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FILE NAME: ZW^W^ DATE: DOC#: W^ DOCUMENT DESCRIPTIONW:Z G}r),v' ' ;cOctober 1966 1,,,,raRAD. r'-"' Mw. J. (1%6), 42, 623. .rnd lhMMO~D, E. C. (1965);, ,,re to A~bestos and Mcso- \f, d., 272, 5C-O. t. ~~~t~>i IA~. A. 'i. (,931): Asbestosis lf 1 ~~t~~ut111~~,.St:rt THE EPIDEMIOLOGY AND CLINICAL FEATURES ... C. J., and COLEMAN, E. H. ]: t of Two Cases, Arch.. Path , ,-- QF ASBESTOSIS AND RELATED DISEASES ~. R. 0., and McDONAU> ' s a Modern Urban Hazari; P. C. ElMf.s, B.M., M.D., M.R.C.P. Asbestosis and the Urba~ : Sci., 132, 196. - ~:- . T. M., and PRATT, P. C. '.~ (1960) udics of Asbestosis, Ard, _, . ~ f ... and MARCHAND, P. :t oma a~d Asbes_tos EXPoSurc f ,, : Province, Brit. J. industr .', Reader in Therapeutics and Pharmacology, Institute of Clinical Science, The Q1tt'e11"s UnfrerJity of Bdfu.11, Be/fu.11 12. 1o0n!!.aEl, CJ.oWmm. 0un9i6c5a)ti:onA.sbcst<is ':;.-. uDsUedRIbNyG itnhdeulsatsrty lf0o0r yaewarhsilme aannyd mthaetnerifaolusnhdavtoe hbeaevne :tention in Rats, Ann. N. Y. / unexpected harmful effects. Usually the risk ceases the steel framework of modern buildings against fire, to form pipes and ducts for water, air and chemicals and to form corrugated roofing. Asbestos ;eseones J. and SMITH, MARIL~~>\;- olonic Mucosa by Asbcst~t Microscope Study in Rats f J111eJ/,. 14, 2029. . , :, hen safety measures are adopted but sometimes measures a~e found to be in~dcquate and new must be introduced. This has happened recently after the re-investigation of flax byssinosis is incorporated in brake pads and linings and in heavy duty flooring. Soft asbestos boarding and tiles are used to give heat and sound insulation to ceilings and asbestos is sprayed on to the insides of .E, S. R. (1930): Pulmonary :' (CareY, Elwood, McAulay, Merrett and Pemberton, air conditioning ducts, roofs and pipes to prevent L S. R. (1934): Pulmon;~,-..' 1965). be h. . . . I One Hundred Cases, Ibid., 2, j But with as stos t e s1tuat1on 1s not so s,mp e. following the report in 1930 (Merewether and Price) .is, Postgrad. med. J., 25, 63 l . on the dangers of exposure to asbestos dust safety condensation. Asbestos is spun and woven to make fire protective clothing, oven cloths, wicks for oil stoves etc. It is even used in the filters of certain types of gas mask. measures were adopted in factories and certain Three types, chrysotile, crocidolite and amosite -orkers kept under medical surveillance. Since :1ien a series of other risks have been recognised make up the bulk of the asbestos used. Of the others such as tremolite and actinolite only which indicate that the measures were either anthophyllite is of particular medical interest. jnadequate or did not cover a sufficiently wide Chrysotile is mined in the greatest quantity and is :ariety of asbestos workers. Both cancer of the mineralogically separate from the others being a ~ng and mesothelioma are now recognised as pyroxene while the others are amphiboles (Table I). it5ulting from levels of exposure to asbestos which They were all formed early in geological history j!ill occur in spite of these measures. probably about 2,000 million years ago. They were . The summary of present knowledge about the produced when the original rocks were subjected to epidemiology of asbestosis and related diseases hot water under pressure. As the rock formation ;1-bich follows is necessarily brief and emphasises cooled these compound silicates crystclllised out in !fiose points at which our knowledge is as yet fibrous form. The type of deposit and length of inC(1fllPlete. fibres depended on the condition of the parent , rock. Most chrysotile asbestos was formed in -l)e Nature and Uses of Asbestos cracks between shattered fragments of serpentine, The word asbestos is used to cover a group of a relatively hard rock. But the amphibole asbestoses ubfous silicate minerals whose chief value is that were deposited in the interstices of sedimentary theY have a high melting point and are non-in- rocks such as banded ironstones. Harrington jlammable. Therefore asbestos is used as strength- (I 962) has demonstrated the presence of oils and ening or insulation where high temperatures occur. waxes which suggest that organic matter must have _Bui t,ecause it is relatively cheap and strong (the fibrb are comparable in tensile strength to steel), been present when the fibres formed. These may be the cause of the fihrogenic and carcinogenic activity ,nd is resistant to many chemicals and to abrasion, of asbestos. asbestos has many other uses. These other uses ,crount for the increased consumption of asbestos Modes of Exposure ...., in an industrial city ~ince 1940 (Fig. I) (Elmes and Mining ;; _\\'ade, 1965). Asbestos cement is used to protect Asbestos is obtained from both open cast and 624 POSTGRADUATE MEDICAL JOURNAL .... 11e,...... T~. 140.100 SI-IIPBUILDING and ASBESTOS IMPORTS. B,elfa!>t. 1906-1960. 1900 10 20 30 40 so 60 70 FIG. 1-The dramatic- increase in tonnage of asbestos imported to Belfast sinc-c 1940, (See Elmes & Wade, 1965). Narr,e Chrysotile Crocidolite .. Blue" Amosite Anthophyllite TABLE l KINDS OF ASB[STOS IN CoMMERCIAL USE Formula and Geological Name Mg3 (Si2 Os) (OH) 4 Chrysotile Na2 Fe3 + + Fe2 + + + (Sis 022) (OH,F}2 Riebeckite (Mg, Fe++ )7 (Sis 022) (OH )2 Cummingtonite ( Mg, Fe + h (Sis 022) (OH, Fh Anthophyllite (always mixed with Gedrite) *Estimated Total Production (1962) 3.2 million tons Including actinolite and tremolite 0,,,,/,.., 19661 October 196(, Percentage of world production 93 3.5 ::?.4 deep mines. D the host rock when it is softer the host rock a teazed out bcfo labour is cheap from fibre is do often accompani large amounts o from the mines miners and mille mining towns an been exposed. It was cu~tom mines to the fac of a whole seri eliminated by us Work in mbestos It was here asbestos dust wa The asbestos is are separated an The next proccs is to be woven binding rnatcria pipes etc. The those used in carding being tt board and cemc11 hazard when the machined. No special efl these factories them. Although offices, were ex~ others. Where dusty air was of high levels of a The protectic processes from under the Gove the publicatior (Merewether an came under co1 there was an inc autopsy when a t very dusty proc< exhaust ventila p:neral air pc environment. Although mea - were started at t. "' ']bey may not , inaY be as ha : widely than the iJse of asbestos, The products :_:l II October 1.966 Ortober 1966 ELMES: Epid!'miology of Asbestosis 625 dctP n1ines. Drilling and explosives are used when usually supplied direct to the public but arc used in the host rock is hard and mechanical excavation the manufacture of factories, houses, power units, when it is softer. The crude ore is milled to remove ships, cars, domestic stoves etc., by a variety of the host rock and the fibrous asbestos is partially skilled tradesmen with their helpers. These men 1eazed out before it is packed into bags. Where Jabour is cheap some of the separation of rock sometimes use powdered material which they mix and apply on the spot or they u~e prefabricated {rom fibre is done by hand (cobbing) by women blocks, quilts etc., which require cutting, sawing or often accomp~nied by their babies. Until recently shaping to make them fit. The materials are Jargc amounts of asbestos fibre escaped into the air usually rough-finished when they leave the factory from the mines and mills so that not only the and release some dust when handled by storemen miners and millers but the whole rorulation of the and transport workers. Insulation workers have mining towns and the surrounding countryside have been using asbestos goods in this way for a long be(n exposed. time. More recently building workers, interior II was customary to transport asbestos from the decorators and many others ha,e starred to u~e mines to the factories in jute bags. This exposure them. Others (electricians, plumbers, fitters, paint- of a whole series of transport workers could be ers etc.) may work in the same confined space as eliminated by using sealed impervious bags. insulators and become exposed to 1he same dust or \ _ :, - - - - - - ._., entage of production 93 f 3.5 ~' 2.4 ------'-, j. !fork ill asbestos factories It was here that the danger of exposure to a_st,estos dust was first recognised and investigated. The asbestos is teazed out again so that the fibres arc separated and particles of rock etc., removed. The next process depends upon whether the fibre is to be woven into a textile or mixed with some binding material for the fabrication of boards, pipes etc. The textile procedures are similar to those used in the wool and cotton industries, carding being the dustiest. In the fabrication of t,oard and cement products there was a considerable bW!rd when the product was cut and trimmed or JlllChined. )-lo special effort was made to suppress dust in theSC factories and the dust was everywhere in thcJll, Although all workers, even the clerks in the offlceS, were exposed, some jobs were worse than omers- Where forced ventilation was used the dUSIY air was often discharged unfiltered producing Jiigh levels of air pollution close to the factories. . The protection of workers at certain scheduled processes from asbestos dust became compulsory under the Government regulations which followed the publication of the Merewether report ~lerewether and Pr:.:e, 1930). The workers also came under compulsory medical supervision and (here was an incentive for the relatives to ask for an ,utopsy wheh a death occurred. Cleaning up the \'f1Y dusty processes and filtering the effiuent of the exhaust ventilation systems also reduced the ,cneral air pollution of the factory- and its environment. Although measurements of the dust concentrations l'CfC started at this time they are technically difficult. l1!CY may not detect the smallest fibres, and these tiaY be as harmful and be disseminated more ,idely than the larger fibres. may create dust cutting or drilling asbestos material in the course of their own work. Most asbestos materials are coated with paint or sandwiched between other materials so that 1hey do not present a continuing risk until the building or installation is demolished. But asbestos roofing\ and brake linings must cause some general atmos- pheric pollution and certain uses such as the lining '\ of air condition ducts with soft asbestos and the use of unscaled ceiling tiles cause continuous, pollution of the air of office and factory buildings where people work all day. A simple industrial history will not necessarily reveal exposure to asbestos when this has occurred. A careful description of the type of work and the \ materials encountered at work will often help but there remains the unpredictable exposures. which will only be revealed by chance. A woman of 53 (Fig. 2) was recently investigated following a spontaneou~ pneumothorax. She had been increasingly breathless and been under observation by the Chest Clinic because of pulmonary fibrosis for several year. The findings were compatible with asbestosis but the patient denied occupational exposure. A few days later she told the house physician that she had helped her husband build I two asbestos bungalows in 1947 - 8. She had held the sheets while her husband sawed them up and \I they lived in one of the bungalows for about two years before painting over the asbestos sheets lining the walls and ceilings. The husband was a deck-hand on a long-haul merchantman and also had no 'occupational' exposure to asbestos. X-rays taken when he was next in port revealed a similar extensive fibrosis although he was still able to work. Similar unexpected sources of exposure can be revealed by retrospective investigation of patients dying of asbestosis or its complications. Newhouse and Thompson (1965) describe the wife who list ofasbestos goods brushed the asbestos dust off her husband's clothes The products of the asbestos factories are not when he came home in the evenings. i I ! i' 626 POSTGRADUATE t-.1EDICAL JOURNAL Octoher 1966 Ocluh le,, 19]1 :ind l')l'J 110 th,m 31 ",, had actiw tuhcr- r culo,is at ncc1 or,~y cornpa1 cd "1th only 4 healed I k,ion.., found in 71 11cc1 op,ic, cari 1ed out het,\ccn 1957 and 1964 on ca,cs from the ,amc ,ourcc (Table 2) (Smither. 1%5). 1 hi,; difference in e,po,Lire and ah,cncc of complicating tuberculosis rc,ult, in a more in,idious on,et or ~ymptonh which m;iy ,tart 20 or 30 years after first c,po,urc to a,bc,to, and may even de,elop yea1 s after the expmure has ceased. Symptom.1 The first symptom, arc hreathlc,,ne~<; on exertion and producti\e cough. The b1eathk~,ncss is relatively severe compared v.ith the accompanying cough and spit and is not a"ociated with upper respiratory infection~ or adver~c weather conditions. But when 50 asbestos workers were carefully FtG. 2-Woman aged 53 "ho helped her husband build two asbestos bungalo,,s 18 years before. Her husband shows similar changc,. Diffu,e libro~is with linear markings in the low!:r 10ncs. Pleural thickening with los, of clear dcman.::llion of diaphragms. The scarring or 'largc opacities' in the middle and upper zones may reprcsent inactive tuberculosis. The Diseases Related to Asbestos E~posurc Asbestosis matched with control-; recently hoth severe cough I and more than minimal sputum production were sigl)ilicantly more frequent. , Pain in the chest i~ empha<;i,ed in the early literature, but our patients more often complain of a 'tightness' than a pain. This is unrelated to effort and comes and goes unpredictably. Sometimes it may be described as a pain by the younger and more apprehensive a,bestos worker who may show no definite evidence of asbc<;to,is. Severe gnawing pain suggests the development of some complication. FIG. 3-P d 1 I) 11 o Many descriptions of asbestosis appeared in the Clubbing and warts: As in other conditions of Il literature between 1924 and I933. Descriptions such as those of Seiler (1928), Cooke (1927), Oliver (1927) and Wood (1928) refer to fibrosis resulting from a level of dust exposure far in excess of those experienced now. There have been two changes since, the disease now comes on more slowly and there has been a virtual disappearance of concomitant tuberculosis. In Wyers' series (Wyers', 1949) collected at an cast London factory between insidious on~ct associated with clubbing of the lingers only the occasional paticnt i<; aware of it. Clubbing docs not seem to occur in the ab~cnce of I significant chest dise,e and is not invariably present when the chest disease i~ ~e,erc. Warts arc common in people who handle asbc,tos and arc liable to ha,c cuts or abrasions of their hands. 42 per cent of l l group of I 00 insulators had these at the time o{ r examination and a further 26 had had them in the past. Th( hyperkcr~ this centr disappear )'C.lfS. Physical .1 Tl\8 1_E 2 I Them: cyanosis, ra.Jcs hear PosT MoRTHI fl~DINGS IN ASllESlOS fACH>RY \VoRKfRS (Al'lllt S~ll 1111 ll 1965) fingers. l 3) with d si:< were c Number of cases Age at death Tu bcrcu losis Carcinoma of lung Primary pleural malignancy Primary peritoneal malignancy Other abdominal malignancy ' 1931-49 115 40.8 36 17 I 0 7 *lesions inactive 1957-64 71 56 4 26 :2 13 7 - . and 13 h frequent r -- J .. " Cou~ (O[~ 5r;t ("Duri1 ---. Jtrathlessn Clubbing o 1:-,d,,. W.arts {)~. . Oct.ober 19G6 October 1966 ELMES: Epidemiology of A.1be.1tosis 627 1d active tuberonly 4 healed ,:d out between c same source id absence of more insidious :?.O or 30 years 111d may even ceased. 4 I ',\ :~~t;irtfttlfi: ... .,,.. 1ess on exertion eathlcssness is accompanying ted with upper thcr conditions. were carefully h se, ere cough ,roduction were d in the early ten complain of ' related to effort fJG. 3-Pipe coverer (insulation worker) for 16 years: Fl<i. 4-l'ipc coverer (in~ulation \1orker) for 26 years; . Sometimes it died at 65 vears of c::ircinoma of the ~lomach. died at the age of 71 )Car, of cor pulmonalc. ,unger and more No mcta,;ta~i~ found in the lung at po,t mortem. In addition to the d1ff11,c fihro,i, there i, . , may show no Diffuse fibrosis with lmear marlsings in the exten,ive calcification of pkural plaque, more ~evere gnawing middle and l011cr lobes. Loss of clear outline marked on the left than the right. There is so111e of both diaphragms. The scarring in the right generalised pleural thiclsening and a lo~, of ne complication. upper zone 11as not tuberculous. clear demarcation of both d1aphrag111s and r conditions of pericardium. fobbing of the is aware of it. 1 the absence of past. They start as a !um:) in t:1c skin which becomes when definite signs of right heart failure appear the variably present hyperkeratotic and a central white area appears. If men arc unable to work and arc unlikely to survive 1rts are common this centre is ricked out with a pin the lesion will the next acute respiratory illness. The ralcs and re liable to have disappear but otherwise it will persist for months or clubbing together present a pattern which it is easy l2 per cent of a years. at the time of to distingui,h from chronic bronchitis. The ralcs have a characteristic fine "dry' character which is had them in the fhl'sical sigm Toe main features of the more severe case are persistent in spite of deep breathing or coughing. They are often mistaken for a rub and are so cyanosis, restricted chest movement, kyphosis, fine described in the earlier literature. These signs are rales heard over the lung bases and clubbing of the of no value in distinguishing asbestosis from 01hcr fingers. In a group of 21 insulation workers (Table forms of chronic inter~titial fibrosis with clubbing l) with definite asbestosis who were still at work, of the fingers. But with re~triction of chest move- ~x were cyanosed, 7 showed clubbing of the fingers ment, kyphosis (loss of height) and cyanosis they and 13 had basal rales. The signs became more are useful in the detection and assessment of frequent and marked as the disease progresses and asbc~tosis in workers on whom serial examinations )57 - 64. 71 TABLE 3 56 4"' SYMPTmlS AND SIGNS IN EARLY ASBESTOSIS IN 21 WORKING Mm 26 WITII Di:rtNITI. RADIOLOGICAL CllANlil.S 2 13 1 Couh (other than 'in mornings only') .. 14 7 Spit('During the day' as well as 'in mornings') 10 Brtathlcssness (M.R.C. grade 2 or more) 4 Clubbing of the fingers . . . . . . 7 Warts . 16 ()'a0OSIS 6 11,lSal 'dry' rales .. 13 I 'I ;] ,,! Ii 1, 'i ,I ' r I \t)l r 628. POSTGRADUATE MEDICAL JOURNAL Octohl.'f 1'161.1 October 1966 are carried out. For instance in this suncy of phragm or pericardium they arc rounded. but o - fibres. These arc no insulation workers it was found that the 21 men with definite pulmonary fibrosis averaged I inches the chest v.all they arc guttatc and lie along the li~t tion. If the spu1um of the ribs usually fro111 the mid-axillary li~t ru,tiformin and the shorter tmaking allowance for age) than those with no evidence of pulmonary fibrosis. f forward. They are not easy to sec on X-ray Unl(I contrast or with th they begin to calcify. When calcified plaques ha11 asbestos bodies shm a characteristic appearance with clear cut margirJ polarised light may X-ray changes and a bilateral distribution (as in Fig. 4) they ar,f asb,estos fibre, Th The changes which result from exposure to asbestos can occur "ith other forms of chronic diffuse fibrosis involving the pleura. Localised ar,f probably diagnostic of asbestos exposure. Th~~ die.ates current ex may appear before the pan:nchymal changes indicate exposure i have been used by Kiviluoto (1965) to plot 1ftt Neither can be com areas of damage resulting from tuberculosis environmental area of asbestos exposure in Finland patient has as bcstos or intcrcurrent infections give rise to an irregular In the Belfast series of dead asbestos worket.f X-ray changes or th scarring in the upper or midzone (Figs. 2 and 3). there v.ere 13 with plaques out of the 87 for whorf on X-ray is due to c Linear markings in the periphery appear first in the lower zones. They run out into the pleura and with increasing change join to produce a honeycomb or cystic appearance at the base. There is loss of the chest X-rays were available. In a survey of 10:, Respiratory Jimcti living pipe covercrs of varying ages in the same arcif groups of asbestos w six showed plaques and the only one under 40 yea_~, able controls there a of age had been exposed in childhood. result from:- clear-cut margin between lung and pleura over the diaphragm and pericardium. By the time this Plaques are very common in and around 1--. anthophyllite mining areas in Finland and 'J':- (i) Low total lung appearance has developed at the bases, linear markings are usually apparent O\er the whole lung workers in Eastern Germany using anthophyllii and other fibres. In South Africa they are seeJ. (ii) Low vital c airways 0bw1 and there are usually some localised scars ("lung both in the blue asbestos and in the amosite miniri (iii) Low pulmon opacities" as defined by the I.LO. classification of areas (Sluis-Cremer, 1965). The incidence in t~ (iv) Low diffusing 1958). The early changes do not reproduce well but all the films (Figs. 2 6) show easily recognisable linear shadowing with loss of the clear-cut line of the pleura. An adaption of the I.LO. classification of X-ray changes in pneumoconiosis to make it applicable to asbestosis is at present under discussion (U.1.C.C. Report, 1965). This will enable the findings of different groups to be compared. Pleural thickening, as opposed to the loss of chrysotilc mining areas of Quebec varies rrom mire Williams and Hugi to mine (Cartier, 1965). Although mesotheliom~~- .:...alities in diffusing have developed in patients with calcified plaqlt! "' X 1 they are not necessarily associated. Mesothelioma~- before . -rayl c iange are un known both .m f'm1and , and m. the amo,, Belfas.t 1tnsu a twn w areas of South Africa where plaques are qu' - d1'ffusJOn esct1 1s 1essfse common (Table 4). '"i: of ear1Yevi ence O a . There is a large r Laboratorr tests trsts and each may b r No test, short of lung biopsy, is diagnostic ( of disease~. Therefor clear demarcation between lung and pleura, can take two forms. The first is a diffuse thickening asbestosis, but some tests rc~ults support t~ the detection ~f earl diagnosis:- : case unless sen al rea with ill-defined margins which is most marked over the lower lobes and is related in se,erity to the parenchymal change. The second is the formation of plaques which are circumscribed areas of hyaline fibrous tissue in the parietal pleura. On the dia- Sp11t11111: The sputum is mucoid unless thereJ. aw.ilable (Bader, B t complicating bronchial infection. There are 1965; _Hunt, 1965)._ 1; specific cytological ch~nges but _malignant cells defect IS the best est11 be found before there 1s other evidence of carcino The sputum may contain both asbestos bodies -f-~ . . - tbe Complications 0 The pattern of mo -.~asb,estos workers hai TABLE 4 ,~ f.ork have improve<'. GEOGRAPHICAL RELATIONSHIP BETWEEN PLAQUES A1"D MESOTHELIOMA~ ,!put into_ the sac~s ~_ainosite m the milb - - - - - - - - - - : - - - - - - - - - - - - : - - - - - - - - - - - - - - - - - ! . C . ( S c h e p e r s , 1965) sc Frequency of ." asbestos board in th( Area Fibre Plaques Mc~othcliomas -; enclosed and subjcch - - - - - - - - - - - ; - - - - - - - - - - - - - 1 - - - - - - - - - - - - - - - - - - - t : _ . In some factorie~ Finland An1hoph~llite Common None E. Germany Anthophyllite and Common 6 ,ince 1957 ~- fibrosis used to occui other fibres :- now men who have , S. Africa Crocidolite Common Common ~\,.ithout any detect -----------------------------------------.1 S. Africa Quebec mines and } related textile mills Insulation Workers: New York Belfast Amosite Chrysotile Mixed Mixed Common { SSoommeettiimmeess craorme mon } Common Common None Rare Common Common - .,'-ro is. Heavily ex ":'v".-'ork in the factorie -complications of asb '.'. tbeY were still at wor _- mier a short period 'arcinoma of che Ii ,:; "'i Ocwber 1966 . ocrob<'r 1966 ELM ES: Epidc111iol,wy of A!Jb<'.1to.1is 629 are rounded, but on and lie along the line ,he mid-axillary line to sec on X-ray Until :alcified plaques have ith clear cut margins 1s in Fig. 4) they are ;tos exposure. They 1chymal changes and :) ( 1965) to plot the s exposure in Finland, ad asbestos workers 11 of the 87 for whom fibres. These arc not easy to sec on diret:t examina- tion. If the sputum is fi~st treated w_ith "Eusol" or !!l!iforrnin and the sediment examined by phase . contrast or with the substage conden~cr lov.ercd asbestos bodies show up clearly (Gloyne, 1932). polarised light may be needed to recognise the 1asbestos fibres. The presence of fibres only inIj. dicates current exposure and asbestos bodies ndicate exposure in the recent or distant past. . ~either can be considered proof either that the patient has asbestosis in the absence of definite X-ray changes or that the pulmonary fibrosis seen on X-ray is due to exposure to asbestos. In a survey of 100 Respiratory /1111ctio11 tests: When applied to ages in the same area groups of asbestos workers compared with compar- ily one under 40 years ible controls there are clear-cut differences. These lildhood. result from:- , in and around the in Finland and in y using anthophyllite Africa they are seen in the amosite mining (i) Low total lung volume. (ii) Low vital capacity without evidence of airways obstruction. (iii) Low pulmonary compliance. The incidence in the (iv) Low diffusing capacity (transfer factor). ebec varies from mine . hough mesotheliomas with calcified plaques :iatcd. Mesotheliomas d, and in the amosite re plaques are quite Williams and Hugh-Jones ( 1960) reported abnormalities in diffusing capacity for carbon dioxide 1,efore X-ray changes in factory workers. But in Belfast insulation workers the carbon monoxide diffusion test is less sensitive than X-rays in detection of early evidence of asbestosis. There is a large range of normal for all these opsy, is diagnostic of results support the iests and each may be made abnormal by a variety of diseases. Therefore the tests are of little value in the detection of early asbestosis in the individual i;ase unless serial readings over previous years are nucoid unless there is ~tion. There are no ut malignant cells may evidence of carcinoma, :h asbestos bodies and, available (Bader, Bader, Tierstein and Selikoff, !965; Hunt, 1965). The extent of the diffusion defect is the best estimate of disability. 'Ibt Complications of Asbestosis The pattern of mor.bidity and mortality amongst &Sbestos workers has changed as the conditions of work have improved. Just as children are no longer put into ti1.: sacks to stamp down the fibrous amosite in the mills in the South African mines (Schepers, 1965) so the machinery for culling f of Mesotheliomas , None 6 since 1957 asbestos board in the modern factory is automated, enclosed and subjected to exhaust ventilation. In some factories where crippling pulmonary fibrosis used to occur in less than 10 years, there arc now men who have worked continuously since 1933 Common None Rare:, 11 ithout any detectable evidence of pulmonary nbro is. Heavily exposed workers were unable to 110rk in the factories for long enough for the late complications of asbestos exposure to appear while Common Common theY were still at work. But those who left the work afler a short period of exposure lived to develop carcinoma of the lung and mesothelioma of the pleura. The,c ca,c, have only recently been brought to light by ~tudie, in which the fate of workers who left factories before 1933 arc being traced (Ne,, house, 1966). The second factor which delayed the recognition of the malignant complications was the long interval between first expo~ure and the de\clopment of malignancy, The asbc,tos induwy had started on a small scale at the end of the last century and continued to employ small numbers of men and women until the first World War. A large population did not reach the length of exposure or age for cancer until 1940 - 50. Since 1931 all workers in the scheduled occupations in Great Britain have been regiqcred and kept under medical supervision. Their deaths are reported lo the coroner and a postmortem is usually carried out so from that time the cause of death amongst workers \~ho were already in certain job<; in the a,hc~!o, indu,try is fairly accurate- ly ~nown. It ,,as not until the figure~ for 1947 were ruhlished (H.M.S.O. 1949) that an undue incidence ( 13 ~{,) of death due to cancer of the lung was noticed. Amongst the m~n there were no ca~es of cancer of the lung under the age of 45 but above that age they amounted to 22 out of 76 with a peak incidence in the 55 - 64 age group. ,Detailed ~tudies on one asbestos textile factory has confirmed the high incidence of cancer of the lung (Knox, Doll and Hill, 1965) but indicate that only workers exposed to the heavy dust concentrations before 1933 were at risk. Although workers taken on after that date in that factory appear to run no greater risk of developing cancer of the lung than other sections of the population, the national figures still show a rising incidence. Nearly 50% of deaths in workers with certified asbestosis in the 1961 - 3 period were due to intrathoracic tumours (Buchanan, 1965). Studies from another a,hcstos factory (Smither, 1965) reveal a similar change in pattern (sec Table 2). Tuberculosis _has been replaced by primary carcinoma of the lung and by mesothelial tumours of the pleura and peritoneum. In Dresden the causes of death for asbestos workers have been recorded separately since 1952 (Jacob and Anspach, 1965). There were no cases of intrathoracic tumours among 18 deaths in the first year but in the next two five-year periods the incidence was 19% and 29 '.';. of 47 and 85 deaths rc,pcctively. One-fifth of these intrathoracic tumours were mcsothcliomas of lhe pleura. The duration of exposure for these cases varied between two and 42 years (average 14.2 years) and the average latent period for all intrathoracic tumours was 30.7 years and for mesothelioma was 31.8 years. The epidemiology and pathogenesis of these two tumours, cancer of the lung and mesothelioma, is 630 l'OSTGRADUAl E MEDICAL JOURNAL Oc1oh'r 1966 still under imestigation m relation to a\bcstos exposure. Cancer of 1'1c {1111g This appears to occur in worl-.crs c,po,cd to any type of asbestos fibre but statistic, arc ,cry f,agmcntary. It has been obscncd in all mining areas, but little accurate information is a\'ailable to compare with the general population allowing for factors such as smoking and atmo~pheric pollution. Finland is a country with a high I ate for cancer of the lung any\\ay and in all countries the rapidly rising incidence which has been attributed to cigarette smoking mal-.cs all such statistics ditlicult to interpret. The factory populations (Knox, Doll and Hill, 1965; Smither, 1965; Jacob and Anspach, 1965) already mentioned show an incidence of rulmonary or pleural neoplasms of the order of 30 '.\, amongst men exposed to dusty conditions which arc not sullicicntly se\'ere to cause death due to pulmonary fibrosis and respiratory failure in more than 20%, This risk of cancer of the lung amongst workers exposed to factory conditions before any effort at dust suppression has been estimated as I5 times that expected. The conditions under which insulators work ha\'e only changed gradually over the years. Part of this change has been due to the introduction of prefabricated materials which arc easier and less dusty to handle. More recently materials which do not contain asbestos have been used. Although masks have been supplied for certain very dusty jobs such as limpet spraying no deliberate effort has been made to reduce the dustiness of this type of work. In Belfa,t all insulator~ o,cr 50 year-; of age and 30 ) cars of c,rosurc so far cxammcd ,how definite e, idence of pulmonary damagc wherca, only about 30"., of 1m:n bet,\cc11 the age... or 30- 40 or with le,, lO- 19 years uf c,po,Lire ,how ,uch evidence This ~uggc,t, a degree of cxro-;ure than that which c.,1stcd in some of the factorie, before 1933 but more than that Jcs::ribed by Knox and other~ (1965) following that date. 107 death, in insulators in Belfast since 1940 l,a\c been inve,tigatcJ so far. The causes of death arc g1v..:n in Table 5. There is a modcratdy high incidence of n:rn-malignant rc,p1ratory death'> but it 1, not far 111 excess of that . cxrectcd a-; in the fit st hair of the period tuberculosis was still relatively common. It has not been easy .. to differentiate between deaths due to cancer of the lung and those due to pleural mesothelioma where I no autor,y material has been prcscned. They ha\'e ... been classified together and arc about five times the expected. C There ha<; been 110 Jd,nite change in pattern of deaths amongst in\ulation workers over the years C (see Fig. 6) apart from the disappearance of 2 pulmonary tuberculosis. The age of death, pro. portion of cases with pulmonary fibrosis and proportion with cancer have all remained the same suggesting a constant level of exro,ure at least until 10- 15 years ago. ' Hammond, SclikofT and Churg ( 1965) have found an incidence of intrathoracic tumours in insulation workers seven times the expected and also a high rate of gaqrointestinal neoplasms. The peak mortality due to lung cancer for men in all reported series of asbestos workers is between 55 and 60 years of age and the only clinical difference between these and other lung cancers is a higher proportion I TABLE 5 CAUSE OF DEATH IN INSULATION WORKERS I BEU AST 1940 65 TOTAL: 107 MEAN AGE: 55.3 :l- 11.25 YEARS Cause MALIGNANT : Jntrathoracic neoplasms Abdominal neoplasms Other neoplasms NON-MALIGNANT : Pulmonary disease Cardiac and circulatory Other causes Unknown Observed 28 15 4 31 21 5 3 Expected - 5.3 9.0 6.7 25.6 37.1 21.3 - This is a rough estimate based on the Registrar General's distribution of deaths in the age group 45 64 in the year 1951 (H.M.S.O. 1953). October 1966 October 1966 ELMES: Lpid<'mio/ogy of ,-fab'.11mis 631 50 years of age and 1mined show definite ' whereas only about s of 30 - 40 or with 10w such evidence. osure less than that .tetories before 1933 by Knox and other;(, deaths in insulators 1 investigated so far. in Table 5. There is ! of non-malignant far in excess of that 1c period tuberculosis I has not been easy due to cancer of the mesothclioma where 1reserved. They have : about five times the change in pattern of , 1kers over the years e disappearance of age of death, pro1onary fibrosis and II remained the same ,f exposure at least irg (1965) have found umours in insulation ~ted and also a high ,plasms. The peak . >r men in all reported : between 55 and 60 : :al difference between ; a higher proportio~ .; Distribution of Death!> by Year of Death. 19 0 - 1945 - 9. 1950 -5-4 1960 -6 . 30- Non Malignant appor~n\ly unmated to asbutos. r 7 ~ul rno~ory l.:.,;Jf1bros1s contributory. C'.iJ Halignont. ... o 10- z 0 0 .. Ht:al'\ Age. 507 ~8 ,,iron Exposur~ 16 25 (Years) 571 571 zn 26"4 F1G. 5-The increasing number of deaths relating to successive five year periods may be due to increasingly efficient case finding rather than a change in the death rate among insulation worker~. ' TABLE 6 MESOTHELIOMAS AND EXPOSURE TO ASBESTOS EXAMPLES OF RETROSPECTIVE STUDIES -- SoJrce -.-_E-x-pe-c-ted-- - . : ', 5.3 9.0 6.7 25.6 37.1 21.3 1,oNOON Newhouse & Thompson (1965) BELFAST Elmes & Wade (1965l L!VERPOOL Owen (1965) SoUTH AFRICA Wagner, Sleggs & Marchand (1960) TOTAL .. .. .. .. 1e age group 45 - 64 in - Total Cases 76 Controls 76 Cases 42 Controls 42 Cases 17 Controls 0 Cases 33 Controls 0 Cases 168 Direct 31 8 8 2 7 14 60 36'.i~ Exposure Casual Environmental or Domestic 0 9 0 I 24 0 7 0 6 0 5 13 35 21% 22 13% None 36 67 10 3 4 I 51 30% 632 POSTGRADUATE ME[)ICAL JOURNAL Octuha 1966 , . t th u; in th be ye m th '\ ~;~'; ., '.~ id ,> ' ' in } (T arc Au arc F1G. 7-Pipc co~crcr (in~ulation worker) for nearly 30 an years: died at 44 years of a me,olhclioma of the left pleura. The tumour i, vi\lblc above the fro level of l he left ba,al cffu,ion. There i<; a partial fac FIG. 6-Pipc coverer (insulation worker) for 26 years: died of a primary carcinoma of the lung aged f.6 collap_~c of the right lower lobe. Pulmonary so fiinbrlohs1c~.retphrooudguhctpiorens.ent, i, not suflicicnt to sho~ tha ext years. Linear marking and small upacitics in WO the middle and lower zones. Loss of clear demarcation of the diaphragm and pericardium. lhe peripheral tumour in the left upper lobe is indistinguishable radiologically from a mcsothclioma. of lower lobe tumours (Jacob and Anspach, 1965). The symptoms, signs and X-ray changes of cancer of the lung are too well known to require description here. Fig. 6 shows the chest film of an insulation worker with both asbestosis and a primary cancer of the lung. In all the cases of proven primary carcinoma of the lung in the Belfast series there was histological evidence of asbestosis, but this was not always obvious on X-ray. cause asbestosis or carcinoma of the lung. In e.\! another third of the cases there is an apparentlv cxr trivial exposure at work or in the home environmcni inc The environmental exposure ranged from playin; anc on the slag heaps outside an asbestos mine up 10 ma the age of seven years in a woman who died of a ( mesothclioma at the age of 35 (Wagner, Slegg, and occ Marchand, 1960) to the woman who developed 1 chi mesothclioma at 63 years and who u~cd to wasf dur out her daughter's overalls when the latter workec yea in an asbestos factory (Newhouse and Thompson_ bet 196S). Casual expo~ure at work ranged froll. exr occa<;ionally having to remove the remains 0, pul lagging from machinery which wa-; heing di-.mantl; for servicing, to the repairing of hes~ian bags sorr Mesothe/ioma of which had been used for a<;be<;tos (Owen, 1965: Epidemiology: This tumour has been the subject of The relatively large group (30",;.) with no hi~tor, inc considerable research an<l comment since Mccaughey of exposure can be accounted for in three way,;: v.e< (1958) described a series of cases in Belfast and I. Occupational exposure which the patient ha, Be, Wagner and others (1960) related an even larger forgotten or in which he was unaware of It< be series to environmental e>,.posure to blue asbestos. nature of the materials handled. adr i. The histological evidence relating mesothelioma to 2. Environmental or domestic expo~urc of whic' se, ( I the inhalation or ingestion of asbestos is very the patient was unaware. rou I' impressive. When a history of exposure to a~bcstos 3. No expo-;ure at all. sur i is looked for in cases of mesothelioma it can usually In (I) and (2) one would expect to find a,bc,tr, of . i be found (Table 6). But in only a third of cases is bodies or fibres in the lungs. In a retrospecti, bot i this exposure of the sort of intensity that might study of 20 patients dying with asbeqos bodies pat firs l oaob,', 1966 October 1966 ELMES: Epidemiology of Asbestosis 633 the Jungs the source of exposure was only found in confined to the affected ,ide of the cl1e,t at first l4 (Elmes and Wade, 1965). This deficit could and then radiates to the shoulder and cpit.a,triurn. account for all the mcsothcliomas for whom no history of exposure is obtained. Nel'erthelcss there ;emains the possibility from epidemiological studies It becomes more severe, a "dull toothache" little influenced by respiration on mO\eir.ent unless there is a ,econdary frozen shoulder. that a small proportion of mcsothcl1ornas occur in patients who have nel'er been e:>-.poscd to a<;bcstos. l. Because of the tril'ial exposures recorded in a third of the cases and the increasing and manifold use to which asbestos has been put we can exrect an increasing number of mesotheliomas at least O\er the next 40 years. (In the London series the interval t,ctwcen first exposure and death varied between 29 years for factory exposure and 48 years for environ- mental exposure. For the Belfast group as a whole the interval was 43 years 13). Numerous cases of mesothclioma ha,c been identified amongst people who have lil'ed or worked in blue asbestos mining areas in South Africa (fable 4) and cases have been reported from the area around the crocidolite mines in Western Australia. No cases have been reported from around the amosite mines in South Africa or the \\orker) for nearly 30 a mesotheliorna of the is visible above the ,ion. There is a partial ,1er lobe. Pulmonary s not sufficient to show .nthophyllite mines in Finland and only two cases {rom the Quebec chrysotile mining area. Much factory work entails exposure to mixed dusts but 50 far the evidence from the factories indicates that frequency of mcsothcliomas may vary with the CAtent to which blue asbestos is used. In insulation \l'Orkers it is usually impossible to identify the c.ttenl to which individual workers have been 1a of the lung. In . ere is an a p p a r e n t l y 0 : 1c home environment, txpos'!d to individual types of asbestos. The jneidence of mesothelioma amongst these workers and amongst other workers exposed to the same ranged from playing materials is relatively high. asbestos mine up to oman who died of a Clinical features of mesothelioma: This tumour i,:curs in either sex and people exposed during (Wagner, Sleggs and 1an who developed a : d who used to wash._. 1en the latter worked dlildhood may develop it earlier than those exposed during adult life. The age of onset varies from 31 -,ears to 83 years and the mode for most series lies l(tll'cen 55 and 65 years. Other evidence of asbestos '.>Use and Thompson, . ~sure (clubbing of the fingers, asbestos warts, or. work. ranged froni : 0\'e the , emi.ins was being dismantled'.. of hessian bags some ; ~bestos (Owen, 1965),. i'"monary fibrosis and basal rales) is often absent. fkural cases ,\{ode of onset: This usually starts with gradually ~sing pain or breathlessness, taking several 30%) with no history ,eeks before the patient seeks medical advice. for in three ways:-./ t:,;3use of this insidious onset the condition may In a few cases breathlessness comes on in a matter of hours or 2 J days, and in the,e ca<;es there is usually a large pleural effusion which is sometimes bloody. But even in the,e case, there is seldom much evidence on examination of a shift of the mcdiastinum to the oppo,ite side. A, the tumour extends around the lung there is re,tnction of movement on that side with a shrinking down of the whole of that side of the che,t and a pulling over the heart and mcdiastinurn to the affected side. Tumour may become palpable in the supraclavicular fossa and between the nbs but seldom grows through the chest wall unless it is along the track of a thoracentesis needle, through a thoracotomy wound, at the site of a fractured rib or through an area of chest wall damaged by deep X-ray therapy. X-ray appearances (sec Fig. 7) arc indistinguishable in most cases from a simple pleural effusion with or without some degree of pulmonary fibrosis. The actual tumour may not be visible until the fluid is aspirated when it usually shows up as a lumpy area in the pleura which also shows some degree of thickening all round the lung. Rib destruction appears late and local lymph node enlargement is rarely apparent on X-ray. Diagnosis: This can often be made on clinical grounds after the exclusion of other causes of persistent pleural effusion in the middle-aged or elderly and the failure to find a di,tanl primary malignancy. It is difficult to verify the diagnosis. The fluid, when clear, is often unusually viscous, but frequently contains fresh or altered blood. Cytological examination of the fluid may reveal cells strongly suggestive of mcsothelioma but the diagnosis should not be based on this alone (Klempman, 1962; Naylor, 1963). The presence of hyaluronic acid {Harringt0n, Wagner anu Sn1ith, 1963) is also strongly suggestive but may occur with other malignant lesions of the pleura. The presence of blood interferes with this test. Especially in the absence of free fluid the diagnosis can only be verified by biopsy, but there is a variation in the histological appearance in different which the patient had [ie found accidentally. One patient recently was e was unaware of the ,imitted to hospital with a fall, another with parts of a single tumour. There are often extensive areas of fibrous tissue which are indistinguishable handled. rtre influenza and yet another was submitted to from chronic inflammatory disease. Therefore stic exposure of which J')lltine chest X-rays as part of an occupational needle biopsy, and even limited surgical biopsy, ;,rvey. Only on direct questi?~ing was the history i. pain or breathlessness elicued. The onset of may fail to provide the pathologist with sufficient material to make the correct diagnosis. An open xpect to find asbestos s. In a retrospective ith asbestos bodies in pJth symptoms is sometimes so gradual that the ~nt is unable to say which symptom started ~ The pain is described as a heavy feeling and thoracotomy must be performed and pieces of tissue from different areas taken. To avoid tumour growing through the thoracotomy wound Thompson I\ I \ I l I I I i i j - 634 POSTGRADUATE MEDICAL JOURNAL October 1966 Octubl'I" (1965) ad\'ocates the instillation of nitrogen mustard into the pleural ca\'ity at the end of procedure. Treat111e11t: Neither radical surgery nor radiotherapy can improve the prognosis and both may encourage direct extension of the tumour through the chest wall. Palliative treatment should be restricted to removal of the pleural fluid to relieve breathles~ncss and instillation of nitrogen mustard into the space if the accumrnulation of fluid is rapid. Pain due to infiltration of the chest wall and vertebrae does not usually respond to radiation or systemic cytotoxic drugs; it is usually too extensive for treatment by regional nerve root section. Course and prognosis: Patients seldom survive more than a year from the time the diagnosis is established. The survival from onset of symptoms or from the earliest X-ray changes may be considerably longer but four years is probably the maximum. Apart from increasing pain and breathlessness the patients usually remain in good health until invasion of the mediastinal tissue interferes with nutrition and they lose weight. Death is usually due to restriction of ventilation but intercurrent chest infection may complicate the terminal illness. Peritoneal cases The onset is even more insidious than in the pleural cases. The symptoms may mimic any form of abdominal neoplasm, presenting as upper or lower gastrointestinal tract obstruction with or without pain. Sometimes painless ascites is the presenting feature. The diagnosis can usually only be established by laparotomy and adequate biopsy but occasionally cytology of the fluid may be sufficient. Weight loss occurs earlier than in the pleural lesion but the interval between diagnosis and death is the same. No treatment is of any value except that the rapid re-accumulation of ascitic fluid can be checked by local nitrogen mustard therapy. Summary al'd Conclusions Pulmonary fibrosis due to exposure to asbestos dust in factory workers has become uncommon and when it occurs is less severe than it was before the introduction of dust suppression measures in 1932 - 33. However there remain occupations which were not covered by the Merewcther report which can cause sufficiently severe fibrosis to lead to death before the retiring age. Insulation workers are a group in which this is likely to occur but the spreading use of asbestos in the building industry may be leading to similar levels of exposure among occupational groups where this hazard has not existed before. An increase in the number of such cases can only be prevented by constant vigilance on the part of the medical profcs\ion in identifying this a<; a cause of diffuse pulmonary fibrosis in individual ca<,es and bringing them to the notice of the factory in<;pectorate. One of the difliculties here i'> the lack of clinical features to distingui,h asbestosi, from other forms of diffuse fibrosi,. When the ~ourcc of expo,urc i, not obviou~ open biopsy of the lung may be nece\sary to C!>tablish the cause and initiate investigation for sources of exposure. Carcinoma of the lung resulting from exposure to asbestos appears lo be common in patients whose expo<;ure to the dust was insufficiently long or intense to cause crippling fibrosi<;. There i<; evidence that the risk may have been eliminated by the application of thorough du<;t suppression under factory conditions. But there may be many other workers handling asbestos v. ho are still at risk as has been shown for insulation workers. The nature age of onset and course of cancer of the lun~ secondary lo asbestos exposure does not appear to differ greatly from cases arising in the general population. A rapidly increasing number of cases of mcsothe. lioma of the pleura and peritoneum have been recognised in the last IO years. It is an invariably fatal tumour for which there is no satisfactory palliative treatment. There is an as~ociation between exposure to asbestos and the development of this tumour. The degree of exposure in many cases is slight and indicates that many people may by now have had sufficient exposure either in the course of their work, hobbies or in the home. As there is no evidence of another factor operating in the initiation of this tumour it seems likely that increasing numbers of cases will arise in the next 30 years. Prevention of further cases beyond that date depends on the restriction of use and greater precautions in the handling of all types of asbestos 1..., fibre now. It is possible that the elimination of one type of fibre (crocidolite) from commercial u1e might reduce the incidence of the tumour very considerably. B~DI F<. : $LIKOI f _ Sc,cral ,v_ r. .- BUCHA'- \ lntrathu 507. CARI,\'. G Mrn1u.n. Fl,n w, CARl J~R. Asbcsto !,;dull. CART/LR. p N. Y. Ac CCXlKf, w. 1 J.. ii, 10~ ELMfS, P. between I in Bclfa, GLOY'-E, s. 1351. HAMMO,D. Ncoplasi States v I Ncopla,1< HARRJ:-;Gro Containir Asbestos, , HARRl'-GTO . (1963): T Fluids of I Brit. J. e: Hu~T. R. 830 Ernrl N. Y. Aca H.M.S.O. (. of Facto H.M.S.O. H.M.S.O. Registrar H.M.S.O. J).COB, G., _ plasia am I Acad. Sci. K1vtLUOTO, further < occupatio1 235. In writing this article I have drawn on information "hich has become available as a result of research won done in the Derartmcnt of Therapeutics and Pharma. _ cology by Professor 0. L. Wade, Dr. Jean H. M Langlands and Dr. W. F. M. Wallace a~ well as myscW some of which has not yet been published. This v.ort is part of a collaborative study of the problem of asbest01 exposure organised by Dr. J. C. Gilson. Director of the M.R.C. Pneumoconiosis Research Unit at Cardiff. The Biological Effects of Asbestos were discu~sed at ill ' International Symposium held in New York under the auspices of the New York Academy of Sciences in October 1964. For convenience I have quoted referencci to the proceedings of this Symposium although much the work has abo been published elsewhe.re. ':Jl ' ohober 1966 i October 1966 ELMES: Epidemiology of A.1hc.1tosis 635 g this as a cause vidual cases and ( f 1c1ory inspector- , 1c lack of clinical omfother for~s , f e o exposure IS ..,, may be nece~sary in,estigation for ; from exposure ,n patients whose iciently long or There is evidence minated by the ppression under 1 be many other c still at risk as ,crs. The nature, 1ccr of the lung ies not appear to : in the general cases of mesothe- neum have been t is an invariably ; no satisfactqry an association the development xposure in many nany people may ;ure either in the:' in the home. As '. 1ctor operating in seems likely that arise in the next ;ases beyond that , ,f use and greater~. types of asbestos ': he elimination or .:. m commercial use> the tumour very ." HEFERE:',;C'ES B~DEil M. E., Ihm R, R. A., T1u<sn.1~. A. S., and srww'rr, 1. J. (1965): Pul111.inary function in A,hc,to,i~. p. ( Several Tests in a Long Term Prosrcctil'C Study. Ann. N )'. A('(/d. Sci., 132. 391. BUCHAJ\~N. ~V. 1965): A,bc,tc;~i~ and .P!imary lntrathoracic Neopl.1,111,, Ann. N. I. Acad. SCI., 132, 501. CAREY, G. C. R., ELWOOD, P. C., l'v1CCALLA\'., l.. ~ \1ERRETT, J. D .. and P[\!HlRTON, J. (1965); Byssmow; Ill Flax Workers in Northern Ireland. Uclfa,t: 11.M.S.O. CARTl[R, P, ,<195~): Some _Clinical Ob,cr\'ations of Asbestosis m Mme and Mill Workers, A.M.A. Ard,. Jndwt. H1,alth. 11. ?04. . (ARTIER, P. (1965): D1scuss1on on Pleural Plaques, A1111. N. Y. Acad. Sci., 132, 387. . (DOKE, W. E. (1927): Pulmonary Asbestosis, Brit. med. , . ii, 1024. . . fLMES P. C., and WADE, 0. L. (1965): Relationship t,e11;een Exposure to Asbestos and Pleural Malignancy in Belfast, Ann. N. Y. Acad. Sci., 132, 549. GLOYNE, S. R. (1932): The Asbe,to,is Body, lancet, i, 1351. HAMMOND, E. C., S1111w1r. I. J., and C'11t11H,, .I. (1965); Neoplasia among lnsuf,Hion Worker~ in tile United States \loith Special Reference to lntraabdominal Ncoplasia, A1111. N. Y. Acad. Sci., 132, 5I9. HARRINGTON, J. S. (1962): Natural Occurrence of Oils Containing 3-4-benzpyrene and Related Substances in Asbestos, Nall/re (Lond.), 193, 43. HARRINGTON, J. S., WAt,NI.R, J. C .. and Srnrn, M. (1963): The Detec\ion o_f Hyaluronic Acid in ~leural fluids of Cases with Diffuse Pleural Mcsothehoma,, Brit. J. exp. Path. 44. 81. }luNT, R. (1965):. Routine Lung Functi.on Studies on 830 Employees m an Asbestos Processmg Plant, Ann. N. Y. Acad. Sci., 132, 406. . }l.M.S.0. (1949): Annual Report of the Chief Inspector of factories for the Year 1947, p. 79. London: HM.S.0. iJJd.S.0. (1953): Thirtieth Annual Report of the Registrar General for the Year 195 I. Belfast: H.M.S.0. JACOB, G., and ANSPACH, M. (1965): Pulmonary Neo- piasia among Dresden Asbestos Workers, Ann. N. Y. Acad. Sci., 132, 536. ~ 1Luoro, R. (1965): Pleural Plaques and Asbestos: further Observation on Endemic and other Nonoccupational Asbestosis, Ann. N. Y. Acad. Sci., 132, 235, ' K 11 Ml'MA S. ( I %:'.J. The Fxfoliali\c C) to logy of D1fft1',c l'kural \1c,othclioma. Canu.,., 15, 691. K~ox. J. F., D011, R. S., and 11111, I. D. t 1965): Cohort An.ily,i, of Change, in l1K1dcncc of Brom:h1al Carcinoma in a Tc,tilc Factory, 11111. N. I'. Arnt!. Sci.. 132, 526. MtCAl'<,IIIY. W. T. E. (1958); 1'1imary Tumours of the Pleura. J. !'ath. Baer., 76. 517. Mrn1.\w.1 Ht R, E. R. A., PRtCI:, C. W. (1930J: Effect, of Asbcsto, Ou,t on 1.ung, and Du,t Supprc,,ion. London: JI.M.S.O. NA\IOlt, B. (1963): The E,foliati\e Cytology of OifTu,e Malignant Mc,othclioma. J. Path. Buer., !!6. 293. N1.w111H 1,1. M. L., and 111<1\11so~, fl. ( 1%5): Mc,olhcli- 0111a of the Pleura and Pc, lloncum ful!(l\lo ,ng E,pmurc to A~bcstos in the Londnn Arca, Brit, J. i11d111tr. Med., 22, :'61. N1.w1mu,r, M. L. (1966); Pcr~onal Communication. Ouv~R, StR T. (1927): Clinical A,r,ecl, of Pulmonary Asbestosis, Brir. med. J., ii, I026. Ow1.N, W. G. (1965); MC\nthcl1al Tumour~ and Ex- posure to Asbcstm Du,t, Ann. N. Y. Acad. Sci., 132, 674. S1111 R, II. E. ( 1928): J\ (';l\c or l'm11111<>con10\I,: the Result or Inhalation of A,bc,ttl\ Du,t, JJ,ir. 111cd. J., ii, 982. Sou l'I RS. A. W. II. ( 1965): Oi,cus,ion on 'llum,rn Exposure to A,bcstos: Community Studies; A1111. N. }'. Acad. Sci., 132, 246. S1.1J1s-C'111 MIR, G. K. (1965): A,bc,to,i, in South Afri..:a ~~ Certain Geographical and Environmental Considerations, A1111. N. Y. Acad. S(i., 132, 215. S~HTIHR, W. J. (1965): Secular Changl', in A~be,to,i, in an A,bc,tos Factory, tl1111. N. Y. Arnd. Sd., 132. I(l,. THOMPSON, V. C. (1965): Clinical A,pects of DifTu~e Mesothelial Tumours, Proc. Thor. Soc., Thorax, 20, 286. U.1.C.C. !NlFRNATIONAL UNION AGA!)';S t CANCER (1965): Report and Recommendations or the Working Group on Asbestos and Cancer, A1111. N. Y. Acad. Sci., 132, 706. WAGNER, J. C., SLEGGS, C. A., and MARCHA:-1D, P. (1960): Diffuse Mesothclioma and Asbestos Exposure in the North West Cape Province, Brir. J. indusrr. Med., 17, 260. WJLLIAMS, R., and H UGH-Jo~ES. P. ( 1960): Lung Function Changes in Asbestosis, Thorax, 15, 109. Wooo, W. R. (1928): Pulmonary Asbestosis, Tubercle (Edinb)., JO, 353. WnRS, H. (1949): Asbestosis, Posfgrad. med. J., 25,631. 1wn on information uh of research work. ~. eutics and Pharma., , Dr. Jean H. M, cc as well as myself 1blished. This work. problem of asbestas son, Director of the Jnit at Cardiff. The: re discussed at ar{ Jew York under the !ITIY of Sciences in ve quoted references m although much of :\\here. - i.