Short-term PM2.5 exposure and early-readmission risk: a retrospective cohort study in North Carolina heart failure patients.

BACKGROUND: Short-term changes in ambient fine particulate matter (PM2.5) 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 PM2.5 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 PM2.5 (µg/m3) concentration and 30-day readmissions was evaluated using time-dependent Cox proportional hazard models. PM2.5 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 PM2.5 associated readmission hazard. Fine-resolution ambient PM2.5 data were assigned to patient residential address and hazard ratios are expressed per 10 µg/m3 of PM2.5. 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 PM2.5-related readmission within 3 days of discharge was 1.33 (95% CI 1.18-1.51). This PM2.5 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.

Associations between neighborhood socioeconomic cluster and hypertension, diabetes, myocardial infarction, and coronary artery disease within a cohort of cardiac catheterization patients.

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.

Exposures to low-levels of fine particulate matter are associated with acute changes in heart rate variability, cardiac repolarization, and circulating blood lipids in coronary artery disease patients.

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 (PM2.5) and ozone were obtained from local central monitoring stations located near the participant's homes. Then, single (PM2.5) and two-pollutant (PM2.5 and ozone) models were used to assess whether there were short-term changes in cardiovascular health markers. Per interquartile range increase in PM2.5, there were decrements in several heart rate variability metrics, including the standard deviation of the normal-to-normal intervals (lag 3, -5.8%, 95% confidence interval (CI) = -11.5, 0.3) and root-mean squared of successive differences (five day moving average, -8.1%, 95% CI = -15.0, -0.7). In addition, increases in PM2.5 were also associated with changes in P complexity (lag 1, 4.4%, 95% CI = 0.5, 8.5), QRS complexity (lag 1, 4.9%, 95% CI = 1.4, 8.5), total cholesterol (five day moving average, -2.1%, 95% CI = -4.1, -0.1), and high-density lipoprotein cholesterol (lag 2, -1.6%, 95% CI = -3.1, -0.1). Comparisons to our previously published work on ozone were conducted. We found that ozone affected inflammation and endothelial function, whereas PM2.5 influenced heart rate variability, repolarization, and lipids. All the health changes from these two studies were found at concentrations below the United States Environmental Protection Agency's National Ambient Air Quality Standards. Our results imply clear differences in the cardiovascular outcomes observed with exposure to the two ubiquitous air pollutants PM2.5 and ozone; this observation suggests different mechanisms of toxicity for these exposures.

Omega-3 fatty acids attenuate cardiovascular effects of short-term exposure to ambient air pollution.

BACKGROUND: Exposure to air pollution is associated with elevated cardiovascular risk. Evidence shows that omega-3 polyunsaturated fatty acids (omega-3 PUFA) may attenuate the adverse cardiovascular effects of exposure to fine particulate matter (PM2.5). However, it is unclear whether habitual dietary intake of omega-3 PUFA protects against the cardiovascular effects of short-term exposure to low-level ambient air pollution in healthy participants. In the present study, sixty-two adults with low or high dietary omega-3 PUFA intake were enrolled. Blood lipids, markers of vascular inflammation, coagulation and fibrinolysis, and heart rate variability (HRV) and repolarization were repeatedly assessed in 5 sessions separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily PM2.5 and maximum 8-h ozone (O3) concentrations were obtained from nearby air quality monitoring stations. Linear mixed-effects models were used to assess the associations between air pollutant concentrations and cardiovascular responses stratified by the omega-3 intake levels. RESULTS: The average concentrations of ambient PM2.5 and O3 were well below the U.S. National Ambient Air Quality Standards during the study period. Significant associations between exposure to PM2.5 and changes in total cholesterol, von Willebrand factor (vWF), tissue plasminogen activator, D-dimer, and very-low frequency HRV were observed in the low omega-3 group, but not in the high group. Similarly, O3-associated adverse changes in cardiovascular biomarkers (total cholesterol, high-density lipoprotein, serum amyloid A, soluable intracellular adhesion molecule 1, and vWF) were mainly observed in the low omega-3 group. Lag-time-dependent biphasic changes were observed for some biomarkers. CONCLUSIONS: This study demonstrates associations between short-term exposure to PM2.5 and O3, at concentrations below regulatory standard, and subclinical cardiovascular responses, and that dietary omega-3 PUFA consumption may provide protection against such cardiovascular effects in healthy adults.

Circulating microRNAs as putative mediators in the association between short-term exposure to ambient air pollution and cardiovascular biomarkers.

BACKGROUND: Exposure to ambient air pollution is associated with increased cardiovascular morbidity and mortality. Circulating microRNAs (miRNAs) may mediate cardiovascular effects of exposure to air pollution. This study aims to investigate whether circulating miRNAs mediate the associations between short-term human exposure to ambient air pollution and cardiovascular biomarkers. METHODS: Twenty-four healthy adults residing in the Research Triangle area of North Carolina, USA were enrolled between December 2016 and July 2019. Circulating miRNAs, protein, and lipid biomarkers were assessed repeatedly for 3 sessions separated by at least 7 days. Linear mixed-effects models were used to assess the associations between air pollutant concentrations obtained from nearby air quality monitoring stations and miRNAs controlling for covariates including omega-3 index, relative humidity, and temperature. miRNAs that were significantly altered were then matched with protein or blood lipid biomarkers using either Ingenuity Pathway Analysis or a literature search. A mediation analysis was performed to test the statistical significance of miRNA's mediating effects between exposure to air pollution and cardiovascular biomarkers. RESULTS: Short-term exposure to ambient fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) was associated with changes in 11, 9, and 24 circulating miRNAs, respectively. Pathway analysis showed that several miRNAs including miR-125b-5p, miR-144-5p, miR-26a-5p, and miR-34a-5p may mediate the effects of air pollutant exposure on the changes of downstream protein / lipid biomarkers including serum amyloid A (SAA), C-reactive protein (CRP), soluble vascular adhesive molecules 1 (sICAM1), total cholesterol, and high-density lipoproteins (HDL). Mediation analysis showed that only miR-26a-5p significantly mediated air pollutant (PM2.5 and NO2)-induced effects on blood CRP and total cholesterol levels. For example, 34.1% of PM2.5-associated changes in CRP were significantly mediated by miR-26a-5p at lag4 [indirect effects, 0.06 (0.02, 0.10), P = 0.005]. Similarly, the proportions of indirect effects of miR-26a-5p on the association between NO2 exposure and CRP were 46.8% at lag2 [0.06 (0.02, 0.11), P = 0.003], 61.2% at lag3 [0.05 (0.00, 0.09), P = 0.04], and 30.8% at 5-day moving average [0.06 (0.02, 0.10), P = 0.01]. In addition, omega-3 index may be a significant modifying factor of the mediated effects of miRNAs. CONCLUSIONS: This study demonstrates that short-term exposure to ambient PM2.5, O3, and NO2 was associated with specific circulating miRNAs, and some of which may mediate their effects on the downstream inflammation and blood lipid markers.

The influence of dietary intake of omega-3 polyunsaturated fatty acids on the association between short-term exposure to ambient nitrogen dioxide and respiratory and cardiovascular outcomes among healthy adults.

BACKGROUND: Short-term exposure to ambient nitrogen dioxide (NO2) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown protection against exposure to fine particulate matter. This study aims to investigate whether habitual omega-3 PUFA intake differentially modify the associations between respiratory and cardiovascular responses and short-term exposure to ambient NO2. METHODS: Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual omega-3 PUFA intake. Each participant was repeatedly assessed for lung function, blood lipids, markers of coagulation and fibrinolysis, vascular function, and heart rate variability (HRV) in up to five sessions, each separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily ambient NO2 concentrations were obtained from an area air quality monitoring station on the day of outcome assessment (Lag0), 4 days prior (Lag1-4), as well as 5-day moving average (5dMA). The associations between short-term exposure to NO2 and the measured indices were evaluated using linear mixed-effects models stratified by omega-3 levels and adjusted by covariates including relative humidity and temperature. RESULTS: The average concentration of ambient NO2 during the study periods was 5.3±3.8 ppb which was below the National Ambient Air Quality Standards (NAAQS). In the high omega-3 group, an interquartile range (IQR) increase in short-term NO2 concentrations was significantly associated with increased lung function [e.g. 1.2% (95%CI: 0.2%, 2.2%) in FVC at lag1, 2.6% (95%CI: 0.4%, 4.8%) in FEV1 at 5dMA], decreased blood lipids [e.g. -2.6% (95%CI: -4.4%, -0.9%) in total cholesterol at lag2, -3.1% (95%CI: -6.1%, 0.0%) in HDL at 5dMA, and -3.1% (95%CI: -5.5%, -0.7%) in LDL at lag2], improved vascular function [e.g. 8.9% (95%CI: 0.6%, 17.2%) increase in FMD and 43.1% (95%CI: -79.8%, -6.3%) decrease in endothelin-1 at 5dMA], and changed HRV parameters [e.g. -7.2% (95%CI: -13.6%, -0.8%) in HFn and 13.4% (95%CI: 0.2%, 28.3%) in LF/HF ratio at lag3]. In the low omega-3 group, an IQR increase in ambient NO2 was associated with elevations in coagulation markers (von Willebrand Factor, D-dimer) and a decrease in HRV (very-low frequency); however, null associations were observed between short-term NO2 exposure and changes in lung function, blood lipids, and vascular function. CONCLUSIONS: The results in this study imply that dietary omega-3 PUFA consumption may offer respiratory and vascular benefits in response to short-term exposure of healthy adults to NO2 levels below the NAAQS. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02921048 ).

Health impacts of a randomized biomass cookstove intervention in northern Ghana.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has adverse health effects. REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) was a randomized cookstove intervention study that aimed to determine the effects of two types of "improved" biomass cookstoves on health using self-reported health symptoms and biomarkers of systemic inflammation from dried blood spots for female adult cooks and children, and anthropometric growth measures for children only. METHODS: Two hundred rural households were randomized into four different cookstove groups. Surveys and health measurements were conducted at four time points over a two-year period. Chi-square tests were conducted to determine differences in self-reported health outcomes. Linear mixed models were used to assess the effect of the stoves on inflammation biomarkers in adults and children, and to assess the z-score deviance for the anthropometric data for children. RESULTS: We find some evidence that two biomarkers of oxidative stress and inflammation, serum amyloid A and C-reactive protein, decreased among adult primary cooks in the intervention groups relative to the control group. We do not find detectable impacts for any of the anthropometry variables or self-reported health. CONCLUSIONS: Overall, we conclude that the REACCTING intervention did not substantially improve the health outcomes examined here, likely due to continued use of traditional stoves, lack of evidence of particulate matter emissions reductions from "improved" stoves, and mixed results for HAP exposure reductions. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov (National Institutes of Health); Trial Registration Number: NCT04633135 ; Date of Registration: 11 November 2020 - Retrospectively registered. URL: https://clinicaltrials.gov/ct2/show/NCT04633135?term=NCT04633135&draw=2&rank=1.

Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults.

BACKGROUND: Fine particulate matter (PM2.5) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies. METHODS: To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM2.5, in the form of concentrated ambient particles (mean: 37.8 µg/m3, SD 6.5), and filtered air (mean: 2.1 µg/m3, SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure. RESULTS: Low-level PM2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM2.5 concentration (37.8 µg/m3) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV1) and FEV1/ forced vital capacity (FEV1/FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure. CONCLUSIONS: This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM2.5 particles at levels near the PM2.5 US NAAQS standard. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrials.gov ; Identifier: NCT03232086 . The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.

C-reactive protein from dried blood spots: Application to household air pollution field studies.

Household air pollution (HAP) is estimated to be an important risk factor for cardiovascular disease, but little clinical evidence exists and collecting biomarkers of disease risk is difficult in low-resource settings. Among 54 Nicaraguan women with woodburning cookstoves, we evaluated cross-sectional associations between 48-hour measures of HAP (eg, fine particulate matter, PM2.5 ) and C-reactive protein (CRP) via dried blood spots; secondary analyses included seven additional biomarkers of systemic injury and inflammation. We conducted sub-studies to calculate the intraclass correlation coefficient (ICC) in biomarkers collected over four consecutive days in Nicaragua and to assess the validity of measuring biomarkers in dried blood by calculating the correlation with paired venous-drawn samples in Colorado. Measures of HAP were associated with CRP (eg, a 25% increase in indoor PM2.5 was associated with a 7.4% increase in CRP [95% confidence interval: 0.7, 14.5]). Most of the variability in CRP concentrations over the 4-day period was between-person (ICC: 0.88), and CRP concentrations were highly correlated between paired dried blood and venous-drawn serum (Spearman ρ = .96). Results for secondary biomarkers were primarily consistent with null associations, and the sub-study ICCs and correlations were lower. Assessing CRP via dried blood spots provides a feasible approach to elucidate the association between HAP and cardiovascular disease risk.

Effects of ambient ozone exposure on circulating extracellular vehicle microRNA levels in coronary artery disease patients.

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. ß-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.

Associations Between Residential Proximity to Traffic and Vascular Disease in a Cardiac Catheterization Cohort.

OBJECTIVE: Exposure to mobile source emissions is nearly ubiquitous in developed nations and is associated with multiple adverse health outcomes. There is an ongoing need to understand the specificity of traffic exposure associations with vascular outcomes, particularly in individuals with cardiovascular disease. APPROACH AND RESULTS: We performed a cross-sectional study using 2124 individuals residing in North Carolina, United States, who received a cardiac catheterization at the Duke University Medical Center. Traffic-related exposure was assessed via 2 metrics: (1) the distance between the primary residence and the nearest major roadway; and (2) location of the primary residence in regions defined based on local traffic patterns. We examined 4 cardiovascular disease outcomes: hypertension, peripheral arterial disease, the number of diseased coronary vessels, and recent myocardial infarction. Statistical models were adjusted for race, sex, smoking, type 2 diabetes mellitus, body mass index, hyperlipidemia, and home value. Results are expressed in terms of the odds ratio (OR). A 23% decrease in residential distance to major roadways was associated with higher prevalence of peripheral arterial disease (OR=1.29; 95% confidence interval, 1.08-1.55) and hypertension (OR=1.15; 95% confidence interval, 1.01-1.31). Associations with peripheral arterial disease were strongest in men (OR=1.42; 95% confidence interval, 1.17-1.74) while associations with hypertension were strongest in women (OR=1.21; 95% confidence interval, 0.99-1.49). Neither myocardial infarction nor the number of diseased coronary vessels were associated with traffic exposure. CONCLUSIONS: Traffic-related exposure is associated with peripheral arterial disease and hypertension while no associations are observed for 2 coronary-specific vascular outcomes.

Short-term effects of fine particulate matter and ozone on the cardiac conduction system in patients undergoing cardiac catheterization.

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.

Community Vulnerability to Health Impacts of Wildland Fire Smoke Exposure.

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 contribution of fire-PM2.5 to annual average ambient PM2.5 was high (>1.5 µg/m3) and that 10.3 million individuals experienced unhealthy air quality levels for more than 10 days due to smoke. Using CHVI we identified the most vulnerable counties and determined that these communities experience more smoke exposures in comparison to less vulnerable communities.

Fine particulate matter and cardiovascular disease: Comparison of assessment methods for long-term exposure.

BACKGROUND: Adverse cardiovascular events have been linked with PM2.5 exposure obtained primarily from air quality monitors, which rarely co-locate with participant residences. Modeled PM2.5 predictions at finer resolution may more accurately predict residential exposure; however few studies have compared results across different exposure assessment methods. METHODS: We utilized a cohort of 5679 patients who had undergone a cardiac catheterization between 2002-2009 and resided in NC. Exposure to PM2.5 for the year prior to catheterization was estimated using data from air quality monitors (AQS), Community Multiscale Air Quality (CMAQ) fused models at the census tract and 12km spatial resolutions, and satellite-based models at 10km and 1km resolutions. Case status was either a coronary artery disease (CAD) index >23 or a recent myocardial infarction (MI). Logistic regression was used to model odds of having CAD or an MI with each 1-unit (µg/m3) increase in PM2.5, adjusting for sex, race, smoking status, socioeconomic status, and urban/rural status. RESULTS: We found that the elevated odds for CAD>23 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. CONCLUSIONS: Long-term air pollution exposure was associated with coronary artery disease for both modeled and monitored data.

Ozone exposure is associated with acute changes in inflammation, fibrinolysis, and endothelial cell function in coronary artery disease patients.

BACKGROUND: Air pollution is a major risk factor for cardiovascular disease, of which ozone is a major contributor. Several studies have found associations between ozone and cardiovascular morbidity, but the results have been inconclusive. We investigated associations between ozone and changes across biological pathways associated with cardiovascular disease. METHODS: Using a panel study design, 13 participants with coronary artery disease were assessed for markers of systemic inflammation, heart rate variability and repolarization, lipids, blood pressure, and endothelial function. Daily measurements of ozone and particulate matter (PM2.5) were obtained from central monitoring stations. Single (ozone) and two-pollutant (ozone and PM2.5) models were used to assess percent changes in measurements per interquartile ranges of pollutants. RESULTS: Per interquartile increase in ozone, changes in tissue plasminogen factor (6.6%, 95% confidence intervals (CI) = 0.4, 13.2), plasminogen activator inhibitor-1 (40.5%, 95% CI = 8.7, 81.6), neutrophils (8.7% 95% CI = 1.5, 16.4), monocytes (10.2%, 95% CI = 1.0, 20.1), interleukin-6 (15.9%, 95% CI = 3.6, 29.6), large-artery elasticity index (-19.5%, 95% CI = -34.0, -1.7), and the baseline diameter of the brachial artery (-2.5%, 95% CI = -5.0, 0.1) were observed. These associations were robust in the two-pollutant model. CONCLUSIONS: We observed alterations across several pathways associated with cardiovascular disease in 13 coronary artery disease patients following ozone exposures, independent of PM2.5. The results support the biological plausibility of ozone-induced cardiovascular effects. The effects were found at concentrations below the EPA National Ambient Air Quality Standards for both ozone and PM2.5.

Association between satellite-based estimates of long-term PM2.5 exposure and coronary artery disease.

BACKGROUND: Epidemiological studies have identified associations between long-term PM2.5 exposure and cardiovascular events, though most have relied on concentrations from central-site air quality monitors. METHODS: We utilized a cohort of 5679 patients who had undergone cardiac catheterization at Duke University between 2002-2009 and resided in North Carolina. We used estimates of daily PM2.5 concentrations for North Carolina during the study period based on satellite derived Aerosol Optical Depth (AOD) measurements and PM2.5 concentrations from ground monitors, which were spatially resolved with a 10×10km resolution, matched to each patient's residential address and averaged for the year prior to catheterization. The Coronary Artery Disease (CAD) index was used to measure severity of CAD; scores >23 represent a hemodynamically significant coronary artery lesion in at least one major coronary vessel. Logistic regression modeled odds of having CAD or an MI with each 1µg/m(3) increase in annual average PM2.5, adjusting for sex, race, smoking status and socioeconomic status. RESULTS: In adjusted models, a 1µg/m(3) increase in annual average PM2.5 was associated with an 11.1% relative increase in the odds of significant CAD (95% CI: 4.0-18.6%) and a 14.2% increase in the odds of having a myocardial infarction (MI) within a year prior (95% CI: 3.7-25.8%). CONCLUSIONS: Satellite-based estimates of long-term PM2.5 exposure were associated with both coronary artery disease (CAD) and incidence of myocardial infarction (MI) in a cohort of cardiac catheterization patients.

Short-term effects of air temperature on plasma metabolite concentrations in patients undergoing cardiac catheterization.

BACKGROUND: Epidemiological studies have shown associations between air temperature and cardiovascular health outcomes. Metabolic dysregulation might also play a role in the development of cardiovascular disease. OBJECTIVES: To investigate short-term temperature effects on metabolites related to cardiovascular disease. METHODS: Concentrations of 45 acylcarnitines, 15 amino acids, ketone bodies and total free fatty acids were available in 2869 participants from the CATHeterization GENetics cohort recruited at the Duke University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten metabolites were selected based on quality criteria and cluster analysis. Daily averages of meteorological variables were obtained from the North American Regional Reanalysis project. Immediate, lagged, and cumulative temperature effects on metabolite concentrations were analyzed using (piecewise) linear regression models. RESULTS: Linear temperature effects were found for glycine, C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5°C increase in temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%] increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1-DC (lag of four days), and a -1.4% [-2.4%; -0.3%] decrease in aspartic acid/asparagine (lag of two days). Non-linear temperature effects were observed for alanine and total ketone bodies with breakpoint of 4°C and 20°C, respectively. Both a 5°C decrease in temperature on colder days (<4°C)and a 5°C increase in temperature on warmer days (≥4°C) were associated with a four day delayed increase in alanine by 6.6% [11.7; 1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate (0-day lag) increases of 4.2% [-0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated with 5°C decreases on colder (<20°C) days and 5°C increases on warmer days (≥20°C), respectively. CONCLUSIONS: We observed multiple effects of air temperature on metabolites several of which are reported to be involved in cardiovascular disease. Our findings might help to understand the link between air temperature and cardiovascular disease.

Diesel exposure suppresses natural killer cell function and resolution of eosinophil inflammation: a randomized controlled trial of exposure in allergic rhinitics.

Exposure to diesel exhaust (DE) is known to exacerbate allergic inflammation, including virus-induced eosinophil activation in laboratory animals. We have previously shown that in human volunteers with allergic rhinitis a short-term exposure to DE prior to infection with the live attenuated influenza virus (LAIV) increases markers of allergic inflammation in the nasal mucosa. Specifically, levels of eosinophilic cationic protein (ECP) were significantly enhanced in individuals exposed to DE prior to inoculation with LAIV and this effect was maintained for at least seven days. However, this previous study was limited in its scope of nasal immune endpoints and did not explore potential mechanisms mediating the prolonged exacerbation of allergic inflammation caused by exposure to DE prior to inoculation with LAIV. In this follow-up study, the methods were modified to expand experimental endpoints and explore the potential role of NK cells. The data presented here suggest DE prolongs viral-induced eosinophil activation, which was accompanied by decreased markers of NK cell recruitment and activation. Separate in vitro studies showed that exposure to DE particles decreases the ability of NK cells to kill eosinophils. Taken together, these follow-up studies suggest that DE-induced exacerbation of allergic inflammation in the context of viral infections may be mediated by decreased activity of NK cells and their ability to clear eosinophils.

Repeated measures of inflammation, blood pressure, and heart rate variability associated with traffic exposures in healthy adults.

BACKGROUND: Previous human exposure studies of traffic-related air pollutants have demonstrated adverse health effects in human populations by comparing areas of high and low traffic, but few studies have utilized microenvironmental monitoring of pollutants at multiple traffic locations while looking at a vast array of health endpoints in the same population. We evaluated inflammatory markers, heart rate variability (HRV), blood pressure, exhaled nitric oxide, and lung function in healthy participants after exposures to varying mixtures of traffic pollutants. METHODS: A repeated-measures, crossover study design was used in which 23 healthy, non-smoking adults had clinical cardiopulmonary and systemic inflammatory measurements taken prior to, immediately after, and 24 hours after intermittent walking for two hours in the summer months along three diverse roadways having unique emission characteristics. Measurements of PM2.5, PM10, black carbon (BC), elemental carbon (EC), and organic carbon (OC) were collected. Mixed effect models were used to assess changes in health effects associated with these specific pollutant classes. RESULTS: Minimal associations were observed with lung function measurements and the pollutants measured. Small decreases in BP measurements and rMSSD, and increases in IL-1ß and the low frequency to high frequency ratio measured in HRV, were observed with increasing concentrations of PM2.5 EC. CONCLUSIONS: Small, acute changes in cardiovascular and inflammation-related effects of microenvironmental exposures to traffic-related air pollution were observed in a group of healthy young adults. The associations were most profound with the diesel-source EC.

Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana (REACCTING): study rationale and protocol.

BACKGROUND: Cooking over open fires using solid fuels is both common practice throughout much of the world and widely recognized to contribute to human health, environmental, and social problems. The public health burden of household air pollution includes an estimated four million premature deaths each year. To be effective and generate useful insight into potential solutions, cookstove intervention studies must select cooking technologies that are appropriate for local socioeconomic conditions and cooking culture, and include interdisciplinary measurement strategies along a continuum of outcomes. METHODS/DESIGN: REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) is an ongoing interdisciplinary randomized cookstove intervention study in the Kassena-Nankana District of Northern Ghana. The study tests two types of biomass burning stoves that have the potential to meet local cooking needs and represent different "rungs" in the cookstove technology ladder: a locally-made low-tech rocket stove and the imported, highly efficient Philips gasifier stove. Intervention households were randomized into four different groups, three of which received different combinations of two improved stoves, while the fourth group serves as a control for the duration of the study. Diverse measurements assess different points along the causal chain linking the intervention to final outcomes of interest. We assess stove use and cooking behavior, cooking emissions, household air pollution and personal exposure, health burden, and local to regional air quality. Integrated analysis and modeling will tackle a range of interdisciplinary science questions, including examining ambient exposures among the regional population, assessing how those exposures might change with different technologies and behaviors, and estimating the comparative impact of local behavior and technological changes versus regional climate variability and change on local air quality and health outcomes. DISCUSSION: REACCTING is well-poised to generate useful data on the impact of a cookstove intervention on a wide range of outcomes. By comparing different technologies side by side and employing an interdisciplinary approach to study this issue from multiple perspectives, this study may help to inform future efforts to improve health and quality of life for populations currently relying on open fires for their cooking needs.