Changyuan Yang

Cardiopulmonary benefits of reducing indoor particles of outdoor origin: a randomized, double-blind crossover trial of air purifiers.

BACKGROUND Indoor exposure to fine particulate matter (PM2.5) from outdoor sources is a major health concern, especially in highly polluted developing countries such as China. Few studies have evaluated the effectiveness of indoor air purification on the improvement of cardiopulmonary health in these areas. OBJECTIVES This study sought to evaluate whether a short-term indoor air purifier intervention improves cardiopulmonary health. METHODS We conducted a randomized, double-blind crossover trial among 35 healthy college students in Shanghai, China, in 2014. These students lived in dormitories that were randomized into 2 groups and alternated the use of true or sham air purifiers for 48 h with a 2-week washout interval. We measured 14 circulating biomarkers of inflammation, coagulation, and vasoconstriction; lung function; blood pressure (BP); and fractional exhaled nitric. We applied linear mixed-effect models to evaluate the effect of the intervention on health outcome variables. RESULTS On average, air purification resulted in a 57% reduction in PM2.5 concentration, from 96.2 to 41.3 μg/m3, within hours of operation. Air purification was significantly associated with decreases in geometric means of several circulating inflammatory and thrombogenic biomarkers, including 17.5% in monocyte chemoattractant protein-1, 68.1% in interleukin-1β, 32.8% in myeloperoxidase, and 64.9% in soluble CD40 ligand. Furthermore, systolic BP, diastolic BP, and fractional exhaled nitrous oxide were significantly decreased by 2.7%, 4.8%, and 17.0% in geometric mean, respectively. The impacts on lung function and vasoconstriction biomarkers were beneficial but not statistically significant. CONCLUSIONS This intervention study demonstrated clear cardiopulmonary benefits of indoor air purification among young, healthy adults in a Chinese city with severe ambient particulate air pollution. (Intervention Study on the Health Impact of Air Filters in Chinese Adults; NCT02239744).

Associations between long-term exposure to ambient particulate air pollution and type 2 diabetes prevalence, blood glucose and glycosylated hemoglobin levels in China.

BACKGROUND The evidence for an association between particulate air pollution and type 2 diabetes mellitus (T2DM) in developing countries was very scarce. OBJECTIVE To investigate the associations of long-term exposure to fine particulate matter (PM2.5) with T2DM prevalence and with fasting glucose and glycosylated hemoglobin (HbA1c) levels in China. METHODS This is a cross-sectional study based on a nation-wide baseline survey of 11,847 adults who participated in the China Health and Retirement Longitudinal Study from June 2011 to March 2012. The average residential exposure to PM2.5 for each participant in the same period was estimated using a satellite-based spatial statistical model. We determined the association between PM2.5 and T2DM prevalence by multivariable logistic regression models. We also evaluated the association between PM2.5 and fasting glucose and HbA1c levels using multivariable linear regression models. Stratification analyses were conducted to explore potential effect modification. RESULTS We identified 1760 cases of T2DM, corresponding to 14.9% of the study population. The average PM2.5 exposure for all participants was 72.6μg/m(3) during the study period. An interquartile range increase in PM2.5 (41.1μg/m(3)) was significantly associated with increased T2DM prevalence (prevalence ratio, PR=1.14), and elevated levels of fasting glucose (0.26mmol/L) and HbA1c (0.08%). The associations of PM2.5 with T2DM prevalence and with fasting glucose and HbA1c were stronger in several subgroups. CONCLUSIONS This nationwide cross-sectional study suggested that long-term exposure to PM2.5 might increase the risk of T2DM in China.

Short-term exposure to ambient air pollution and coronary heart disease mortality in 8 Chinese cities

BACKGROUND Coronary heart disease (CHD) accounted for a large fraction of death globally. The association between air pollution and CHD has been reported, but evidence from highly-polluted regions was scarce. We aimed to estimate the acute effects of outdoor air pollution on daily CHD mortality in China. METHODS We collected daily CHD deaths in 8 large Chinese cities from 1996 to 2008. We firstly obtained the city-specific effect estimates of air pollution using generalized additive models with quasi-Poisson regression, controlling for time trends, meteorological indicators and day of the week. The random-effect model in meta-analysis was used to pool the exposure-response relationships. RESULTS We identified a total of 0.13 million CHD deaths. On average, an increase of 10μg/m(3) in 2-day moving average concentrations of particulate matter≤10μm in aerodynamic diameter (PM10), sulfur dioxide (SO2) and nitrogen dioxide (NO2) was significantly associated with increases of 0.36% [95% confidence intervals (CIs): 0.12%, 0.61%], 0.86% (95% CIs: 0.30%,1.41%) and 1.30% (95% CIs: 0.45%, 2.14%) in daily CHD mortality over the 8 Chinese cities, respectively. The pooled exposure-response curves were almost linear and no apparent thresholds were identified. The effects were more pronounced in cities with lower levels of air pollution. The effects of PM10 and NO2 were more robust than SO2. CONCLUSION Our findings contributed to the very limited evidence regarding the hazardous effects of ambient air pollution on CHD mortality in highly-polluted regions such as China.

Ambient air pollution, temperature and out-of-hospital coronary deaths in Shanghai, China.

Few studies have evaluated the effects of ambient air pollution and temperature in triggering out-of-hospital coronary deaths (OHCDs) in China. We evaluated the associations of air pollution and temperature with daily OHCDs in Shanghai, China from 2006 to 2011. We applied an over-dispersed generalized additive model and a distributed lag nonlinear model to analyze the effects of air pollution and temperature, respectively. A 10 μg/m(3) increase in the present-day PM10, PM2.5, SO2, NO2 and CO were associated with increases in OHCD mortality of 0.49%, 0.68%, 0.88%, 1.60% and 0.08%, respectively. A 1 °C decrease below the minimum-mortality temperature corresponded to a 3.81% increase in OHCD mortality on lags days 0-21, and a 1 °C increase above minimum-mortality temperature corresponded to a 4.61% increase over lag days 0-3. No effects were found for in-hospital coronary deaths. This analysis suggests that air pollution, low temperature and high temperature may increase the risk of OHCDs.

Associations between size-fractionated particulate air pollution and blood pressure in a panel of type II diabetes mellitus patients.

Little is known regarding how the size distribution of particulate matter (PM) air pollution influences its effect on blood pressure (BP), especially among patients with diabetes. The objective of this study was to explore the short-term associations between size-fractionated PM and BP among diabetes patients. We scheduled 6 repeated BP examinations every 2 weeks from 13 April 2013 to 30 June 2013 in a panel of 35 type 2 diabetes mellitus patients recruited from an urban community in Shanghai, China. We measured real-time PM concentrations in the size range of 0.25 to 10 μm. We used linear mixed-effect models to examine the short-term association of size-fractionated PM and BP after controlling for individual characteristics, mean temperature, relative humidity, day of the week, years with diabetes and use of antihypertensive medication. The association with systolic BP and pulse pressure strengthened with decreasing diameter. The size fractions with the strongest associations were 0.25 to 0.40 μm for number concentrations and ≤ 2.5 μm for mass concentrations. Furthermore, these effects occurred immediately even after 0-2h and lasted for up to 48 h following exposure. An interquartile range increase in 24-h average number concentrations of PM0.25-0.40 was associated with increases of 3.61 mmHg in systolic BP and 2.96 mmHg in pulse pressure. Females, patients younger than 65 years of age and patients without antihypertensive treatment were more susceptible to these effects. Our results revealed important size and temporal patterns of PM in elevating BP among diabetes patients in China.

Personal exposure to fine particulate matter and blood pressure: A role of angiotensin converting enzyme and its DNA methylation.

BACKGROUND The underlying intermediate mechanisms about the association between fine particulate matter (PM2.5) air pollution and blood pressure (BP) were unclear. Few epidemiological studies have explored the potential mediation effects of angiotensin-converting enzyme (ACE) and its DNA methylation. METHODS We designed a longitudinal panel study with 4 follow-ups among 36 healthy college students in Shanghai, China from December 17, 2014 to July 11, 2015. We measured personal real-time exposure to PM2.5, serum ACE level, and blood methylation of ACE gene and the repetitive elements. We applied linear mixed-effects models to examine the effects of PM2.5 on ACE protein, DNA methylation and BP markers. Furthermore, we conducted mediation analyses to evaluate the potential pathways. RESULTS An interquartile range increase (26.78μg/m(3)) in 24-h average exposure to PM2.5 was significantly associated with 1.12 decreases in ACE average methylation (%5mC), 13.27% increase in ACE protein, and increments of 1.13mmHg in systolic BP, 0.66mmHg in diastolic BP and 0.82mmHg in mean arterial pressure. ACE hypomethylation mediated 11.78% (P=0.03) of the elevated ACE protein by PM2.5. Increased ACE protein accounted for 3.90~13.44% (P=0.35~0.68) of the elevated BP by PM2.5. Repetitive-element methylation was also decreased but did not significantly mediate the association between PM2.5 and BP. CONCLUSIONS This investigation provided strong evidence that short-term exposure to PM2.5 was significantly associated with BP, ACE protein and ACE methylation. Our findings highlighted a possible involvement of ACE and ACE methylation in the effects of PM2.5 on elevating BP.

DNA hypomethylation and its mediation in the effects of fine particulate air pollution on cardiovascular biomarkers: A randomized crossover trial

BACKGROUND Short-term exposure to fine particulate matter (PM2.5) air pollution has been associated with altered DNA methylation in observational studies, but it remains unclear whether this change mediates the effects on cardiovascular biomarkers. OBJECTIVE To examine the impact of ambient PM2.5 on gene-specific DNA methylation and its potential mediation in the acute effects of PM2.5 on cardiovascular biomarkers. METHODS We designed a randomized, double-blind crossover trial using true or sham air purifiers for 48h among 35 healthy college students in Shanghai, China, in 2014. We measured blood global methylation estimated in long interspersed nucleotide element-1 (LINE‑1) and Alu repetitive elements, methylation in ten specific genes, and ten cardiovascular biomarkers. We used linear mixed-effect models to examine the associations between PM2.5 and methylation. We also performed causal mediation analyses to evaluate the potential mediation of methylation in the associations between PM2.5 and biomarkers. RESULTS Air purification increased DNA methylation in repetitive elements and all candidate genes. An IQR increase (64μg/m(3)) in PM2.5 was significantly associated with reduction of methylation in LINE-1 (1.44%), one pro-inflammatory gene (CD40LG, 9.13%), two pro-coagulant genes (F3, 15.20%; SERPINE1, 3.69%), and two pro-vasoconstriction genes (ACE, 4.64%; EDN1, 9.74%). There was a significant mediated effect (17.82%, P=0.03) of PM2.5 on sCD40L protein through CD40LG hypomethylation. Hypomethylation in other candidate genes generally showed positive but non-significant mediation. CONCLUSIONS This intervention study provided robust human evidence that ambient PM2.5 could induce rapid decreases in DNA methylation and consequently partly mediate its effects on cardiovascular biomarkers.

Long-term variations in the association between ambient temperature and daily cardiovascular mortality in Shanghai, China

OBJECTIVE The objective of this study was to explore the long-term variation in the association between ambient temperature and daily cardiovascular (CVD) mortality in Shanghai, China. MATERIALS AND METHODS We collected daily data on ambient temperature and CVD mortality from a central urban district in Shanghai, China, during the period from 1981 to 2012. We used overdispersed generalized additive Poisson regression together with a distributed lag nonlinear model to estimate potentially lagged and nonlinear effects of temperature on CVD mortality after controlling for the seasonality, relative humidity, day of the week, holidays and population size. To allow for the evaluation of long-term variations in the effects, we divided the entire study period into six sub-periods (1981-1985, 1986-1990, 1991-1995, 1996-2000, 2001-2005, and 2006-2012) and analyzed the effect estimates in each sub-period separately. RESULTS The association between temperature and daily CVD mortality was J-shaped with both low and high temperatures increasing the risk of CVD deaths. The effects of extremely low temperatures were delayed and persisted for two weeks, while extreme hot effects were limited to the first five days followed by a significant mortality displacement (9days). The relative risks (RRs) of extremely low, moderately low, moderately high, and extremely high temperatures comparing the 1st, 10th, 90th, and 99th percentile with the reference temperature (26°C) over the cumulative lags of 0-14days were 1.95 [95% confidence interval (CI): 1.84,2.07], 1.61 (95% CI: 1.57,1.66), 1.03 (95% CI: 1.01,1.05), and 1.14 (95% CI: 1.07,1.21). The RRs for extremely low and moderately low temperature attenuated substantially from 9.78 and 5.52 in 1981-1985 to 1.42 and 1.18 in 2006-2012, respectively, but the RRs remained almost stable for extremely high and moderately high temperatures. CONCLUSIONS This time-series study suggested that there might have been some human adaptation to low ambient temperature in Shanghai, China, over the last 3 decades.

Cardiovascular Benefits of Wearing Particulate-Filtering Respirators: A Randomized Crossover Trial.

Background: Practical approaches to protect individuals from ambient particulate matter (PM) are urgently needed in developing countries. Evidence on the health benefits of wearing particulate-filtering respirators is limited. Objectives: We evaluated the short-term cardiovascular health effects of wearing respirators in China. Methods: A randomized crossover trial was performed in 24 healthy young adults in Shanghai, China in 2014. The subjects were randomized into two groups and wore particulate-filtering respirators for 48 hr alternating with a 3-week washout interval. Heart rate variability (HRV) and ambulatory blood pressure (BP) were continuously monitored during the 2nd 24 hr in each intervention. Circulating biomarkers were measured at the end of each intervention. Linear mixed-effect models were applied to evaluate the effects of wearing respirators on health outcomes. Results: During the intervention periods, the mean daily average concentration of PM with an aerodynamic diameter < 2.5 μm (PM2.5) was 74.2 μg/m3. Compared with the absence of respirators, wearing respirators was associated with a decrease of 2.7 mmHg [95% confidence interval (CI): 0.1, 5.2 mmHg] in systolic BP and increases of HRV parameters, including 12.5% (95% CI: 3.8%, 21.2%) in high frequency (HF) power, 10.9% (95% CI: 1.8%, 20.0%) in the root mean square of the successive differences, and 22.1% (95% CI: 3.6%, 40.7%) in the percentage of normal RR intervals with duration > 50 msec different from the previous normal RR interval (pNN50). The presence of respirators was also associated with a decrease of 7.8% (95% CI: 3.5%, 12.1%) in the ratio of low frequency (LF)/HF power. Conclusions: Short-term wearing of particulate-filtering respirators may produce cardiovascular benefits by improving autonomic nervous function and reducing BP. Citation: Shi J, Lin Z, Chen R, Wang C, Yang C, Cai J, Lin J, Xu X, Ross JA, Zhao Z, Kan H. 2017. Cardiovascular benefits of wearing particulate-filtering respirators: a randomized crossover trial. Environ Health Perspect 125:175–180; http://dx.doi.org/10.1289/EHP73

Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution

Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m3 increase in average PM2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM2.5 on inflammatory pathways.