Tingming Shi

Exposure-Response Analysis and Risk Assessment for Lung Cancer in Relationship to Silica Exposure: A 44-Year Cohort Study of 34,018 Workers

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960-2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m(3) of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.

Association between ambient particulate matter exposure and semen quality in Wuhan, China.

BACKGROUND Health effects of exposure to particulate matter (PM) on male reproductive health remain unclear. Only a limited number of studies have investigated the effects of PM2.5 or PM10 exposure on semen quality, and the results were largely inconsistent. OBJECTIVES To quantitatively assess the exposure-response association between PM exposure and semen quality in Chinese men who were exposed to a wide concentration range of PM. METHODS We investigated 1759 men from Wuhan, China, who were partners of women undergoing assisted reproductive technology procedures, and had semen examined at least once between 2013 and 2015. Individual PM2.5 and PM10 exposures during 0-90, 0-9, 10-14 and 70-90days before each semen examination (corresponding to the entire and three key periods of sperm development, respectively) were retrospectively estimated by inverse distance weighting interpolation. Linear mixed models were used to assess exposure-response relations of PM exposure with sperm concentration, count and motility. RESULTS PM2.5 exposure during 0-90 lag days ranged from 27.3 to 172.4μg/m3. It was linearly and inversely associated with sperm concentration (β: -0.20; 95% CI: -0.34, -0.07) and count (-0.22; -0.35, -0.08). For the three key exposure periods, only PM2.5 exposure during the 70-90 lag days was significantly associated with sperm concentration (-0.12; -0.22, -0.03) and count (-0.12; -0.21, -0.02). Sensitivity analyses for a subgroup (n=1146) excluding subjects with abnormal sperm concentration, count or motility yielded similar results. Compared with PM2.5, we found generally similar associations for PM10 exposure in relation to sperm concentration and count, except that the associations appeared to be nonlinear with inverted J-shaped relationships. Neither PM2.5 nor PM10 exposure was significantly associated with sperm motility (all p>0.05). CONCLUSIONS Our results suggest that ambient PM exposure during sperm development adversely affects semen quality, in particular sperm concentration and count.

Polychlorinated dibenzo-p-dioxins and dibenzofurans and their association with cancer mortality among workers in one automobile foundry factory

Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) have been reported as possible carcinogenic hazards to humans. However, epidemiological studies on their carcinogenic roles are limited. The current study was designed to determine the concentrations and characteristics of PCDD/Fs and evaluate their association with cancer mortality in exposed workers in one automobile foundry factory. PCDD/F levels in factory and surrounding environment were analyzed through air and settling dust sampling. The cancer mortalities among workers in this foundry factory were calculated using data from a cohort study. The results showed that the PCDD/F concentrations of air in workplace ranged 0.36-2.25 pg World Health Organization-Toxic Equivalent (WHO-TEQ) Nm(-3) (average 1.01 pg WHO-TEQ Nm(-3)), which were 1.16-7.26 times higher than those outside the factory. The PCDD/F concentrations of settling dust in the workplace ranged 3.34-18.64 pg WHO-TEQ g(-1) (average 8.25 pg WHO-TEQ g(-1)), which were lower than those just outside the factory (average 16.13 pg WHO-TEQ g(-1)). Furthermore, a cohort study of workers in this factory with average follow-up of 24.52 years showed that cancer was the leading cause of death, with significant elevated mortality (standardized mortality ratio (SMR)=1.70, 95% confidence interval (CI): 1.35-2.13) among workers, when compared with Chinese national mortality. The cancer mortality among front-line workers was increased significantly (adjusted relative risk (RR)=1.73, 95% CI: 1.14-2.60), particularly among melting and casting workers, when compared with that among assistant workers. Our results indicated that there was a dose-response relationship between PCDD/F exposure and cancer mortality among foundry workers.

Short-term Effects of Outdoor Air Pollution on Lung Function among Female Non-smokers in China

Short-term exposures to outdoor air pollutants have been associated with lower lung function, but the results are inconsistence. The effects of different pollutant levels on lung function changes are still unclear. We quantified the effects of outdoor air pollution exposure (NO2, PM10, O3, and PM2.5) on lung function among 1,694 female non-smokers from the Wuhan-Zhuhai Cohort in China by using linear mixed model. We further investigated the associations in the two cities with different air quality levels separately to quantify the effects of different pollutant level exposure on lung function. We found the moving averages of NO2, PM10, and PM2.5 concentrations were significantly associated with reduced FVC. In city at high pollutant level, the moving average of NO2, PM10, O3, and PM2.5 exposures were significantly associated with both FVC and FEV1 reductions. In the low-level air pollution city, PM10 (Lag03-Lag05) and O3 concentrations (Lag01-Lag03) were significantly associated with reduced FVC, while PM10 (Lag03-Lag05), O3 (Lag0-Lag03), and PM2.5 (Lag04-Lag06) exposure were significantly associated with reduced FEV1. Our results suggest that outdoor air pollution is associated with short-term adverse effects on lung function among female non-smokers. The adverse effects may persist for longer durations within 7 days at higher air pollutant levels.

Effects of silica exposure on the cardiac and renal inflammatory and fibrotic response and the antagonistic role of interleukin-1 beta in C57BL/6 mice

Current epidemiological studies suggest that crystalline silica exposure is associated with an increased risk of cardiovascular and renal disease; however, the potential pathological damage of the heart and kidney and its underlying mechanisms have not been completely elucidated. This study tried to investigate the silica-induced inflammatory and fibrotic changes in the heart and kidney and evaluate the role of interleukin (IL)-1 beta (β) in silica-induced cardiac and renal damage. In this study, a silica-exposed model was generated by intratracheally instilling silica dust in mice. The anti-IL-1β monoclonal antibody (mAb) was used to neutralise IL-1β in the pulmonary alveolus and serum. The real-time PCR studies showed that (1) inhalational silica induced inflammatory responses in the heart and kidney by elevated mRNA levels of TNF-α, IL-6 and MCP-1; (2) early fibrotic responses in the heart were observed as elevated mRNA levels of collagen I and fibronectin. What is more, fibrosis of the kidney was demonstrated by pathological results and significantly increased mRNA levels of TGF-β, collagen I, collagen III and fibronectin. Further studies showed that usage of anti-IL-1β mAb decreased the inflammatory response of the heart and kidney induced by inhalational silica and also attenuated fibrosis in the mouse kidney. In conclusion, this study found that inhaled silica induced inflammatory and early fibrotic responses in the mouse heart and inflammatory response and fibrosis in the mouse kidney. Neutralisation of IL-1β attenuated the silica-induced inflammatory response of the heart and kidney and decreased fibrosis in the mouse kidney.

Short-term effects of ambient air pollution on pediatric outpatient visits for respiratory diseases in Yichang city, China

Previous studies have suggested that short-term exposure to ambient air pollution was associated with pediatric hospital admissions and emergency room visits for certain respiratory diseases; however, there is limited evidence on the association between short-term air pollution exposure and pediatric outpatient visits. Our aim was to quantitatively assess the short-term effects of ambient air pollution on pediatric outpatient visits for respiratory diseases. We conducted a time-series study in Yichang city, China between Jan 1, 2014 and Dec 31, 2015. Daily counts of pediatric respiratory outpatient visits were collected from 3 large hospitals, and then linked with air pollution data from 5 air quality monitoring stations by date. We used generalized additive Poisson models to conduct linear and nonlinear exposure-response analyses between air pollutant exposures and pediatric respiratory outpatient visits, adjusting for seasonality, day of week, public holiday, temperature, and relative humidity. Each interquartile range (IQR) increase in PM2.5 (lag 0), PM10 (lag 0), NO2 (lag 0), CO (lag 0), and O3 (lag 4) concentrations was significantly associated with a 1.91% (95% CI: 0.60%, 3.23%), 2.46% (1.09%, 3.85%), 1.88% (0.49%, 3.29%), 2.00% (0.43%, 3.59%), and 1.91% (0.45%, 3.39%) increase of pediatric respiratory outpatient visits, respectively. Similarly, the nonlinear exposure-response analyses showed monotonic increases of pediatric respiratory outpatient visits by increasing air pollutant exposures, though the associations for NO2 and CO attenuated at higher concentrations. These associations were unlikely modified by season. We did not observe significant association for SO2 exposure. Our results suggest that short-term exposures to PM2.5, PM10, NO2, CO, and O3 may account for increased risk of pediatric outpatient visits for respiratory diseases, and emphasize the needs for reduction of air pollutant exposures for children.

Occupational Hearing Loss among Chinese Municipal Solid Waste Landfill Workers: A Cross-Sectional Study

Background Occupational hearing loss is an increasingly prevalent occupational condition worldwide, and has been reported to occur in a wide range of workplaces; however, its prevalence among workers from municipal solid waste landfills (MSWLs) remains less clear. This study aimed to investigate the occupational hearing loss among Chinese MSWL workers. Methods A cross-sectional study of 247 workers from 4 Chinese MSWLs was conducted. Noise and total volatile organic compounds (TVOCs) levels at worksites were determined. We conducted hearing examinations to determine hearing thresholds. A worker was identified as having hearing loss if the mean threshold at 2000, 3000 and 4000 Hz in either ear was equal to or greater than 25 dB. Prevalence of occupational hearing loss was then evaluated. Using unconditional Logistic regression models, we estimated the odds ratios (ORs) of MSWL work associated with hearing loss. Results According to the job title for each worker, the study subjects were divided into 3 groups, including group 1 of 63 workers without MSWL occupational hazards exposure (control group), group 2 of 84 workers with a few or short-period MSWL occupational hazards exposure, and group 3 of 100 workers with continuous MSWL occupational hazards exposure. Both noise and TVOCs levels were significantly higher at worksites for group 3. Significantly poorer hearing thresholds at frequencies of 2000, 3000 and 4000 Hz were found in group 3, compared with that in group 1 and group 2. The overall prevalence rate of hearing loss was 23. 5%, with the highest in group 3 (36.0%). The OR of MSWL work associated with hearing loss was 3.39 (95% confidence interval [CI]: 1.28-8.96). Conclusion The results of this study suggest significantly higher prevalence of hearing loss among MSWL workers. Further studies are needed to explore possible exposure-response relationship between MSWL occupational hazards exposure and hearing loss.

Size-dependent biological effects on vascular endothelial cells induced by different particulate matters

SummaryThe contribution of particles to cardiovascular mortality and morbidity has been enlightened by epidemiologic and experimental studies. However, adverse biological effects of the particles with different sizes on cardiovascular cells have not been well recognized. In this study, sub-cultured human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of pure quartz particles (DQ) of three sizes (DQPM1, <1 μm; DQPM3-5, 3-5 μm; DQPM5, 5 μm) and carbon black particles of two sizes (CB0.1, <0.1 μm; CB1, <1 μm) for 24 h. Cytotoxicity was estimated by measuring the activity of lactate dehydrogenase (LDH) and cell viability. Nitric oxide (NO) generation and cytokines (TNF-α and IL-1β) releases were analyzed by using NO assay and enzyme-linked immunoabsorbent assay (ELISA), respectively. It was found that both particles induced adverse biological effects on HUVECs in a dose-dependent manner. The size of particle directly influenced the biological activity. For quartz, the smaller particles induced stronger cytotoxicity and higher levels of cytokine responses than those particles of big size. For carbon black particles, CB0.1 was more capable of inducing adverse responses on HUVECs than CB1 only at lower particle concentrations, in contrast to those at higher concentrations. Meanwhile, our data also revealed that quartz particles performed stronger cell damage and produced higher levels of TNF-α than carbon black particles, even if particles size was similar. In conclusion, particle size as well as particle composition should be both considered in assessing vascular endothelial cells injury and inflammation responses induced by particles.The contribution of particles to cardiovascular mortality and morbidity has been enlightened by epidemiologic and experimental studies. However, adverse biological effects of the particles with different sizes on cardiovascular cells have not been well recognized. In this study, sub-cultured human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of pure quartz particles (DQ) of three sizes (DQPM1, <1 μm; DQPM3-5, 3-5 μm; DQPM5, 5 μm) and carbon black particles of two sizes (CB0.1, <0.1 μm; CB1, <1 μm) for 24 h. Cytotoxicity was estimated by measuring the activity of lactate dehydrogenase (LDH) and cell viability. Nitric oxide (NO) generation and cytokines (TNF-α and IL-1β) releases were analyzed by using NO assay and enzyme-linked immunoabsorbent assay (ELISA), respectively. It was found that both particles induced adverse biological effects on HUVECs in a dose-dependent manner. The size of particle directly influenced the biological activity. For quartz, the smaller particles induced stronger cytotoxicity and higher levels of cytokine responses than those particles of big size. For carbon black particles, CB0.1 was more capable of inducing adverse responses on HUVECs than CB1 only at lower particle concentrations, in contrast to those at higher concentrations. Meanwhile, our data also revealed that quartz particles performed stronger cell damage and produced higher levels of TNF-α than carbon black particles, even if particles size was similar. In conclusion, particle size as well as particle composition should be both considered in assessing vascular endothelial cells injury and inflammation responses induced by particles.

Urinary polycyclic aromatic hydrocarbon metabolites, Club cell secretory protein and lung function

BACKGROUND Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with lung function decline. However, the underlying mechanisms for the association remain unclear. OBJECTIVES To explore potential role of a lung epithelial biomarker, Club cell secretory protein (CC16), in associations between PAH exposures and lung function decline. METHODS We investigated 3384 adults from the Wuhan-Zhuhai cohort, and followed up at three years after first examination. Linear mixed models was used to quantify dose-response relationships between urinary monohydroxylated PAH metabolites (OH-PAHs) and lung function, as well as OH-PAHs and plasma CC16. Mediation analysis was conducted to investigate role of CC16 in the association between OH-PAHs and lung function. We also estimated the relationships between OH-PAHs and lung function change in three years among participants with different levels of CC16. RESULTS Each 1-unit increase of log-transformed total urinary high and low molecular weight OH-PAHs (∑HMW OH-PAH and ∑LMW OH-PAHs) were associated with a 22.59 and 25.25ml reduction of FEV1 respectively, while∑HMW OH-PAH was associated with a 30.38ml reduction of FVC. Moreover, these negative associations between OH-PAHs and lung function levels were significant only among low CC16 group (<15.83ng/ml). CC16 concentration decreased monotonically with increased high molecular weight OH-PAHs (∑HMW OH-PAHs) when ∑HMW OH-PAH concentration was over 0.67μg/mmol Cr. CC16 mediated 22.13% of the association between ∑HMW OH-PAH and FVC among individuals with higher ∑HMW OH-PAH. After three years of follow-up, subjects with low level of plasma CC16 had a significant decline of FVC when exposed to high level of ∑HMW OH-PAH. CONCLUSIONS CC16 play an important role in the association between high molecular weight PAHs and FVC. Individuals with low plasma CC16 level might suffer a decline in lung function when exposed to high level of high molecular weight PAHs.

Inverse association between ambient sulfur dioxide exposure and semen quality in Wuhan, China

Evidence concerning the association between ambient gaseous air pollutant exposures and semen quality is sparse, and findings in previous studies remain largely inconsistent. We enrolled 1759 men and performed 2184 semen examinations at a large reproductive medical center in Wuhan, China, between 2013 and 2015. Inverse distance weighting interpolation was performed to estimate individual exposures to SO2, NO2, CO, and O3 during the entire period (lag 0-90 days) and key periods (lag 0-9, 10-14, 70-90 days) of sperm development. Linear mixed models were used to analyze exposure-response relationships. SO2 exposure with 0-90 days lag was significantly associated with monotonically decreased sperm concentration (β for each interquartile range increase of exposure: -0.14; 95% CI: -0.23, -0.05), sperm count (-0.21; -0.30, -0.12) and total motile sperm count (-0.16; -0.25, -0.08). Significant associations were observed for total and progressive motility only when SO2 exposure was at the highest quintile (all Ptrend < 0.05). Similar trends were observed for SO2 exposure with 70-90 days lag. NO2, CO, or O3 exposure was not significantly associated with semen quality. Our results suggest that ambient SO2 exposure adversely affects semen quality and highlight the potential to improve semen quality by reducing ambient SO2 exposure during early stages of sperm development.