Cohort Mortality Study Of Workers With Long-Term Exposure To Silica Dust

Silica dust is a very common hazard to human. It is quite popular during the productions and processing in metal mines, refractory plant, pottery factories etc. The most serious outcome of long-term exposure to silica dust is developing silicosis. According to report of Chinese Ministry of Health in 2010, a total of 18,128 cases of occupational disease were reported in 2009, including 14,495 cases of pneumoconiosis (80%). About ninety two percent of the pneumoconiosis cases were silicosis or coal worker's pneumoconiosis (CWP). Pneumoconiosis, including silicosis, has become the most serious occupational disease in China. It not only has serious health effects on workers with exposure to silica dust, but also has long impact to limit the development of China's economy. Millions of workers, from either developing or developed countries, are in jobs where they could to be exposed to silica dust. For example, there are over 23,000,000 workers directly or indirectly exposed to silica dust in China, and over 10,000,000 in India, over 3,000,000 in Europe, over 1,700,000 in the United States. In order to minimize the health effects of silica dust, many countries all over the world have required that the concentration of silica dust should be under its occupational exposure limit, for example, the occupational exposure limit was set to 0.1mg/m3 by US occupational safety and health administration (OSHA).The health effects of silica dust have been studied since several decades before. It has been reported that long-term exposure to silica dust can not only cause silicosis, but also cause other diseases, including diseases of respiratory system (chronic obstructive pulmonary disease [COPD], etc.), infectious diseases (pulmonary tuberculosis, etc.), and lung cancer, etc. In 1997, a panel from the international agency for research on cancer (IARC) classified silica as a human carcinogen (group 1). However, the working group noted that the carcinogenicity in humans was not detected in all industrial circumstances studied and was perhaps dependent on the inherent characteristics of respirable silica or on external factors affecting its biological activity or distribution of its polymorphs. Since then, extensive studies, including cohort study, case-control study, meta-analysis and pooled analyses, have been conducted to explore the association between silica exposure and lung cancer risk. However, the results remain inconsistent. The number of either silicosis or workers exposed to silica dust in China is the largest worldwide, but there is no sufficient study data with large sample size and long-term follow up. The present study is to study the association of silica exposure and mortality risk on the basis of data of Chinese silica cohort.Lung cancer is the most common malignant neoplasm worldwide, and its incidence has been increasing year by year. Currently, lung cancer is the leading cause of death among all malignant neoplasms. Most epidemiological studies have consistently observed increased risk of lung cancer among silicotics, but detected no or slightly increased risks among non-silicotic subjects. Results from several meta-analyses also remain inconsistent. Furthermore, data on smoking were not considered in most studies, because the data were rather difficult to collect, especially in retrospective cohort studies. The biological interaction of silica exposure and smoking in lung cancer risk remains unclear, and some studies have suggested that the investigation is at the same stage asbestos was 20 years ago.Several studies have confirmed that the air pollution by particulate matter (PM) is associated with an increased risk of either mortality or incidence of cardiovascular diseases. However, only a few studies were conducted to learn the relationship between silica dust exposure and risk of cardiovascular diseases; furthermore, most of these studies were restricted to calculate standardized mortality ratio (SMR), which compared the mortality of silica-exposed workers with the general population. The results have limitations and remain inconsistent.In the late 1980s, a large cohort of silica-exposed workers from 29 Chinese mines and pottery factories was established by US National Cancer Institute and Tongji Medical University. The initial objective of this study was to study the relationship between silica, silicosis and lung cancer. The study included 74,040 workers who registered between 1960 and 1974 and had worked for at least one year. The cohort was retrospectively followed up to 1960 and prospectively followed up to the end of 2003. The present study aims to discuss the associations between silica exposure and risk of mortality from cardiovascular diseases, diseases of respiratory system, lung cancer, etc. This study includes three parts:Partâ… Mortality study of workers with long-term exposure to silica dustExtensive studies have been undertaken since several decades before. The results showed that silica dust could not only cause silicosis, but also cause other diseases, especially diseases of respiratory system. However, the health effects by long-term exposure to silica are not restricted to these diseases. Some studies showed that silica might be associated with increased risk of cardiovascular diseases;however, the association has not been confirmed by well-designed studies. To our best knowledge, the population attributable risk (PAR) of long-term exposure to silica has not been reported.This cohort study included 74,040 workers from 29 metal mines and pottery factories in south central China. It was retrospectively followed up to Jan 1,1960, and prospectively followed up until the end of 2003. During the follow-up, we collect the data on environmental monitoring in the workplace, the work history and vital status of each participant, etc. The cumulative exposure to silica dust was estimated by linking a job-exposure matrix (JEM) and participants' work histories. In comparison with the mortality of Chinese general population, we calculated the standardized mortality ratio (SMR) and its 95% confidence interval (CI). The Cox proportional-hazards model was used to estimate the hazard ratio (HR) and its 95% CI for levels of cumulative exposure to silica dust.With a median of 33.1 years of follow-up (2,306,428 person-years), we identified 19,516 deaths. The average age of participants when they entered the cohort was 27.2. A total of 49,309 (66.6%) participants were ever exposed to silica dust. The mortality of the entire cohort was 846.2 per 100,000 person-years, with 992.6 per 100,000 person-years among silica-exposed workers and 550.7 per 100,000 person-years among non-silica-exposed workers. The major causes of deaths for the entire cohort were cardiovascular diseases (4,425), diseases of respiratory system (4,309), malignant neoplasms (3,621), infectious diseases (3,401) and cerebrovascular diseases (2,662). Compared to the mortality of Chinese general population, elevated mortalities were observed for all causes of death, malignant neoplasm of nasopharynx, malignant neoplasm of liver and intrahepatic bile ducts, certain infectious and parasitic diseases, pulmonary tuberculosis, cardiovascular diseases, pulmonary heart disease, diseases of respiratory disease, pneumoconiosis. For workers exposed to silica dust, SMRs of all causes of deaths by different periods of follow up were all higher than 1, but decreased from 1974 to 2003. Elevated SMRs of malignant neoplasm of nasopharynx, certain infectious and parasitic diseases, pulmonary tuberculosis, cardiovascular diseases, pulmonary heart disease and diseases of respiratory system were observed in silicotics, compared to non-silicotic subjects. Significant exposure-response relationships were found between increasing levels of cumulative exposure to silica dust and increased risk of death from all causes, lung cancer, certain infectious and parasitic diseases (including pulmonary tuberculosis), cardiovascular diseases (including pulmonary heart disease) and diseases of respiratory system. According to the proportion of workers exposed to silica dust in the cohort, the population attributable risk of silica dust for deaths from all causes, diseases of respiratory system and cardiovascular diseases were estimated to be 19.3%,70.2% and 25.7% respectively.This study indicates that long-term exposure to silica dust were positively associated with increased risk of deaths from all causes, malignant neoplasms (including lung cancer), certain infectious and parasitic diseases (including pulmonary tuberculosis), cardiovascular diseases (including pulmonary heart disease), diseases of respiratory system and accidents. An estimated of 19.3 percent of workers in the cohort have been died due to exposure to silica dust.Partâ…¡Association study of long-term exposure to silica dust and cardiovascular mortalityA number of studies have reported that the air pollution by particulate matter (PM) is associated an increased risk of either incidence or mortality of cardiovascular diseases; however, the association between silica dust in air and risk of cardiovascular disease has not been well studied, and the results remain inconsistent. The first part of this study indicated that there were significant exposure-response relationship between long-term exposure to silica dust and mortality from cardiovascular diseases, but this part did not take smoking status and types of mine/factory into consideration. In this part, we conducted detailed exposure-response analyses to explore the relationship between silica dust and cardiovascular diseases, considering smoking and types of mine/factory.This study included 57,920 workers with detailed work history from 8 tungsten mines, 2 iron and copper mines,4 tin mines and 8 pottery factories. With a median of 32 years follow-up,16,622 deaths were reported, including 3,616 deaths from cardiovascular diseases (including 2,044 pulmonary heart disease) and 3,641 diseases of respiratory system (including 2,272 silicosis). Compared to the national mortality of cardiopulmonary diseases, elevated mortalities of diseases of respiratory system were observed for the entire cohort and 4 types of mine/factory. Mortality of cardiovascular diseases for tungsten mines and pottery factories significantly increased, but the mortality of ischaemic heart disease was found to be significantly lower than the national mortality. Mortality of cardiovascular diseases for iron and copper mines, tin mines were not different from the national mortality; however, the mortality of ischaemic heart diseases for iron and copper mines, and the mortality of pulmonary heart disease and hypertensive heart disease for tin mines significantly increased. The Cox proportional-hazards model showed that there was significant exposure-response relationship between cumulative exposure to silica dust and mortality of cardiovascular diseases (P<0.01). Compared to unexposed workers, the risk of cardiovascular diseases of workers with exposure to silica dust increased 94% for tungsten mines, and 1.42 for iron and copper mines. No associations were observed for tin mines and pottery factories (P>0.05). The risk of pulmonary heart diseases increased with elevated levels of exposure to silica dust for the entire cohort (P<0.01), with the highest for tungsten mines (hazard ratio,8.63; 95% CI,6.65-11.19;15-year lag). Significant exposure-response relationships between silica dust and diseases of respiratory system were found for the entire cohort and all types of mine/factory (P<0.01), with the highest hazard ratio in tin mines and the lowest in pottery factories. The Cox proportional-hazard models with penalized splines yielded similar results with the above categorical analyses.This part of study indicates that long-term exposure to silica dust is associated with elevated risk of diseases of respiratory system and cardiovascular diseases, but the associations varies from the 4 types of mine/factory, especially for cardiovascular diseases.Partâ…¢Association study of long-term exposure to silica dust and mortality from lung cancerThe association between silica and lung cancer continues to be inconsistent. The biological interaction between smoking and silica in lung cancer risk also remains unclear. This part was focus on exploring the relationship among silica, silicosis and lung cancer, and detecting if there were biological interactions between smoking and silica exposure in lung cancer risk. Participants without detailed data on work history and smoking were excluded in this part. Cumulative exposure to silica dust was estimated by linking a job-exposure matrix and the participants'work histories; data on smoking included smoking status and smoking amount (see details in Partâ… ). Cox proportional-hazards models with time-dependent variables were employed to estimate the hazard ratio and its 95% CI of cumulative exposure to silica dust. The relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP) and the synergy index (S) were calculated to evaluate the biological interaction between smoking and silica in lung cancer risk.This part included 44,461 workers,37,986 male. With a median 38.4 years of follow-up (1,705,223 person-years),13,597 deaths (including 877 lung cancer cases) were observed. The average duration of silica exposure was 19.0 years. About 62% of the study population was ever smokers.The Cox proportional-hazards model showed that lung cancer risk increased 47% for workers ever exposed to silica dust, compared workers who had never exposed to silica dust. The hazard ratios for tin mines, pottery factories and iron/copper mines were 1.96 (95%CI,1.39-2.76),1.673(95% CI,1.15-2.42) and 1.50 (95% CI,1.14-1.94), respectively, and there were significant exposure-response relationships (P< 0.05); no association between silica and lung cancer risk was found for tungsten mines. Presence of silicosis was estimated to increase 74% of the lung cancer risk for the entire cohort. The hazard ratios of presence of silicosis for iron/copper mines, tin mines and pottery factories were 2.79 (95% CI,1.86-4.19),1.78 (95% CI,1.30-2.43) and 2.00 (95% CI,1.34-2.97), respectively; there was no significant increased hazard ratio for tungsten mines. The result indicated a significant joint effect of synergism (RERI>0, AP>0, S>1) and no multiplicative effect (P>0.05) between silica and smoking in lung cancer risk.This study estimated that exposure to silica dust can lead an average of 47% lung cancer risk;however, the association varies from different types of mine/factory, with the highest in tin mines, the second in pottery factories, and the lowest in iron/copper mines; no association was found in tungsten mines. Presence of silicosis can increase 74% of lung cancer risk which is related to types of mine/factory. There is significant joint effect of synergism between silica and smoking in risk of mortality from lung cancer.In conclusion, long-term exposure to silica dust is associated with an increased risk of mortality from all causes, malignant neoplasms (including lung cancer), infectious diseases (including pulmonary tuberculosis), cardiovascular diseases (including pulmonary heart disease), diseases of respiratory system and accidents. About 19.3% of workers have been died due to exposure silica dust in this cohort. There are significant exposure-response relationships between cumulative exposure to silica dust and cardiovascular diseases, diseases of respiratory system and lung cancer, but the association varies in different types of mine/factory. Smoking and exposure to silica dust act synergistically on the risk of lung cancer.