•We used metabolomics to identify biologic pathways linking air pollution to live birth.•In total, we identified 190 metabolic features and 18 metabolic pathways.•Eight metabolic features were ...confirmed at Level 1 confidence.•Several of these metabolites are implicated in oxidative stress and inflammation.
Air pollution exposure has been linked with diminished fertility. Identifying the metabolic changes induced by periconception air pollution exposure among women could enhance our understanding of the potential biological pathways underlying air pollution’s reproductive toxicity.
To identify serum metabolites associated with periconception air pollution exposure and evaluate the extent to which these metabolites mediate the association between air pollution and live birth.
We included 200 women undergoing a fresh assisted reproductive technology (ART) cycle at Massachusetts General Hospital Fertility Center (2005–2015). A serum sample was collected during stimulation, and untargeted metabolic profiling was conducted using liquid chromatography with ultra-high-resolution mass spectrometry. Exposure to nitrogen dioxide (NO2), ozone (O3), fine particulate matter <2.5 µm (PM2.5), and black carbon (BC) was estimated using validated spatiotemporal models. Multivariable linear regression models were used to evaluate the associations between the air pollutants, live birth, and metabolic feature intensities. A meet in the middle approach was used to identify overlapping features and metabolic pathways.
From the C18 and HILIC chromatography columns, 10,803 and 12,968 metabolic features were extracted. There were 190 metabolic features and 18 pathways that were significantly associated with both air pollution and live birth (P < 0.05) across chromatography columns. Eight features were confirmed metabolites implicated in amino acid and nutrient metabolism with downstream effects on oxidative stress and inflammation. Six confirmed metabolites fell into two intuitive clusters – “antioxidants” and “oxidants”- which could potentially mediate some of the association between air pollution and lower odds of live birth. Tryptophan and vitamin B3 metabolism were common pathways linking air pollution exposure to decreased probability of live birth.
Higher periconception air pollution exposure was associated with metabolites and biologic pathways involved in inflammation and oxidative stress that may mediate the observed associations with lower probability of live birth following ART.
Is there an association between air pollution exposures and the risk of spontaneous abortion (SAB)?
Higher exposure to particulate matter (PM) air pollution above and beyond a woman's average ...exposure may be associated with greater risk of SAB, particularly among women experiencing at least one SAB during follow-up.
There is sufficient biologic plausibility to suggest that air pollution adversely affects early pregnancy outcomes, particularly pregnancy loss; however, the evidence is limited.
Our prospective cohort study included 19 309 women in the Nurses' Health Study II who contributed a total of 35 025 pregnancies between 1990 and 2008. We also conducted a case-crossover analysis among 3585 women (11 212 pregnancies) with at least one SAB and one live birth during follow-up.
Proximity to major roadways and exposure to PM <10 microns (PM10), 2.5-10 microns (PM2.5-10) and <2.5 microns (PM2.5) were determined for residential addresses between 1989 and 2007. Pregnancy outcomes were self-reported biannually throughout follow-up and comprehensively in 2009. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the risk ratios and 95% CIs of SAB. Conditional logistic regression was used for the case-crossover analysis.
During the 19 years of follow-up, 6599 SABs (18.8% of pregnancies) were reported. In the main analysis, living closer to a major roadway and average exposure to PM10, PM10-2.5 or PM2.5 in the 1 or 2 years prior to pregnancy were not associated with an increased risk of SAB. However, small positive associations between PM exposures and SAB were observed when restricting the analysis to women experiencing at least one SAB during follow-up. In the case-crossover analysis, an increase in PM10 (per 3.9 μg/m3), PM2.5-10 (per 2.3 μg/m3) and PM2.5 (per 2.0 μg/m3) in the year prior to pregnancy was associated with 1.12 (95% CI 1.06, 1.19), 1.09 (95% CI 1.03, 1.14) and 1.10 (95% CI 1.04, 1.17) higher odds of SAB, respectively.
We did not have information on the month or day of SAB, which precluded our ability to examine specific windows of susceptibility or acute exposures. We also used ambient air pollution exposures as a proxy for personal exposure, potentially leading to exposure misclassification.
In our case-crossover analysis (but not in the entire cohort) we observed positive associations between exposure to all size fractions of PM exposure and risk of SAB. This may suggest that changes in PM exposure confer greater risk of SAB or that women with a history of SAB are a particularly vulnerable subgroup.
The authors are supported by the following NIH grants UM1CA176726, R00ES026648 and P30ES000002. The authors have no actual or potential competing financial interests to disclose.
A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants.
We examined the relation of lung cancer incidence with long-term ...residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures.
For participants in the Nurses' Health Study, a nationwide prospective cohort of women, we estimated 72-month average exposures to PM2.5, PM2.5-10, and PM10 and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined.
During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10-μg/m3 increase in 72-month average PM10 hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14, PM2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM2.5-10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00, 1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5-10: HR = 1.11; 95% CI: 0.90, 1.37). RESULTS were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent.
Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers.
BACKGROUND: Understanding the shape of the concentration-response curve for particles is important for public health, and lack of such understanding was recently cited by U.S. Environmental ...Protection Agency (EPA) as a reason for not tightening the standards. Similarly, the delay between changes in exposure and changes in health is also important in public health decision making. We addressed these issues using an extended follow-up of the Harvard Six Cities Study. METHODS: Cox proportional hazards models were fit controlling for smoking, body mass index, and other covariates. Two approaches were used. First, we used penalized splines, which fit a flexible functional form to the concentration response to examine its shape, and chose the degrees of freedom for the curve based on Akaike's information criterion. Because the uncertainties around the resultant curve do not reflect the uncertainty in model choice, we also used model averaging as an alternative approach, where multiple models are fit explicitly and averaged, weighted by their probability of being correct given the data. We examined the lag relationship by model averaging across a range of unconstrained distributed lag models. RESULTS: We found that the concentration-response curve is linear, clearly continuing below the current U.S. standard of 15 µg/m³, and that the effects of changes in exposure on mortality are seen within two years. CONCLUSIONS: Reduction in particle concentrations below U.S. EPA standards would increase life expectancy.
BACKGROUND:An increasing number of studies have linked air pollution to decreased fertility. Whether this is due to an effect on ovarian reserve is unknown.
METHOD:Our study included 632 women ...attending the Massachusetts General Hospital Fertility Center (2004–2015) who had a measured antral follicle count. Validated spatiotemporal models estimated daily particulate matter <2.5 µg/m (PM2.5) (based on residential address) for the 3 months before the antral follicle count. We analyzed associations with Poisson regression.
RESULTS:Every 2 µg/m increase in estimated PM2.5 exposure was associated with a −7.2% (95% confidence interval = −10.4%, −3.8%) lower antral follicle count adjusting for age, body mass index, smoking status, and year and season of the count. The association of PM2.5 with antral follicle count was stronger among women with female factor infertility (−16.3% per 2 µg/m).
CONCLUSIONS:Among women from an infertility clinic, higher PM2.5 exposure was associated with lower ovarian reserve, raising concern that air pollution may accelerate reproductive aging.
In 2010, the American Heart Association published a statement concluding that the existing scientific evidence was consistent with a causal relationship between exposure to fine particulate matter ...and cardiovascular morbidity and mortality, and that fine particulate matter exposure is a modifiable cardiovascular risk factor. Since the publication of that statement, evidence linking air pollution exposure to cardiovascular health has continued to accumulate and the biological processes underlying these effects have become better understood. This increasingly persuasive evidence necessitates policies to reduce harmful exposures and the need to act even as the scientific evidence base continues to evolve.Policy options to mitigate the adverse health impacts of air pollutants must include the reduction of emissions through action on air quality, vehicle emissions, and renewable portfolio standards, taking into account racial, ethnic, and economic inequality in air pollutant exposure. Policy interventions to improve air quality can also be in alignment with policies that benefit community and transportation infrastructure, sustainable food systems, reduction in climate forcing agents, and reduction in wildfires. The health care sector has a leadership role in adopting policies to contribute to improved environmental air quality as well. There is also potentially significant private sector leadership and industry innovation occurring in the absence of and in addition to public policy action, demonstrating the important role of public-private partnerships. In addition to supporting education and research in this area, the American Heart Association has an important leadership role to encourage and support public policies, private sector innovation, and public-private partnerships to reduce the adverse impact of air pollution on current and future cardiovascular health in the United States.
Circadian misalignment may increase the risk of developing hepatocellular carcinoma (HCC). The aim of this study was to examine the association between distance from time zone meridian, a proxy for ...circadian misalignment, and HCC risk in the United States adjusting for known HCC risk factors.
Surveillance, Epidemiology, and End Results (SEER) provided information on 56,347 HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries in the United States. Distance from time zone meridian was estimated using the location of each SEER county's Center of Population in a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between distance from time zone meridian and HCC risk adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level prevalence of health conditions, lifestyle factors, shift work occupation, socioeconomic status, and demographic and environmental factors.
A 5-degree increase in longitude moving east to west within a time zone was associated with a statistically significant increased risk for HCC (IRR, 1.07; 95% CI, 1.01-1.14,
= 0.03). A statistically significant positive association was observed among those <65 years old, while no association was observed among individuals ≥65 years old (
< 0.01).
Circadian misalignment from residing in the western region of a time zone may impact hepatocarcinogenesis.
Circadian misalignment may be an independent risk factor for HCC.
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While previous epidemiological studies report adverse effects of long-term noise exposure on cardiovascular health, the mechanisms responsible for these effects are unclear. We sought to elucidate ...the cardiovascular and stress response to short-term, low (31.5–125Hz) and high (500–2000Hz) frequency noise exposures.
Healthy male (n=10) participants were monitored on multiple visits during no noise, low- or high-frequency noise exposure scenarios lasting 40min. Participants were fitted with an ambulatory electrocardiogram (ECG) and blood pressure measures and saliva samples were taken before, during and after noise exposures. ECGs were processed for measures of heart rate variability (HRV): high-frequency power (HF), low-frequency power (LF), the root of the mean squared difference between adjacent normal heart beats (N-N) intervals (RMSSD), and the standard deviation of N-N intervals (SDNN). Systolic blood pressure (SBP), diastolic blood pressure (DPB), and pulse were reported and saliva was analyzed for salivary cortisol and amylase. Multivariate mixed-effects linear regression models adjusted for age were used to identify statistically significant difference in outcomes by no noise, during noise or after noise exposure periods and whether this differed by noise frequency.
A total of 658, 205, and 122, HRV, saliva, and blood pressure measurements were performed over 41 person days. Reductions in HRV (LF and RMSSD) were observed during noise exposure (a reduction of 19% (-35,-3.5) and 9.1% (-17,-1.1), respectively). After adjusting for noise frequency, during low frequency noise exposure, HF, LF, and SDNN were reduced (a reduction of 32% (-57,-6.2), 34% (-52,-15), and 16% (-26,-6.1), respectively) and during high frequency noise exposure, a 21% (-39,-2.3) reduction in LF, as compared to during no noise exposure, was found. No significant (p<0.05) changes in blood pressure, salivary cortisol, or amylase were observed.
These results suggest that exposure to noise, and in particular, to low-frequency noise, negatively impacts HRV. The frequencies of noise should be considered when evaluating the cardiovascular health impacts of exposure.
•Cardiovascular and stress responses to low and high frequency noise exposures was investigated in a study of males (n=10).•Reductions in heart rate variability (HRV) were observed during noise exposure.•During low frequency noise exposure, the HRV parameters HF, LF, and SDNN were reduced.•During high frequency noise exposure, the HRV parameter LF was reduced.•No statistically significant changes in blood pressure, salivary cortisol, or amylase were observed.
Background: The relationship of fine particulate matter < 2.5 μm in diameter (PM₂.₅) air pollution with mortality and cardiovascular disease is well established, with more recent long-term studies ...reporting larger effect sizes than earlier long-term studies. Some studies have suggested the coarse fraction, particles between 2.5 and 10 μm (PM₁₀-₂.₅), may also be important. With respect to mortality and cardiovascular events, questions remain regarding the relative strength of effect sizes for chronic exposure to Hne and coarse particles. Objectives: We examined the relationship of chronic PM₂.₅ and PM₁₀-₂.₅; exposures with all-cause mortality and fatal and nonfatal incident coronary heart disease (CHD), adjusting for time-varying covariates. Methods: The current study included women from the Nurses' Health Study living in metropolitan areas of the northeastern and midwestem United States. Follow-up was from 1992 to 2002. We used geographic information systems-based spatial smoothing models to estimate monthly exposures at each participants residence. Results: We found increased risk of all-cause mortality hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.02-1.54 and fatal CHD (HR = 2.02; 95% CI, 1.07-3.78) associated with each 10-μg/m³ increase in annual PM₂.₅ exposure. Ihe association between fatal CHD and PM₁₀-₂.₅) was weaker. Conclusions: Our findings contribute to growing evidence that chronic PM₂.₅ exposure is associated with risk of all-cause and cardiovascular mortality.
Uncertainty in the relevant spatial context may drive heterogeneity in findings on the built environment and energy balance. To estimate the effect of this uncertainty, we conducted a sensitivity ...analysis defining intersection and business densities and counts within different buffer sizes and shapes on associations with self-reported walking and body mass index. Linear regression results indicated that the scale and shape of buffers influenced study results and may partly explain the inconsistent findings in the built environment and energy balance literature.
•Findings in research on the built environment and energy balance are inconsistent.•Uncertainty on the context relevant to energy balance drives this inconsistency.•We constructed built environment measures of varying buffer sizes and shapes.•We modeled the effect of these measures on self-reported walking and BMI.•Effect sizes and statistical significance varied by buffer size and shape.
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