Document zopZzmYqK1NERZ3GLdEqYwLog

Downloaded from oem.bmj.com on 16 August 2007 OEM Online First, published on April 20, 2007 as 10.1136/oem.2006.031005 FOLLOW-UP STUDY OF CHRYSOTILE TEXTILE WORKERS: COHORT MORTALITY AND EXPOSURE-RESPONSE Misty J. Hein 1, Leslie T. Stayner 2, 3 , Everett Lehman 4, John M. Dement 5 1 Industrywide Studies Branch Division of Surveillance, Hazard Evaluations and Field Studies National Institute for Occupational Safety and Health 4676 Columbia Parkway, R-13 Cincinnati, Ohio 45226 USA MHein@cdc.gov 513-841-4207 telephone 513-841-4486 fax 2 Division of Epidemiology and Biostatistics University of Illinois School of Public Health Chicago, Illinois, USA 3 Risk Evaluation Branch Education and Information Division National Institute for Occupational Safety and Health Cincinnati, Ohio, USA 4 Industrywide Studies Branch Division of Surveillance, Hazard Evaluations and Field Studies National Institute for Occupational Safety and Health Cincinnati, Ohio, USA 5 Department of Community and Family Medicine Division of Occupational and Environmental Medicine Duke University Medical Center Durham, North Carolina, USA Keywords: asbestos; asbestos, serpentine; asbestosis; respiratory tract diseases; cohort studies The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article to be published in OEM and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence (http://oem.bmiiournals.com/ifora/licence.pdf). 1 Copyright Article author (or their employer) 2007. Produced by BMJ Publishing Group Ltd under licence. Downloaded from oem.bmj.com on 16 August 2007 ABSTRACT Objectives This report provides an update of the mortality experience of a cohort of South Carolina asbestos textile workers. Methods A cohort of 3,072 workers exposed to chrysotile in a South Carolina asbestos textile plant (1916-1977) was followed up for mortality through 2001. Standardized mortality ratios (SMRs) were computed using U.S. and South Carolina mortality rates. A job exposure matrix provided calendar time dependent estimates of chrysotile exposure concentrations. Poisson regression models were fitted for lung cancer and asbestosis. Covariates considered included sex, race, age, calendar time, birth cohort, and time since first exposure. Cumulative exposure lags of 5 and 10 years were considered by disregarding exposure in the most recent 5 and 10 years, respectively. Results A majority of the cohort was deceased (64%) and 702 of the 1,961 deaths occurred since the previous update. Mortality was elevated based on U.S. referent rates for a priori causes of interest including all causes combined (SMR 1.33, 95% confidence interval (CI) 1.28-1.39); all cancers (SMR 1.27, 95% CI 1.16-1.39); esophageal cancer (SMR 1.87, 95% CI 1.09-2.99); lung cancer (SMR 1.95, 95% CI 1.68-2.24); ischemic heart disease (SMR 1.20, 95% CI 1.10-1.32); and pneumoconiosis and other respiratory diseases (SMR 4.81, 95% CI 3.84-5.94). Mortality remained elevated for these causes when South Carolina referent rates were used. Three cases of mesothelioma were observed among cohort members. Exposure-response modeling for lung cancer, using a linear relative risk model, produced a slope coefficient of 0.0198 (fiber-years/ml)-1 (standard error 0.00496), when cumulative exposure was lagged 10 years. Poisson regression modeling confirmed significant positive relationships between estimated chrysotile exposure and lung cancer and asbestosis mortality observed in previous updates of this cohort. Conclusions This study confirms the findings from previous investigations of excess mortality from lung cancer and asbestosis and a strong exposure-response relationship between estimated exposure to chrysotile and mortality from lung cancer and asbestosis. 2 Downloaded from oem.bmj.com on 16 August 2007 during 1991-1998. Mesothelioma deaths occurring after 1998 were identified by ICD-10 code C45 in the NDI cause of death file. Exposure assessment Detailed work histories listing beginning and ending dates in departments and operations were available for each member of the cohort. A department-, operation-, and calendar year-specific job exposure matrix (JEM) was available to link with the detailed work histories to calculate cumulative exposure to chrysotile. [9] Chrysotile exposure concentrations (expressed as fibers longer than 5 micrometers per milliliter of air) were estimated using statistical modeling of nearly 6000 industrial hygiene sampling measurements taken over the period 1930-1975 and analyzed using phase contrast microscopy. Exposure concentrations were considerably higher prior to 1940, before engineering dust control measures were put into place. This JEM has been used in previous mortality studies and exposure-response analyses of this cohort.[5-8, 13] Each day in the work history was assigned an exposure level based on the JEM and cumulative exposure was defined as the sum of the assigned exposure concentrations over all days worked. SMRs were calculated by cumulative exposure for cancer of the trachea, bronchus, and lung (hereafter referred to as lung cancer) and pneumoconiosis and other respiratory diseases. Cutpoints of cumulative exposure were selected to give six exposure strata with approximately equal numbers of deaths (cause-specific). Internal exposure-response modeling Since stratified SMRs are not directly comparable, rate ratios (RRs) for each cumulative exposure category relative to the lowest group, adjusted for sex, race, age (<50, 50-54...75-79, and 80 years), and calendar-year (<1970, 1970-1979, 1980-1989, and >1990), were obtained by Poisson regression. Exposure lags of 5 and 10 years were considered by disregarding exposures in the most recent 5 and 10 years, respectively. More detailed Poisson regression analyses were conducted by treating cumulative exposure as a continuous variable. In these analyses, cumulative exposure was partitioned into 30 categories with approximately equal numbers of deaths (causespecific) and modeled as a continuous variable using the mean exposure, weighted by PYAR, in each exposure category.[14] Birth cohort (<1900, 1900-1909, 1910-1919, 1920-1929, and >1930), was used, in the absence of smoking information for all cohort members, as a surrogate for smoking. Additional covariates considered included sex, race, age, calendar-year, and time since first exposure (TSFE; <20, 20-39, and >40 years). For lung cancer, the underlying cause of death was used to define the response and the model form was based on a linear relative risk model that was similar to the 1986 U.S. Environmental Protection Agency lung cancer model.[15] In a previous analysis of this cohort, this model was found to best fit the lung cancer exposure-response. [8] Background incidence was modeled as a log (ln) linear function of the covariates (sex, race, birth cohort, age, and calendar year). Second-order interactions were assessed among the covariates in the baseline function. The predicted incidence rate (A) was modeled as the product of the background incidence (A0) and a linear function of cumulative exposure, i.e., A = A0 x (1 + pE10), where E10 represents cumulative exposure to chrysotile (fiber-years/ml, as measured by phase contrast microscopy) omitting any 5 Downloaded from oem.bmj.com on 16 August 2007 Table 1. Characteristics of the South Carolina asbestos textile workers cohort White males White females Non-white males Non-white females Total Total number of workers 1256 1244 551 21 3072 Vital status through 12-31-2001 Alive Dead, cause of death known Dead, cause of death unknown Lost to follow-up 373 (29.7%) 841 (67.0%) 27 (2.1%) 15 (1.2%) 339 (27.3%) 647 (52.0%) 50 (4.0%) 208 (16.7%) 129 (23.4%) 345 (62.6%) 39 (7.1%) 38 (6.9%) 5 (23.8%) 8 (38.1%) 4 (19.0%) 4 (19.0%) 846 (27.5%) 1841 (59.9%) 120 (3.9%) 265 (8.6%) Person-years at risk vital status through 2001 a vital status through 1990 b 49,409.8 43,898.8 49,163.9 43,743.8 19,180.9 17,406.1 758.0 674.6 118,512.6 105,723.3 Age at death, years median (range) 64.5 (18.1 - 95.8) 73.4 (22.6 - 101.0) 61.0 (22.1 - 96.5) 66.2 (47.5 - 90.0) 67.1 (18.1 - 101.0) Age at date last observed, years median (range) 66.6 (18.1 - 95.8) 74.1 (16.9 - 101.0) 63.3 (16.9 - 96.5) 72.8 (21.1 - 90.0) 68.8 (16.9 - 101.0) Cumulative exposure, fiber-years/ml median (range) 4.4 (0.1 - 699.8) 4.2 (0.2 - 317.1) 14.5 (0.4 - 682.7) 5.9 (0.5 - 216.0) 5.5 (0.1 - 699.8) Duration of employment, years median (range) 1.1 (0.1 - 46.8) 0.9 (0.1 - 43.7) 1.5 (0.1 - 43.8) 0.9 (0.1 - 30.9) 1.1 (0.1 - 46.8) a Length of follow-up through 2001. Person-years at risk was calculated from the later of (rate file begin date, date achieve 15 years of age, and date achieve 1 month of employment between January 1, 1940 and December 31, 1965) through the earlier of (date of death, study end date (31 December 2001), and date last observed to be alive). b Length of follow-up through 1990. 7 Downloaded from oem.bmj.com on 16 August 2007 The distribution of duration of employment was strongly right skewed with approximately half of the workers employed for 1 year or less (i.e., "short-term workers"). Short-term workers were more likely to have been hired during the World War II years of 1939-1945. Most of the short-term and many of the long-term workers hired during these years did not continue working at the plant after the war. Table 2 gives the results of the mortality analysis by race and sex based on the use of U.S. mortality rates. Mortality was elevated for all causes combined and all cancers. Among the a priori causes of interest, mortality from cancers of the digestive organs was not elevated, with the exception of excess mortality from esophageal cancer; mortality from cancers of the respiratory system was elevated, largely due to excess mortality from lung cancer; mortality from ischemic heart disease was elevated; and mortality from diseases of the respiratory system was elevated, particularly chronic obstructive pulmonary disease and pneumoconiosis and other respiratory diseases. These elevations persisted in subsequent analyses (not shown) in which South Carolina referent rates were used to generate expected numbers of deaths. When short-term workers were excluded, elevations in mortality from lung cancer (SMR 2.44, 95% CI 2.04-2.90) and pneumoconiosis and other respiratory diseases (SMR 7.07, 95% CI 5.49-8.97) persisted. 8 Downloaded from oem.bmj.com on 16 August 2007 Hypertension with heart disease Other diseases of the heart Other diseases of the circulatory system Hypertension without heart disease Cerebrovascular disease Diseases of the respiratory system Chronic obstructive pulmonary disease Asthma Pneumoconiosis and other respiratory diseases Asbestosis b Diseases of the digestive system Cirrhosis and other chronic liver diseases Diseases of the genitourinary system Diseases of the skin and subcutaneous tissue Diseases of the musculoskeletal system and connective tissue Symptoms and ill-defined conditions Accidents Transportation accidents Suicide Homicide Unknown cause Residual 12 2.25 * 28 1.28 65 1.46 ** 2 1.10 49 1.70 ** 84 2.00 ** 29 1.41 1 1.08 41 5.67 ** 20 172.5 ** 35 1.33 20 1.48 13 1.66 1 2.28 0 11 1.99 52 1.45 * 28 1.43 8 0.66 5 1.47 27 17 1.70 1.16 - 3.93 0.85 - 1.86 1.12 - 1.86 0.13 - 3.99 1.25 - 2.24 1.60 - 2.48 0.94 - 2.02 0.03 - 6.01 4.07 - 7.69 105.3 - 266.4 0.92 - 1.84 0.91 - 2.29 0.88 - 2.84 0.06 - 12.7 0.99 - 3.56 1.08 - 1.90 0.95 - 2.06 0.29 - 1.31 0.48 - 3.43 0.99 - 2.72 9 0.86 0.39 - 1.64 20 1.16 0.71 - 1.78 42 1.11 0.80 - 1.50 7 2.10 0.84 - 4.33 28 1.03 0.69 - 1.49 33 1.42 0.98 - 2.00 6 0.90 0.33 - 1.96 0 12 3.02 ** 1.56 - 5.28 4 129.5 ** 35.3 - 331.2 12 0.77 0.40 - 1.35 5 0.70 0.23 - 1.63 8 0.89 0.38 - 1.75 0 0 10 1.33 0.63 - 2.44 25 1.11 0.72 - 1.64 10 0.99 0.48 - 1.83 0 7 0.55 0.22 - 1.13 39 7 0.78 0.31 - 1.61 7 0.97 33 1.34 78 1.25 4 1.40 54 1.19 72 1.67 ** 26 1.36 0 32 4.94 ** 12 1500 ** 34 1.45 * 11 1.34 16 1.46 2 2.22 3 1.05 6 1.32 13 0.88 7 1.10 1 0.23 1 0.87 54 12 0.85 0.40 - 2.00 0.92 - 1.88 0.99 - 1.56 0.38 - 3.59 0.90 - 1.56 1.30 - 2.10 0.89 - 1.99 3.38 - 6.98 771.7 - 2611 1.00 - 2.03 0.67 - 2.39 0.84 - 2.38 0.27 - 8.00 0.22 - 3.08 0.48 - 2.87 0.47 - 1.51 0.44 - 2.27 0.01 - 1.29 0.02 - 4.83 0.44 - 1.49 28 23.0 1.22 0.81 - 1.76 81 63.7 1.27 * 1.01 - 1.58 185 145.0 1.28 ** 1.10 - 1.47 13 8.0 1.63 0.87 - 2.78 131 101.3 1.29 ** 1.08 - 1.53 189 108.4 1.74 ** 1.50 - 2.01 61 46.4 1.31 * 1.01 - 1.69 1 3.3 0.30 0.01 - 1.67 85 17.7 4.81 ** 3.84 - 5.94 36 0.2 232.5 ** 162.8 - 321.9 81 65.4 1.24 0.98 - 1.54 36 28.9 1.25 0.87 - 1.73 37 27.8 1.33 0.94 - 1.84 3 2.0 1.51 0.31 - 4.41 3 4.8 0.63 0.13 - 1.84 27 17.6 1.53 * 1.01 - 2.23 90 73.1 1.23 0.99 - 1.51 45 36.0 1.25 0.91 - 1.67 9 18.6 0.48 * 0.22 - 0.92 13 17.3 0.75 0.40 - 1.28 120 36 33.0 1.09 0.76 - 1.51 a O, observed number of deaths; SMR, standardized mortality ratio; CI, confidence interval; E, expected number of deaths (based on U.S. referent rates); MN, malignant neoplasm. b Observed deaths, SMRs and 95% CIs for asbestosis are for the time period 1960-2001 due to rate file restrictions. * two-sided p-value < 0.05. ** two-sided p-value < 0.01. 10 Downloaded from oem.bmj.com on 16 August 2007 Mortality was elevated from diabetes mellitus and diseases of the digestive system; these elevations persisted when South Carolina referent rates were used. Mortality was elevated based on U.S., but not South Carolina, referent rates for other diseases of the heart, other diseases of the circulatory system including cerebrovascular disease, and accidents. Reduced mortality was observed for cancer of the intestine (excluding the rectum) and suicide. Among white males, excess mortality was also observed for cirrhosis and other chronic liver diseases, particularly when South Carolina referent rates were used (SMR 1.88, 95% CI 1.15-2.91). Mortality from asbestosis was highly elevated based on U.S. referent rates (observed 36, expected 0.15, SMR 232.5, 95% CI 162.8-321.9) and remained highly elevated based on South Carolina referent rates (expected 0.33, SMR 108.2, 95% CI 75.8-149.8). A manual review of the death certificates identified three mesothelioma deaths, all among white males. Two of these have been described in a previous update of this cohort (Dement et al., 1994). The third mesothelioma death occurred in 1995, nearly 50 years after the employee began working in the mule spinning department for approximately 2.5 years. None of the deaths under the tenth revision of the ICD were due to mesothelioma. A mortality analysis among workers actively employed, which considered person time and deaths from the person-year begin date through termination of employment at the plant, indicated reduced mortality overall (63 deaths, SMR 0.59, 95% CI 0.46-0.76), however, excess mortality was observed for pneumoconiosis and other respiratory diseases (7 deaths, SMR 8.14, 95% CI 3.26-16.8). Mortality in the first year post termination of employment was elevated overall (59 deaths, SMR 4.36, 95% CI 3.32 5.63) and for all cancers combined (18 deaths, SMR 7.87, 95% CI 4.66-12.4) with much of the elevation was due to cancers of the digestive organs (4 deaths, SMR 6.63, 95% CI 1.81-17.0), lung cancer (11 deaths, SMR 21.6, 95% CI 10.8-38.7), and pneumoconiosis and other respiratory diseases (6 deaths, SMR 46.4, 95% CI 17.0-101); all of these deaths were among workers with cumulative exposure to chrysotile in excess of 10,000 fiberdays/ml. All of the lung cancer and pneumoconiosis deaths in the first year post termination of employment occurred more than 10 years since first exposure and 3 (out of 4) digestive organ cancer deaths occurred more than 20 years since first exposure. The results of the mortality analysis for lung cancer by cumulative exposure to chrysotile fibers are provided in Table 3. A majority (96%) of the 198 lung cancer deaths occurred 20 years or more after first exposure. Increasing trends in lung cancer SMRs with increasing cumulative exposure were observed for white males, non-white males, females and overall. Increasing and highly significant trends were also observed for lung cancer mortality in internal analyses using Poisson regression, which adjusted for sex, race, age and calendar-year. Results were similar and there was no improvement in model fit when a five- or ten-year lag was employed. RRs relative to the lowest cumulative exposure group were particularly elevated in the highest cumulative exposure category. The trend persisted when short-term workers were excluded from the analysis. 11 Downloaded from oem.bmj.com on 16 August 2007 DISCUSSION The primary focus of this update was to re-examine both mortality and the exposure-response relationships between cumulative exposure to chrysotile and mortality from lung cancer and asbestosis in the South Carolina asbestos textile workers cohort with an additional eleven years of follow-up. All cause mortality remained elevated, as was mortality from all cancers including esophageal and lung cancer, ischemic heart disease, pneumoconiosis and other respiratory diseases, diabetes, chronic obstructive pulmonary disease, and diseases of the digestive system. The number of deaths from mesothelioma is consistent with the results of other cohort mortality studies where workers were predominantly exposed to the chrysotile form of asbestos.[2,17] Increasing and highly statistically significant trends with increasing cumulative exposure were observed for both lung cancer and asbestosis, with 72 and 17 additional deaths since the last update, respectively. Standardized mortality ratios were elevated for lung cancer and pneumoconiosis and other respiratory diseases even among the lowest exposure group. Previous analyses of the exposure-response relation between chrysotile and lung cancer mortality in this cohort selected the linear relative risk model over other model forms and estimated the relative rate for cumulative chrysotile exposure (E, fiberyears/ml) to be (1 + 0.022 E) for a worker with 15-29 years of TSFE, (1 + 0.037 E) for a worker with 30-39 years of TSFE and (1 + 0.011 E) for a worker with 40 or more years of TSFE. [8] Using the updated data, and employing a 10-year lag on cumulative exposure, the relative rate was estimated to be (1 + 0.020 E10); however, there was no evidence of an interaction between TSFE and exposure. Previous analysis of the exposure-response relation between chrysotile and mortality from asbestosis in this cohort selected the power model over other model forms and estimated the relative rate for cumulative chrysotile exposure (E, fibers-years/ml) to be equal to (E + 0.5) 1'3/(0.5)1'3.[8] The power model, which fit the data better than other models tested (results not shown), is still a reasonable model for asbestosis mortality in this cohort, but was improved by adding an interaction with age. Smoking information on the cohort is limited. The U.S. Public Health Service administered surveys to active workers in 1964 and again to active workers in 1971. These surveys indicated that, compared to the U.S. population in 1965, smoking prevalence among white males (n = 292) was similar to the prevalence among U.S. white males; however, prevalence among non-white males (n = 113) was lower than the prevalence among U.S. non-white males and prevalence among white females (n = 124) was higher than the prevalence among U.S. white females.[7] The strong exposureresponse patterns observed for lung cancer is unlikely to be fully explained by uncontrolled confounding by smoking since these analyses were conducted within the cohort and smoking is unlikely to vary by level of asbestos exposure. In a study examining the potential for tobacco and alcohol to confound the relationship between laryngeal cancer and metal working fluids, Kriebel et al. concluded that, for large studies, systematic or chance differences in smoking and drinking habits among the exposure groups are unlikely to cause more than a 17% change in the relative risk.[18] Smoking prevalence in the U.S. is related to sex, race, education and birth cohort.[19, 20] In the absence of smoking information, others have used birth year or birth cohort as a surrogate for smoking.[21] Birth cohort, however, was neither an effect modifier nor a confounder in our models of lung cancer with cumulative exposure. In our models of asbestosis 21 Downloaded from oem.bmj.com on 16 August 2007 asbestosis.[25] Plans are underway for the re-analysis of this cohort using an updated JEM based on a transmission electron microscopy analysis of the air samples that considers the size distribution of the fibers in addition to the number of fibers. In conclusion, this study confirms the findings from previous investigations of excess mortality from lung cancer and asbestosis and a strong exposure-response relationship between exposure to chrysotile and mortality from lung cancer and asbestosis. DISCLAIMER The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health. ACKNOWLEDGEMENTS The authors express their appreciation to Ms. Christine M. Gersic for her assistance with the data files. Figure 1. Estimated lung cancer mortality for white males, 60-64 years of age as a function of cumulative exposure to chrysotile (10 year lag) based on the model described in Table 5 (linear relative risk model - solid curve; restricted cubic spline model - dashed curve; categorical model - step function). Figure 2. Estimated asbestosis mortality for white males, 60-74 years of age, and born in 1920 or later as a function of cumulative exposure to chrysotile based on the model described in Table 6 (power model - solid curve; restricted cubic spline model - dashed curve; categorical model - step function). REFERENCES 1 McDonald JC, McDonald AD. Chrysotile, tremolite and carcinogenicity. Ann Occup Hyg 1997 ;41 (6):699-705. 2 Stayner LT, Dankovic DA, Lemen RA. Occupational exposure to chrysotile asbestos and cancer risk: a review of the amphibole hypothesis. Am JPublic Health 1996;86(2):179-86. 3 Landrigan PJ, Nicholson WJ, Suzuki Y, et al. The hazards of chrysotile asbestos: a critical review. Ind Health 1999;37(3):271-80. 4 Yano E, Wang Z, Wang X, et al. Cancer mortality among workers exposed to amphibole-free chrysotile asbestos. Am J Epidemiol 2001;154(6):538-43. 5 Dement JM, Harris RL Jr, Symons MJ, et al. Exposures and mortality among chrysotile asbestos workers. Part II: Mortality. Am J Ind Med 1983;4(3):421-33. 6 Brown DP, Dement JM, Okun A. Mortality patterns among female and male chrysotile asbestos textile workers. J Occup Med 1994;36(8):882-8. 7 Dement JM, Brown DP, Okun A. Follow-up study of chrysotile asbestos textile workers: cohort mortality and case-control analyses. Am J Ind Med 1994;26 (4):431-47. 23