Person:

Zhang, Jinming

Background: Although it has been well recognized that exposure to secondhand tobacco smoke (SHS) is associated with cardiovascular mortality, the mechanisms and time course by which SHS exposure may lead to cardiovascular effects are still being explored. Methods: Non-smoking workers were recruited from a local union and monitored inside a union hall while exposed to SHS over approximately 6 hours. Participants were fitted with a continuous electrocardiographic monitor upon enrollment which was removed at the end of a 24-hr monitoring period. A repeated measures study design was used where resting ECGs and blood samples were taken from individuals before SHS exposure (baseline), immediately following SHS exposure (post) and the morning following SHS exposure (next-morning). Inflammatory markers, including high sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were analyzed. Heart rate variability (HRV) was analyzed from the ECG recordings in time (SDNN, rMSSD) and frequency (LF, HF) domain parameters over 5-minute periods. SHS exposure was quantified using a personal fine particulate matter (PM2.5) monitor. Linear mixed effects regression models were used to examine within-person changes in inflammatory and HRV parameters across the 3 time periods. Exposure-response relationships with PM2.5 were examined using mixed effects models. All models were adjusted for age, BMI and circadian variation. Results: A total of 32 male non-smokers were monitored between June 2010 and June 2012. The mean PM2.5 from SHS exposure was 132 μg/m3. Immediately following SHS exposure, a 100 μg/m3 increase in PM2.5 was associated with declines in HRV (7.8% [standard error (SE) =3%] SDNN, 8.0% (SE = 3.9%) rMSSD, 17.2% (SE = 6.3%) LF, 29.0% (SE = 10.1%) HF) and increases in WBC count 0.42 (SE = 0.14) k/μl. Eighteen hours following SHS exposure, a 100 μg/m3 increase in PM2.5 was associated with 24.2% higher CRP levels. Conclusions: Our study suggest that short-term SHS exposure is associated with significantly lower HRV and higher levels of inflammatory markers. Exposure-associated declines in HRV were observed immediately following exposure while higher levels of CRP were not observed until 18 hours following exposure. Cardiovascular autonomic and inflammation responses may contribute to the pathophysiologic pathways that link SHS exposure with adverse cardiovascular outcomes.

Background: welders are often exposed to various types of metals from the welding fumes and they also have high risks of cardiac autonomic dysfunction. Knowing the hazardous components within metals mixture as well as understanding the potential underlying mechanisms is essential for environmental and occupational regulations. Objective: to identify metal components which are associated with cardiac autonomic responses, as measured by two novel markers -acceleration capacity (AC) and deceleration capacity (DC); to examine whether inflammation mediates effects of metals exposure on AC/DC changes; to identify epigenetic variants which are associated with AC/DC changes. Methods: we collected urine, blood and electrocardiogram (ECG) samples from 75 welders over six sampling occasions between June 2003 and June 2012. Urinary concentrations of 16 types of metals were determined. Blood serum samples were analyzed for inflammatory cytokines levels including CRP, IL-2, IL4, IL6 and IL8. AC and DC values were quantified from ECG recordings. Firstly, we used linear mixed-effects models with Lasso to identify hazardous metals that were significantly associated with AC or DC changes. We fitted the co-pollutants model with “selected” metals in the linear mixed model to estimate the exposure-response relationship. Then, we conducted a mediation analysis to examine whether inflammatory cytokines mediated the effects of metals exposure on AC or DC changes. We report both direct and indirect effects in single pollutant model as well as co-pollutants models. Finally, we conducted the epigenome-wide association study (EWAS) to identify epigenetic variants that were associated with AC or DC changes. Results: we observed negative associations between urinary mercury and chromium concentrations with both DC and AC changes. Indirect effects of metals exposure on AC or DC through inflammation pathway were not significant. We identified GPR133 gene at which methylation level changes were associated with DC values. Conclusion: metals exposures are associated with impaired cardiac autonomic functions. Our study did not provide evidence that these effects were mediated through inflammation pathway. However, DNA methylation of specific genes may be a potential pathway linking environmental and occupational pollutants exposure and alterations in cardiac autonomic responses.