Eva Hnizdo

Pooled exposure–response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study

AbstractObjectives: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure–response data. We have conducted a pooled exposure–response analysis of 10 silica-exposed cohorts to investigate lung cancer. Methods: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m3) across cohorts. Results: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0, 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m3 respirable crystalline silica (the permissible level in many countries) was 1.1–1.7%, above background risks of 3–6%. Conclusions: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure–response analysis and risk assessment for silica using data from multiple studies.

Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment.

BACKGROUND A study was undertaken to establish the chronic effect of initial and recurrent treated pulmonary tuberculosis on impairment of lung function. METHODS A total of 27 660 black South African gold miners who had reliable pulmonary function tests from January 1995 to August 1996 were retrospectively followed for the incidence of pulmonary tuberculosis to 1970. The lung function measurements in 1995–6 were related to the number of previous episodes of tuberculosis and to the time that had lapsed from the diagnosis of the last episode of tuberculosis to the lung function test. Miners without tuberculosis or pneumoconiosis served as a comparison group. RESULTS There were 2137 miners who had one episode of tuberculosis, 366 who had two, and 96 who had three or more episodes. The average time between the diagnosis of the last episode of tuberculosis and the lung function test was 4.6 years (range one month to 31 years). The loss of lung function was highest within six months of the diagnosis of tuberculosis and stabilised after 12 months when the loss was considered to be chronic. The estimated average chronic deficit in forced expiratory volume in one second (FEV1) after one, two, and three or more episodes of tuberculosis was 153 ml, 326 ml, and 410 ml, respectively. The corresponding deficits for forced vital capacity (FVC) were 96 ml, 286 ml, and 345 ml. The loss of function due to tuberculosis was not biased by the presence of HIV as HIV positive and HIV negative subjects had similar losses. The percentage of subjects with chronic airflow impairment (FEV1 <80% predicted) was 18.4% in those with one episode, 27.1% in those with two, and 35.2% in those with three or more episodes of tuberculosis. CONCLUSIONS Tuberculosis can cause chronic impairment of lung function which increases incrementally with the number of episodes of tuberculosis. Clearly, prevention of tuberculosis and its effect on lung function is important and can be achieved by early detection and by reduction of the risk of tuberculosis through intervention on risk factors such as HIV, silica dust exposure, silicosis, and socioeconomic factors.

Risk of pulmonary tuberculosis relative to silicosis and exposure to silica dust in South African gold miners.

OBJECTIVES: To investigate the following questions. (1) Is silica dust on its own, without the presence of silicosis, associated with an increased risk of pulmonary tuberculosis (PTB) in workers exposed to silica dust? (2) In the absence of silicosis is the excess risk dose related? (3) What is the predominant chronological sequence between the development of PTB and the development of silicosis after the end of exposure to dust? METHODS: A cohort of 2255 white South African gold miners has been followed up from 1968 to 1971, when they were 45-55 years of age, to 31 December 1995 for the incidence of PTB. During the follow up 1592 (71%) men died. Of these, 1296 (81%) had a necropsy done at the National Centre for Occupational Health (NCOH) to determine the presence of silicosis and PTB. The incidence of PTB in the cohort was studied relative to cumulative exposure to dust and the onset of silicosis. For the miners with necropsy, the incidence for PTB was studied relative to the severity of silicosis found at necropsy. RESULTS: There were 115 subjects who developed PTB. The total person-years of follow up was 39,319. For the whole cohort, the factors associated with increased risk of PTB were cumulative exposure to dust (mg/m3.y) (the adjusted rate ratio (RR) 1.07; (95% confidence interval (95% CI) 1.04 to 1.10)), silicosis diagnosed radiologically (3.96 (2.59 to 6.06)), and tobacco pack-years (1.02 (1.01 to 1.03)). The RR (95% CI) for PTB increased with increasing quartiles of cumulative exposure to dust 1.0, 1.51 (0.78 to 2.91), 2.35 (1.28 to 4.32), and 3.22 (1.75 to 5.90). In miners who did not have radiologically diagnosed silicosis (n = 1934, PTB = 74), the adjusted RR (95% CI) for PTB and cumulative exposure to dust was 1.10 (1.06 to 1.13), and increased with quartiles of cumulative exposure to dust as 1.00, 1.46 (0.70 to 3.03), 2.67 (1.37 to 5.23), and 4.01 (2.04 to 7.88). For the subjects who had a necropsy (n = 1296, PTB = 70), the adjusted RR (95% CI) for PTB increased with the severity of silicosis found at necropsy; 1.0 for no silicosis, 1.88 (0.97 to 3.64) for negligible, 2.69 (1.35 to 5.37) for slight, and 2.30 (1.16 to 4.58) for moderate or marked silicosis. For subjects who had a necropsy and no silicosis (n = 577, PTB = 18), the adjusted RR (95% CI) increased slightly with quartiles of cumulative dust 1.0, 1.11 (0.31 to 4.00), 1.42 (0.43 to 4.72), and 1.38 (0.33 to 5.62). CONCLUSION: Exposure to silica dust is a risk factor for the development of PTB in the absence of silicosis, even after exposure to silica dust ends. The risk of PTB increases with the presence of silicosis, and in miners without radiological silicosis, with quartiles of exposure to dust. The severity of silicosis diagnosed at necropsy was associated with increasing risk of PTB and even < 5 nodules--that is, undetectable radiologically--was associated with an increased risk of PTB. The diagnosis of PTB was on average 7.6 years after the end of exposure to dust, at around 60 years of age. The onset of radiological silicosis preceded the diagnosis of PTB in 90.2% of the cases with PTB who had silicosis. The results have implications for medical surveillance of workers exposed to silica dust after the end of exposure.

Case Definitions for Chronic Obstructive Pulmonary Disease

The objective of this study was to evaluate the definitions for classification of chronic obstructive pulmonary disease (COPD) recommended by the American Thoracic Society (ATS) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Using data from the U.S. population-based third National Health and Nutrition Examination Survey (NHANES III), we compared the number of individuals in the U.S. population who met definitions of airflow obstruction based on the fixed ratio of FEV1/FVC < 0.70 criterion and on the ATS lower 95% confidence limit (lower limits of normal LLN) criterion. Further, we evaluated the definitions in the context of physician-diagnosed obstructive airways diseases and respiratory symptoms. In comparison to the FEV1/FVC < LLN and FEV1 < 100% predicted definition, the fixed ratio-based definition for mild COPD underestimates airflow obstruction by 29% in 20–49-year-olds and overestimates it by 58% in 50–80-year-olds. In comparison to the FEV1/FVC < LLN and FEV1 < LLN definition, the fixed ratio-based definition for moderate COPD underestimates airflow obstruction by 31% in 20–49-year-olds and overestimates it by 37% in 50–80 year olds. Based on our estimation, approximately 0.9 million (26%) of symptomatic individuals out of the 3.6 million U.S. adults aged 20–49 years who have airflow obstruction (FEV1/FVC < LLN and FEV1 < LLN definition) may have undiagnosed respiratory disease. In conclusion, using the FEV1/FVC < 0.70 criterion will substantially under-diagnose airway obstruction in younger individuals and substantially over-diagnose COPD in older individuals.

Long-Term Exposure to Silica Dust and Risk of Total and Cause-Specific Mortality in Chinese Workers: A Cohort Study

A retro-prospective cohort study by Weihong Chen and colleagues provides new estimates for the risk of total and cause-specific mortality due to long-term silica dust exposure among Chinese workers.

Silica exposure, silicosis, and lung cancer: a mortality study of South African gold miners.

The effects of exposure to gold mining dust with a high concentration of free silica and tobacco smoking on mortality from lung cancer was assessed in a sample of 2209 white South African gold miners who started mining exposure during 1936-43, and were selected for a study of respiratory disorders in 1968-71 when they were aged 45-54. The mortality follow up was from 1968-71 to 30 December 1986. The relative risk for the effect of dust cumulated to the start of the follow up period was estimated as 1.023 (95% confidence interval (CI) 1.005-1.042) for a unit of 1000 particle-years. The combined effect of dust and tobacco smoking was better fitted by the multiplicative model than the additive model, suggesting that the two exposures act synergistically. No association between lung cancer and silicosis of the parenchyma or pleura was found, but a positive association existed between silicosis of the hilar glands and lung cancer.

Estimating the U.S. prevalence of chronic obstructive pulmonary disease using pre- and post-bronchodilator spirometry: the National Health and Nutrition Examination Survey (NHANES) 2007–2010

BackgroundDuring 2007–2010, the National Health and Nutrition Examination Survey (NHANES) conducted a spirometry component which obtained pre-bronchodilator pulmonary lung function data on a nationally representative sample of US adults aged 6–79 years and post-bronchodilator pulmonary lung function data for the subset of adults with airflow limitation. The goals of this study were to 1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD) using pre-bronchodilator and post-bronchodilator spirometry measurements and fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine the potential impact of nonresponse on the estimates.MethodsThis analysis was limited to those aged 40–79 years who were eligible for NHANES pre-bronchodilator spirometry (n=7,104). Examinees with likely airflow limitation were further eligible for post-bronchodilator testing (n=1,110). Persons were classified as having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of normal (LLN) based on person’s age, sex, height, and race/ethnicity. Those without spirometry but self-reporting both daytime supplemental oxygen therapy plus emphysema and/or current chronic bronchitis were also classified as having COPD. The final analytic samples for pre-bronchodilator and post-bronchodilator analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively. To account for non-response, NHANES examination weights were adjusted to the eligible pre-bronchodilator and post-bronchodilator subpopulations.ResultsIn 2007–2010, using the fixed ratio criterion and pre-bronchodilator test results, COPD prevalence was 20.9% (SE 1.1) among US adults aged 40–79 years. Applying the same criterion to post-bronchodilator test results, prevalence was 14.0% (SE 1.0). Using the LLN criterion and pre-bronchodilator test results, the COPD prevalence was 15.4% (SE 0.8), while applying the same criterion to post-bronchodilator test results, prevalence was 10.2% (SE 0.8).ConclusionsThe overall COPD prevalence among US adults aged 40–79 years varied from 10.2% to 20.9% based on whether pre- or post-bronchodilator values were used and which diagnostic criterion (fixed ratio or LLN) was applied. The overall prevalence decreased by approximately 33% when airflow limitation was based on post-bronchodilator as compared to pre-bronchodilator spirometry, regardless of which diagnostic criterion was used.

COPD and occupational exposures: a case-control study.

Objective: Evidence demonstrates that occupational exposures are causally linked with chronic obstructive pulmonary disease (COPD). This case-control study evaluated the association between occupational exposures and prevalent COPD based on lifetime occupational history. Methods: Cases (n = 388) aged 45 years and older with COPD were compared with controls (n = 356), frequency matched on age, sex, and cigarette smoking history. Odds ratios for exposure to each of eight occupational hazard categories and three composite measures of exposure were computed using logistic regression. Results: Occupational exposures most strongly associated with COPD were diesel exhaust, irritant gases and vapors, mineral dust, and metal dust. The composite measures describing aggregate exposure to gases, vapors, solvents, or sensitizers (GVSS) and aggregate exposure to dust, GVSS, or diesel exhaust were also associated with COPD. In the small group of never-smokers, a similar pattern was evident. Conclusion: These population-based findings add to the literature linking occupational exposures to COPD.

Loss of lung function associated with exposure to silica dust and with smoking and its relation to disability and mortality in South African gold miners

The data from a lung function study on 2209 white 45-54 year old South African gold miners in 1968-71 and at a five year follow up examination, were analysed to establish the actual loss of lung function associated with exposure to silica dust and with smoking. Ex-smokers were excluded from the analysis. Of the remaining 1625 subjects, 1249 had the five year follow up test of lung function. The estimated excess loss of lung function for a 50 year old gold miner, associated with 24 years of underground dust exposure of an average respirable dust concentration of 0.30 mg m-3 (14.4 ghm-3) was 236 ml of FEV1 (95% confidence interval (95% CI 134-337) and 217 ml of FVC (95% CI 110-324). By comparison, the effect of smoking one packet of cigarettes a day over 30 years was associated with an estimated loss of 552 ml of FEV1 (95% CI 461-644) and 335 ml of FVC (95% CI 170-500). The cumulative dust exposure was not associated with the longitudinal loss of FEV1 or FVC when the initial FEV1 and FVC were adjusted in the models. According to the predicted values, however, gold miners appear to have a greater loss of lung function from 50 to 55 years of age than that predicted for a general population.

Combined effect of silica dust and tobacco smoking on mortality from chronic obstructive lung disease in gold miners.

A sample of 2209 white South African gold miners aged 45-54 between 1968-71, who started mining exposure during 1936-43, was investigated from 1968-71 to 30 December 1986. The effect of silica dust and tobacco smoking on mortality from chronic obstructive lung disease (COLD) was assessed. The relative risk (RR) for dust exposure before 1950 was estimated as 2.5 (95% confidence interval (CI) 1.5-4.2), for 10 units of 1000 particle-years. The combined effect of dust exposure before 1950 and years of cigarette smoking on mortality from COLD was best estimated by the multiplicative model, indicating that the two exposures act synergistically. All those that died of the disease were smokers. According to the estimates of attributable risk about 5% of the deaths from COLD were from the effect of dust, 34% were from smoking, and 59% were from the combined effect of dust and smoking. In conclusion, the results indicate that workers exposed to silica dust who smoke are at higher risk of dying from COLD than smokers not exposed to silica dust, as the two exposures act synergistically in causing COLD.