Exposure-response of silicosis mortality in Swedish iron ore miners

OBJECTIVES: To assess the exposure-response relationship between exposure to quartz and fatal silicosis. METHODS: The mortality from silicosis in 7729 miners was analyzed and compared to their estimated exposure to respirable quartz. The miners had been working as a miner for at least 1 year between 1923 and 1996. Their mortality between 1952 and 2001 was studied by using information from the national cause of death register. Both underlying and contributing causes of death were considered in the analysis. The exposure to quartz was estimated from job titles and using 3239 measurements of personal exposure to respirable quartz from 1965 to 1999. The mortality rates were adjusted to attained age and years of birth using a Poisson regression. RESULTS: The median cumulative exposure among the 7729 miners was 0.9 mg x years m(-3). There were 58 deaths from silicosis. Their median cumulative exposure was 4.8 mg x years m(-3). The crude mortality rate was 53 cases per 100,000 person-years with an exposure-response relationship. CONCLUSION: There seems to be an increased risk of fatal silicosis at exposure levels around 3 mg x years m(-3) for respirable quartz.     

Development of quantitative exposure data for a pooled exposure-response analysis of 10 silica cohorts

BACKGROUND: Comprehensive quantitative silica exposure estimates over time, measured in the same units across a number of cohorts, would make possible a pooled exposure-response analysis for lung cancer. Such an analysis would help clarify the continuing controversy regarding whether silica causes lung cancer. METHODS: Existing quantitative exposure data for 10 silica-exposed cohorts were retrieved from the original investigators. Occupation- and time-specific exposure estimates were either adopted/adapted or developed for each cohort, and converted to milligram per cubic meter (mg/m(3)) respirable crystalline silica. RESULTS: Quantitative exposure assignments were typically based on a large number (thousands) of raw measurements, or otherwise consisted of exposure estimates by experts (for two cohorts). Median exposure level of the cohorts ranged between 0.04 and 0.59 mg/m(3) respirable crystalline silica. Exposure estimates were partially validated via their successful prediction of silicosis in these cohorts. CONCLUSIONS: Existing data were successfully adopted or modified to create comparable quantitative exposure estimates over time for 10 silica-exposed cohorts, permitting a pooled exposure-response analysis. The difficulties encountered in deriving common exposure estimates across cohorts are discussed.     

Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts

BACKGROUND: Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear. OBJECTIVE: We studied the relation between the intake of antioxidant vitamins and CHD risk. DESIGN: A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were free of CHD at baseline. RESULTS: Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P=0.17) and 1.23 (1.04, 1.45; P=0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend <0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk. CONCLUSIONS: The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small.     

The association between leisure-time physical activity,low HDL-cholesterol and mortality in a pooled analysis of nine population-based cohorts

The objective of this study was to investigate associations between leisure-time physical activity, low high-density lipoprotein cholesterol (HDL-C) and mortality. Self-reported leisure-time physical activity, HDL-C concentration, and mortality were assessed in 37,059 adults in Health Survey for England and Scottish Health Survey. Meeting physical activity guidelines was defined as ≥150 min wk^?1 of moderate-intensity activity, ≥75 min wk^?1 of vigorous-intensity activity, or equivalent combinations. Low HDL-C was defined as <1.03 mmol L^?1. Cox proportional hazard models were adjusted for age, sex, smoking, total cholesterol, systolic blood pressure, body mass index, longstanding illness, and socioeconomic status. There were 2250 deaths during 326,016 person-years of follow-up. Compared with those who met physical activity guidelines and whose HDL-C was normal (reference group), all-cause mortality risk was not elevated in those who met physical activity guidelines and whose HDL-C concentration was low (hazard ratio: 1.07; 95% confidence interval: 0.75, 1.53). Compared with the reference group, all-cause mortality risk was elevated in those who did not meet physical activity guidelines and whose HDL-C was normal (1.37; 1.16, 1.61), and in those who did not meet physical activity guidelines and whose HDL-C was low (1.65; 1.37, 1.98). Cardiovascular disease mortality hazard ratios were similar, although confidence intervals were wider. There was no statistically significant evidence of biological interaction between physical inactivity and low HDL-C. This novel study supports the notion that leisure-time physical activity be recommended in those with low HDL-C concentration who may be resistant to the HDL-raising effect of exercise training.     

Exposure to silica and silicosis among tin miners in China: exposure-response analyses and risk assessment

OBJECTIVES—To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust).
METHODS—A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker''s work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III—similar to an International Labour Organisation (ILO) classification of 1/1 or greater.
RESULTS—There were 1015 (33.7%) miners identified with silicosis, who had a mean age of 48.3 years, with a mean of 21.3 years after first exposure (equivalent to 11.0 net years in a dusty job). Among those who had silicosis, 684 miners (67.4%) developed silicosis after exposure ended (a mean of 3.7 years after). The risk of silicosis was strongly related to cumulative exposure to silica dust and was well fitted by the Weibull distribution, with the risk of silicosis less than 0.1% when the Chinese measure of cumulative exposure to total dust (CTD) was under 10 mg/m³-years (or 0.36 mg/m³-years of respirable crystalline silica), increasing to 68.7% when CTD exposure was 150 mg/m³-years (or 5.4 mg/m³-years of respirable crystalline silica). Latency period was not correlated to the risk of silicosis or cumulative dose of exposure. This study predicts about a 36% cumulative risk of silicosis for a 45 year lifetime exposure to these tin mine dusts at the CTD exposure standard of 2 mg/m³, and a 55% risk at 45 years exposure to the current United States Occupational Safety and Health Administration and Mine Safety and Health Administration standards of 0.1 mg/m³ 100% respirable crystalline silica dust.
CONCLUSIONS—A clear exposure-response relation was detected for silicosis in Chinese tin miners. The study results were similar to most, but not all, findings from other large scale exposure-response studies.


     

Exposure-response analysis of mortality among coal miners in the United States

The quantitative relationship between exposure to respirable coal mine dust and mortality from nonmalignant respiratory diseases was investigated in a study of 8,878 working male coal miners who were medically examined from 1969 to 1971 and followed to 1979. Exposure-related mortality was evaluated using Cox proportional hazards modeling for underlying or contributing causes of death and modified lifetable methods for underlying causes. For pneumoconiosis mortality, the lifetable analyses showed increasing standardized mortality ratios (SMRs) with increasing cumulative exposure category. Significant exposure-response relationships for mortality from pneumoconiosis (P < 0.001) and from chronic bronchitis or emphysema (P < 0.05) were observed in the proportional hazards models after controlling for age and smoking. No exposure-related increases in lung cancer or stomach cancer were observed. Pneumo coniosis mortality was found to vary significantly by the rank of coal dust to which miners were exposed. Miners exposed at or below the current U.S. coal dust standard of 2 mg/m³ over a working lifetime, based on these analyses, have an elevated risk of dying from pneumoconiosis or from chronic bronchitis or emphysema.     

Crystalline silica exposure and lung cancer mortality in diatomaceous earth industry workers: a quantitative risk assessment

OBJECTIVE—To use various exposure-response models to estimate the risk of mortality from lung cancer due to occupational exposure to respirable crystalline silica dust.
METHODS—Data from a cohort mortality study of 2342 white male California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly cristobalite) were reanalyzed with Poisson regression and Cox's proportional hazards models. Internal and external adjustments were used to control for potential confounding from the effects of time since first observation, calendar time, age, and Hispanic ethnicity. Cubic smoothing spline models were used to assess the fit of the models. Exposures were lagged by 10 years. Evaluations of the fit of the models were performed by comparing their deviances. Lifetime risks of lung cancer were estimated up to age 85 with an actuarial approach that accounted for competing causes of death.
RESULTS—Exposure to respirable crystalline silica dust was a significant predictor (p<0.05) in nearly all of the models evaluated and the linear relative rate model with a 10 year exposure lag seemed to give the best fit in the Poisson regression analysis. For those who died of lung cancer the linear relative rate model predicted rate ratios for mortality from lung cancer of about 1.6 for the mean cumulative exposure to respirable silica compared with no exposure. The excess lifetime risk (to age 85) of mortality from lung cancer for white men exposed for 45 years and with a 10 year lag period at the current Occupational Safety and Health Administration (OSHA) standard of about 0.05 mg/m³ for respirable cristobalite dust is 19/1000 (95% confidence interval (95% CI) 5/1000 to 46/1000).
CONCLUSIONS—There was a significant risk of mortality from lung cancer that increased with cumulative exposure to respirable crystalline silica dust. The predicted number of deaths from lung cancer suggests that current occupational health standards may not be adequately protecting workers from the risk of lung cancer.


Keywords: crystalline silica; cristobalite; lung cancer     

Cancer risk in oil refinery workers: a pooled mortality study in Italy

Background:Oil refinery workers are exposed to several well-established carcinogens and working in this type of industry has been classified by IARC as probable carcinogen to humans (Group 2A).Objectives:To examine the mortality experience of workers employed in four Italian oil refineries.Methods:The cohort included 5112 male workers ever employed between 1949 and 2011. The average follow-up period was 49 years. Standardized mortality ratios (SMR) and 95% Confidence Intervals (CI) were calculated using as reference age-gender-calendar specific regional rates. Analyses by duration of employment and latency were performed.Results:In the whole cohort, pleural cancer (6 deaths, SMR 1.59; 95% CI 0.71-3.53), brain cancer (14 deaths, SMR 1.47; 95% CI 0.87-2.49) and lymphatic leukemia (LL) (8 deaths, SMR 1.81; 95% CI 0.91-3.62) showed increased risks. All pleural cancers occurred after 10 years of latency and the highest risk was observed among workers with duration ≥20 years; the brain cancer excess was confined in the shortest duration and latency. The LL (and chronic lymphatic leukemia in particular) excess regarded workers with latency and duration longer than 20 years. Four deaths from acute myeloid leukemia (AML) were observed and all occurred after 20 years of latency (SMR 1.55, 95% CI 0.58-4.12); a two-fold-increased risk was observed in the longest duration. No increased risk for skin cancer has been observed in our study population.Conclusion:Our findings are consistent with recent evidence of an increased mortality from pleural and hematopoietic malignancies (AML and LL) among oil refinery workers. However, the lack of individual quantitative exposure data and the small number of observed events prevent the identification of the possible causal role of individual chemicals, including benzene, especially at the current very low exposure levels.Key words: Cohort study, cancer mortality, benzene, petrochemical industry, standardized mortality ratios     

Exposures to silica mixed dust and cohort mortality study in tin mines: exposure-response analysis and risk assessment of lung cancer

BACKGROUND: Mineral dusts that contain crystalline silica have been associated directly or indirectly with the development of pneumoconiosis or silicosis, non-malignant respiratory diseases, lung cancer, and other diseases. The health impacts on workers with silica mixed dust exposure in tin mines and dose-response relationships between cumulative dust exposure and the mortality from lung cancer are investigated. METHODS: A cohort of 7,837 workers registered in the employment records in 4 Chinese tin mines between 1972 and 1974 was identified for this study and the mortality follow-up was traced through 1994. Of the cohort, the cause of death was ascertained for 1,061 (97%) of the 1,094 deceased workers. Standardized mortality ratios (SMRs) were calculated for all workers, non-exposed workers, and dust-exposed workers with different exposure levels, silicotics, and non-silicotics based on Chinese national rates. RESULTS: The mortality from all causes in four tin mines was nearly the same as the national mortality. Malignant neoplasm, cerebrovascular disease, and cardiovascular disease accounted for 68.6% of all deaths. Mortality excess from lung cancer, liver cancer, all malignant diseases, and non-malignant respiratory diseases was observed among dust-exposed workers; a 50-fold excess of pneumoconiosis was observed. There was an upward trend for SMRs of lung cancer was noted from no exposure to low, medium, and high exposure levels (SMRs=1.29, 2.65, 2.66, 3.33). The shape of the exposure-response curve for risk of lung cancer at high exposure levels was inconsistent in these four mines. CONCLUSIONS: The findings indicated a positive dose-response relation between exposure to cumulative dust and the mortality of lung cancer. High arsenic content in dust particles, together with crystalline silica, may play an important role in causing increased mortality from lung cancer.     

Exposure to crystalline silica, silicosis, and lung disease other than cancer in diatomaceous earth industry workers: a quantitative risk assessment

Objectives: To estimate excess lifetime risk of (a) mortality from lung disease other than cancer (LDOC), and, (b) onset of radiographic silicosis, arising from occupational exposure to respirable crystalline silica dust.

Methods: Data from a cohort of California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly as cristobalite) were reanalyzed with Poisson regression methods with internal and external adjustments for potential confounding by calendar time, age, smoking, Hispanic ethnicity, and time since first observation. Model fit was evaluated by comparing deviances and fitting cubic spline models. Lifetime risks of death from LDOC and radiographic silicosis were estimated up to age 85 with an actuarial approach accounting for competing causes of death.

Results: For deaths due to LDOC, a linear relative rate model gave the best fit in Poisson regression analyses. At the mean cumulative exposure of LDOC cases to silica, after adjustment for smoking, the estimated rate ratio was 4.2 (p<0.0001); at the maximum cumulative exposure of cases, the rate ratio was 18.4. The excess lifetime risk for white men exposed to respirable cristobalite dust for 45 years at the current permissible exposure limit (PEL; about 0.05 mg/m³) of the Occupational Safety and Health Administration was 54/1000 (95% confidence interval (95% CI) 17 to 150). For 70 incident cases of radiographic silicosis largely manifest before the end of employment, the best fit was also the linear relative rate model, predicting a rate ratio of 25.6 for silicosis at the mean cumulative exposure of the cases (p<0.0001). The excess lifetime risk for silicosis at the current PEL was 75/1000.

Conclusion: Current occupational health standards for crystalline silica permit risks of lung disease other than cancer far in excess of what is usually considered acceptable by the Occupational Safety and Health Administration (a lifetime risk of less than one in a thousand deaths).

     

Fine particulate matter and mortality: a comparison of the six cities and American Cancer Society cohorts with a medicare cohort

BACKGROUND: The American Cancer Society study and the Harvard Six Cities study are 2 landmark cohort studies for estimating the chronic effects of fine particulate air pollution (PM2.5) on mortality. Using Medicare data, we assessed the association of PM2.5 with mortality for the same locations included in these studies. METHODS: We estimated the chronic effects of PM2.5 on mortality for the period 2000-2002 using mortality data for cohorts of Medicare participants and average PM2.5 levels from monitors in the same counties included in the 2 studies. We estimated mortality risk associated with air pollution adjusting for individual-level (age and sex) and area-level covariates (education, income level, poverty, and employment). We controlled for potential confounding by cigarette smoking by including standardized mortality ratios for lung cancer and chronic obstructive pulmonary disease. RESULTS: Using the Medicare data, we estimated that a 10 microg/m increase in the yearly average PM2.5 concentration is associated with 10.9% (95% confidence interval = 9.0-12.8) and with 20.8% (14.8-27.1) increases in all-cause mortality for the American Cancer Society and Harvard Six Cities study counties, respectively. The estimates are somewhat higher than those reported by the original investigators. CONCLUSION: Although Medicare data lack information on some potential confounding factors, we estimated risks similar to those in the previously published reports, which incorporated more extensive information on individual-level confounders. We propose that the Medicare files can be used to construct on-going cohorts for tracking the risk of air pollution over time.     

Significance of genetic information in risk assessment and individual classification using silicosis as a case model

Over the last decade the role of genetic data in epidemiological research has expanded considerably. We recently published a case-control study that evaluated the interaction between silica exposure and minor variants in the genes coding for interleukin-1alpha (IL-1alpha), interleukin-1 receptor antagonist (IL-1RA) and tumor necrosis factor alpha (TNFalpha) as risk factors associated with silicosis, a fibrotic lung disease. In contrast, this report uses data generated from these studies to illustrate the utility of genetic information for the purposes of risk assessment and clinical prediction. Specifically, this study will address how, given a known exposure, genetic information affects the characterization of risk groups. Relative operating characteristic (ROC) curves were then used to determine the impact of genetic information on individual classification. Logistic regression modeling procedures were used to estimate the predicted probability of developing silicosis. This probability was then used to construct predicted risk deciles, first for a model with occupational exposure only and then for a model containing occupational exposure and genetic main effects and interactions. Results indicate that the exposure-only model effectively captures an increasing relationship between predicted risk deciles and prevalence of observed silicosis cases. Individuals comprising the highest risk decile were almost four times as likely to have silicosis as opposed to the lowest risk decile. The addition of genetic data, however, substantially improved characterization of risk categories; the proportion of cases in the highest risk decile was almost eight times that in the lowest risk decile. However, the ROC curve and classification analysis demonstrated that the addition of genetic main effects and interactions did not significantly impact on prediction of the individual's case status. These results indicate that genetic information plays a valuable role in effectively characterizing risk groups and mechanisms of disease operating in a substantial proportion of the population. However, in the case of fibrotic lung disease caused by silica exposure, information about the presence or absence of the minor variants of IL-1alpha, IL-1RA and TNFalpha is unlikely to be a useful tool for individual classification.     

Risk of silicosis in cohorts of Chinese tin and tungsten miners and pottery workers (II): Workplace-specific silica particle surface composition

BACKGROUND: It is hypothesized that surface occlusion by alumino-silicate affects the toxic activity of silica particles in respirable dust. In conjunction with an epidemiological investigation of silicosis disease risk in Chinese tin and tungsten mine and pottery workplaces, we analyzed respirable silica dusts using a multiple-voltage scanning electron microscopy-energy dispersive X-ray spectroscopy (MVSEM-EDS). METHODS: Forty-seven samples of respirable sized dust were collected on filters from 13 worksites and were analyzed by MVSEM-EDS using high (20 keV) and low (5 keV) electron beam accelerating voltages. Changes in the silicon-to-aluminum X-ray line intensity ratio between the two voltages are compared particle-by-particle with the 90th percentile value of the same measurements for a ground glass homogeneous control sample. This provides an index that distinguishes a silica particle that is homogeneously aluminum-contaminated from a clay-coated silica particle. RESULTS: The average sample percentages of respirable-sized silica particles alumino-silicate occlusion were: 45% for potteries, 18% for tin mines, and 13% for tungsten mines. The difference between the pottery and the metal mine worksites accounted for one third of an overall chi-square statistic for differences in change in measured silicon fraction between the samples. CONCLUSION: The companion epidemiological study found lower silicosis risk per unit cumulative respirable silica dust exposure for pottery workers compared to metal miners. Using these surface analysis results resolves differences in risk when exposure is normalized to cumulative respirable surface-available silica dust.     

Infant mortality in Pelotas, Brazil: a comparison of risk factors in two birth cohorts.

OBJECTIVES: To compare two population-based birth cohorts to assess trends in infant mortality rates and the distribution of relevant risk factors, and how these changed after an 11-year period. METHODS: Data from two population-based prospective birth cohorts (1982 and 1993) were analyzed. Both studies included all children born in a hospital (> 99% of all births) in the city of Pelotas, Southern Brazil. Infant mortality was monitored through surveillance of all maternity hospitals, mortality registries and cemeteries. RESULTS: There were 5,914 live-born children in 1982 and 5,249 in 1993. The infant mortality rate decreased by 41%, from 36.0 per 1,000 live births in 1982 to 21.1 per 1,000 in 1993. Socioeconomic and maternal factors tended to become more favorable during the study period, but there were unfavorable changes in birthweight and gestational age. Poverty, high parity, low birthweight, preterm delivery, and intrauterine growth restriction were the main risk factors for infant mortality in both cohorts. The 41% reduction in infant mortality between 1982 and 1993 would have been even greater had the prevalence of risk factors remained constant during the period studied here. CONCLUSIONS: There were impressive declines in infant mortality which were not due to changes in the risk factors we studied. Because no reduction was seen in the large social inequalities documented in the 1982 cohort, it is likely that the reduction in infant mortality resulted largely from improvements in health care.     

某金矿作业农民工矽肺及死亡调查

目的了解某金矿农民工职业病危害状况，为防止职业病危害发生提供依据。方法用统一的调查表由专业人员对贵州省某县到过广西某金矿务工的人员进行逐个走访。结果306名金矿粉碎作业工中，发现矽肺34例，矽肺的Ⅰ期、Ⅱ期和Ⅲ期患者数分别为17、11和6人；患者最小年龄22岁，最短接尘工龄7个月；其中Ⅱ、Ⅲ期矽肺的越期诊断率41．18％。调查对象中死亡13人，其中仅1人在职业病防治机构作过检查，并确诊为Ⅲ期矽肺。结论改善农民工的工作环境，宣传和普及职业卫生知识，建立农民工职业病保障体制是亟须解决的问题。     

Dietary carotenoids and risk of colorectal cancer in a pooled analysis of 11 cohort studies

Dietary carotenoids have been hypothesized to protect against epithelial cancers. The authors analyzed the associations between intakes of specific carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene) and risk of colorectal cancer using the primary data from 11 cohort studies carried out in North America and Europe. Carotenoid intakes were estimated from food frequency questionnaires administered at baseline in each study. During 6-20 years of follow-up between 1980 and 2003, 7,885 incident cases of colorectal cancer were diagnosed among 702,647 participants. The authors calculated study-specific multivariate relative risks and then combined them using a random-effects model. In general, intakes of specific carotenoids were not associated with colorectal cancer risk. The pooled multivariate relative risks of colorectal cancer comparing the highest quintile of intake with the lowest ranged from 0.92 for lutein + zeaxanthin to 1.04 for lycopene; only for lutein + zeaxanthin intake was the result borderline statistically significant (95% confidence interval: 0.84, 1.00). The associations observed were generally similar across studies, for both sexes, and for colon cancer and rectal cancer. These pooled data did not suggest that carotenoids play an important role in the etiology of colorectal cancer.