Document 2r9d61aaON42qzaX414YEJdL

"MHO THE NEW ENGLAND JOURNAL OK MEDICINE June 17, 1982 The New England Journal of Medicine J EXPOSURE TOl HUMAf iND Official Organ of The Massachusetts Medical Society During the past two decades, ill health resulting from exposure to asbestos has been the subject of in Percy W. Watlman, M.D. President William B. Miinier, M.D. Charles S. Amorosino, Jr. Executive Vice-preiident Executive Secretary tensive observation and research1--probably more intensive than research on any other environmental agent.2 In the most direct target organ, the lung, and in its pleural coverings, there is a wide spectrum of response after exposure; not only acute and chronic Published Weekly by the Committee on Publications of the Massachusetts Mechcal Society inflammatory diseases but also cancer of these organs may occur. Research has been stimulated by the belief James F. McDonough, M.D., Chairman John I. Sandson, M.D. John C. Ayres, M.D. William H. Sweet, M.D., D.Sc. William B. Schwartz, M.D. Frank E. Bixby, Jr., M.D. Samuel K. Stewart, M.D. that the more complete our understanding of the mechanisms of pathogenesis, the better will be our ability to control the continued use of this mineral in today's complex technologic world.3 Arnold S. Reiman, M.D., Editor Marcia Angell, M.D., Deputy Editor Edwin W. Salzman, M.D., Deputy Editor Associate Editors The review by Craighead and Mossman of the pathogenesis of asbestos-related diseases in this issue of the Journal,4 which covers recent work in cell biol ogy, is set in the context ofpathology but also discusses the use of these minerals and regulatory consider Jane F. Desforges, M.D. Norman K. Hollenberg, M.D., Ph.D. Ronald A. Malt, M.D. Morton N. Swartz, M.D. Franklin H. Epstein, M.D. ations; it complements other recent reviews of the epi demiology of these diseases,5 their impact on public health,6 and current clinical issues.7 Also important is Francis D. Moore, M.D., Book Review Editor John C. Bailar, III, M.D., Statistical Consultant a recent report that provides criteria for grading the pathologic changes in the lungs associated with asbes Joseph J. Elia, Jr., Manager of Editorial Operations Emily S. Bom, Assistant Editor tos exposure.8 Systematization of pathological assess ments can only enhance the pooling orexperience from Marlene A. Thayer, Editorial Office Manager Editorial Board different centers or countries by maximizing the com parability ofstudies. The international classification of radiographs of pneumoconiosis9 by the International Richard H. Egdahl, M.D. Paul Calabresi, M.D. Park Gerald, M.D. Aram V. Chobanian, M.D. Joseph B. Martin, M.D. John T. Harrington, M.D. Robert J. Mayer, M.D. Homayoun Kazemi, M.D. Frederick Naftolin, M.D. Kenneth McIntosh, M.D. Kenneth J. Rothman, Dr.P.H. David G. Nathan, M.D. Kurt J. Bloch, M.D. Lawrence G. Raisz, M.D. Thomas J. Ryan, M.D. Labour Office is an example of such systematization, and the dividends associated with its use are generally recognized. Perhaps the major contribution of the review by Craighead and Mossman (and this may surprise read ers not familiar with the field) is the emphasis placed on the shortcomings of our present knowledge of the John K. Iglchart, Special Correspondent Frederick Bowes, III, Director op Business Operations Ronald H. Brown, Manager op Advertising & Marketing William H. Paige, Manager of Production & Distribution Milton C. Paige, Jr., Consultant pathogenesis of asbestos-related disease. Considering .- first the fate of inhaled fibers in the lung, it is now f.-j: evident that the dust burden of the lung is primarily in .the form of uncoatcd asbestos particles,4 whether or not these conform to the definition of a fiber (i.c., a Prospective authors should consult "Information for Authors," which appears in the first issue of every volume and may he obtained from the Journal office. Articles with origin.)! materia! are accepted for consideration with the understanding that, except for abstracts, no part of the data has been pub lished, or will be submitted for publication elsewhere, before appearing in this Journal. Majekial primed in the New EnglandJournal ofMedicine is covered by copyright. TheJournal d*- not hold itselfresponsible for statements made by any contributor. Notices should he sent at least 3d day* before publication dale. Ali mouc;h all advertising material accepted is expected to conform to ethi cal medical standards, acceptance df>cs not imply endorsement by theJournal. Reprints: The Journal tines not stock reprints, and reprints of the MCH CPCs are not available. ------- Subscription Priced. USA: $48 j>er year (interns, residents 535 per year; students $30 per year). Canada (U.S. funds only): Sj8 per year (interns, residents $45 per year; students $40 per year). Mail checks to Subscription Payments, P.O. Box 4772, Boston, MA 02212. Editorial Omur-s: lu Shattuck St., Boston, MA 02115. :__ Business and Subscription Offices: 1172 Commonwealth Avr., Boston, MA 02134. particle with a length-to-width ratio of 3:1). This defi nition probably originated rather arbitrarily from a need to standardize what was considered a fiber for purposes of industrial hygiene6; it is now widely be lieved that a much higher ratio, perhaps 10:1, would have been a better choice. Both fiber length40 and mincralogic type" arc important determinants of whether a fiber becomes coated and so takes on the familiar appearance of the asbestos body. Most asbes tos bodies found in human lungs contain an amphihole fiber as a core," even though chrysotile accounts for the greatest use and presumably the most exposure.7 VVliat permits some particles to lie apparently dormant in the lungs for long periods before evoking an organ response is not known, and there is no good explana tion for the fact that all the disease consequent to as bestos exposure (including fibrosis of the lungs and MON-335 6113 21337 mm . r ' Vol. 306 No. 21- EDITORIAL 1481 pleura as well as cancer of these organs) may appear differences in the pathogenic potential of the various long after exposure has ceased. fibers in this mineral group. Of particular concern is Fibrosis of the lung (asbestosis) was recognized by whether chrysotile (which has accounted for over 90 the first decade of this century and has been the subject per cent of commercial uses during the past several of much research in animal models. Nevertheless, decades) differs from the twoaniphibole fibers, crocid- Craighead and Mossman conclude that the patho olite and amosite, which were used extensively during genesis of asbestosis remains to be established,4 as World War II and in the postwar building boom. The docs the importance of exposure dose as compared issue has been bedeviled by problems of comparing with individual "susceptibility" in the initiation and like with like,5 by the difficulty of sorting out the rela the progression of the fibrotic reaction. The finding of tive contributions of exposure (duration, level, and an acute inflammatory response in some early human particle size) and fiber type, and by the dillerences lesions4 raises the issue of whether there is a reversible between exposure in the mining and milling of fiber component to the acute response in human beings, as and the secondary application of fibers in manufactur suggested by work in animals.12 Long-term studies in ing. Thus, although it is clear that the rates ofmesothe sheep13 may help to answer this question. As for lioma are different in different exposed populations, it whether asbestos acts as an initiator or as a promoter has usually not been possible to assess the extent to of lung cancer, the authors of the review4 favor the which these differences are due to fiber type or to other latter view; perhaps pardcles act as physical carriers of factors. Some clarification has come from the applica other environmental carcinogens to the basal epithe tion of modem methods oflung-dust analysis to autop lial cells. It is also possible that more than one mecha sy material. In two case-control studies of mesotheli nism is involved.7 oma, an excess of amphiboles (amosite in North There is perhaps even more uncertainty about the America and crocidolite in the United Kingdom) was pathogenesis of pleural reactions than there is about found in the lungs of the cases, whereas chrysotile parenchymal lesions. For instance, it is not clear how contents were similar in cases and controls.5,16 In a often acute exudative reactions, such as effusions (pre study of chrysotile miners in Quebec, almost as much sumably usually clinically silent), precede the more tremolite (an amphibole contaminating some of the chronic diffuse or localized fibrotic reactions ofvisceral mined rock deposits) was found in the lungs as chryso or parietal pleura. It is also unclear how fibers reach tile, although the latter was clearly the main environ the parietal pleura and concentrate there in such a way mental contaminant.17 These results are consistent as to evoke plaque production after a long delay while with what has long been believed on the basis ovmore leaving the visceral pleura intact; an adequate hypoth tenuous evidence -- that there is preferential clear esis for the pathogenesis ofpleural plaques is needed to ance ofchrysotile, as compared with amphibole fibers, explain all these features. Perhaps even more puz from body tissues and that this may contribute to the zling is what determines whether the pleural reaction differences in the pathogenic potential of the minerals. will be benign or malignant. Not all would agree with Epidemiologic evidence for a fiber gradient in the view expressed in the article4 that malignant pathogenic potential is strongest for mesothelioma, mesotheliomas are pathognomonic of asbestos expo with crocidolite more strongly implicated than chryso sure: these tumors were described by European pa tile, and amosite probably in between. The evidence is thologists in the 19th century -- long before major .-also reasonably strong for lung cancer, with crocidolite commercial exploration of the asbestos minerals15 -- >,^again more strongly implicated than chrysotile. For and there is little evidence even today that asbestos is pleural reactions (pleural plaques and fibrosis), there responsible for many cases in men or women outside may also be a fiber gradient, although other factors are industrial centers.3,15 What are described in the pres almost certainly involved; for parenchymal fibrosis the ent review as "casual" exposures (i.e., usually domes evidence for a fiber gradient is minimal. At present it is tic or neighborhood) are exposures that are intermit believed that the biologic activity of asbestos particles tent but have often turned out to be to very heavy dust relates to the degree of penetration and the amount of clouds of fine particles.3 ` deposition in the lower respiratory tract, both ofwhich In spite of considerable current interest in the depend mainly on their physical characteristics, in topic,7 the issue of whether asbestos exposure is associ cluding their aerodynamic properties. Particle size ated with airway abnormalities is not addressed by (and particularly length and fineness) may also deter Craighead and Mossman. The involvement of small mine oncogenicity. However, biologic activity is likely airways in the early stages of asbestos-related lung to be modified by the length of time that particles fibrosis has in all likelihood its clinical counterpart, survive in the lung without denaturing, which may be although there is no evidence about whether these ab related to their chemical characteristics. The most normalities are reversible or not. The association be plausible explanation for differences in the pathogenic tween asbestos exposure and other forms of airway potential of various fibers is that these differences re response, such as bronchitis or emphysema in the ab sult from differences in both the physical and chemical sence of asbestosis, also remains to be clarified-, as do properties of the fibers. the confounding effects of cigarette smoking. YVhat is the clinical importance of the issues raised Finally, there is the question of whether there are by the review in the Journal? Perhaps the most impor- 6113 21338 - f ' 1^82 THE NEW ENGLAND J O URNAL MEDICINE June 17, 1982 taut is that health risks in relation to exposure to asbes tos vary according to environmental factors. Some of these factors (such as exposure dose, particle size, and fiber type) are known, but there are undoubtedly oth ers not yet recognized. Host characteristics probably also influence the response to exposure. Thus, in con sidering the individual patient with a disease known to be related to asbestos exposure, the wise clinician should avoid regarding any particular exposure as too short, too remote, or at too low a level (even ifenviron mental counts were in compliance with the present regulations) to have accounted for the disease. Assess ment of the importance of particular environmental exposures is often outside the clinician's expertise; it should be referred to appropriate consultants in indus trial hygiene, engineering, or physics. In lung cancer the statistical probability that a given case is attribut able to asbestos exposure may be estimated from expo sure-response data,10 which for practical purposes can probably be assumed to be linear, provided that the data available are applicable to the industry in which the subject was employed. Finally, the unpredictable clinical course of these diseases demands vigilance by the clinician with respect to past exposures, and the most powerful indicator remains the careful, complete, and precise occupational history.7 Whether the dust concentrations permitted by cur rent regulations will in fact eliminate the future risk of asbestosis, as Craighead and Mossman suggest,4 re mains to be established. Similar suggestions in the 1930s proved to be premature. Evaluation of the im pact of present controls on health issues is an urgent matter for research. Furthermore, a total ban on use seems unlikely in technologic societies,3 in which it may be considered preferable to retain these versatile minerals for certain uses. Until it is established that asbestos substitutes do not carry health risks,19 re search into the mechanisms by which asbestos parti cles produce ill health should be vigorously pursued. McGill University Montreal, PQ H3A 2B4, Canada MARGARET R. BeCKLAKE, M.D. References 1. Acheson ED, Gardner M. Exposure limites --the scientificcnterii. In: McDonald JC, ml. Recent advances in occupational health. Edinburgh: Churchill Livingstone, 1981:257-69. 2. Peter GA, Peters UJ. Source book on asbestos disease. New York: Garland STPMpres*, 1980:Ai-Kl8. 3. Gloag D. Asbestos -- can it be used safely? Br Med J. 1981; 282:551-3. 4. Craighead JE, Mossman BT. The pathogenesis of asbestos-associated dis eases. N Engl J Med. 1982; 306:1446-55. 5. McDonald JC. Asbestos-related disease: an epidemiological review. In: Wagner JC, ed. Biological effects of mineral fibres. Lyon: International Agency for Research on Cancer, 1980:587-601. (IARC scientific publica tion no. 30). 6. Liddell D. Asbestos and public health. Thorax. 1981; 36:241-4. 7. Beckiake MR. Asbesto* related diseases of the lung and pleura: current clinical issues. Am Rev Respir Dis. (in press). 8. Craighead JE, Abraham Jl.. Churg A, et al. The pathology of asbestosassociated diseases of the lungs and pleural cavities. Arch Pathol Lab Med. (in press). 9. International Labour Office, Guidelines for the use of the ILO International Classification of fodiogrtphs of pneumonconioses. Geneva: International Labour Office, 1980:1-48. (Occupational health and safety series no. 22). 10. Morgan A, Holmes A. Concentrations and dimensionsofcoated and uncoated asbestos fibres in the human lung. Br J Ind Med. 1980; 37:25-32. It. Churg AM, Wamock ML. Asbestos and other ferruginous bodies: their formation and clinical significance. Am j Pathol. 1981; 102:447-56. 12. Hiett DM. Experimental asbestosis: an investigation of functional and patho logical disturbances. 1. Methods, control animals and exposure conditions. Br J Ind Med. 1978; 35:129-34. 13. Begin R, Pieszczynski M, Masse S, et al. Asbestos-induced lung injury in the sheep model: the initial alveolitis. Environ Res. (in press). 14. Hillerdal G. The pathogenesis of pleural plaques and pulmonary asbestosis: possibilities and impossibilities. Eur J Respir Dis. 19S0; 61:129-38. 15. McDonald JC, McDonald AD. Epidemiology of mesothelioma from esti mated incidence. Prev Med. 1977; 6:426-46. 16. McDonald AD. McDonald JC, Pooley FD. Mineral fibre content of the lung in mesothelial tumours in North America. Anfi Occup Hyg. (in press). 17. Rowlands N, Gibbs GW, McDonald AD. Asbestos fibers in the lungs of chrysotile miners and millers -- a preliminary report. Ann Occup Hyg. (in press). 18. Enteriine PE. Attributability in the face of uncertainty. Chest. 1980; 78: Suppl (August):377-9. 19. Wagner JC, Elmes PC. The mineral fibre problem. In: McDonald JC, ed. Recent advances in occupational health. Edinburgh: Churchill Livingstone, 1981:1-13. SOUNDING BOARDS AFTER LAETRILE, WHAT? Laetrile was moribund before Moertel et al. laid it to rest with the recent report of their prospective clini cal trial.1,2 It had been replaced in popularity by an approach unusual in the annals of unorthodox cancer therapy -- one that represents more of a challenge than did Laetrile or its predecessors. This is the "natu ral" approach to malignant disease, which emphasizes cure through purification and the body's capacity to heal itself. The currently popular alternative approach is rooted in homeopathic and naturopathic beliefs, Indian and Oriental philosophy, and 19th-century theories of intestinal putrefaction. Promoters often evoke the time-worn conspiracy dogma, which states that the medical system, the Food and Drug Adminis tration, and the federal government withhold true r cures from the public, thereby perpetuating therapeutically useless and biologically harmful cancer treat ments in order to further the Establishment's econom ic interests.3,4 Alternative cancer therapies in vogue today differ importantly from Laetrile and from other unproved remedies of the past. Previous unorthodox treatments were "medicines" or at least "medicinal." Examples were Dr. Bye's Combination Oil Cure, Dr. Chamlee's remedy for removing cancer viruses from the blood. Dr. Leach's Cancerol, Dr. Koch's glyoxylide, and many others that attained great prominence in their day. They came in ampules, vials, or syringes, mim icking standard medications, and they were sold and administered in the usual clinical fashion by people in white coats. Today's alternative remedies explicitly reject associ ation with standard treatments, environments, and paraphernalia. These are anti-medicines, emphasizing purification through dietary regimens, detoxification 6113 21339