abraham JL, Churg A, et ah Asbestos-associated disnem Arck Palkol lab lied 1982;106:544-697. . 8. Craighead JE, Moeeman BT: The pathogen- cel* of asbestos-associated disease N J Med 1982306:1446*1455. 4. Enterline PE, Harsh GM, Eemen NA: Res piratory dieeeee among workers exposed to man-made mineral fibers. Am Rev Respir Die 1983;128:1-7. 6. Levine RV: Asbestosis: An Information Resource? Dept of Health* Education, and Wel fare publication (NIH) 78-1981. Bethesda, Md, National institutes of Health, 1978. 6. Workplace Exposure to Asbestos, Dept of Health and Human Servicee publication 81-103. New York, National Inatltute for Occupational Safety and Health, 1981. 7. Preger L (ed): Asbestos-Related Disease. New York, Grune A Stratton Inc, 1978. 8. Selikoff U, Hammond EC (ed*): Health hazards of asbestos exposure. Ass NYAcad Set 1979,33031-116. 9. Selikoff U. Lee DHK: Asbestos end Disease. New York, Academic Preaa Inc, 1978. 10. Simpson W (ed): Asbestos: Final Reports the Advisory Committee on Asbestos. London, Advisory Committee on Asbestos, I960. 11. Epler GR, McCloud TC, Gaenaler EA: Prevalence and incidence of benign asbestos pleural effusion In a working population. JAMA 1982347317-622. 12. Hammond EC, Selikoff U, Seidman H: Asbestos exposure, cigarette smoking and death rates. Ass NYAcad Set 1979330:474-490. JAMA, Nov 0. 1984--Vol 2S2, No. 18 I * Asbestos-Related Diseases--Council on Scientific Affairs 2507 CAP CO JEN 0012539