Document 5b5DMQkpaZpDYgOKgXMqb2e3V

of Sciences t es Lungenkrebses bei be.'.I. Intern. Kongress f. Arbeits- ipiungsrr.assn&hrnen in asber,9S9-J960. Intern. J. Prophyj. graphie bei diffusen Lungenin, Ed. J- A. Earth.. Leipzig. : bei der Asbestlungenfibrose. .logischen Komplikationen der :5I6. ,. , gkeit und Besonaerneiten des bepat'r. 14: 1". krebsersvartur.it d e r.Dc-i,t=c,.er. Krebsbekmpfung, Vol. III. H. hwarzenberg. Mnchen-Berlin, n des Bronchialbaumes bei der 8:247. >. Die Asbestose der Lungen: ittgart, Germany. p. 1964. Asbestos exposure and Klinische Grundlagen der 46 an & Schwarzenberg. Mnchen- of cancer of the lung other than uman environment. Arch. Path. lives of occupational cancer re- :hwabe & Co. Basel, Switzerland. d. 1960. Diffuse pleural mesothe.Vestem Cape Province. Brit. J. E lmes. 1962. Exposure_to as oma. Brit. Med. J. 2: 1397. 1 neoplasms. Lancet 2 : 1211. . Gewerbepath. 18: 159. Peritoneal tumors in asbestosis. and exposure to asbestos dust in D. 1965. Relation of mesothelioma . 272: 560-565. rnational University Press. New und gewerbliche Krebshygiene. Ann. N.Y. Acad. S e i . , 132:549-557, 1965. RELATIONSHIP BET.VEEN EXPOSURE TO ASEESTOS AND PLEURAL MALIGNANCY IN BELFAST P. C. Eirr.-i and 0 . L. Wade Department of Therapeutic* arid Pharmacology, Queen'* University of Belfast, Northern Ireland Belfast is an industrial city and shipbuilding port. The city and sur rounding residential area has a population of about three-quarters of a million people. The largest employers of labor during the first half of this century were h rtn and sr.itbuilding industries, both of which have declined in recent years. Major unemployment has been prevented by diver sification of industry. There is no asbestos mining or processing in the area. The working population is stable because of a system of work permits which prevents the entrance of transient labor from other parts of the British Isles or abroad. Although asbestos has been used in the shipyards and, more recently, in the building industry, asbestosis has not yet been regarded as a common industrial disease. Successful claims for industrial injuries benefit for asbestosis are less than ten per year and deaths due to this cause are seldom recorded. McCaughey had already <1953> reported 15 cases of pleural mesothe lioma. When the association between pleural mesothelioma and exposure to asbestos was recognised elsewhere, we then decided to investigate the effects of exposure to asbesto&in. Belfast more closely. With his cooperation the following lines of investigation have been pursued. (1) Exhaustive search for further patients with mesothelioma: (2) Investigation of the evidence of exposure to asbestos of patients with mesothelioma, ( a ' by obtaining occupational histories; (b_) by histological examination of the underlying lung; (3) Analysis of information obtained in a comparable way from control groups of the population; (4> Study of the causes of illness and death in men handling asbestos in their work; (5) Study of Belfast as an environment in which asbestos is used and cases of mesothelioma occur. The investigations are not complete and some of the earlier results have already been reported elsewhere vMcCaughey et al.. 1962; Elmes et at., 19651. This paper is another interim report. Method* (II Seeking patients with mesothelioma. All thej.likely people (path ologists, chest surgeons, and physicians and doctors interested in occupa- 549 m j .IHJ.hu immmifi 350 Annals Xew York Academy o f Sciences Elmes & tional disease were asked to notify us of all suspected cases of mesothelioma (4' Asbestos Worl of the pleura. All these cases were investigated, histological and autopsy rials used in heat ai material was examined wherever possible and the diagnosis confirmed or : single branch of the rejected. The diagnosis has only been accepted after histological confirms- these men are employ tion by W. T, E, McCaughey. taking insulating wo (2> Exposure to asbestos. their lives. The Unit ( a 1 Occupational history. When the patient was still alive and well branch, and the first enough, he was interviewed and a full retrograde occupational history of causes of death. : obtained. When not alive, the next of kin were visited and an occupa members in 1957 ha tional history obtained either from them or from companions at work. < books after retiremet (b> Histological data. Whenever histological material from the lung ; have been interviewee near the mesothelioma or from the other side of the chest was available ` of hospital visits wer this was submitted to W. T. E. McCaughey who searched it for asbestos ; collect all the hospita bodies under standardized conditions. (.3.) Control patients. Matched controls for the mesothelioma group and autopsy reports, reviewed wherever po: were obtained by picking from the biopsy or autopsy register the nearest (5 Belfast as an t entry concerning a patient of the same age and sex to the mesothelioma and various factories patient's entry. If the diagnosis of mesothelioma was based'on a biopsy tional information ha the nearest patient of the same age and sex in the biopsy register was tories and from the taken. If the diagnosis was made at autopsy then the nearest patient of the s industrial hygiene. D same age and sex in the autopsy register was taken. The same procedure j and boiler compositio was then used in obtaining an occupational history for these patients as j sioners. Finally, the for the mesothelioma patients. For the patients with mesothelioma who came to autopsy, controls for lung histology were obtained from the autopsy register by choosing the nearest patient of the same age and sex dying of nonmalignant disease. The lung sections from these patients were examined for asbestos bodies under the same standardized conditions as was used for the mesothelioma ; were plotted on the m, j sion of those cases w, \ possible to get aecure > in the different indust , Ing population of Belfa j patients. I J*i Three further studies were made: fa. Twenty patients, with asbestos bodies in the lungs, were chosen at . ' I ndustrial Exposure, random from relevant autopsy material, and 20 matched controlled pa- * tients were selected as previously. These 40 people were then investi- ' Patients with gated for occupational exposure to asbestos by the method described 5 above. This was carried out without the investigator knowing which patients had asbestos bodies in the lungs. fb. , The lungs from 200 recent autopsies on men without malignant dis- ; ; ' Mesothelioma Matched control: i ( ease of the lung were investigated by the standardized technique for asbestos bodies. One hundred of these men had died aged -50 to 50 veara : Asbestos bedies No asbestos bedi and 100 aged 60 to 69 year.-;. f c . The lungs from 100 men dying of carcinoma of the bronchus were examined by the standardized technique for asbestos bodies. Matched Combining the light tween Mesothelioma ai I | controls for the most recent 50 of the-e were also studied. . none 0.02 ^ P > 0.01. jjjJrsi j util, 1^ ^ l'MSu' jy w v n w j-1-'i-1,! j(i i jjWU%W pT ' Sciences cted cases of mesothelioma . histological ar.d autop-y he diagnosis confirmed or f:er histological confirma- was still alive and well ra.de occupational history ;re visited and an occuparom companions at work. ] material from the lung of the chest was- available eo searched it for asbestos the mesothelioma group topsv register the nearest 3 sex to the mesothelioma na was based on a biopsy n the biopsy register was 1 the nearest patient of the aken. The same procedure tory for these patients as :e to autopsy, controls for register by choosing the of nomnalignant disease. mined for asbestos bodies used for the mesothelioma the lungs were chosen at 20 matched controlled papeople were then investibv the method described vestigator knowing which ten without malignant distandardized technique for d died aged 50 to 59 years oma o f the bronchus were asbestos bodies. Matched also studied. Elmes & Wade: Pleural Malignancy in Belfast 551 -5 Asbestos Worker.-. Tr.e work of handling asbestos, and other mate rials used in heat ar.d fire insulation is ail done by men belonging to a ...r.gie branch of the Transport ar.d General Workers Union. Although these men are employed at various times by any of the contractors under taking insulating work, the men remain at insulating work for most 0 : their lives. The Union agreed to a complete survey of the health of this branch, ana the first p-art of the investigation has been an investigation of causes of death. So far the cause o f death of men wfco were branch members in 1957 have been investigated. The names are kept on the books after retirement because of pension arrangements. Their relatives . have been interviewed, and the date and place of death determined. Details cf ho*p.tai visi:; were a;.so noted and then every effort ha.- been made to collect all the hospital documents belonging to each man including biopsy and autopsy reports. The material was analyzed, and histological material ? reviewed wherever possible. ' 5 1 Belfast as an environment. The authors have visited the shipyards ; ar.d various factories in Belfast, and seen asbestos being handled. Addi j tional information has been obtained from the Medical Inspector of Fac i tories and from the various other doctors and officials concerned with { industrial hygiene. Data for the import of raw and manufactured asbestos j and boiler composition was obtained from the Belfast Harbour Commis j sioners. Finally, the homes of all the patients with pleura! mesothelioma j were plotted on the map and photographed both before and after the exclu sion of those cases with obvious occupational exposure. It was net found I possible to get accurate information about the number of men employed t in the different industries during the last 50 years in relation to the work ing population of Belfast as a whole. Table 1 I ndustrial E xposure. Asbestos Bodies and Mesothelioma of t h e P leura Patients with Heavy Exposure Light None Total Mesothelioma 8 24 10 42 Matched controls 2 7 33 42 Asbestos bodies 2 12 6 20 j No asbestos bodies 1 4 15 20 * Combining the light and heavy groups the differences are significant: Be f tween Mesothelioma and controls P < 0.001; Between Asbestos bodies and | none 0.02 > P > 0.01. ommnw 552 Annals New- Yoi'k Academy o Sciences Table 2 Asbestos Bodies at A utopsy and Malignancy of P leura and Lung Patients With mesothelioma Matched controls With carcinoma of bronchus Most recent 50 of these Matched controls Without cancer of lung Aged 50 to 59 Aged 60 to 69 Number examined 24 24 100 50 50 100 100 Per cent with bodies 83 25, 20 18 26 14 27 Significance of difference * 19.05 P < 0.0005 X2 = 0.94 0.4>P>0.3 X2 = 5.18 0.05 > P > 0.02 Results <1) Number of patients with mesothelioma. Including W. T. E. McCaughey's original 15 cases, 45 cases of pleural mesothelioma had been detected in Belfast up to July 1964. Of these, three of McCaughey's original cases died before 1950 and it proved impossible to obtain enough clinical details to include them in the rest of the investi gation. The patients were diagnosed between the ages of SB and 88 (mean 59 = 10.9 years standard deviation.. There were only 2 women. (2) Exposure to asbestos. (a.) Occupational histories (table 1. There are significantly more patic-nts-in the mesothelioma .group who had been exposed to asbestos. The numbers who had actually been employed full time on insulating work (classified under "Heavy", were not enough to be significant. The pre dominance of patients employed in occupations such as shipyard plumber and boiler repairer, known to be exposed to asbestos dust intermittently, is very marked in the mesothelioma group. <b) Histological evidence ' table 2. There is a highly significant dif ference between the mesothelioma and the control grout similar to the difference in occupational histories. Over three-quarters of the mesothe lioma lungs contained asbestos bodies whereas only a quarter of the control lungs contained bodies. ii Elmes ( i 3 2 7 1 1 1 1 1 ;3 2 1 Mean age 55.3 y (3) Comparable in} (a) Occupationa bodies in the lung, the patients with i exposure and only a history (table 1). (b Histological c monary malignancy tos bodies were mo m the age group 10 of the bronchus sho lung as the various e <U) Cato<es of death Of 43 deaths reco liable information is at death was 35.3 y< ot malignant diseas< high but until a prop ot this finding cann were brought to ligl 4 iihi1~rint,iiMi*iflWi,l>.^Tiitvii8iiii ~ _ ' - , s4 .. " `" l- . Sciences , or P leura a.''ll Lung Elmes & Wade: Pleural Malignancy in Belfast T able 3 Causes of Death in 30 A sbestos V.'oskers 553 r cent vith xiies 88 25 20 18 26 Significance of difference X2 = 19.05 P <0.0005 ` X2 = 0,94 0.4>P>0.3 14 X2 " 5.18 27 0.05 > P > 0.02 ! X 5 \ Malignant disease 16 cases 3 2 Pleura*631 ( mesotheliomas 7 Bronchial carcinomas 1 Bronchial carcinoma or mesothelioma 1 Malignant ascites with lung shadow 1 Bladder carcinoma .1 Stna,!!,intestine .carcinoma. Konmalignant disease 14 cases 6 Cor pulmonale due to asbestosis 1 Bronchopneumonia with severe asbestosis. 1 Suicide 3 Coronaries 2 Cerebral hemorrhages 1 Mesenteric thrombosis. Mean age 55,3 years (range 37-66 years). cases, 45 cases of pleural July 1964. Of these, three and it proved impossible in the rest of the investiages of 38 and 88 (mean e only 2 women. <3/ Comparable information about other groups of the population. (a) Occupational histories of patients dying with and without asbestos bodies in the lung. This study was done "blind.-' About three-quarters of the patients with asbestos bodies in the lung had a positive history of exposure and only a quarter of those without asbestos bodies had a similar history (.table 1 ). (b ) Histological evidence. Of the 200 autopsies on patients without pul e are significantly more monary malignancy, one in five had asbestos bodies in the lung. The asbes exposed to asbestos. The tos bodies were more frequent in patients between 60 and 69 years than time on insulating work f in the age group 10 years younger than this. The patients with carcinoma be significant. The pre- of the bronchus showed about the same incidence of asbestos bodies in the ;ueh as shipyard plumber lung as the various control groups. estos dust intermittently, ? (4) Causes of death in asbestos workers. s a highly significant dif- f Of 43 deaths recorded in the Union records in the last seven years, re liable information is available in 30 so far tsee table 3 '. The average age :rol group similar to the at death was 55.3 years and the oldest was only 66 years. The incidence -quarters of the mesothe- of malignant disease (.over half of the deaths were due to this > is very ly a quarter of the control high but until a proper control series has been investigated the significance of this finding cannot be determined. Three cases of peritoneal tumor were brought to light by this investigation. Complete autopsies are not  } I i UM* m&m 554 Annals New York Academy of Sciences available on two of these patients so that a sure diagnosis cannot be made, but the histological and clinical picture is entirely consistent with peri toneal mesothelioma. (of Btifagt as an environment. Belfast lou gh is a narrow inlet and runs inland from the Irish Sea in a southwest direction for about 12 miles. The prevailing wind is south westerly and the heavier industrial areas, including the shipyards, are grouped around the inland end of the loch with the residential areas on the periphery. The most densely populated residential area is close to the industrial but, except on the north shore, on the windward side of it. Most Nt ffcgjstfr SHIPBUILDING and ASBESTOS IMPORTS, Belfast. 1906- I960- Elmes . of the industrial at is one small factory the shipyards. Most of the insul tractors based on th I of their time worki: yards until slum cl& the outskirts of Be countered except i n . tal exposure would b a history of more th. plotted on the map cause. The importation < position (.which is a tos fiber >into Bellas of materia! importer yard. But the recent the very rapid incre As this latter increas nant disease, no atte asbestos on workers : F iches 1, Shipbuilding and Asbestos Imports. Belfast 1906-60. Raw &r.d manufactured asbestos includes both material used for insulation and building m aterial, .rich as corrugated roofing. Boner composition is a powder of S3 per cent magnesia and 13 per cent asbestos fiber. It is mixed with w ater or. site to form a thick paste ano .sed to insulate boilers ar.d steam pipes. Tonnage of a shir, built is recorded aga.nst the year the ship is commissioned. Insulating work may have been done or. it os er a year before this. The use of asbesto the provision of firej precautions introduce factoring industry m and right sided heart The investigations de pulmonary fibrosis a; nevertheless, there is ; is invariably fatal an lot of pain which is nc workers before their and exposure to ashes thelioma both to a hi a.-.bestos bodies in the thekoma had a histor three-quarters of thos liu %- In carefully mat -re and of asbestos h< of detecting both previ ' Sciences diagnosis cannot be made, rely consistent with peri- fcrid from the Irish Sea in nrevaiiing wind is southluding the shipyards, are he residential areas on the d ia l area is close to the windward side-of.it. Host DS IM PORTS. 50* To m * Belfast lSiOG-riX ~ material used for insulation jfing. Boiler composition is a asbestos fiber. It is mixed with -.sulate boilers and steam pi pea . year the ship is commissioned, i year before this. Eimes & Wade: Pleural Malijmancy in Belfast 555 of the industrial atmospheric pollution is blown out over the loch. There i? one small factory handling a-bestos in a dense residential area south of the shipyards. Most of the insulating -work for the province is done by a group of con tractors based on the shipyards, and the -workers they employ .-pend much of their time working on ships. They lived in the area south of the ship yards until slum clearance and rehousing has recently scattered them over the outskirts of Belfast. No eases of manifest asbestosis have been en countered except in asbestos workers so that the only index of environmen tal exposure would be those cases of pleural mesothelioma who did not give a hit-irct;. of-more thamaligr.: industrial exposuie: Wherrtheir .cremes were plotted on the map there was no grouping to suggest an environmental cause. The importation of asbestos and asbestos goods including boiler com position which is a mixture of Bo per cent magnesia and 15 per cent asbes tos fiber into Belfast is shown in figure 1. For the earlier years the volume of material imported correlates fairly well with the activity of the ship yard. But the recent and very marked rise in imports is an indication of the very rapid increase in the use of asbestos in the building industry. As this latter increase Is too recent to be manifest by an increase in malig nant disease, no attempt has yet been made to investigate the effects of asbestos on workers in the building industry. Discussion The use of asbestos both for insulating boilers and steam pipes, and in the provision ox fireproof layers in modern buildings is increasing. The precautions introduced for the protection of workers in the asbestos manu facturing industry may have reduced the incidence of pulmonary fibrosis and right sided heart failure, but the problem of malignant disease remains. The investigations described above have been carried out in an area where pulmonary fibrosis and cor pulmonale due to asbestosis is not common: nevertheless, there is a high incidence of pleural mesothelioma. This tumor Is invariably fatal and runs a prolonged course usually associated with a lot of pain which is not amenable to palliative treatment. It usually affects workers before their retiring age. The association between this tumor and exposure to asbestos is clearly shown by our data which relates meso thelioma both to a history of exposure to asbestos and the presence of asbestos bodies in the lungs. Three-quarters of the patients with meso thelioma had a history of exposure to asbestos at some time in life and three-quarters of those examined had asbestos bodies in the underlying lung. In carefu ly matched control groups the incidence of asbestos expos ure and o f asbestos bodies in the lung is only one in four. The methods of detecting both previous exposure to asbestos and the presence of asbestos ^w*1 ui-iu>i w 1 -!i r im m m d& m m wm &i 556 Annals New York Academy o f Sciences in the lungs used in this study are net very efficient, and our data indicate that in both instances about one quarter of the patients were incorrectly recorded as negative. This means that we have underestimated the statistical correlation between asbestos and mesothelioma but it does not alter our conclusion. The two additional facts which arise from this part of the study are: (1) That the majority of the patients with mesothelioma were not directly employed in the insulating industry. A history of intermittent or casual exposure only was obtained in most o f the cases and sometimes this had occurred manyyears ago. (2 > That about a fifth of the male population of Belfast had asbestos bodies in the lungs atautopsy. These two facts indicate that the exposure to asbestos needed to induce mesothelioma is much less than that acquired by the insulating worker and that the population at risk is very much larger than previously suspected. Without further information it is impossible to say how large, but it appears that about a quarter of the male and a smaller proportion of the female population, of this industrial area may have been exposed to sufficient asbestos to cause mesothelioma in susceptible individuals. Although the lungs of the older men surveyed showed more frequent evidence of exposure than the younger, evidence derived from the increasing use of asbestos indicates that the population at risk may be increasing. The information derived from the study of deaths of insulation workers is incomplete but presents a different aspect of the problem (table 3 ). About half the deaths so far investigated occurred in men who had started in the industry before the dangers of asbestos were first appreciated. There were two cases of classical fibrosis and cor pulmonale derived from this era. But one man died of cor pulmonale after only 18 years in the industry, and left it only at the time of his terminal illness. There is a high incidence of carcinoma of the lung. The c'her statistics failed to show that exposure to asbestos was a significant cause for carcinoma of the lung. Presumably other factors suea as .-mcaing and aiino.-phVric polhl- ` ' tion are more important causes in the population of Belfast as a whole. Among asbestos workers carcinoma of the lung i3 at least as important as the more specific mesotheiial tumor of pleura or peritoneum. This investigation is not sufficiently advanced to confirm the relationship between asbestos and other alimentary tumors iSelikoff ef a l, 1SS4 >. Summary A study o f 43 eases in Eelfast has revealed a relationship between expo.sure to asbestos at work and the development of mesotheiial tumor of the pleura. Evidence has been produced which indicates that the exposure assoiciated | i i : \ : I j | | s ; , ; j j ` t ! | | l | j i j ; , 1 { J < ! ' - Elmes & V with this tumor need quarter of the male p exposure. Among asbestos wo: a cause of death as n asbestos may be expos secondary neoplasia. This work was carr of the Department of Pathology. Trinity Co The home visits am Dudgeon and Mrs. Ma: colleagues for cases, tc ployees >for informat i* of imports. Elmes. P. C., W. T. E. McCavghey. W. T. E. IS McCacchey, W. T. E,, Selikoft, f. J., J. Chit mp mmp*9r.\ i if Sciences Elrnes & Wade: Pleural Malignancy in Belfast 557 ;ient, and our data indicate with this tumor need not be severe or prolonged, and that as many as a 2 patients were incorrectly quarter of the male population of this area may have received sufficient inderestimated the statisti- exposure. ma but it does not alter our Among asbestos workers carcinoma of the lung is at least as frequent rise from this part of the a cause of death as mesothelioma but the increasing widespread use of asbestos may be exposing a wide section of the population to the risk of mesothelioma were not di secondary neoplasia. A history of intermittent of the eases and sometimes Ackm w h d g merits This work was carried out in collaboration with W. T, E. JleCaugkey on of Belfast had asbestos of the Department of Pathology, Queen's University, (now Professor of . Pathology. Trinity College. Dublin >. , 0 asbestos needed to induce 1 by the insulating worker larger than previously susissible to say how large, but tnd a smaller proportion of ' ' ! The home visits and much o f the case work was done by Mrs. Yvonne Dudgeon and Mrs. Marion Simpson, We are indebted to many professional colleagues for cases, to members of the industry (both employers and em ployees.) for information and to the Belfast Harbour Commission for figures of imports. may have been exposed to j References susceptible individuals. Alwed more frequent evidence ed from the increasing use k may be increasing. j : j \ Elmes, P. C., W. T, E. McCaughey & O. L, Wade, I960. Brit. Med. J. 1: 350. McCavghey, W. T. E. 1953. J. Path. Bact. 76:517. McCAfGHEY, w . T. E., O. L. Wade & P. C. Elmes. 1962. B rit Med. J. 2: 1397. Seukoff, I. J ., J . Chueg & E. C. Hammond. 1964. J. A. M. A. 18S: 22. leaths of insulation workers | of the problem (table 3 ). j rred in men who had started ! stos were first appreciated. j cor pulmonale derived from [ ; after oniy 18 years in the \ terminal illness. There is a ; ther statistics failed to show | cause for carcinoma of the \ ting and atmospheric poilu- , ition of Belfast as a whole. g is at least as important as ; t i jr peritoneum. This investi- i the relationship between as- 't etaL, 1964). | i relationship between exposof mesothelial tumor of the that the exposure associated j ; j ; mmm. 11mwni J i iwwa p pp