Document 2Bm7x682Oqb3x98Y2kp8wjJR

- *y S \3 ; III. COMMUNITY EFFECTS OF NONOCCUPATIONAL ENVIRONMENTAL ASBESTOS EXPOSURE Irving ]. Selikoff, M.D., F.A.P.H.A., and E. Cuyler Hammond, Sc.D., F.A.P.I1.A. Introduction T here has long been curiosity concern ing community exposure to pneumo coniosis-producing dusts, partly because the assumed "spill-over" from primary industrial sources might be expected to yield information concerning effects of minimal exposure and partly because community studies were needed to give base-line data against which to evaluate findings in groups of miners living in these communities.1,2 Nevertheless, it was not until the serious consequences of neighborhood beryllium disease were clarified2,4 that the important potential of community exposure to pneumoconiotic dusts was widely recognized. In the recent past, there has been growing interest in this problem, rang ing from the health effects on children of cement and similar industrial dusts in Rumania and neighborhood byssinosis in Egypt,8 to environmental pneu moconiosis adjacent to the Rajasthan desert.7 We may anticipate that such interest will increase for a number of reasons. First, because of growing con cern over air pollution in general and particulate air pollution in particular; second, because of the appreciation that the biological activity of known pneumoconiotic dusts is not limited to heavily exposed workmen, but may affect others indirectly exposed in the community; and, lastly, because study of community effects of pneumoconiotic dusts may sug gest methodology and technics suitable for the investigation of other environ mental factors, including inhaled dusts largely unidentified at present and of unstudied biological importance. Environmental Asbestos Disease It may be profitable to review studies of one pneumoconiotic dust, asbestos, in the light of these suggestions. The pos sibility of community asbestos disease has been known almost as long as asbestosis itself. In 1927, shortly after republication of the case report which gave the pneumoconiosis its name,8 Haddow9 reported finding asbestos bodies in the lungs of a person living close by an asbestos factory. Other neighborhood cases of asbestos disease have been re ported since.10' 12 Bobileva, et al.,18 re ported experiences suggesting impaired health in children living downwind of an asbestos plant in the Soviet Union. The import of such scattered observa tions was muffled, however, until the re ports of three germinal studies, within a short time of each other; Kiviluoto (I9 6 0 )14; Wagner, Sleggs, and March and (I9 6 0 )15: and Thomson, Kaschula, anti MacDonald (1963).18 In each, a pathological "marker," considered al most pathognomonic for asbestos expo sure, was unexpectedly found in groups in tbe general population not known to be industrially exposed to asbestos. Stigmata of Environmental Asbestos Exposure Pleural Calcification -- Scattered in stances of calcification of the pleura, particularly the parietal pleura, were ob served in asbestos workers during the 1658 VOL. 58. NO. 9. A.J.P.H. NONOCCf 1930s and 1940s, but their significance as a roentgenc'agic sign of asbestos exposure was not appreciated until the report of Jacob and Bolilig in 1955, in which such calcification was described in approximately 5 per cent of 343 Dresden asbestos workers.17 Investigations since then have demonstrated the extraordinary frequency of this finding among asbestos workers and have emphasized a cardinal feature--that it is rarely seen in less than 20 years from onset of exposure (Table 1) .18 Kiviluoto discovered 499 instances of such calcification during a community x-ray survey among 6,312 adults in the Kuusjarvi commune in Finland. Struck by this, and the absence of any such cases among 7,101 adults in the neighboring Ilomantsi commune, he astutely ob served that the first commune contained an asbestos mine and postulated that the people with calcification (farmers, housewives) had been subject to endemic environmental asbestos exposure.14 His countrymen, Faamanen. Noro and Raunio, subsequently reported air studies showing asbestos dust at dist ances up to 50 km from the mines, in cluding deposits ranging from 1.52 gm/ 100 m2/month 4 km away to 34.6 gm/ 100 m2/month at 0.5 km.19 Pleural Plaques--Pleural fibrosis is : : i i f < ; ; t ; i | < ' 1 ' T able 1-- T im e of onset o f radiotogi am ong 1,117 asbestos insulation worf Years from onset of exposure 40 + 30-39 20-29 10-19 0-9 No. 121 194 77 379 346 Chest roentgc % normal % fi 42.1 65.4 89.6 98.9 100.0 Total 1,117 SEPTEMBER. 1968 NONOCCUPATIONAL >S EXPOSURE '. Cuyler Hammond, Sc.D., F.A.P.H.A. :ernjmoause nary d to s of ause give luate g in i, it nces were ntial rmod. been angdren fusts bysneuthan such r of conand liar ; that lmoivily hers lity; mity sugabfe ironlosts largely unidentified at present and of unstudied biological importance. Environmental Asbestos Disease It may be profitable to review studies of one pneumoeoniotic dust, asbestos, in the light of these suggestions. The pos sibility of community asbestos disease has been known almost as long as asbestosis itself. In 1927, shortly after republication of the case report which gave the pneumoconiosis its name,8 Haddow8 reported finding asbestos bodies in the lungs of a person living close by an asbestos factory. Other neighborhood cases of asbestos disease have been re ported since.10"12 Bobileva, et al.,13 re ported e v p e rie n re s nyrestiti irnmired health in children living downwind of an asbestos plant in the Soviet Union. The import of such scattered observa tions was mufUed, however, until the re ports of three germinal studies, within a short time of each other: Kiviluoto (I9 6 0 )14; Wagner, Sleggs, and March and (I9 6 0 )15; and Thomson, Kaschula, and MacDonald (1963).18 In each, a pathological "marker." considered al most pathognomonic for asbestos expo sure, was unexpectedly found in groups in the general population not known to be industrially exposed to asbestos. Stigmata of Environmental Asbestos Exposure Pleural Calcification -- Scattered in stances of calcification of the pleura, particularly the parietal pleura, were ob served in asbestos workers during the VOL. 58, NO. 9. A.J.P.H. NONOCCUPATIONAL ENVIRONMENTAL EXPOSURE 1930s and 1940s, but their significance as a roentgenologic sign of asbestos ex posure was not appreciated until the re port of Jacob and Bohlig in 1955, in which such calcification was described in approximately 5 per cent of 343 Dres den asbestos workers.17 Investigations since then have demonstrated the ex traordinary frequency of this finding among asbestos workers and have em phasized a cardinal feature--that it is rarely seen in less than 20 years from onset of exposure (Table 1) ,18 Kiviluoto discovered 499 instances of such calcification during a community x-ray survey among 6,312 adults in the Kuusjarvi commune in Finland. Struck by this, and the absence of any such cases among 7,101 adults in the neighboring Ilomantsi commune, he astutely ob served that the first commune contained an asbestos mine and postulated that the people with calcification (farmers, housewives) had been subject to endemic environmental asbestos exposure.14 His countrymen, Laamanen, Noro and Raunio, subsequently reported air studies showing asbestos dust at dist ances up to 50 km from the mines, in cluding deposits ranging from 1.52 gm/ 100 m2/month 4 km away to 34.6 gm/ 100 m2/month at 0.5 km.18 Pleural Plaques--Pleural fibrosis is mother common pleural complication of asbestos exposure but, when diffuse, need not have the same diagnostic sig nificance as calcification. However, such fibrosis may occur in more or less dis crete plaques, and Kiviluoto has called attention to these as additional pleural stigmata of asbestos exposure.20 Pleural Mesothelioma--Neoplasms of the pleural surface in association with asbestosis have been known for over 30 years. Weiss suggested an etiologic relationship in 1953,21 but such pro posals faced the difficulty of infrequency of reported cases and the absence of epi demiological studies to suggest that these were other than chance associations. Wagner's report changed this. He in vestigated 33 cases of diffuse pleural mesothelioma in the North Western Cape Province of South Africa (an asbestosproducing area) and in 32 cases demon strated at least suggestive evidence of potential asbestos contact, usually non occupational, as, for example, residence in an asbestos area.15 Since this report, diagnosis of pleural mesothelioma has been a signal to seek previous asbestos exposure. Asbestos Bodies in General Popula tion--Asbestos fibers when in the lung, have the capacity of becoming charac teristically coated; these fibers form T a b le 1-- T im e o f o n se t o f ra d io lo tsic ally e v id e n t p le u r a l c a lcifica tio n am ong 1,117 asbestos insulation w orkers Year onset of exposure 40+ 30-39 20-29 10-19 0-9 No. 121* 194 77 379 346 Chest roentgenogram -- * ---------- Grade of calcification normal fication 1 42.1 57.9 37 65.4 34.5 46 89.6 10.4 8 98.9 1.1 5 100.0 0.0 0 2 20 15 0 0 0 3 13 6 0 0 0 Total 1,117 96 35 19 SEPTEMBER, 1958 1459 asbestos bodies which, when seen, can hardly fail to attract attention. This was so even before asbestos disease was known (Marchand, 1906) ,22 Thomson took advantage of this phenomenon to demonstrate the frequency of inhalation of asbestos by the general public. He examined smears of lung bases in 500 consecutive autopsies in Cape Town, and in 26.4 per cent found asbestos bodies.16 While asbestos bodies do not have the same significance as calcification or mesothelioma (disease may be absent and no conclusion concerning time of in* halation can be draw n), Thomson's ob* servations have been very important in demonstrating the frequency of commu nity exposure to asbestos at present in many areas of the world. Simultaneously these observations raise the serious ques tion whether inhalation of presumably small amounts carries a concomitant risk of widespread community asbestos disease. Recent Epidemiological Investigations Stimulated by the above observations, studies of environmental asbestos dis ease have been extended. First, the re lationship of mesothelioma to asbestos has been clarified. Peritoneal meso thelioma has also been shown to be as sociated ; Enticknap and Smither23 found 9 such tumors in 52 consecutive autop sies in one asbestos factory. Large col lections of asbestos-associated meso theliomas have been published.24' 28 The significant incidence of asbestos-related mesothelioma has now been demon strated in our laboratory. In a prospec tive 52-month study of 370 experienced asbestos insulation workers, from Jan uary 1, 1963, to April 30, 1967 (sur vivors of a larger group of 632 fol lowed 1943-1962), there were 94 deaths. Ten were due to mesothelioma, three to pleural and seven to peritoneal27 (Table 2 ). Perhaps more germane have been the studies of Newhouse and Thompson.28 Investigating 76 mesotheliomas at Lon don Hospital, they found 31 occurred in asbestos workers. Of the remaining 45, 20 occurred in individuals living within half a mile of an asbestos fac tory or in the household of an asbestos worker. Similar findings were reported by Elraes and Wade in Belfast.29 Thom son's observations have also been con firmed: 25 per cent to 50 per cent of adults coming to autopsy in Pittsburgh,30 Finland,31 Miami,32 Montreal,33 New York,34 and Belfast,35 are now found to have asbestos bodies in their lungs. T able 2-- O bserved and expected num ber o f deaths am ong 370 asbestos insula tion workers during the 52-m onth period from January 1, 1963, through A pril 30, 1967. Expected num bers are based u pon U nited States m ortality data disregarding the sm oking habits o f the subjects. Cause ol death Observed Expected deaths deaths Total, all causes Total cancer (all sites) Cancer of lung, pleura, bronchus, and trachea Bronchogenic carcinoma Pleural mesothelioma Peritoneal mesothelioma Cancer of stomach Cancer of colon and rectum Cancer of all other sites combined Asbestosis Heart and circulatory disease, including stroke All other causes of death 94 49 27 24 3 7 3 5 7 15 22 8 47.5 8.6 2.3 t t 0.6 1.2 4.5 0 28.5 10.4 ' * U nited States data not available, b u t figure should b e only sjigiill* le than 2.3. t U nited States data n ot available, b u t these are rare cause* of death in tbe general population. 1*60 V O L 58, NO. 9. A.J.P.H. .. .iiw j i jiijMWtm lim i! 9* NONOCCUP, Problems and Perspectives con tlO J The foregoing overview indicates that ina at least one pneumoconiotic dust, asbes- oce tos, may be widely disseminated into ov< the general community from industry exj sources or end-product use; that such 1 dissemination may produce detectable dir disease; and that methods to study the ha* question can be designed. It would be net misleading, howrever, to suggest that the cui situation has been clarified, even con- of cerning asbestos, and totally inaccurate url concerning other pneumoconiotic dusts. me The following questions, for example, in require study and explanation: in\ 1. Epidemiologic studies are concerned th; with the " general public." But insofar as the pneumoconiotic dusts are concerned, lat how "general" is the public? E. L. Col- in< Iis many years ago described pneumo- soi coniosis in dock workers after inhaling en coal dust;36 their counterparts, 50 years of later, were truck drivers who inhaled lai asbestos at a construction site. When we lu. consider that in some countries 5 per th cent of the employed population works in the asbestos-rich construction indus- fr try, we may appreciate that indirect oc- be cupational exposure may constitute a ca significant proportion of "community cl exposure." to be supplemented by con* r< siderable unrecognized occupational as- e\ bestos exposure. The latter would in clude the occasional use of asbestos ma terials by workmen not usually con- ^ sidered prone to asbestos exposure; such uses would include a carpenter sawing asbestos building board, a plumber using asbestos rovings for joints, and an elec- ~ trician stripping asbestos-covered wire and cable. With over 3,000 uses for asbestos, now currently known,37 oppor tunities for indirect and otherwise un- -- recognized occupational exposures may M be frequent. We are now studying asbestos bodies in the lungs at autopsy in several thou- ^ sand consecutive deaths in three general hospitals in New York City, and con- SEPTEMBER. 19*8 JIW U! can was was nson n to ttion He 500 and or >sent >f in ob it in mult in jusly jucslably itant estos studies of Newhousc and Thompson.28 Investigating 76 mesotheliomas at Lon don Hospital, they found 31 occurred in asbestos workers. Of the remaining 45, 20 occurred in individuals living within half a mile of an asbestos fac tory or in the household of an asbestos worker. Similar findings were reported by Elmes and Wade in Belfast.29 Thom son's observations have also been confilmed: 25 per cent to 50 per cent of adults coming to autopsy in Pittsburgh,30 Finland,31 Miami,32 Montreal,33 New York,34 and Belfast,35 are now found to have asbestos bodies in their lungs. T a b le 2---O b serv ed a n d e x p ec te d n u m b e r o f deaths am ong 370 asbestos insula tion workers during the 52-m onth period from January 1, 1963, through A pril 30, 1967, Fxpeeted num bers are based u p o n U nited Stales m ortality data disregarding the sm oking habits of the subjects. HJ ions, dis e re* estos nesoe asound utop; colnesoThe rlated monfspecmeed Jan(sur ! fob ;aths. ee to ieal27 n the Cause of death O bsened Expected deaths deaths Total, all causes Total cancer (all sites) Cancer of lung, pleura, bronchus, and trachea Bronchogenic carcinoma Pleural mesothelioma Peritoneal mesothelioma Cancer of stomach Cancer of colon and rectum Cancer of all other sites combined Asbestosis Heart and circulatory disease, including stroke All other causes of death 94 49 27 24 3 7 3 5 7 15 22 8 47.5 8.6 2.3 t 't 0.6 1.2 4.5 0 28.5 10.4 * U nited States data not available, b a t Scare ahould be only slightly less than 2.3. + U nited Stales data not available, b u t theae ate rare rausea of death n the general population. VOL. 58, NO. 9. .J.P.H. NONOCCUPATIONAL ENVIRONMENTAL EXPOSURE Problems and Perspectives The foregoing overview indicates that at least one pneumoconiotic dust, asbes tos, may be widely disseminated into the general community from industry sources or end-product use; that such dissemination may produce detectable disease; find that methods to study the question can be designed. It would be misleading, however, to suggest that the situation has been clarified, even con cerning asbestos, and totally inaccurate concerning other pneumoconiotic dusts. The following questions, for example, require study and explanation: 1. Epidemiologic studies are concerned with the "general public." But insofar as pneumoconiotic dusts are concerned, how "general" is the public? E. L. Col lis many years ago described pneumo coniosis in dock workers after inhaling coal dust;36 their counterparts, 50 years later, were truck drivers who inhaled asbestos at a construction site. When wc consider that in some countries 5 per cent of the employed population works in the asbestos-rich construction indus try. we may appreciate that indirect oc cupational exposure may constitute a significant proportion of "community exposure," to be supplemented by con siderable unrecognized occupational as bestos exposure. The latter would in clude the occasional use of asbestos ma terials by workmen not usually con sidered prone to asbestos exposure; such uses would include a carpenter sawing asbestos building board, a plumber using asbestos rovings for joints, and an elec trician stripping asbestos-covered wire and cable. With over 3,000 uses for asbestos, now currently known,37 oppor tunities for indirect and otherwise un recognized occupational exposures may be frequent. We are now studying asbestos bodies in the lungs at autopsy in several thou sand consecutive deaths in three general hospitals in New York City, and con comitantly we are investigating occupa tional and other characteristics. Prelim inary data suggest that unrecognized occupational sources may add to, and override, general community asbestos exposure (Table 3). 2. The existence of wide potential for direct or indirect occupational exposure has not been considered sufficient, nevertheless, to explain the frequent oc currence of asbestos bodies in the lungs of people coming to post mortem in urban communities. It should immemediately be said that neither Thomson in his original communication nor other investigators since undertook to prove that the "asbestos bodies" found by them were actually the result of inha lation of asbestos fibers and were not, indeed, the result of tissue reaction to .some other mineral fiber yielding an end-product which had the appearance of those bodies characteristically scon in large numbers in an asbestos worker's lungs. Studies to clarify this aspect of the problem arc in progress. While there is no doubt concerning the frequency of what appear to be asbestos bodies in autopsied lungs, the signifi cance of this observation is not currently clear. Discovery of asbestos bodies in routine post-mortem studies is simply evidence at best that at some time as T a b le 3-- Asbestos bodies in th e lungs o f a sam ple o f persons in the general p o p u latio n at autopsy in New York City, 1966. P relim in ary analysis by occupational categories. Sex and occupation No. of subjects Men Blue collar workers White collar workers Women: Housewhes 197 111 47 With asbestos bodies No. % 120 60 45 41 14 30 Total 355 179 50 SEPTEMBER. 1958 1551 bestos fibers have been inhaled, with cruited from the farming population) in out indicating when such inhalation oc a nearby asbestos mine. The mine could curred. It has long been known that hardly have been the only source, since asbestos bodies can be formed in human it had been open for less than two lungs in two or three months, or per decades (latent period). Examination of haps less.38 Disease could be anticipated the soils worked by the affected farmers only as a result of inhalation that had demonstrated asbestos minerals to be occurred a considerable time before.39 present; even the stone fences were made On the other hand, it is likely that most of outcroppings of anthophyllite mineral. asbestos now being discovered post mor Such pleural disease must be categorized tem in persons who have not been in as the result of'intimate exposure under dustrially exposed has been of recent unique conditions, among certain agri deposition, since there was previously cultural workmen and their families, much less asbestos about to pollute the rather than what may be called general air. For example, annual world produc asbestos air pollution. tion of asbestos was 500 tons in 1890, Much more study of asbestos air pol 200,000 tons in 1920, 500,000 tons in lution is required--its extent, sources, 1930, compared with 4,000,000 tons per range, persistence--as a background for year at present appropriate epidemiological investiga 3. Asbestos air pollution -- General tions concerned with its disease potential. community air pollution by asbestos 4. Mesothelioma -- Asbestos workers microparticles may occur from indus frequently die of mesothelioma, and trial sources or frem disintegration or other cases are often found to have had use of asbestos products. Under certain close environmental contact.15'28'35,42,48 circumstances, as noted, it is probable But is there any disease potential as the that asbestos disease may occur. But it result of general asbestos air pollution? is by no means proved that such gen So far, there seem to be few mesotheli eral asbestos air pollution, presumably oma deaths in the general population. A with only small numbers of fibers in review of 31,652 consecutive deaths, haled, results in widespread disease. among over 1,018,183 people in the gen Cases of pleural calcification among eral public (1959-1962), revealed only Kiviluoto's farmers may not be evidence 3 cases of mesothelioma.44 Moreover, is of asbestos air pollution from the local asbestos the only pneumoconiotic cause mine and mill, a facile explanation. This of mesothelioma? Wagner produced ex explanation is not available, for exam perimental mesothelial tumors with silica ple, for Hromek's finding of 273 in as well as with asbestos,45 as did Hueper stances of similar pleural calcification with polyurethane.48 during a survey of 9,871 persons in an 5. The statistical and epidemiological agricultural area of Czechoslovakia with difficulties in evaluating the community no asbestos mine or other known ex effect of an environmental agent, in a posure.40 disease process with multiple potential An alternative explanation can be de causes, is seen with lung cancer. This is rived from the recent experiences of the most common tumor among asbestos Zolov, Bourilkov, and Babadjov.41 These insulation workers at this time; one in investigators found instances of pleural five deaths is caused by this neoplasm.47 calcification among farmers (largely With this lead, asbestos bodies are tobacco) in the Av en region of Bulgaria being sought by a number of investiga (5.6 per cent of males and 2.8 per cent tors among random cases of lung cancer of females examined), in about the same in the general population to find a pos percentage as among the workmen (re sible link to asbestos. But how allow for 1662 VOL. 58. NO. V. A.J.P.H. NONOCCU T a b le 4-- O bserved a n d e x p ec te d bronchogenic carcinom a anion w orkers d u rin g (lie 52-m onlh pc through A pril 30, 1967, by sm ok Smoking habits W orker observe Never smoked regularly History of pipe, cigar smoking only History of regular cigarette smokingt 48 39 283 Total 370 * AH w ith m ore than 20 y e a n from on se t o f e ij t Include cigarette sm okers who also sm oked the effect of cigarette smoking which overwhelms the asbestos effect? Thus, of the 370 asbestos workers referred to above, all with more than 20 years since onset of exposure, followed prospectively for Z'2 months (January ], 1963 to April 30, 1967), 87 did not smoke cigarettes. None of these men died of lung cancer. On the other hand, 283 had a history of cigarette smoking; 24 died of lung cancer or eight times the expected num- b< a> et ej dla e. d g a* Table 5-- Years from onset o f asbestos * who died o f bronchogenic carcinom a, Years onset of exposure to death Total ] Bronchogenic carcinoma tl 20-24 3 3 25-29 9 8 30-34 25 17 35-39 30 16 40-44 17 11 45-49 20 9 50-54 5 4 55-59 4 i Total 113 69 No te: 14 of th 17 m esotheliom a* w ere w ell es diagnosis was less firmly eilsb U tb ed . SEPTEMBER. 1968 rith- cruited from the farming population) in . oc- a nearby asbestos mine. The mine could that hardly have been the only source, since man it had been open for less than two per- decades (latent period). Examination of ated the soils worked by the affected fanners had demonstrated asbestos minerals to be re." present; even the stone fences were made Host of outcroppings of anthophyllite mineral. nor- Such pleural disease must be categorized in* as the result of intimate exposure under cent unique conditions, among certain agri usly cultural workmen and their families, the rather than what may be called general 3uc* asbestos air pollution. 390, Much more study of asbestos air pol i in lution is required--its extent, sources, per range, persistence---as a background for appropriate epidemiological investiga eral tions concerned with its disease potential. stos 4. Mesothelioma -- Asbestos workers jus* frequently die of mesothelioma, and t or other cases are often found to have had tain close environmental contact.15,23'35,42'43 ble But is there any disease potential as the it it result of general asbestos air pollution? ;en. So far, there seem to be few mesotheli ibly oma deaths in the general population. A in review of 31,652 consecutive deaths, ase. among over 1,018,133 people in the gen ong eral public (1959-1962), revealed only nee 3 cases of mesothelioma.44 Moreover, is acal asbestos the only prieumoconiotic cause This of mesothelioma? Wagner produced ex am perimental mesotheUal tumors with silica in as well as with asbestos,45 as did Hueper lion with polyurethane.48 % an 5. The statistical and epidemiological rith difficulties in evaluating the community ex effect of an environmental agent, in a disease process with multiple potential de- causes, is seen with lung cancer. This is of the most common tumor among asbestos ese insulation workers at this time; one in irai five deaths is caused by this neoplasm.47 jely With this lead, asbestos bodies are tria being sought by a number of investiga nt tors among random cases of lung cancer tme in the general population to find a pos (re- sible link to asbestos. Put how allow for V O L 58. NO. 9. A.J.P.H. NONOCCUPATIONAL ENVIRONMENTAL EXPOSURE T a b le 4-*--O b se rv e d a n d e x p e c te d n u m b e r o f d c a tlis d u e to bronchogenic carcinom a am ong 370 asbestos insulation w orkers during the 52-m onth period from Jan u a ry 1, 1963, through A pril 30, 1967, by sm oking habits Smoking habits Never smoked regularly History of pipe, cigar smoking only History of regular cigarette smokingt W orkers observed* 48 39 283 Observed deaths 0 0 24 Expected deaths 0.05 0.13 2.98 Total 370 24 3.16 * A ll w ith m ore th an 20 year from onset o f exposure, t Include* cigarette sm okers who also sm oked p ip e o r cigar. the effect of cigarette smoking which overwhelms the asbestos effect? Thus, of the 370 asbestos workers referred to above, all with more than 20 years since onset of exposure, followed prospectively for 52 months (January 1, 1963 to April 30, 1967), 87 did not smoke cigarettes. None of these men died of lung cancer. On the other hand, 283 had a history of cigarette smoking; 24 died of lung cancer or eight times the expected num ber, age and smoking habits taken into account (Table 4). 6. In demonstrating pathogenetic and etiological relationships, chronic disease epidemiology has frequently faced the difficulty of a long period of clinical latency. Asbestos disease is another example. We have recently been able to define the range of such latency for one group of workmen exposed to asbestos-- asbestos insulation workers. Table 5 T a b le 5-- Year? fro m o n s e t o i a sb e sto s e x p o s u r e lo d e a th o f 1 1 3 w orkers who died o f bronchogenic carcinom a, m esotheliom a, o r asbestosis. Years onset of exposure to death Total Pleural Bronchogenic meso carcinoma thelioma Peritoneal mesothelioma Asbestosis 20-24 .3 3- - - 25-29 9 8 - - i 30-34 25 17 3 2 3 35-39 ' 30 16 3 4 7 40-44 17 11 - 45-49 20 9- 50-54 5 4 - 55-59 4 1 - 24 29 -i 12 Total 113 69 6 11 27 Ndts: 14 of th e 17 m esotheliom as w ere w ell established as soch. l a th re e th e histological diagnosis was leas firmly eaU biU hcd. SEPTEMBER, 1958 1663 T a b le in--A ge a t tim e o f d e a th o f 1 13 a sb e sto s w o rk e rs w ho d ie d o f bronchogenic carcinom a, m esotheliom a o r asbestosis. Age at death Total Bronchogenic carcinoma Pleural meso thelioma Peritoneal mesothelioma Asbestosis 35-39 i i- 40-44 i i- 45-49 i i- 50-54 16 93 55-59 24 15 2 - - 3 2 - i 5 60-64 21 11 1 65-69 22 16 - 70-74 10 6 75-79 14 6- 80-34 3 3- 36 1. 5 -4 26 -" Total 113 69 6 11 27 shows the number of years from first asbestos exposure to time of death of 113 consecutive deaths due to asbestosrelated diseases (bronchogenic carci noma, pleural mesothelioma, peritoneal mesothelioma and asbestosis). None of the 113 men died in less than 20 years from onset of exposure, and 101 (89 per cent) of them did not die until 30 or more years had elapsed since onset of exposure. Table 6 shows these same 113 men classified by age at time of death. Only three of the men died under the age of 50 while 49 of them died after age 65. In epidemiological studies designed to ascertain potential asbestos disease, par ticularly neoplasia, it is obviously neces sary to consider such latency and, in the case of joint exposure to two agents, latency of both must be considered. In practical terms, populations studied should contain as many individuals as possible, with more than 20 years from onset of exposure. Asbestos exposure rarely causes disease in less than 20 years from onset; inclusion of young sters or others with inadequate duration of exposure will teach us little of the po tential of asbestos exposure, and will serve only to dilute pertinent observa tions. Moreover, investigations should aim to follow exposed individuals as long as possible, since risk does not stop at retirement age or with cessation of occupational exposure. Data from studies which do not en compass such periods of observation may be difficult to interpret.45 In one recent study, limited to review of social security records of individuals working in as bestos factories between 1948 and 1951. although 21,755 records were examined, a considerable portion represented men who could not have reached 20 years from first employment at the end of the period of observation. Compounding this difficulty was the fact that over 90 per cent were under the age 55 in 1950, and therefore relatively few had reached even age 65 at the end of the study pe riod. For those who had reached age 65, no data were recorded concerning their fate after that age. Conclusions drawn from such data can only be guardedly accepted. 1644 VOL. 58. NO. 9. A.J.P.H. NONOCCUP/ The answer to these and other equally intricate problems will require original approaches and diligent efforts. While animal studies outside the laboratory may be interesting [Webster (1963) studied wild baboons and rats to demon strate asbestos in the environs of an asbestos mine48 and we have been study ing wild rats trapped in urban and rural areas], no reliable conclusions will be available without appropriate epidemio logical studies of well-defined cohorts. This especially applies to human popu lations with graduated degrees of expo sure* including groups with indirect oc cupational and endemic environmental exposure. As noted, these will have to be investi gated with a long latent period in mind. Various disciplines will have to be en listed--pathologists, clinicians, epidemi ologists, basic scientists, and many others--but the results will warrant the efforts. Indeed, they may lead to a new dimension of the word "pneumoconiosis" winch, after all, is only 100 years old.50 13. 14. w. 20. 22 23 24 REFERENCES 1. E n te th n e , P . M ortality Rate Among C oal M iner. A .J.P .H . 54,5:759-768 (M ay ), 1964. 2. Stock, P. On th e D eath Rate from C ancer o f the Stom ach and R espiratory Dweaae in 1949-53 Among Coal M iner and O ther M ale R esidente in Counties o f E ngland an d W ale. B rit. J . C ancer 16.4:592-598 (D e c .), 1962. 3 E isenbud, M .; W ants. R. C .; Sunataa, C .; Stead m an. I.. T .: H arri. W . B .; and W olf, B. S. N on O ccupational B erylliosis. J . lo d u st. H yg. 31:282-294, 1949. 4. C hesner, C. C hronic Pulm onary G ranulom atosis io Resident* o f C om m unity N ear Beryllium *Plant: T h ree A utopsied C ajes. A nn. In t. M ed. 32-1028, 1950. 5. Lnpu, N ., and Vetik&n, K . Pneum oconiosis in C hildren o f In d u stria l C ities, w ith SiO* A ir Pollu tion. Cig. i S am t. 10-13 (D e e .), 1958. 6 Bataw i, M. A. E l. and H ussein. M. Endemic B\sino*ls in an Egyptian Village. B rit. J. Indust. M ed. 21 231-234. 1964. 7. C o )a l, A. R- Pneum oconiosis in the N on-Industrial Population of R ajasthan. J. Indian M. A. 30,3: 79-82, 1958 8. C ooke, W. E. Pulm onary Asbestosis. B rit. M. J. 2 1024. 1927. 9. H addow , A. C. R eport of Annual M eeting of B ritish M edical A ssociation, M anchester, 1929. L aacet 2-230. 1929. 10 W aglcr, F . : M lle r, H . ; a n d A n sp ach . M . G ib t e s eine endem isch aabestoae7 Z tschr. gea. Hyg. 8: 246. 1962. 11. C apnoglio, A. inquinaitiento atm osferico da eem ento: alteration! polm onari nelle m aestranxe del cetneoto- SEPTEMBER, 1948 Rth o f 113 asb esto s w o rk ers w ho d ie d o f othcliom a o r asbestosis. Pleural hogenic meso noma thelioma i1- i93 IS 2 11 1 16 663---- 9 6 Peritoneal mesothelioma _ _ 3 2 3 1 - 2 _ ___ 11 Asbestosis _ _ _ i 5 6 5 4 6 _ _ 27 first of exposure will teach us little of the po 1 of tential of asbestos exposure, and will stos- serve only to dilute pertinent observairci- ` tions. Moreover, investigations should neal aim to follow exposed individuals as 2 of long as possible, since risk does not ears stop at retirement age or with cessation (89 of occupational exposure. ! 30 Data from studies which do not en nset compass such periods of observation may ame be difficult to interpret.48 In one recent of study, limited to review of social security ider records of individuals working in as died bestos factories between 1948 and 1951. although 21,755 records were examined, d to a considerable portion represented men par- who could not have reached 20 years es- from first employment at the end of the the period of observation. Compounding :nts, this difficulty was the fact that over 90 . In per cent were under the age 55 in 1950, lied and therefore relatively few had reached > as even age 65 at the end of the study pe tom riod. For those who had reached age 65, >ure no data were recorded concerning their 20 fate after that age. Conclusions drawn mg- from such data can only he guardedly tion accepted. ' v o i. ss. no. , A.J.P.H. NONOCCUPATION AL ENVIRONMENTAL EXPOSURE The answer to these and other equally intricate problems will require original approaches and diligent efforts. While animal studies outside the laboratory may be interesting [Webster (1963) studied wild baboons and rats to demon strate asbestos in the environs of an asbestos mine49 and we have been study ing wild rats trapped in urban and rural areas], no reliable conclusions will be available without appropriate epidemio logical studies of wTeIl-defined cohorts. This especially applies to human popu lations w'ith graduated degrees of expo sure, including groups with indirect oc cupational and endemic environmental exposure. As noted, these will have to be investi gated with a long latent period in mind. Various disciplines will have to be en listed--pathologists, clinicians, epidemi ologists, basic scientists, and many others--but the results will warrant the efforts. Indeed, they may lead to a new dimension of the word "pneumoconiosis" which, after all, is only 100 years old.60 REFERENCES 1. E nterlm e, P . M ortality R atet Among Coal M inera. A J .P .H . 54.5:758-768 (M a y ). 1964. 2. Stocka, P. O n the D eath Rate from Cancer of th e Stom ach and R espiratory Disease# in 1949-53 Among Coal M inera and O th er M ale Resident in Counties o f E n g lan d a n d W a le s. B rit. ] . C a n c e r 16.4:592--598 (D e e .). 1962. 3. E itenbud, M .: W ants, R. C -: Sunstan, C .; S tead m an, L. T . ; H arris, W . B .; and W olf, B. S. NonO cenpational Berylliosis. J. Indust. Hyg. 31:282-294, 1949. 4. Chesner, C. Chronic Pulm onary G ranulom atosis in ' Residents of Com m unity Near Beryllium P lan t: T h ree A utopsied Case. A nn. In t. M ed. 32:1028. 1950. 5. Lopu. N ., and V etikan, K . Pneum oconiosis in C hildren o f In d u stria l C ities, w ith SiOs A ir P o llu tion. Cig- t S a n it. 10-13 (D e c .). 1958. 6. B e ta s'!, M . A . E l, s o d H u sse in . M. E n d e n jic Byssinoflis in a n E gyptian V illage. B rit. J . Induat. M ed. 21:231-234. 1964. 7. C oyal. A. R Pneum oeoniosia in the N on-Industrial Population of R ajasthan. J. Indian M. A. 30,3: 79-82. 1958. 8. Cooke, W . E . Pulm onary Asbestosis. B rit. M . J. 2 : 1024. 1927. 9. Haddow, A. C. R eport of Annual M eeting of B ritish M edical A ssociation, M anchester, 1929. L ancet 2*230, 1929. 10. W agler, F . ; M uller, H .; and Anspach. M. G ibt es eine endem ische asbestoae? Zttchr. ge#. H yg. 8 : 246, 1962. 11. C aprioglio, A. In q uinam ento atm osferieo d a cem en to : alterazioni polm onari nelle m aestrante del cem ento- am ianto e nella popolasione. Rasa. M ed. Indust. 29.375-379 (S e p t.- O c t.) . 1960. 12. Petrovic. L. J . A sbestosis In Serbia. H igtjena 11: 166-175, 1959. 13. B o b ilev a. A. T . ; B u k h a n tse v a , R . M .; L ovtsova. S. E .. an d S adiloxa, M . S . T h e A m ount o f D uat in R esidential D istrict# of A sbest and Its Effect on the C h ild re n 's H e a lth . H ig . 2 3 :9 -1 2 . 1958. 14. K iviiuoto. R. P leural C alcification as a R oentgeno logic Sign of N on-O ccupational Endem ic Antbophyllite-A abeatoaia. A cta rad io !. 194 (S uppl. 1 ), 1960. 15. W agner, J . C .; Sleggs, C. A .: and M archand. P. D iffuse P leural M esotheliom a and A sbestos Exposure in N orth W estern Cape Province. B rit. J. Indust. M ed. 17^260, I960. 16. Thom son. J . G .: K ascbula. R. 0 . C .; and M acDonald, R . R. A sbestos aa a M odern U rban H azard. South A frican M. J. 27:77. 1963. 17. Jacob. G .. and B oblig. H . R oentgenological Com plication# in P ulm onary A abestosis. Fortachr. Geb. R ontgenstrablen 83:515, 1955. _ 18. Selikoff. I. J- T he O ccu rren ce o f P le u ra l C alcifica tio n Among A sbestos Insu latio n W orker#. A nn. New Y ork A cad. S c. 132:351, 1965. 19. Laam anen. A .; N oro. L .; and Raunio, V. Observa- tioo on A tm ospheric A ir P ollution Caused by A sbestos. Ib id . 132*240. 1965. 20. K iviiuoto. R . Pleura! Plaques and A sbeatoa: Further O bservation# on E ndem ie an d O ther N onoecupational A sbestosis. Ib id . 132:235, 1965. _ 21. W eiss. A. P le u ra k re b s bei lungenasbestose, in vivo m orpholgisch g esichert. M edizinische. 1953. p. 93. 22. M archand. F. U eb er eigentiinhche pigm entknstalle in d en lu n g e n . V e rb a n d l. D e u ts c h G e se ll. 17 223-228, 1906. , 23. E nticknap, J . B ., and Sm ilher, W . J . Peritoneal T um ors in A abeatoaia. B rit. J . In d u st. M ed. 21*20, 1964. 24. M cCaughey. W . T . E . ; W ade. O. L .; and E W s . T . C. E x p o su re to A sbestos D ust and Diffuse Pleura! M esotheliom as. (C orrespondence.) B rit. M. J. 2 1937. 1962 25. L eichner. F. Prim ary M esotheliom a of Peritoneum in a Ce o f A sb esto sis. A rc h . C e v re rb e p a th 13* 382 1954. 26. W ehster. I. M esotheliom atous Turn in South Africa Pathology and E xperim ental Pathology. Ann. New Y ork A cad. Sc. 132-623. 1963. 27. Selikoff. I J .: Ham m ond. E. C .: and Churg. J. Asbestos E xposure, Sm oking and N eoplasia. J.A .M A 204:106, 1968. 28. New house. M- I... and T hom pson. H . M esotheliom a o f P leu ra and P erito n eu m Follow ing E xposure to A sbestos in th e L ondon A res. B rit J. Ind u st Med 22:261. 1965 _ 29. FJmes, P . C-. and W ade. O. L. R elationship Be tw een' E xposure to A sbestos and P leural M alignancy in B elfast. A on. New Y ork A cad. Sc. 132.549-557, 1965 30. C aun, D .; T o tte n , R . S .; *nd C roat. P . Asbeatoa Bodie# in H um an Lungs at A utopay. J.A .M .A . 192 37!. 1965. 31 M eu rm an , L . A sbestos B o d ie s a n d P le u ra l P laq u e* in a Finnish Series of Autopsy Cases. A cta p ath , et m ic ro b io l. se a n d in a v . 181,1 ( S u p p . ) , 1966. 32. Thom son. J . G .. and G raves, W . M . Asbestos ss an U rb an A ir C on tam in an t. A reb. P ath . 81:458. 1966 33. A njilvel. L ily, and T hurlbeck. W . M. The Incidence of Asbestos Bodies in the Lungs a t Random N e c ro p sy in M o n tre a t. C a n a d . M . A . J 9 5 ,2 3 '117^* 1182 (D ec. 3 ) . 1966. 34 Selikoff. I. J . : Ham m ond. E . C .: and Churg. J. U npublished d ats. 1967. 35. E im e s. P C . ; M eC au g h e y . W . T . E.*. an d W ad e. O L. D iffuse M esotheliom a of the Pleura and A sbestos. B rit. M . J . I -350, 1965 SEPTEMBER, I96S 1665 T 36. Collis, E . i . . od C ilcb rst, J. C. E ffects of D ust U pon C ost T .im m ers. J. In d u st. H yg. 10:101, 1928. 37. R osato, V. A sbestos. Its Industrial A pplications. New York, N . Y .: R eiohold, 1959. p. 478. 38. Sim son, F . W ., and Strcbn, A , S . A sbestosis Bodies io the S p utum : A Study o f S pecim ens from F ifty W orkers in an A sbestos M ill. J . P a th . & B act. 34:1, 1931. 39. Selikoff, I. I . ; B ader. R . A ., B ader, M . E .; C hare, J .; and H am m ond, E . C . Asbestosis and N eoplasia. Am. J. M ed. 42:487, 1967. 40. Hrom ek, J. T he M ass Incidence of C haracteristics! P leural Changes in C itizens o f the W estern P a rt of the Form er Jih lav s Region. RozhL v T n h erk . 22: 405, 1962. 41. Zolov, C. ; B ounlkov, T . ; and B abadjov, L . P leu ral A sbestosis in A gricultural W orkers. E nviron. Res. 1:287, 1967. 42. I.ieben, J ., and P istaw ka. H . M esotheliom a and A sbestos E xposure. A reb . E n viron. H e a lth 14:559, 1967. 43. Borow, M . ; Conaton, A . : L ivornese. L, L . ; and S ch alet, N . M esotheliom a an d Its A ssociation with A sb e sto sis. J.A .M .A . 2 0 1 :587, 1967. 44. Selikoff, I. Cburg, and Hammond, . C. R elation Betw een Exposure to A sbestos and M eso theliom a. New E ngland J . M ed. 272.560, 1965. 45. W agner, J . C. E x p erim en tal P roduction o f M sothlial T um ours of th e P leu ra by Im plantation o f Duata in L aboratory A nim als. N stu re 196,4850:180-181 (O ct. 1 3 ), 1962. 46. H ueper, W . C. C ao ier Induction by Polyurethane, an d Polysilicone Plastics. J. N at. C ancer Inst. 33 : 1005-1027, 1964. 47. Selikoff, I. J. ; Cburg, J. ; and H am m ond, E . C. A sbestos E xposure and N eoplasia. J.A .M .A . 188:22, 1964. 48. E nterlin e, P . E ., and K endrick. M. A. A sbestos- D ust E xposures a t V arious Levels and M ortality. A rcb. E n v iro n . H ealth 15:181, 1967. 49. W ebster, I. A sbestosis in N on-E xperim ental A nim als in S outh A fric i. N ature 197:506 (F e b . 2 ), 1963. 50. Zenker, F. A. U eber staubinbslationskrankheiten der lu n g en . D eutsche A rch. K lin . M ed. 2:116, 1867. Dr. Selikoff is Professor of Environmental Medicine, Mount Sinai School of M edicine of the City University of New York (F ifth A \enue and 100th Street) New York, N. Y. 10029. Dr. Hammond is Vice-President for Epidemiology and Statistics, American Cancer Society (219 East 42nd Street), New York, N . Y, 10017 This paper was presented before a Joint Session of the Epidemiology, Engi neering and Sanitation, M aternal and Child Health, Occupational Health, and Radiological Health Sections of the American Public Health Association at the Ninety-Fifth Annual M eeting in Miami Beach. Fla., October 25, 1967. This study was supported in part by U SPHS G rant No. UI-00440. U&& V O I. 58, NO. , A.J.P.H. IV. CHRONIC RESPIRATORY DISI A NINE-YEAR FOLLOW-UP ST Ian T. T. Higgins, M.D., M.R.C.P.; John C M.D., M . Esslyn IPaiers, M .D.; M.D., D .P JI. IN 1957 the British Medical Researcl Council's Pneumoconiosis Researcl Unit carried out a survey of chroni' respiratory disease in Staveley, England Stavelcy is an industrial town whos 18,000 inhabitants are engaged main! in mining, foundry, chemical, and rail way work. A random sample of mer stratified by age and occupation wa seen (Higgins, et al., 1959).2 Ther were two age groups, 25-34 and 55-6 years, and four occupation groups miners and ex-miners, foundry and e? foundry workers, other dusty and nor dusty workers. Ninety-two per cent < the 1957 sample was seen; 8 per cent r( fused. Respiratory symptoms and ver tilatory lung function were related t occupational exposure to dusts and fumt and to smoking habits. The prevalenc of symptoms was higher and lung fnm tion lower in miners and ex-miners an men exposed to chemical fumes than i men who had worked only in nondusl jobs. A higher prevalence of sympton and lower lung function was also o served in smokers compared with no smokers. ' It is often difficult to interpret ass ciations found in a cross-sectional stui of this kind. For example, an individu may be found to have low lung functio Is this because his lung function has ways been low or is it because it h undergone an exceptional decline Again the average lung function of group of people may be found to be lo This could be because of an exception decline in lung function of the group SEPTEMBER. I98