PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression

Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1β, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.

Quantile-specific heritability of plasma fibrinogen concentrations

Background Fibrinogen is a moderately heritable blood protein showing different genetic effects by sex, race, smoking status, pollution exposure, and disease status. These interactions may be explained in part by “quantile-dependent expressivity”, where the effect size of a genetic variant depends upon whether the phenotype (e.g. plasma fibrinogen concentration) is high or low relative to its distribution. Purpose Determine whether fibrinogen heritability (h2) is quantile-specific, and whether quantile-specific h2 could account for fibrinogen gene-environment interactions. Methods Plasma fibrinogen concentrations from 5689 offspring-parent pairs and 1932 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (βOP, h2 = 2βOP/(1+rspouse)) and full-sib regression slopes (βFS, h2 = {(1+8rspouseβFS)0.05–1}/(2rspouse)) were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted fibrinogen distribution when estimated from βOP (Ptrend = 5.5x10-6): 0.30±0.05 at the 10th, 0.37±0.04 at the 25th, 0.48±0.05 at the 50th, 0.61±0.06 at the 75th, and 0.65±0.08 at the 90th percentile, and when estimated from βFS (Ptrend = 0.008): 0.28±0.04 at the 10th, 0.31±0.04 at the 25th, 0.36±0.03 at the 50th, 0.41±0.05 at the 75th, and 0.50±0.06 at the 90th percentile. The larger genetic effect at higher average fibrinogen concentrations may contribute to fibrinogen’s greater heritability in women than men and in Blacks than Whites, and greater increase from smoking and air pollution for the FGB -455G>A A-allele. It may also explain greater fibrinogen differences between: 1) FGB -455G>A genotypes during acute phase reactions than usual conditions, 2) GTSM1 and IL-6 -572C>G genotypes in smokers than nonsmokers, 3) FGB -148C>T genotypes in untreated than treated diabetics, and LPL PvuII genotypes in macroalbuminuric than normoalbuminuric patients. Conclusion Fibrinogen heritability is quantile specific, which may explain or contribute to its gene-environment interactions. The analyses do not disprove the traditional gene-environment interpretations of these examples, rather quantile-dependent expressivity provides an alternative explanation that warrants consideration.

Air Pollution Exposure and the Development of Chronic Rhinosinusitis in the Active Duty Population

ABSTRACT Introduction It has been shown that combat environment exposure, including burn pits that produce particulate matter 2.5 (PM2.5), is associated with lower respiratory tract disease in the military population with increased hypothetical risk of upper respiratory disease, but no study has been done that examines the effects of non-combat environmental exposures on the development of chronic rhinosinusitis (CRS) in the active duty population. The primary goal of this study is to evaluate how air pollution exposure correlates to the development of CRS in active duty service members in the United States. Methods The military electronic medical record was queried for active duty service members diagnosed with CRS by an otolaryngologist between January 2016 and January 2018, who have never deployed, stationed in the United States from 2015 to 2018 (n = 399). For each subject, the 1-year mean exposure of PM2.5, particulate matter 10 (PM10), nitrogen dioxide (NO2), and ozone was calculated. The control group was comprised of the same criteria except these patients were diagnosed with cerumen impaction and matched to the case group by age and gender (n = 399). Pollution exposure was calculated based on the Environmental Protection Agency’s data tables for each subject. Values were calculated using chi-square test for categorical variables and the Mann–Whitney U-test for continuous variables. Results Matched cases and controls (n = 399) with 33.1% male showed a statistically significant odds ratio (OR) of 5.99 (95% CI, 2.55-14.03) for exposure of every 5 µg/m3 of PM2.5 increase and the development of CRS when controlling for age, gender, and diagnosis year. When further adjusting for smoking status, the OR was still statistically significant at 3.15 (95% CI, 1.03-9.68). Particulate matter 10, ozone, and NO2 did not show any statistical significance. Odds ratios remained statistically significant when further adjusting for PM10 and ozone, but not NO2. Dose-dependent curves largely did not show a statistical significance; however, they did trend towards increased exposure of PM2.5 leading to an elevated OR. Conclusion This study showed that PM2.5 exposure is a major independent contributor to the development of CRS. Exposure to elevated levels produced statistically significant odds even among smokers and remained significant when controlling for other measured pollutants. There is still much to be understood about the genesis of CRS. From a pollution exposure perspective, a prospective cohort study would better elucidate the risk of the development of CRS among those exposed to other pollutants.

Air Pollution Exposure and Risk of Spontaneous Pneumothorax in Children: A Longitudinal, Nationwide Study

Spontaneous pneumothorax (SP) involves the spontaneous appearance of air in the pleural space. Atmospheric pressure, temperature change, and seasonal factors may precipitate SP, but its association with air pollution remains unclear. Therefore, we conducted this nationwide, retrospective population-based study to evaluate the risk of SP in Taiwanese children exposed to air pollution. We collected data on SP incidence from the Longitudinal Health Insurance Database; the Taiwan Air Quality-Monitoring Database provided daily concentrations of nitric oxide (NO), nitrogen dioxide (NO2), and hydrocarbons in 2000–2012. SP risk was evaluated for four quartiles (Q1, Q2, Q3, Q4). The NO adjusted hazard ratios (aHRs) for Q2, Q3, and Q4 compared to Q1 were 1.11 (95% confidence interval (CI): 0.77–1.61), 1.24 (95% CI: 0.88–1.76), and 1.66 (95% CI: 1.17–2.34), respectively. The NO2 aHRs for Q2, Q3, and Q4 were 1.12 (95% CI: 0.77–1.64), 1.31 (95% CI: 0.0.90–1.90), and 1.51 (95% CI: 1.04–2.19), respectively. Hydrocarbons aHRs for Q2, Q3, and Q4 were 0.87 (95% CI: 0.64–1.18), 1.16 (95% CI: 0.90–1.49), and 1.40 (95% CI: 1.06–1.85), respectively. Increased exposure to NO, NO2, and hydrocarbons is associated with increased SP risk in Taiwanese children.