Mortality among British asbestos workers undergoing regular medical examinations ( )

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1 Mortality among British asbestos workers undergoing regular medial examinations ( ) A-H Harding, 1 A Darnton, 2 J Wegerdt, 1 D MElvenny 3,4 1 Health and Safety Laboratory, Buxton, Derbyshire, UK; 2 Health and Safety Exeutive, Bootle, Merseyside, UK; 3 Department of Epidemiology and Genetis, Westlakes Researh Institute, Moor Row, Cumbria, UK; 4 Faulty of Health and Soial Care, University of Central Lanashire, Preston, Lanashire, UK Correspondene to: A-H Harding, Health and Safety Laboratory, Harpur Hill, Buxton, Derbyshire SK17 6RN, UK; anne-helen.harding@hsl.gov.uk Aepted 7 February 2009 Published Online First 1 Marh 2009 ABSTRACT Objetives: The Great Britain Asbestos Survey was established to monitor mortality among workers overed by regulations to ontrol oupational exposure to asbestos. This study updates the estimated burden of asbestos-related mortality in the ohort, and identifies risk fators assoiated with mortality. Methods: From 1971, workers were reruited during initially voluntary and later statutory medial examinations. A brief questionnaire was ompleted during the medial, and partiipants were flagged for death registrations. Standardised mortality ratios (SMRs) and proportional mortality ratios (PMRs) were alulated for deaths ourring before Poisson regression analyses were undertaken for diseases with signifiant exess mortality. Results: There were deaths among workers followed-up for person-years. The SMR for all ause mortality was 141 (95% CI 139 to 143) and for all malignant neoplasms 163 (95% CI 159 to 167). The SMRs for aners of the stomah (166), lung (187), peritoneum (3730) and pleura (968), mesothelioma (513), erebrovasular disease (164) and asbestosis (5594) were statistially signifiantly elevated, as were the orresponding PMRs. In age and sex adjusted analysis, birth ohort, age at first exposure, year of first exposure, duration of exposure, lateny and job type were assoiated with the relative risk of lung, pleural and peritoneal aners, asbestosis and mesothelioma mortality. Conlusions: Known assoiations between asbestos exposure and mortality from lung, peritoneal and pleural aners, mesothelioma and asbestosis were onfirmed, and evidene of assoiations with stroke and stomah aner mortality was observed. Limited evidene suggested that asbestos-related disease risk may be lower among those first exposed in more reent times. Asbestos has beome the leading ause of oupational mortality in Great Britain. 1 Asbestos produts first appeared in England in the 1850s and the British asbestos industry began to develop during the 1870s. Medial papers reporting disease among asbestos workers emerged during the 1920s and the first legislation ontrolling oupational exposure to asbestos in Britain was passed in This was followed by further regulations aimed at reduing the risk of asbestos-related disease among asbestos workers. Sine systemati reording of mesothelioma deaths began in Britain in the late 1960s, the number of annual deaths has inreased more than 10-fold, and urrently is more than Despite progressively more stringent laws to redue oupational exposure, due to long lateny, the asbestos-related aner epidemi in Britain has not yet peaked and substantial numbers of deaths are likely to be seen for a number of deades to ome. 3 An estimated 2 3% of lung aner deaths in Britain in the period (exluding 1981) may be attributable to asbestos, 4 while the most reent projetions suggest that mesothelioma, formerly a very rare aner, now aounts for around 0.7% of all deaths among men born in the late 1930s or early 1940s. 3 The Health and Safety Exeutive s national survey of asbestos workers was established in 1970 in order to monitor the long-term health of workers primarily employed in asbestos produt manufature. 5 Substantial numbers of asbestos removal workers were subsequently reruited and sine the deline and eventual ban of asbestos manufature and use in Britain, these formed the majority of new entrants into the ohort. Mortality up to 1991 has been reported previously. 5 The aim of this study was to update the mortality analysis, inluding all deaths to the end of 2005, in order to identify risk fators assoiated with mortality. METHODS Survey population Following approval for the study by the British Medial Assoiation Researh Ethis Committee, starting in 1971, workers at fatories and workplaes in Great Britain that were overed by the 1969 Asbestos Regulations were invited to partiipate in the survey. Partiipants attended a voluntary medial examination at 2-yearly intervals and at the same time ompleted the survey questionnaire. The 1983 Asbestos Liensing Regulations (ALR) required people who worked with asbestos insulation or asbestos oating to be liensed and to attend statutory medial examinations. These were undertaken before employment and at 2- yearly intervals while the individual was still engaged in this type of work. The 1987 Control of Asbestos at Work Regulations (CAWR) extended the requirement for statutory medials to all those oupationally exposed to asbestos above a ertain ation level. 5 Everyone who was medially examined under the 1983 or 1987 regulations beame part of the asbestos survey unless they hose to opt out. Consequently, the survey inluded most liensed asbestos workers in Great Britain. Oup Environ Med 2009;66: doi: /oem

2 The survey questionnaire The questionnaire hanged during the ourse of the survey. 5 Personal details for identifiation, the date of first exposure to asbestos and smoking history were olleted throughout. For workers reruited under the 1983 ALR, no information on job type was olleted sine they all worked with asbestos insulation or asbestos oating. For the remaining workers, information on the urrent job was olleted. Limited, jobspeifi information on urrent asbestos exposure and ontrol praties was reorded for workers reruited under the 1987 CAWR, although this did not inlude quantitative exposure estimates. Follow-up All survey partiipants were flagged for aner and death registrations on the National Health Servie Central Register (NHSCR) after their first medial. Smoking status and job details were updated when workers attended further medials. Job ategories Jobs were lassified into four major industrial ategories: manufaturing, stripping/removal, other exposed oupations, and insulation workers. Within these industries there were setors overing: asbestos textile manufature; asbestos ement mixture, board and pipe manufature; asbestos/rubber/ resin bitumen mixtures manufature; asbestos board and paper manufature; asbestos garment manufature; dry mixes for insulation and plastering manufature; maintenane workers in all industries; stripping/removal workers; shipbuilding, repair and breaking; building and onstrution; and misellaneous fatory proesses. The other exposed workers enompassed the shipbuilding, onstrution and misellaneous setors. For the purposes of the analysis, workers who attended more than one medial were alloated to the job type they had spent most time in. If there was a tie, then the worker was alloated to the job type whih was previously reported to have higher mortality. 5 Causes of death The auses of death for analysis were seleted on the basis of evidene in the literature of an assoiation, or a possible assoiation, with asbestos exposure. The period overed by the survey inluded deaths oded aording to the International Classifiation of Diseases (ICD) revisions 8 to 10. There was no speifi mortality ode for mesothelioma before ICD-10, whih was introdued for reording of underlying ause of death in Sotland from 2000 and in England and Wales from Mesothelioma deaths annot be identified onsistently from oded ause of death using earlier ICD revisions sine they gave more prominene to tumour site and beause mesothelioma was often reorded on the death ertifiate without mention of the tumour site. Consequently, mesothelioma was oded to a range of auses, suh as lung aner and aner of ill-defined and unspeified sites, whih typially also inluded many nonmesothelioma deaths. We therefore restrited the analysis of mesothelioma deaths to those ourring during the period only. To be onsistent with ICD oding in England and Wales, deaths ourring in Sotland during 2000 were reoded to ICD-9. Statistial analysis Men and women inluded in the analysis had valid data on age, sex and date of medial examination, and were between the minimum shool leaving age and 85 years of age at their first medial examination. Person-years at risk were alulated from the date of the first medial examination. Standardised mortality ratios (SMRs) were alulated as the ratio of observed to expeted deaths, with expeted numbers alulated using the 5-year age-, period- and sex-speifi mortality rates for Great Britain. To explore issues of potential onfounding in the ontext of the population omparison, in partiular by smoking status, proportional mortality ratios (PMRs) were also alulated based on the proportional mortality of eah ause of death in Great Britain. SMRs and PMRs were alulated using OCMAP-PLUS V4?00 (Release 01e) (Department of Biostatistis, University of Pittsburgh, Pittsburgh, PA). To further explore the issue of onfounding, and to investigate the risk fators assoiated with mortality, internal analysis was undertaken using Poisson regression with Stata SE v 10.1 software (StataCorp LP, College Station, TX). Those auses of death whih indiated a statistially signifiant exess mortality in the SMR and PMR analysis or statistially signifiantly raised SMR and non-signifiant PMR, were inluded in the internal analysis. The potential explanatory variables tested were age, sex, alendar period of death, birth ohort, year of first exposure, age at first exposure, length of exposure, lateny (years sine first oupational exposure), smoking status, main job, and whether a short- or longer-term worker. Workers were lassed as longer-term if they had attended more than one medial and short-term otherwise. The first level of any ategorial variable was used as the referene ategory, unless there were less than five deaths in this ategory. When this ourred, the seond level of the variable was used as the referene ategory. Changing the referene ategory did not alter the nature of the assoiation with mortality, but it did inrease the preision of the estimates. The model inluding age and sex was the starting point for the internal analysis. Separate models for eah explanatory variable, adjusted for age and sex, were then fitted. The ombined effets of variables were examined by inluding more than one explanatory variable at a time in the model adjusted for age and sex (full results not shown). The final models seleted inluded variables whih made a statistially signifiant ontribution to the model (p(0.05) and whih had stable oeffiients. Near ollinearity between time-related variables, suh as age, age at first exposure and lateny, led to unstable regression oeffiients when they were inluded in the model simultaneously. Sine asbestosrelated diseases typially have a long lateny, short-term followup beyond first exposure will be largely uninformative, and its inlusion may dilute any observed assoiations. In order to hek for this, the age and sex adjusted analysis of eah explanatory variable was repeated by restriting the analysis to those individuals with at least 20 years follow-up. In the restrited analysis, person-years follow-up started aumulating after 20 years follow-up had been reahed. Signifiane of model parameters was determined using the likelihood ratio test, and model goodness of fit was tested. RESULTS Altogether, men and women ompleted survey questionnaires from the start of the survey in 1971 to the end of Of these, 98% were suessfully traed for follow-up through the NHSCR. With exlusions for inomplete data, age less than the minimum shool leaving age (n = 13) or age greater than 85 years (n = 1) at the first medial examination, individuals remained in the analysis. 488 Oup Environ Med 2009;66: doi: /oem

3 Overall, 95% of the ohort was male, and at the time of the medial examinations 5% of the workers were based in Sotland. The mean age at the first medial examination was 35 years (SD 12) (table 1). At the last reorded medial, 53% of men and 47% of women were urrent smokers. Overall, 57% of survey partiipants attended one medial examination only, while the remaining workers attended between two and 19 medials. In 1975, 62% of partiipants were employed in the asbestos manufaturing industry and 5% in the asbestos removal industry (fig 1). By 2005, the manufaturing industry had eased and 94% of workers were employed in the asbestos removal industry. The majority of manufaturing workers joined the survey before 1984, while the majority of removal workers joined after Standardised and proportional mortality ratio analyses There was a statistially signifiant exess of deaths from all auses among the asbestos workers (SMR 141; 95% CI 139 to 143) (table 2). SMRs were also statistially signifiantly elevated for all malignant neoplasms, aners of the oesophagus, stomah, olon, retum, liver, larynx, lung, peritoneum, pleura, kidney and bladder, mesothelioma, irulatory diseases and respiratory disease inluding asbestosis. PMRs for all malignant neoplasms, aners of the stomah, lung, peritoneum and pleura, and mesothelioma, erebrovasular disease and asbestosis were signifiantly elevated above 100; PMRs for aners of the olon, retum, liver, larynx, bladder and kidney were not statistially signifiant. Asbestosis mortality Poisson regression analysis indiated that, adjusted for age and sex, the following were statistially signifiantly assoiated with asbestosis mortality: birth ohort, year first oupationally exposed to asbestos, age first exposed, length of exposure, lateny, smoking status at the last medial examination and main job (table 3). When entered into the model simultaneously, only year first exposed, smoking status and main job were statistially signifiant in the final model. The relative risk of asbestosis was signifiantly lower for workers first exposed after 1959 than for workers first exposed before 1960 (RR 0.11 for first exposure in ompared to in the final model, 95% CI 0.03 to 0.38). Current and former smokers had similar relative risks of asbestosis, whih were more than three times higher than the relative risk for never smokers. Insulation workers had the highest risk of asbestosis: RR 5.98 (95% CI 3.84 to 9.31) ompared to manufaturing workers, followed by removal workers (RR 2.21; 95% CI 1.24 to 3.93). Cerebrovasular disease mortality In the analysis adjusted for age and sex, the following were statistially signifiantly assoiated with stroke mortality: birth ohort, year first oupationally exposed to asbestos, smoking status and main job (table 3). Main job was no longer statistially signifiant in the final model in whih variables were inluded simultaneously. The relative risk of stroke dereased in later birth ohorts and for workers first exposed in more reent years. Current smokers, but not former smokers, had a signifiantly inreased risk of mortality ompared with never smokers (RR 1.56 in the final model; 95% CI 1.29 to 1.89). Lung aner mortality In models adjusted only for age and sex, the following were statistially signifiantly assoiated with lung aner mortality: period of death, birth ohort, year first oupationally exposed to asbestos, age at first exposure, length of exposure, lateny, smoking status and main job (table 3). In the final model with variables inluded simultaneously, ohort, year first exposed, lateny, smoking status and main job were statistially signifiant. The relative risk of lung aner dereased steadily from the oldest to the youngest ohort, and for those first exposed in later years, with relative risks very similar to those observed in the analysis adjusted for age and sex. Current and former smokers had a higher risk of lung aner (RR 14.3 in the final model; 95% CI 10.2 to 20.1, and RR 4.55; 95% CI 3.20 to 6.46, respetively) than never smokers. Insulation workers and removal workers had signifiantly higher risks of lung aner than manufaturing workers (RR 1.84 in the final model; 95% CI 1.60 to 2.10, and RR 1.30; 95% CI 1.12 to 1.50, respetively). Stomah aner mortality Adjusted for age and sex, the following were statistially signifiantly assoiated with stomah aner mortality: period Figure 1 Number of workers reruited into the survey eah year, by main job ( ). ALR, Asbestos Liensing Regulations. Oup Environ Med 2009;66: doi: /oem

4 Table 1 The Great Britain Asbestos Survey population ( ) Men Women Number of individuals Person-years at risk Age (at first exam, years) 35 (SD 12) 36 (SD 13) Current smokers (at last exam) (53%) 2115 (47%) Attended one exam only (short-term worker) (57%) 2400 (53%) Main industry ategories* Manufaturing workers (28%) 2895 (65%) Removal workers (54%) 599 (13%) Other exposed workers (13%) 819 (18%) Insulation workers 5039 (5%) 173 (4%) *Information on job type was available for workers. of death, birth ohort, year first oupationally exposed to asbestos, smoking status and main job (table 4). In the final model, birth ohort and smoking status were statistially signifiant. The relative risk of stomah aner fell in the younger birth ohorts (RR for the ohort ompared to the,1920 ohort in the final model: 0.11; 95% CI 0.05 to 0.24), and there were no deaths from stomah aner among workers born after Current smokers, but not former smokers, had an inreased risk of mortality (RR 1.42; 95% CI 1.00 to 2.02) ompared to never smokers. Pleural and peritoneal aner mortality Although the relative risks were larger in the peritoneal aner analysis, the variables assoiated with mortality were similar for pleural and peritoneal aners. In the analysis adjusted for age and sex only, period, birth ohort, year first exposed, age at first exposure, length of exposure, lateny and main job were statistially signifiantly assoiated with the relative risk of pleural aner and peritoneal aner mortality, and smoking status was statistially signifiantly assoiated with peritoneal aner mortality (table 4). In the final model with variables inluded simultaneously, period of death, length of exposure and main job were statistially signifiant. In these models, ompared to workers with less than 10 years exposure, the relative risk of pleural aner was 4.35 (95% CI 2.18 to 8.68) and of peritoneal aner 14.9 (95% CI 5.80 to 38.5) for workers with at least 40 years oupational exposure to asbestos. Manufaturing workers had lower risks of both aners than other workers. Compared with manufaturing workers, for insulation and removal workers the relative risks of pleural aner were 3.19 (95% CI 2.04 to 5.01) and 1.61 (95% CI 0.98 to 2.64), respetively, and the relative risks of peritoneal aner were 20.6 (95% CI 9.53 to 44.6) and 9.69 (95% CI 4.28 to 21.9), respetively. Mesothelioma mortality Period of death ould not be analysed for mesothelioma mortality sine deaths were only identified in one period. This also resulted in birth ohort and age being highly orrelated and so they were not inluded together in any of the models. In age and sex adjusted models, the following were statistially signifiantly assoiated with mesothelioma mortality: year first exposed, age first exposed, length of exposure, lateny, main job and short/longer-term worker. In the final model when explanatory variables were inluded in the model simultaneously, only lateny and main job were statistially signifiant. The relative risk of mesothelioma inreased with lateny, reahing a maximum years after first exposure (RR for years lateny ompared with,20 years : 28.1; 95% CI Table 2 Mortality among the Great Britain Asbestos Survey workers ( ) Cause of death Observed no of deaths Standardised mortality ratio (95% CI) Proportional mortality ratio (95% CI) All auses (139 to 143) All malignant neoplasms (159 to 167) 113 (111 to 116) MN of lip, oral (83 to 133) 73 (58 to 92) avity and pharynx MN of oesophagus (101 to 132) 83 (73 to 95) MN of stomah (149 to 186) 114 (102 to 127) MN of olon (114 to 144) 90 (80 to 100) MN of retum (130 to 174) 100 (86 to 115) MN of liver (109 to 170) 101 (81 to 125) (primary) MN of larynx (109 to 195) 101 (76 to 134) MN of lung (179 to 196) 129 (123 to 134) MN of peritoneum (2979 to 4612) 2246 (1941 to 2599) MN of pleura (817 to 1139) 568 (492 to 656) Mesothelioma* (435 to 601) 489 (424 to 564) MN of breast (66 to 180) 58 (45 to 75) MN of ovary (66 to 180) 68 (43 to 108) MN of kidney (126 to 183) 101 (84 to 122) MN of bladder (123 to 170) 103 (84 to 122) MN of lymphati (90 to 114) 74 (66 to 82) and haematopoieti tissue Cirulatory disease (138 to 145) 97 (96 to 99) Ishaemi heart (136 to 144) 95 (93 to 97) disease Cerebrovasular (154 to 174) 115 (109 to 122) disease Respiratory disease (154 to 170) 118 (113 to 124) Asbestosis (4634 to 6694) 3944 (3541 to 4393) *ICD-10 mesothelioma (deaths ). MN, malignant neoplasm to 64.6). Removal workers and insulation workers had the highest relative risk of mesothelioma (RR 3.19; 95% CI 2.16 to 4.72 ompared with manufaturing workers in the final model, and RR 2.65; 95% CI 1.64 to 4.30, respetively). Poisson regression analysis of auses of death with signifiantly raised SMR but non-signifiant PMR In Poisson regression analysis adjusted for age and sex, the assoiations observed with potential explanatory variables were generally weak, and the assoiations tended not to be with variables speifially related to asbestos exposure, namely length of exposure and main job. Colon aner mortality was assoiated with birth ohort, year exposed, age exposed, smoking status and main job; bladder aner mortality was assoiated with period, ohort, year exposed and smoking status; laryngeal aner was assoiated with age exposed, length of exposure and smoking status; aner of the retum was assoiated with ohort and main job; and kidney aner mortality was assoiated with lateny. There were no statistially signifiant assoiations with liver aner mortality. Analysis restrited to death with a minimum of 20 years lateny The separate age and sex adjusted analysis of eah explanatory variable was repeated with deaths restrited to those ourring at least 20 years after first oupational exposure to asbestos (results not shown). The trends observed in the restrited analysis tended to be stronger than those in the unrestrited 490 Oup Environ Med 2009;66: doi: /oem

5 Table 3 Risk fator of asbestosis, erebrovasular disease and lung aner mortality, adjusted for age and sex Asbestosis Cerebrovasular disease Lung aner Deaths (95% CI) Deaths (95% CI) Deaths (95% CI) Period, (0.38 to 1.99) (0.71 to 1.38) (0.73 to 1.08) (0.23 to 1.18) (0.69 to 1.31) (0.49 to 0.72) (0.23 to 1.19) (0.54 to 1.04) (0.44 to 0.66) Cohort, (0.53 to 1.28) (0.48 to 0.65) (0.66 to 0.84) (0.34 to 1.03) (0.32 to 0.47) (0.49 to 0.65) (0.09 to 0.59) (0.18 to 0.34) (0.32 to 0.47) (0.01 to 0.50) (0.16 to 0.39) (0.10 to 0.20) (0.12 to 0.51) (0.01 to 0.08) (0.04 to 2.04) 0 Year first exposed, (0.76 to 9.31) (0.28 to 0.83) (0.46 to 1.50) (0.46 to 1.74) (0.21 to 0.62) (0.45 to 1.43) (0.50 to 1.74) (0.17 to 0.49) (0.41 to 1.30) (0.12 to 0.50) (0.21 to 0.59) (0.31 to 0.98) (0.05 to 0.26) (0.20 to 0.56) (0.29 to 0.92) (0.01 to 0.24) (0.13 to 0.42) (0.21 to 0.70) (0.06 to 0.30) (0.08 to 0.36) Age first exposed (years), (0.33 to 0.84) (0.76 to 1.20) (0.57 to 0.77) (0.20 to 0.55) (0.89 to 1.37) (0.71 to 0.95) (0.12 to 0.39) (0.98 to 1.50) (0.71 to 0.95) (0.05 to 0.26) (0.95 to 1.50) (0.66 to 0.92) Length of exposure (years), (0.95 to 18.6) (0.87 to 1.43) (0.95 to 1.34) (1.18 to 22.6) (0.74 to 1.22) (0.91 to 1.30) (2.06 to 39.2) (0.71 to 1.20) (1.06 to 1.53) (4.51 to 85.6) (0.84 to 1.42) (1.07 to 1.57) Lateny (years sine first exposure), (0.75 to 3.30) (0.85 to 1.20) (0.86 to 1.11) (1.54 to 6.31) (0.78 to 1.14) (0.97 to 1.28) (2.59 to 11.0) (0.76 to 1.16) (1.06 to 1.44) (4.80 to 22.3) (0.83 to 1.37) (1.02 to 1.50) (4.34 to 33.0) (1.51 to 2.90) (0.82 to 1.68) Smoking status Never Former (1.61 to 7.96) (0.84 to 1.27) (3.49 to 6.98) Current (1.49 to 7.10) (1.41 to 2.04) (10.7 to 20.7) Main job Manufaturing Removal (0.84 to 2.51) (0.50 to 0.72) (0.76 to 0.98) Other (0.70 to 2.18) (0.70 to 0.97) (0.78 to 1.02) Insulation (4.45 to 10.7) (0.70 to 1.10) (1.68 to 2.18) Short/longer-term worker (referene ategory short-term) Short-term Long-term (0.61 to 1.26) (0.79 to 1.01) (0.86 to 1.03) analysis. However, with some exeptions, the restrited analysis did not hange the onlusions about whih explanatory variables were important. Changes in the observed assoiations ourred in the assoiation between age at first exposure and the risk of stroke and the risk of stomah aner; in the restrited analysis adjusted for age and sex, the relative risks of mortality were signifiantly lower for workers first exposed at older ages. In addition, statistially signifiant positive assoiations were observed between duration of exposure and stroke mortality, and between lateny and the risk of stomah aner. Oup Environ Med 2009;66: doi: /oem

6 Table 4 Risk fator of stomah, pleural and peritoneal aner and mesothelioma mortality, adjusted for age and sex Stomah aner Pleural aner Peritoneal aner Mesothelioma* Deaths (95% CI) Deaths (95% CI) Deaths (95% CI) Deaths (95% CI) Period, (0.51 to 1.22) (0.70 to 2.89) (0.56 to 2.83) (0.34 to 0.81) (0.42 to 1.73) (0.33 to 1.68) (0.19 to 0.48) (0.06 to 0.36) (0.01 to 0.22) 160 Cohort, { (0.49 to 0.85) (0.53 to 1.34) (0.56 to 2.27) (0.82 to 4.76) (0.33 to 0.65) (0.26 to 0.77) (0.36 to 1.61) (1.14 to 6.12) (0.13 to 0.35) (0.09 to 0.38) (0.08 to 0.57) (0.74 to 4.02) (0.06 to 0.25) (0.01 to 0.12) (0.002 to 0.13) (0.10 to 0.74) (0.02 to 0.41) Year first exposed, (0.24 to 4.25) (0.10 to 5.50) (0.35 to 1.03) (0.31 to 1.07) (0.47 to 2.16) (0.42 to 1.10) (0.27 to 0.86) (0.25 to 1.16) (1.69 to 6.13) (0.38 to 0.97) (0.10 to 0.35) (0.02 to 0.17) (0.88 to 3.31) (0.38 to 0.97) (0.05 to 0.18) (0.01 to 0.09) (0.37 to 1.54) (0.19 to 0.64) (0.02 to 0.14) (0.003 to 0.07) (0.32 to 1.80) (0.01 to 0.40) (0.31 to 3.31) Age first exposed (years), (0.69 to 1.49) (0.39 to 0.90) (0.15 to 0.43) (0.25 to 0.54) (0.81 to 1.72) (0.14 to 0.43) (0.03 to 0.16) (0.14 to 0.34) (0.80 to 1.72) (0.09 to 0.33) (0.01 to 0.14) (0.06 to 0.19) (0.76 to 1.75) (0.22 to 0.68) (0.07 to 0.34) (0.06 to 0.23) Length of exposure (years), (0.88 to 2.01) (0.15 to 0.83) (0.01 to 0.93) (0.48 to 5.38) (0.70 to 1.63) (0.94 to 3.08) (1.10 to 6.55) (2.12 to 18.5) (0.66 to 1.64) (1.49 to 5.49) (3.97 to 24.6) (5.16 to 45.0) (0.72 to 1.83) (1.74 to 7.23) (7.69 to 60.6) (12.4 to 114) Lateny (years sine first exposure), (0.70 to 1.28) (1.19 to 3.64) (1.43 to 8.44) (1.54 to 7.33) (0.63 to 1.22) (1.95 to 6.11) (5.99 to 33.4) (5.40 to 23.4) (0.57 to 1.22) (3.40 to 11.4) (14.4 to 94.9) (11.2 to 51.1) (0.55 to 1.45) (2.04 to 10.4) (12.1 to 127) (13.7 to 74.0) (0.54 to 2.60) (2.68 to 228) (2.17 to 52.6) Smoking status{ Never Former (1.03 to 2.17) (0.84 to 2.58) (1.11 to 4.65) (0.61 to 1.55) Current (1.12 to 2.24) (0.86 to 2.44) (0.75 to 3.00) (0.61 to 1.44) Main job{ Manufaturing Removal (0.44 to 0.92) (0.66 to 1.69) (2.88 to 14.1) (2.23 to 4.86) Other (0.77 to 1.50) (0.79 to 2.08) (1.18 to 7.92) (0.65 to 1.88) Insulation (0.84 to 2.01) (2.30 to 5.62) (12.1 to 56.1) (2.09 to 5.44) Short/longer-term worker (referene ategory short-term) Short-term Long-term (0.81 to 1.26) (0.90 to 1.78) (0.88 to 2.09) (1.06 to 2.01) *ICD-10 mesothelioma deaths ( ); {ohort only adjusted for sex due to ollinearity with age; {missing values ourred in this variable. DISCUSSION The Great Britain Asbestos Survey is one of the largest and longest running surveys undertaken on asbestos workers in the world. It inludes a substantial proportion of workers in asbestos produt manufature sine 1970 and most asbestos workers undergoing statutory medial surveillane. This analysis demonstrated onvining evidene of inreased mortality from aners of the lung, peritoneum and pleura, mesothelioma and asbestosis, and provided some evidene of an assoiation between asbestos exposure and mortality from stroke and stomah aner. Less onvining evidene of an assoiation with asbestos was observed for aners of the olon and the larynx, but for other auses of death there was insuffiient evidene to support an assoiation with oupational exposure to asbestos. 492 Oup Environ Med 2009;66: doi: /oem

7 The SMRs were likely to be onfounded by other risk fators, partiularly smoking. Over 50% of the Great Britain asbestos workers were urrent smokers. When broken down by year of medial examination, the proportion of urrent smokers remained at over 50% throughout the survey period. Smoking prevalene among the asbestos workers was similar to the Great Britain population in the early 1970s, but by 2005, the prevalene of smoking in the Great Britain population had fallen to 24%. 6 Smoking is assoiated with many aners, as well as respiratory and irulatory diseases. 7 Several auses of death assoiated with smoking had statistially signifiantly raised SMRs but did not have statistially signifiantly raised PMRs, whih suggests that the observed exesses might be due to onfounding fators suh as smoking rather than to asbestos exposure. This was the ase for aners of the oesophagus, olon, retum, liver, larynx, kidney and bladder, and for irulatory disease overall. However, some aution is required sine the PMR analysis annot be onsidered to be a formal adjustment for onfounding fators. Poisson regression analysis onfirmed that smoking status was assoiated with mortality from aners of the olon, larynx and bladder. The SMR/PMR analysis added to the body of evidene, whih onsistently shows that asbestos exposure is assoiated with exess mortality from lung, pleural and peritoneal aners, asbestosis and mesothelioma The internal analysis showed that year of first oupational exposure to asbestos, age at first exposure, duration of exposure, lateny and job type were all assoiated with mortality in the age and sex adjusted models. Together the SMR/PMR and Poisson regression analyses provided onvining evidene of the assoiation between oupational exposure to asbestos and inreased mortality from these diseases. The Poisson regression analysis gave some indiation that the relative risk of these diseases may be falling among workers first exposed in more reent times and in later birth ohorts; the relative risks of asbestosis, lung, pleural and peritoneal aners were lower for workers born after 1939 and workers first exposed after This may be a onsequene of progressively more stringent laws to redue oupational exposure to asbestos, starting with the Asbestos Regulations in However, it may also reflet the long lateny of these diseases whereby the highest risks our 40 or more years after first exposure. The introdution of a separate ICD ode for mesothelioma may have resulted in spurious trends with time. The large fall in the relative risks of pleural and peritoneal aners in the alendar period was likely to be a onsequene of pleural and peritoneal mesotheliomas being oded to the new ICD-10 ode for mesothelioma after 2001, leaving only pleural and peritoneal aners in these two ause of death ategories. An exess of deaths from erebrovasular disease and from stomah aner was observed among the Great Britain asbestos workers, and the Poisson regression analysis provided some evidene of an assoiation with asbestos exposure. In the restrited Poisson regression, where observed effets tended to be stronger, birth ohort, year of first exposure, age at first exposure, duration of exposure (stroke only) and lateny (stomah aner only) were statistially signifiantly assoiated with mortality. Elevated risk of stroke has been reported in a number of asbestos-exposed ohorts, but a large study of Swedish onstrution workers found no assoiation between exposure to inorgani dust, inluding asbestos, and stroke. 16 The published evidene for an assoiation between stomah aner and asbestos exposure is also inonlusive. 17 The 1987 IARC 18 review of the strength of evidene for a ausal relationship between asbestos exposure and gastrointestinal aner found suffiient evidene, while the 2006 US Institute of Mediine (US IoM) Committee on Asbestos 19 found the evidene was suggestive but not suffiient. On the other hand, there is strong evidene that stroke and stomah aner are assoiated with smoking The exess mortality from stroke and stomah aner observed in this ohort is likely to be at least partially attributable to smoking and other risk fators; however, there was also some evidene of an assoiation with asbestos exposure. The SMR/PMR analysis inluded other diseases whih have been linked with asbestos or studied in asbestos-exposed ohorts. There is suffiient evidene to infer a ausal relationship between asbestos exposure and laryngeal aner aording to both IARC 18 and US IoM 19 reviews; however, the results from the Great Britain asbestos workers were not onsistent with there being a strong relationship between asbestos exposure and laryngeal aner or other aners of the upper respiratory trat. Similarly, the results in relation to oloretal aner were not onsistent with a strong effet due to asbestos. Among the Great Britain asbestos workers, mortality from laryngeal and oloretal aners was more likely to be due to smoking and other established risk fators, 23 although an assoiation with asbestos exposure ould not be ruled out. The analysis has some important limitations. The mortality analysis was based on the underlying ause of death as reported on death ertifiates. Consequently, the true burden of some asbestos-related diseases may have been underestimated, although the SMRs were unlikely to be biased. For individuals with asbestosis or mesothelioma, the underlying ause of death is often not reorded as asbestosis or mesothelioma. Sine asbestosis is a hroni ondition, many deeased individuals with asbestosis are assigned a different underlying ause of death. The Great Britain Asbestosis Register shows that of the 373 deaths with asbestosis mentioned on the death ertifiate in 2005, 134 deaths had underlying ause reorded as asbestosis. 24 Before the use of ICD-10 many mesotheliomas were not reorded as pleural or peritoneal aner as the underlying ause of death, 5 25 but were oded as malignant neoplasm of illdefined, seondary and unspeified sites. Furthermore, the majority of national deaths reorded as pleural aner as the underlying ause prior to the use of ICD-10 were in fat mesotheliomas, but only a minority (approximately 20% during the period ) of national deaths reorded as peritoneal aner were mesotheliomas. The results for peritoneal aner therefore annot be taken to desribe peritoneal mesothelioma alone. Mislassifiation of mesothelioma deaths may have ourred beyond the introdution of ICD-10 with some pleural mesotheliomas being misdiagnosed as lung aners, and peritoneal mesotheliomas being misdiagnosed as gastrointestinal aners. 26 The survey olleted no information on potentially important risk fators suh as diet and physial ativity, and only limited information on exposure to asbestos. Partiipation in the survey was assumed to imply oupational exposure to asbestos; no diret information was available for all the workers about important determinants of risk suh as type of asbestos, intensity and length of exposure, although job type gave some insight into exposures. Clear differenes in mortality were observed between job types. Insulation, and to a lesser degree removal and other exposed workers, in the Great Britain survey were at higher risk of mortality than manufaturing workers. Employment in the asbestos insulation industry was Oup Environ Med 2009;66: doi: /oem

8 Main messages The analysis onfirmed known assoiations between asbestos exposure and mortality from asbestosis, lung, pleural and peritoneal aners and mesothelioma, and provided some evidene of an assoiation with stroke and stomah aner mortality; it did not provide onlusive evidene to support a priori suspeted assoiations between asbestos exposure and other auses of death. Insulation workers had the highest mortality from asbestosrelated diseases; although asbestos removal is a relatively reent development in the asbestos industry, mortality among removal workers was higher than among manufaturing workers. Smoking was an important risk fator for asbestosis and for lung aner but not for the mesotheliomas. likely to involve exposure to substantial quantities of amphibole asbestos. Exept in populations with high amphibole exposures, the inidene of pleural mesothelioma is typially an order of magnitude greater than that of peritoneal mesothelioma. 10 The ratios of peritoneal to pleural aners found in the insulation and removal workers in this study were about 1:1, whih was suggestive of high amphibole exposure among these groups. For manufaturing and other exposed workers, the ratios were approximately 1:6 and 1:4, respetively. The length of follow-up was both a strength and a limitation of the survey. Workers reruited at the beginning of the survey had up to 35 years follow-up. For them, the full extent of the burden of asbestos-related disease is now emerging. The mortality experiene of those employed in the asbestos stripping/removal industry is of partiular interest given the rapid expansion of this industry during the mid-1980s. For most of these workers, there was less than 20 years follow-up, whih was insuffiient to determine the full extent of diseases with a long latent period. Consequently, it was not possible to demonstrate onlusively any effets on mortality of hanges in ontrol pratie sine the introdution of the 1983 ALR or later regulations. Conlusion The asbestos-exposed workers inluded in this study did not demonstrate the usual healthy-worker effet but experiened statistially signifiantly higher mortality than the Great Britain population, and greatly inreased mortality for a number of speifi auses of death. Inreased mortality from ertain auses may be attributable at least in part to smoking, sine a large proportion of the ohort were urrent or former smokers. The analysis onfirmed known assoiations between asbestos exposure and mortality from asbestosis, lung, pleural and peritoneal aners and mesothelioma, and provided evidene of assoiations between asbestos exposure and stroke and stomah aner mortality, but there was no onlusive evidene of other a priori suspeted assoiations with asbestos exposure, suh as laryngeal aner. Elevated mortality from these diseases was more likely to be attributable to smoking and other risk fators than to asbestos exposure. The study provided some evidene that as a result of legislation to redue oupational exposure to asbestos, the risk of asbestos-related disease mortality may be lower among those first oupationally exposed to asbestos in more reent times, but due to the long lateny of these diseases further follow-up is required to onfirm this trend. Poliy impliations A strategy for smoking essation among asbestos workers would have potentially large health benefits. Some evidene is emerging that asbestos legislation is beginning to have an impat on the level of disease. Continued surveillane of asbestos workers is essential in order to monitor the effetiveness of regulations to ontrol oupational exposure to asbestos in reduing asbestosrelated mortality. Aknowledgements: We would like to thank the staff at the Health and Safety Laboratory and the Health and Safety Exeutive, who worked on the Asbestos Survey. We would also like to thank the staff at the NHSCR, the oupational physiians and the asbestos workers for their support. Funding: The Health and Safety Exeutive funded the study. Competing interests: None. Ethis approval: This study was approved by the British Medial Assoiation Researh Ethis Committee. Authors ontributions: JW and A-HH had full aess to the study data and take responsibility for the integrity of the data. A-HH, AD and DM oneptualised this analysis. 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10 Mortality among British asbestos workers undergoing regular medial examinations ( ) A-H Harding, A Darnton, J Wegerdt, et al. Oup Environ Med : originally published online Marh 1, 2009 doi: /oem Updated information and servies an be found at: Referenes alerting servie These inlude: This artile ites 20 artiles, 11 of whih an be aessed free at: Artile ited in: Reeive free alerts when new artiles ite this artile. Sign up in the box at the top right orner of the online artile. Topi Colletions Artiles on similar topis an be found in the following olletions Respiratory (136 artiles) Asbestos (44 artiles) Other exposures (530 artiles) Notes To request permissions go to: To order reprints go to: To subsribe to BMJ go to: