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Inhaled irritant air pollutants may trigger stress-related metabolic dysfunction associated with altered circulating adrenal-derived hormones.We used implantable telemetry in rats to assess real-time changes in circulating glucose during and after exposure to ozone and mechanistically linked responses to neuroendocrine stress hormones.First, using a cross-over design, we monitored glucose during ozone exposures (0.0, 0.2, 0.4, andOzone (We demonstrated the temporality of neuroendocrine-stress-mediated biological sequalae responsible for ozone-induced glucose metabolic dysfunction and mechanism in a rodent model. Stress hormones assessment with real-time glucose monitoring may be useful in identifying interactions among irritant pollutants and stress-related illnesses. https://doi.org/10.1289/EHP11088.

Inhaled chemical/material exposures are a ubiquitous part of daily life around the world. There is a need to evaluate potential adverse effects of both single and repeat exposures for thousands of chemicals and an exponentially larger number of exposure scenarios (eg, repeated exposures). Meeting this challenge will require the development and use of in vitro new approach methodologies (NAMs); however, 2 major challenges face the deployment of NAMs in risk assessment are (1) characterizing what apical outcome(s) acute assays inform regarding the trajectory to long-term events, especially under repeated exposure conditions, and (2) capturing interindividual variability as it informs considerations of potentially susceptible and/or vulnerable populations. To address these questions, we used a primary human bronchial epithelial cell air-liquid interface model exposed to ozone (O3), a model oxidant and ubiquitous environmental chemical. Here we report that O3-induced proinflammatory gene induction is attenuated in repeated exposures thus demonstrating that single acute exposure outcomes do not reliably represent the trajectory of responses after repeated or chronic exposures. Further, we observed 10.1-, 10.3-, 14.2-, and 7-fold ranges of induction of interleukin (IL)-8, IL-6, heme oxygenase 1, and cyclooxygenase 2 transcripts, respectively, within in our population of 25 unique donors. Calculation of sample size estimates that indicated that 27, 24, 299, and 13 donors would be required to significantly power similar in vitro studies to identify a 2-fold change in IL-8, IL-6, HMOX1, and cyclooxygenase 2 transcript induction, respectively, to inform considerations of the uncertainty factors to reflect variability within the human population for in vitro studies.

Background Neighborhood-level socioeconomic status (SES) is associated with health outcomes, including cardiovascular disease and diabetes, but these associations are rarely studied across large, diverse populations. Methods We used Ward’s Hierarchical clustering to define eight neighborhood clusters across North Carolina using 11 census-based indicators of SES, race, housing, and urbanicity and assigned 6992 cardiac catheterization patients at Duke University Hospital from 2001 to 2010 to clusters. We examined associations between clusters and coronary artery disease index > 23 (CAD), history of myocardial infarction, hypertension, and diabetes using logistic regression adjusted for age, race, sex, body mass index, region of North Carolina, distance to Duke University Hospital, and smoking status. Results Four clusters were urban, three rural, and one suburban higher-middle-SES (referent). We observed greater odds of myocardial infarction in all six clusters with lower or middle-SES. Odds of CAD were elevated in the rural cluster that was low-SES and plurality Black (OR 1.16, 95% CI 0.94-1.43) and in the rural cluster that was majority American Indian (OR 1.31, 95% CI 0.91-1.90). Odds of diabetes and hypertension were elevated in two urban and one rural low- and lower-middle SES clusters with large Black populations. Conclusions We observed higher prevalence of cardiovascular disease and diabetes in neighborhoods that were predominantly rural, low-SES, and non-White, highlighting the importance of public health and healthcare system outreach into these communities to promote cardiometabolic health and prevent and manage hypertension, diabetes and coronary artery disease.

Background Accelerated epigenetic age has been proposed as a biomarker of increased aging, which may indicate disruptions in cellular and organ system homeostasis and thus contribute to sensitivity to environmental exposures. Methods Using 497 participants from the CATHGEN cohort, we evaluated whether accelerated epigenetic aging increases cardiovascular sensitivity to traffic-related air pollution (TRAP) exposure. We used residential proximity to major roadways and source apportioned air pollution models as measures of TRAP exposure, and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used Horvath epigenetic age acceleration (AAD) and phenotypic age acceleration (PhenoAAD) as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, and socioeconomic status. Results We observed significant interactions between TRAP and both AAD and PhenoAAD. Interactions indicated that increased epigenetic age acceleration elevated associations between proximity to roadways and PAD. Interactions were also observed between AAD and gasoline and diesel source apportioned PM2.5. Conclusion Epigenetic age acceleration may be a biomarker of sensitivity to air pollution, particularly for TRAP in urban cohorts. This presents a novel means by which to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.

BACKGROUND: Short-term changes in ambient fine particulate matter (PM(2.5)) increase the risk for unplanned hospital readmissions. However, this association has not been fully evaluated for high-risk patients or examined to determine if the readmission risk differs based on time since discharge. Here we investigate the relation between ambient PM(2.5) and 30-day readmission risk in heart failure (HF) patients using daily time windows and examine how this risk varies with respect to time following discharge. METHODS: We performed a retrospective cohort study of 17,674 patients with a recorded HF diagnosis between 2004 and 2016. The cohort was identified using the EPA CARES electronic health record resource. The association between ambient daily PM(2.5) (μg/m(3)) concentration and 30-day readmissions was evaluated using time-dependent Cox proportional hazard models. PM(2.5) associated readmission risk was examined throughout the 30-day readmission period and for early readmissions (1–3 days post-discharge). Models for 30-day readmissions included a parametric continuous function to estimate the daily PM(2.5) associated readmission hazard. Fine-resolution ambient PM(2.5) data were assigned to patient residential address and hazard ratios are expressed per 10 μg/m(3) of PM(2.5). Secondary analyses examined potential effect modification based on the time after a HF diagnosis, urbanicity, medication prescription, comorbidities, and type of HF. RESULTS: The hazard of a PM(2.5)-related readmission within three days of discharge was 1.33 (95% CI 1.18–1.51). This PM(2.5) readmission hazard was slightly elevated in patients residing in non-urban areas (1.43, 95%CI 1.22–1.67) and for HF patients without a beta-blocker prescription prior to the readmission (1.35; 95% CI 1.19–1.53). CONCLUSION: Our findings add to the evidence indicating substantial air quality-related health risks in individuals with underlying cardiovascular disease. Hospital readmissions are key metrics for patients and providers alike. As a potentially modifiable risk factor, air pollution-related interventions may be enacted that might assist in reducing costly and burdensome unplanned readmissions.

Per and polyfluoroalkyl substances (PFAS) are associated with health outcomes ranging from cancer to high cholesterol. However, there has been little examination of how PFAS exposure might impact the development of multiple chronic diseases, known as multimorbidity. Here, we associated the presence of one or more PFAS in water systems serving the zip code of residence with chronic disease and multimorbidity.We used data from the unregulated contaminant monitoring rule 3 to estimate exposure to PFAS for a random sample of 10,168 patients from the University of North Carolina Healthcare System. The presence of 16 chronic diseases was determined via. their electronic health records. We used a logistic regression model in a cross-sectional study design to associate the presence of one or more PFAS with multimorbidity. Models were adjusted for age, race, sex, smoking status, socioeconomic status, and 20 county-level confounders.There were four PFAS found in water systems that served at least one zip code represented in our patient data: PFOA, PFHpA, PFOS, and PFHxS. Exposure to any PFAS was associated with a odds ratio of 1.25 for multimorbidity (95% confidence interval = 1.09, 1.45). Among the chronic diseases with at least 300 cases, we observed associations with dyslipidemia, hypertension, ischemic heart disease, and osteoporosis.Exposure to PFAS is associated with a range of chronic diseases as well as multimorbidity. Accounting for the joint impacts of PFAS on multiple chronic conditions may give an increasingly clear picture of the public health impacts of PFAS.

We used a randomized crossover experiment to estimate the effects of ozone (vs. clean air) exposure on genome-wide DNA methylation of target bronchial epithelial cells, using 17 volunteers, each randomly exposed on two separated occasions to clean air or 0.3-ppm ozone for two hours. Twenty-four hours after exposure, participants underwent bronchoscopy to collect epithelial cells whose DNA methylation was measured using the Illumina 450 K platform. We performed global and regional tests examining the ozone versus clean air effect on the DNA methylome and calculated Fisher-exact p-values for a series of univariate tests. We found little evidence of an overall effect of ozone on the DNA methylome but some suggestive changes in PLSCR1, HCAR1, and LINC00336 DNA methylation after ozone exposure relative to clean air. We observed some participant-to-participant heterogeneity in ozone responses.

Rationale Exposure to air pollution is associated with adverse respiratory effects. Omega-3 polyunsaturated fatty acids (n-3 FA) appear to attenuate the health effects to air pollution. Objective This panel study evaluated whether n-3 FA intake and blood levels of omega-6 polyunsaturated fatty acids (n-6 FA) can modulate the associations between respiratory effects and short-term exposure to ambient air pollution in healthy adults. Methods Sixty-two healthy adults were enrolled into either high or low n-3 groups based on n-3 FA intake and erythrocytes n-3 FA concentrations. Low and high n-6 groups were dichotomized on blood n-6 FA levels. Participants underwent 3-5 testing sessions separated by at least seven days. At each session, FVC, FEV1, plasma markers of inflammation (IL-6) and oxidative stress (ox-LDL) were measured. Associations between ambient ozone and fine particulate matter (PM2.5) levels and lung function and blood markers were assessed using mixed-effects models stratified by fatty acids levels. Results Average concentrations of ozone (40.8±11.1 ppb) and PM2.5 (10.2±4.1 µg/m3) were below national ambient air quality standards during the study period. FVC was positively associated with ozone at lag0 in the high n-3 group while the association was null in the low n-3 group [for an IQR increase in ozone, 1.8%(95% CI:0.5-3.2) vs. 0.0%(95% CI:-1.4-1.5)]; however, the association shifted to negative at lag4 [-1.9%(95% CI:-3.2- -0.5) vs. 0.2%(95% CI:-1.2-1.5)] and lag5 [-1.2%(95% CI:-2.4-0.0) vs. 0.9%(-0.4-2.3)]. A similar pattern was observed in the low n-6 group compared to the high n-6 group [lag0:1.7%(95% CI:0.3-3.0) vs. 0.5%(95% CI:-0.9-2.0) and lag4:-1.4%(95% CI:-2.8-0.0) vs. -0.5%(95% CI:-1.8-0.9)]. The associations between FEV1 and ozone and between FVC and PM2.5 also followed a similar pattern. Elevated ozone levels were associated with an immediate decrease in ox-LDL in the high n-3 group atlag0 [-12.3%(95% CI:-24.8-0.1)] while no change in the low n-3 group [-7.5%(95% CI: -21.4-6.5)], and a delayed increase in IL-6 in the high n-3 group compared with the low n-3 group [lag4: 66.9%(95% CI:27.9-106.0) vs. 8.9%(95% CI:-31.8-49.6), lag5: 58.2%(95% CI:22.4-94.1) vs. -7.4%(95% CI:-48.8-34.0), and lag6: 45.8%(95% CI:8.7-82.9) vs. -8.5%(95% CI:-49.7-32.6)]. Conclusions We observed lag-dependent associations between short-term ambient air pollutants and lung function that were differentially modulated by n-3 and n-6 FAs, suggesting that n-3 and n-6 FAs counteract the respiratory response to low levels of ambient air pollution in healthy adults. Clinical trial registered with ClinicalTrials.gov (NCT02921048).

Smoke Sense is a citizen science project with investigative, educational, and action‐oriented objectives at the intersection of wildland fire smoke and public health. Participants engage with a smartphone application to explore current and forecast visualizations of air quality, learn about how to protect health from wildfire smoke, and record their smoke experiences, health symptoms, and behaviors taken to reduce their exposures to smoke. Through participation in the project, individuals engage in observing changes in their environment and recording changes in their health, thus facilitating progression on awareness of health effects of air pollution and adoption of desired health‐promoting behaviors. Participants can also view what others are reporting. Data from the pilot season (1 August 2017 to 7 January 2018; 5,598 downloads) suggest that there is a clear demand for personally relevant data during wildfire episodes motivated by recognition of environmental hazard and the personal concern for health. However, while participants shared clear perceptions of the environmental hazard and health risks in general, they did not consistently recognize their own personal health risk. The engagement in health protective behavior was driven in response to symptoms rather than as preventive courses of action. We also observed clear differences in the adoption likelihood of various health protective behaviors attributed to barriers and perceived benefits of these actions. As users experience a greater number and severity of symptoms, the perceived benefits of taking health protective actions exceeded the costs associated with the barriers and thus increased adoption of those actions. Based on pilot season data, we summarize key insights which may improve current health risk communications in nudging individuals toward health protective behavior; there is a need to increase personal awareness of risk and compelling evidence that health protective behaviors are beneficial., Key Points With Smoke Sense, citizen scientists become human sensors of their own behavior in relation to their environmentSmoke Sense reaches participants when and where they experience wildfire smokeIncreasing personal awareness of risk and providing compelling evidence of health benefit is needed

BackgroundStress-related neurobehavioral and metabolic disorders are associated with altered circulating adrenal-derived hormones and hyperglycemia. Temporal assessment of glucose and these hormones is critical for insights on an individual’s health.ObjectivesHere we used implantable-telemetry in rats to assess real-time changes in circulating glucose during and after exposure to the air pollutant ozone, and link responses to circulating neuroendocrine stress and metabolic hormones. We also compared rodent glucose and corticosterone (cortisol in humans) responses to humans exposed to ozone.MethodsFirst, using a cross-over design, we monitored glucose levels during single or repeated ozone exposures (0.0, 0.2, 0.4 and 0.8-ppm) and non-exposure periods in male Wistar-Kyoto-rats implanted with glucose-telemeters. A second cohort of un-implanted rats was exposed to ozone (0.0, 0.4 or 0.8-ppm) for 30-min, 1-hour, 2-hour, or 4-hour with hormones measured immediately after exposure. Then we assessed glucose metabolism in sham and adrenalectomized rats with or without pharmacological interventions of adrenergic and glucocorticoid receptors. Finally, we assessed glucose and cortisol in serum samples from a clinical study involving exposure of human volunteers to air or 0.3 ppm ozone.ResultsOzone (0.8-ppm) caused hyperglycemia and hypothermia beginning 90-min into exposure, with reversal of effects 4-6 hours post-exposure. Glucose monitoring during four daily 4-hour ozone exposures revealed duration of hyperglycemia, adaptation, and diurnal variations. Ozone-induced hyperglycemia was preceded by increased adrenocorticotropic hormone, corticosterone, and epinephrine, but depletion of thyroid-stimulating, prolactin, and luteinizing hormones. Hyperglycemia was inhibited in rats that were adrenalectomized and/or treated with glucocorticoid inhibitor. The depletion of cortisol was dampened in humans exposed to ozone during intermittent exercise.DiscussionWe demonstrate for the first time the temporality of neuroendocrine-stress-mediated biological sequalae responsible for ozone-induced metabolic dysfunction as exposure occurs. Real-time glucose monitoring with stress hormones assessment may be useful in identifying interactions among pollutants and stress-related illnesses.

Introduction: Exposure to ambient nitrogen dioxide (NO 2 ) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown health benefits against exposure to air pollution. Hypothesis: Dietary omega-3 PUFA intake offers cardiovascular and respiratory benefits against short-term exposure to ambient NO 2 in healthy adults. Methods: Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual dietary omega-3 PUFA intake. Each participant was repeatedly assessed for blood lipids, markers of coagulation and fibrinolysis, vascular function, heart rate variability (HRV), and lung function up to five times separated by at least 7 days between October 2016 and September 2019. Daily ambient NO 2 concentrations were obtained from nearby air quality monitoring stations. The associations between NO 2 concentrations and the measured biomarkers were evaluated using the linear mixed-effects models stratified by the omega-3 intake levels. Results: In the high omega-3 group, an IQR increase in NO 2 concentrations was associated with reductions in total cholesterol at lag2 [-2.6% (-4.4, -0.9)], LDL at lag2 [-3.1% (-5.5, -0.7)], and HDL at lag1 [-2.4% (-4.4, -0.3)] and lag2 [-2.0% (-3.8, -0.1)]; increases in flow-mediated dilatation of brachial artery at lag1[5.7% (0.1, 11.2)] and lag2 [5.7% (0.8, 10.6)]; decreases in plasma levels of endothelin-1at lag3 [-25.6% (-50.0, -1.2)] and lag4 [-22.9% (-45.9, -0.01)]; decreased high frequency (HFn) of HRV [-7.2% (-13.6, -0.8)] and increased LF/HF ratio [13.4% (0.2, 28.3)] at lag3; as well as increased lung function. In the low omega-3 group, blood lipids, vascular function biomarkers and lung function were not significantly associated with NO 2 exposure. However, NO 2 exposure was associated with elevations in coagulation markers (von Willebrand Factor and D-dimer) and a decrease in very-low frequency of HRV at lag0 in the low omega-3 group. Conclusions: The results imply that high dietary omega-3 PUFA intake may offer benefits to cardiovascular and respiratory health in response to exposure to low-level ambient NO 2 in healthy adults. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.

Exposure to air pollution is a major risk factor for cardiovascular disease, disease risk factors, and mortality. Specifically, particulate matter (PM), and to some extent ozone, are contributors to these effects. In addition, exposures to these pollutants may be especially dangerous for susceptible populations. In this repeated-visit panel study, cardiovascular markers were collected from thirteen male participants with stable coronary artery disease. For 0-4 days prior to the health measurement collections, daily concentrations of fine PM (PM

Short-term ambient fine particulate matter (PMWe conducted a retrospective cohort study of 2924 patients identified using electronic health records from the University of North Carolina Healthcare System who had a recorded MI between 2004 and 2016. Troponin I measurements were available from 2014 to 2016, and were required to be at least 1 week away from a clinically diagnosed MI. Daily ambient PMA 10 µg/mDaily elevations in PM

BACKGROUND AND AIM: Although the biological mechanisms remain uncertain, non-optimal air temperatures have been associated with cardiovascular mortality. Dietary intake of omega-3 fatty acids (n-3 ...

Over one-third of the U.S. population is exposed to unsafe levels of ozone (OForty-three participants (26 ± 4 years old; 47% female) were randomized to receive 3 g/day of FO, 3 g/day OO, or no supplementation (CTL) for 4 weeks prior to undergoing 2-hour exposures to filtered air and 300 ppb OCompared with filtered air, OFO supplementation appears to offer protective effects against lung function decrements caused by acute O

Immunization of rats with a bystander antigen and the toxic lectin, ricin, results in a dramatically potentiated IgE response which was only seen when ricin was administered together with antigen, or 24 h later, suggesting that the toxin was acting on cells which were activated as the result of immunization. The identity of these activated cells was investigated in radioligand bindings studies with 125I ricin. No difference was seen in the number of ricin binding sites on splenic CD4+ and CD8+ T cells from untreated rats, but the number of ricin binding sites was 13-fold higher on CD8+ but not on CD4+ T cells from immunized rats. Adoptive transfer of 1 × 10899% pure CD8+ T cells from animals, immunized 3 days before with antigen alone, suppressed the IgE response to antigen plus alum by over 90%. The IgE suppressive effect of these CD8+ T cells was not antigen specific, and they had no effect on the IgG antibody response. CD4+ T cells from none of these animals had any effect on the subsequent IgE of IgG antibody response. The capacity of CD4+ and CD8+ T cells stimulated with PHA or PMA and ionomycin to secrete the cytokines IL-2 and IFN-γ or to make IL-4 mRNA was also compared. CD8+ T cells were the highest producers of IFN-γ and accounted for 65% oftotal splenic IFN-γ. Immunization with ricin plus antigen reduced the amount of IFN-γ secreted by CD4+ (OX22+/--) and CD8+ T cells 5- to 10-fold. Over 95% of the IL-2 produced was derived from OX22+CD4+ T cells, and this did not change. In spleen cells from unimmunized animals, the largest amounts of IL-4 mRNA were found in CD8+ T cells. Following immunization with antigen plus ricin, total splenic IL-4 mRNA production was increased 3- to 4-fold and following boosting with ricin plus antigen was increased a further 3 to 4-fold. These results show: (i) that approximately 50% of splenic CD8+T cells are activated within24h of immunization with antigen, (ii) that adoptive transfer of these cells suppresses IgE production, (iii) that co-administration of ricin and antigen selectively depletes them, (iv) that this is associated with a massive increase in serum IgE a decreased capacity of T cells to produce IFN-γ and an increased capacity to make IL-4. These data suggest that CD8+ T cells, activated early in the immune response, play an important part in regulating cytokine and IgE production.

Long-term air pollution exposure, notably fine particulate matter, is a global contributor to morbidity and mortality and a known risk factor for coronary artery disease (CAD) and myocardial infarctions (MI). Knowledge of impacts related to source-apportioned PM(2.5) is limited. New modeling methods allow researchers to estimate source-specific long-term impacts on the prevalence of CAD and MI. The Catheterization Genetics (CATHGEN) cohort consists of patients who underwent a cardiac catheterization at Duke University Medical Center between 2002 and 2010. Severity of coronary blockage was determined by coronary angiography and converted into a binary indicator of clinical CAD. History of MI was extracted from medical records. Annual averages of source specific PM(2.5) were estimated using an improved gas-constrained source apportionment model for North Carolina from 2002 to 2010. We tested six sources of PM(2.5) mass for associations with CAD and MI using mixed effects multivariable logistic regression with a random intercept for county and multiple adjustments. PM(2.5) fractions of ammonium bisulfate and ammonium nitrate were associated with increased prevalence of CAD (odds ratio [OR] 1.20; 95% CI = 1.11, 1.22 and OR 1.18; 95% CI = 1.05, 1.32, respectively). PM(2.5) from ammonium bisulfate and ammonium nitrate were also associated with increased prevalence of MI (OR 1.20; 95% CI = 1.10, 1.29 and OR 1.35; 95% CI = 1.20, 1.53, respectively). Greater PM(2.5) concentrations of ammonium bisulfate and ammonium nitrate are associated with greater MI and CAD prevalence. The association with bisulfate suggests aerosol acidity may play a role. Our findings suggest analyses of source specific PM(2.5) mass can reveal novel associations.

Background: Fine particulate matter (PM2.5) exposure is associated with increased morbidity and mortality, particularly for cardiovascular disease. The association between long-term exposure to PM2.5 and measures of lipoprotein subfractions remains unclear. Therefore, we examined associations between long-term PM2.5 exposure and traditional and novel lipoprotein measures in a cardiac catheterization cohort in North Carolina. Methods: This cross-sectional study included 6587 patients who had visited Duke University for a cardiac catheterization between 2001 and 2010 and resided in North Carolina. We used estimates of daily PM2.5 concentrations on a 1 km-grid based on satellite measurements. PM2.5 predictions were matched to the address of each patient and averaged for the year prior to catheterization date. Serum lipids included HDL, LDL, and triglyceride-rich particle, and apolipoprotein B concentrations (HDL-P, LDL-P, TRL-P, and apoB, respectively). Linear and quantile regression models were used to estimate change in lipoprotein levels with each μg/m3 increase in annual average PM2.5. Models were adjusted for age, sex, race/ethnicity, history of smoking, area-level education, urban/rural status, body mass index, and diabetes. Results: For a 1-μg/m3 increment in PM2.5 exposure, we observed increases in total and small LDL-P, LDL-C, TRL-P, apoB, total cholesterol, and triglycerides. The percent change from the mean outcome level was 2.00% (95% CI: 1.38%, 2.64%) for total LDL-P and 2.25% (95% CI: 1.43%, 3.06%) for small LDL-P. Conclusion: Among this sample of cardiac catheterization patients residing in North Carolina, long-term PM2.5 exposure was associated with increases in several lipoprotein concentrations. This abstract does not necessarily reflect U.S. EPA policy. Keywords: Fine particulate matter, Lipids, Cardiovascular disease, Air pollution

ObjectiveShort-term ambient fine particulate matter (PM2.5) is associated with adverse cardiovascular events including myocardial infarction (MI). However, few studies have examined associations between PM2.5 and subclinical cardiomyocyte damage outside of overt cardiovascular events. Here we evaluate the impact of daily PM2.5 on cardiac troponin I, a cardiomyocyte specific biomarker of cellular damage.MethodsWe conducted a retrospective cohort study of 2924 patients identified using electronic health records from the University of North Carolina Healthcare System who had a recorded MI between 2004 and 2016. Troponin I measurements were available from 2014 to 2016, and were required to be at least 1 week away from a clinically diagnosed MI. Daily ambient PM2.5 concentrations were estimated at 1 km resolution and assigned to patient residence. Associations between log-transformed troponin I and daily PM2.5 were evaluated using distributed lag linear mixed effects models adjusted for patient demographics, socioeconomic status and meteorology.ResultsA 10 µg/m3 elevation in PM2.5 3 days before troponin I measurement was associated with 0.06 ng/mL higher troponin I (95% CI=0.004 to 0.12). In stratified models, this association was strongest in patients that were men, white and living in less urban areas. Similar associations were observed when using 2-day rolling averages and were consistently strongest when using the average exposure over the 5 days prior to troponin I measurement.ConclusionsDaily elevations in PM2.5 were associated with damage to cardiomyocytes, outside of the occurrence of an MI. Poor air quality may cause persistent damage to the cardiovascular system leading to increased risk of cardiovascular disease and adverse cardiovascular events.

Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact P-value of P = 2.44 × 10−4 (i.e. 2/213). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (C5orf63; 7-CpGs) and unc-45 myosin chaperone A gene (UNC45A; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.

Household air pollution from solid fuel combustion was estimated to cause 2.31 million deaths worldwide in 2019; cardiovascular disease is a substantial contributor to the global burden. We evaluated the cross-sectional association between household air pollution (24-hour gravimetric kitchen and personal particulate matter (PM(2.5)) and black carbon (BC)) and C-reactive protein (CRP) measured in dried blood spots among 107 women in rural Honduras using wood-burning traditional or Justa (an engineered combustion chamber) stoves. A suite of 6 additional markers of systemic injury and inflammation were considered in secondary analyses. We adjusted for potential confounders and assessed effect modification of several cardiovascular-disease risk factors. The median (25th, 75th percentiles) 24-hour-average personal PM(2.5) concentration was 115 μg/m(3) (65,154 μg/m(3)) for traditional stove users and 52 μg/m(3) (39, 81 μg/m(3)) for Justa stove users; kitchen PM(2.5) and BC had similar patterns. Higher concentrations of PM(2.5) and BC were associated with higher levels of CRP (e.g., a 25% increase in personal PM(2.5) was associated with a 10.5% increase in CRP [95% CI: 1.2–20.6]). In secondary analyses results were generally consistent with a null association. Evidence for effect modification between pollutant measures and four different cardiovascular risk factors (e.g., high blood pressure) was inconsistent. These results support the growing evidence linking household air pollution and cardiovascular disease.

Background/Aim: Fine particles (PM2.5) are associated with a higher risk for coronary events. Cardiac troponin T (cTnT) is a myocardium-specific protein which is measured clinically for the diagnos...

Presentation to the International Society of Environmental Epidemiology 2020 Virtual Meeting (ISEE) August 2020

Background/Aim: Short-term changes in ambient fine particulate matter (diameter ≤ 2.5 μm, PM2.5) air pollution increase the risk for hospital admission and readmission. Additional research is neede...

Background Environmental health risks for individuals with heart failure ( HF ) have been inadequately studied, as these individuals are not well represented in traditional cohort studies. To address this we studied associations between long‐term air pollution exposure and mortality in HF patients. Methods and Results The study population was a hospital‐based cohort of individuals diagnosed with HF between July 1, 2004 and December 31, 2016 compiled using electronic health records. Individuals were followed from 1 year after initial diagnosis until death or the end of the observation period (December 31, 2016). We used Cox proportional hazards models to evaluate the association of annual average fine particulate matter ( PM 2.5 ) exposure at the time of initial HF diagnosis with all‐cause mortality, adjusted for age, race, sex, distance to the nearest air pollution monitor, and socioeconomic status indicators. Among 23 302 HF patients, a 1 μg/m 3 increase in annual average PM 2.5 was associated with an elevated risk of all‐cause mortality (hazard ratio 1.13; 95% CI, 1.10–1.15). As compared with people with exposures below the current national PM 2.5 exposure standard (12 μg/m 3 ), those with elevated exposures experienced 0.84 (95% CI, 0.73–0.95) years of life lost over a 5‐year period, an observation that persisted even for those residing in areas with PM 2.5 concentrations below current standards. Conclusions Residential exposure to elevated concentrations of PM 2.5 is a significant mortality risk factor for HF patients. Elevated PM 2.5 exposures result in substantial years of life lost even at concentrations below current national standards.

Exposure to ambient air pollutants such as ozone (O3) and particulate matter (PM) is associated with increased cardiovascular morbidity and rate of mortality, but the underlying biological mechanisms have yet to be described. Emerging evidence shows that extracellular vehicle (EV) microRNAs (miRNAs) may facilitate cell-to-cell and organ-to-organ communications and play a role in the air pollution-induced cardiovascular effects. This study aims to explore the association between air pollutant exposure and miRNA changes related to cardiovascular diseases. Using a panel study design, 14 participants with coronary artery diseases were enrolled in this study. Each participant had up to 10 clinical visits and their plasma samples were collected and measured for expression of miRNA-21 (miR-21), miR-126, miR-146, miR-150, and miR-155. Mixed effects models adjusted for temperature, humidity, and season were used to examine the association between miRNA levels and exposure to 8-hr O3 or 24-hr PM2.5 up to 4 days prior. Results demonstrated that miR-150 expression was positively associated with O3 exposure at 1–4 days lag and 5day moving average while miR-155 expression tracked with O3 exposure at lag 0. No significant association was found between miRNA expression and ambient PM2.5 at any time point. β-blocker and diabetic medication usage significantly modified the correlation between O3 exposure and miR-150 expression where the link was more prominent among non-users. In conclusion, evidence indicated an association between exposure to ambient O3 and circulating levels of EV miR-150 and miR-155 was observed. These findings pointed to a future research direction involving miRNA-mediated mechanisms of O3-induced cardiovascular effects.

Background Air pollution-induced changes in cardiac electrophysiological properties could be a pathway linking air pollution and cardiovascular events. The evidence of air pollution effects on the cardiac conduction system is incomplete yet. We investigated short-term effects of particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) and ozone (O3) on cardiac electrical impulse propagation and repolarization as recorded in surface electrocardiograms (ECG). Methods We analyzed repeated 12-lead ECG measurements performed on 5,332 patients between 2001 and 2012. The participants came from the Duke CATHGEN Study who underwent cardiac catheterization and resided in North Carolina, United States (NC, U.S.). Daily concentrations of PM2.5 and O3 at each participant’s home address were predicted with a hybrid air quality exposure model. We used generalized additive mixed models to investigate the associations of PM2.5 and O3 with the PR interval, QRS interval, heart rate-corrected QT interval (QTc), and heart rate (HR). The temporal lag structures of the associations were examined using distributed-lag models. Results Elevated PM2.5 and O3 were associated with four-day lagged lengthening of the PR and QRS intervals, and with one-day lagged increases in HR. We observed immediate effects on the lengthening of the QTc interval for both PM2.5 and O3, as well as delayed effects for PM2.5 (lagged by 3 – 4 days). The associations of PM2.5 and O3 with the PR interval and the association of O3 with the QRS interval persisted until up to seven days after exposure. Conclusions In patients undergoing cardiac catheterization, short-term exposure to air pollution was associated with increased HR and delays in atrioventricular conduction, ventricular depolarization and repolarization. Electronic supplementary material The online version of this article (10.1186/s12989-018-0275-z) contains supplementary material, which is available to authorized users.

Adverse cardiovascular events have been linked with PMWe utilized a cohort of 5679 patients who had undergone a cardiac catheterization between 2002-2009 and resided in NC. Exposure to PMWe found that the elevated odds for CAD23 and MI were nearly equivalent for all exposure assessment methods. One difference was that data from AQS and the census tract CMAQ showed a rural/urban difference in relative risk, which was not apparent with the satellite or 12km-CMAQ models.Long-term air pollution exposure was associated with coronary artery disease for both modeled and monitored data.

The field of toxicoepigenetics is rapidly emerging to provide new insights into the relationship between environmental factors, the epigenome, and public health. Toxicoepigenetic data have the potential to revolutionize our understanding of environmental exposure effects and susceptibility. Studies in recent years have demonstrated that exposure to air pollution alters epigenetic modification states; however, continued advancement of the field is limited by the intrinsic complexity of the epigenome and inherent limitations of different types of studies (epidemiological, clinical, and in vitro) that are used in toxicoepigenetics. Overcoming these challenges will require a concerted and collaborative effort between molecular and cellular biologists, toxicologists, epidemiologists, and risk assessors to develop a thorough and practical understanding of the relationship between air pollution exposure, the epigenome, and health effects. Here we review the current state of air pollution epigenetics and discuss perspectives on the necessary steps to move the field forward to determine the role that the epigenome plays in air pollution exposure effects and susceptibility.

Identifying communities vulnerable to adverse health effects from exposure to wildfire smoke may help prepare responses, increase the resilience to smoke and improve public health outcomes during smoke days. We developed a Community Health-Vulnerability Index (CHVI) based on factors known to increase the risks of health effects from air pollution and wildfire smoke exposures. These factors included county prevalence rates for asthma in children and adults, chronic obstructive pulmonary disease, hypertension, diabetes, obesity, percent of population 65 years of age and older, and indicators of socioeconomic status including poverty, education, income and unemployment. Using air quality simulated for the period between 2008 and 2012 over the continental U.S. we also characterized the population size at risk with respect to the level and duration of exposure to fire-originated fine particulate matter (fire-PM2.5) and CHVI. We estimate that 10% of the population (30.5 million) lived in the areas where the con...

Rationale: Exposure to ambient particulate matter (PM) and ozone has been associated with cardiovascular disease (CVD). However, the mechanisms linking PM and ozone exposure to CVD remain poorly understood. Objective: This study explored associations between short-term exposures to PM with a diameter