Triggering of ST-elevation myocardial infarction by ultrafine particles in New York: Changes following Tier 3 vehicle introduction.

BACKGROUND: Previously, we found increased rates of ST-elevation myocardial infarction (STEMI) associated with increased ultrafine particle (UFP; <100 nm) concentrations in the previous few hours in Rochester, New York. Relative rates were higher after air quality policies and a recession reduced pollutant concentrations (2014-2016 versus 2005-2013), suggesting PM composition had changed and the same PM mass concentration had become more toxic. Tier 3 light duty vehicles, which should produce less primary organic aerosols and oxidizable gaseous compounds, likely making PM less toxic, were introduced in 2017. Thus, we hypothesized we would observe a lower relative STEMI rate in 2017-2019 than 2014-2016. METHODS: Using STEMI events treated at the University of Rochester Medical Center (2014-2019), UFP and other pollutants measured in Rochester, a case-crossover design, and conditional logistic regression models, we estimated the rate of STEMI associated with increased UFP and other pollutants in the previous hours and days in the 2014-2016 and 2017-2019 periods. RESULTS: An increased rate of STEMI was associated with each 3111 particles/cm3 increase in UFP concentration in the previous hour in 2014-2016 (lag hour 0: OR = 1.22; 95% CI = 1.06, 1.39), but not in 2017-2019 (OR = 0.94; 95% CI = 0.80, 1.10). There were similar patterns for black carbon, UFP11-50nm, and UFP51-100nm. In contrast, increased rates of STEMI were associated with each 0.6 ppb increase in SO2 concentration in the previous 120 h in both periods (2014-2016: OR = 1.26, 95% CI = 1.03, 1.55; 2017-2019: OR = 1.21, 95% CI = 0.87, 1.68). CONCLUSIONS: Greater rates of STEMI were associated with short term increases in concentrations of UFP and other motor vehicle related pollutants before Tier 3 introduction (2014-2016), but not afterwards (2017-2019). This change may be due to changes in PM composition after Tier 3 introduction, as well as to increased exposure misclassification and greater underestimation of effects from 2017 to 2019.

Generating High Spatial Resolution Exposure Estimates from Sparse Regulatory Monitoring Data.

Random Forest algorithms have extensively been used to estimate ambient air pollutant concentrations. However, the accuracy of model-predicted estimates can suffer from extrapolation problems associated with limited measurement data to train the machine learning algorithms. In this study, we developed and evaluated two approaches, incorporating low-cost sensor data, that enhanced the extrapolating ability of random-forest models in areas with sparse monitoring data. Rochester, NY is the area of a pregnancy-cohort study. Daily PM2.5 concentrations from the NAMS/SLAMS sites were obtained and used as the response variable in the model, with satellite data, meteorological, and land-use variables included as predictors. To improve the base random-forest models, we used PM2.5 measurements from a pre-existing low-cost sensors network, and then conducted a two-step backward selection to gradually eliminate variables with potential emission heterogeneity from the base models. We then introduced the regression-enhanced random forest method into the model development. Finally, contemporaneous urinary 1-hydroxypyrene was used to evaluate the PM2.5 predictions generated from the two approaches. The two-step approach increased the average external validation R2 from 0.49 to 0.65, and decreased the RMSE from 3.56 µg/m3 to 2.96 µg/m3. For the regression-enhanced random forest models, the average R2 of the external validation was 0.54, and the RMSE was 3.40 µg/m3. We also observed significant and comparable relationships between urinary 1-hydroxypyrene levels and PM2.5 predictions from both improved models. This PM2.5 model estimation strategy could improve the extrapolating ability of random forest models in areas with sparse monitoring data.

Sex-Specific Platelet Activation Through Protease-Activated Receptors Reverses in Myocardial Infarction.

OBJECTIVE: The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. Approach and Results: We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI. CONCLUSIONS: Sex-specific signaling in platelets seems to be a cross-species phenomenon. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.

Prehospital time intervals and management of ischemic stroke patients.

OBJECTIVE: Quantify prehospital time intervals, describe prehospital stroke management, and estimate potential time saved if certain procedures were performed en route to the emergency department (ED). METHODS: Acute ischemic stroke patients who arrived via emergency medical services (EMS) between 2012 and 2016 were identified. We determined the following prehospital time intervals: chute, response, on-scene, transport, and total prehospital times. Proportions of patients receiving the following were determined: Cincinnati Prehospital Stroke Scale (CPSS) assessment, prenotification, glucose assessment, vascular access, and 12-lead electrocardiography (ECG). For glucose assessment, ECG acquisition, and vascular access, the location (on-scene vs. en route) in which they were performed was described. Difference in on-scene times among patients who had these three interventions performed on-scene vs. en route was assessed. RESULTS: Data from 870 patients were analyzed. Median total prehospital time was 39 min and comprised the following: chute time: 1 min; response time: 9 min; on-scene time: 15 min; and transport time: 14 min. CPSS was assessed in 64.7% of patients and prenotification was provided for 52.0% of patients. Glucose assessment, vascular access initiation, and ECG acquisition was performed on 84.1%, 72.6%, and 67.2% of patients, respectively. 59.0% of glucose assessments, 51.2% of vascular access initiations, and 49.8% of ECGs were performed on-scene. On-scene time was 9 min shorter among patients who had glucose assessments, vascular access initiations, and ECG acquisitions all performed en route vs. on-scene. CONCLUSIONS: On-scene time comprised 38.5% of total prehospital time. Limiting on-scene performance of glucose assessments, vascular access initiations, and ECG acquisitions may decrease prehospital time.

Associations between Source-Specific Particulate Matter and Respiratory Infections in New York State Adults.

The response of respiratory infections to source-specific particulate matter (PM) is an area of active research. Using source-specific PM2.5 concentrations at six urban sites in New York State, a case-crossover design, and conditional logistic regression, we examined the association between source-specific PM and the rate of hospitalizations and emergency department (ED) visits for influenza or culture-negative pneumonia from 2005 to 2016. There were at most N = 14 764 influenza hospitalizations, N = 57 522 influenza ED visits, N = 274 226 culture-negative pneumonia hospitalizations, and N = 113 997 culture-negative pneumonia ED visits included in our analyses. We separately estimated the rate of respiratory infection associated with increased concentrations of source-specific PM2.5, including secondary sulfate (SS), secondary nitrate (SN), biomass burning (BB), pyrolyzed organic carbon (OP), road dust (RD), residual oil (RO), diesel (DIE), and spark ignition vehicle emissions (GAS). Increased rates of ED visits for influenza were associated with interquartile range increases in concentrations of GAS (excess rate [ER] = 9.2%; 95% CI: 4.3%, 14.3%) and DIE (ER = 3.9%; 95% CI: 1.1%, 6.8%) for lag days 0-3. There were similar associations between BB, SS, OP, and RO, and ED visits or hospitalizations for influenza, but not culture-negative pneumonia hospitalizations or ED visits. Short-term increases in PM2.5 from traffic and other combustion sources appear to be a potential risk factor for increased rates of influenza hospitalizations and ED visits.

Temporal changes in short-term associations between cardiorespiratory emergency department visits and PM2.5 in Los Angeles, 2005 to 2016.

BACKGROUND: Emissions control programs targeting certain air pollution sources may alter PM2.5 composition, as well as the risk of adverse health outcomes associated with PM2.5. OBJECTIVES: We examined temporal changes in the risk of emergency department (ED) visits for cardiovascular diseases (CVDs) and asthma associated with short-term increases in ambient PM2.5 concentrations in Los Angeles, California. METHODS: Poisson log-linear models with unconstrained distributed exposure lags were used to estimate the risk of CVD and asthma ED visits associated with short-term increases in daily PM2.5 concentrations, controlling for temporal and meteorological confounders. The models were run separately for three predefined time periods, which were selected based on the implementation of multiple emissions control programs (EARLY: 2005-2008; MIDDLE: 2009-2012; LATE: 2013-2016). Two-pollutant models with individual PM2.5 components and the remaining PM2.5 mass were also considered to assess the influence of changes in PM2.5 composition on changes in the risk of CVD and asthma ED visits associated with PM2.5 over time. RESULTS: The relative risk of CVD ED visits associated with a 10 µg/m3 increase in 4-day PM2.5 concentration (lag 0-3) was higher in the LATE period (rate ratio = 1.020, 95% confidence interval = [1.010, 1.030]) compared to the EARLY period (1.003, [0.996, 1.010]). In contrast, for asthma, relative risk estimates were largest in the EARLY period (1.018, [1.006, 1.029]), but smaller in the following periods. Similar temporal differences in relative risk estimates for CVD and asthma were observed among different age and season groups. No single component was identified as an obvious contributor to the changing risk estimates over time, and some components exhibited different temporal patterns in risk estimates from PM2.5 total mass, such as a decreased risk of CVD ED visits associated with sulfate over time. CONCLUSIONS: Temporal changes in the risk of CVD and asthma ED visits associated with short-term increases in ambient PM2.5 concentrations were observed. These changes could be related to changes in PM2.5 composition (e.g., an increasing fraction of organic carbon and a decreasing fraction of sulfate in PM2.5). Other factors such as improvements in healthcare and differential exposure misclassification might also contribute to the changes.

Changes in the hospitalization and ED visit rates for respiratory diseases associated with source-specific PM2.5 in New York State from 2005 to 2016.

Prior work found increased rates for emergency department (ED) visits for asthma and hospitalizations for chronic obstructive pulmonary disease per unit mass of PM2.5 across New York State (NYS) during 2014-2016 after significant reductions in ambient PM2.5 concentrations had occurred following implementation of various policy actions and major economic disruptions. The associations of source-specific PM2.5 concentrations with these respiratory diseases were assessed with a time-stratified case-cossover design and logistic regression models to identify the changes in the PM2.5 that have led to the apparently increased toxicity per unit mass. The rates of ED visits and hospitalizations for asthma and COPD associated with increases in source-specific PM2.5 concentrations in the prior 1, 4, and 7 days were estimated for 6 urban sites in New York State. Overall, there were similar numbers of significantly increased (n = 9) and decreased rates (n = 8) of respiratory events (asthma and COPD hospitalizations and ED visits) associated with increased source-specific PM2.5 concentrations in the previous 1, 4, and 7 days. Associations of source-specific PM2.5 concentrations with excess rates of hospitalizations for COPD for spark- and compression ignition vehicles increased in the 2014-2016 period, but the values were not statistically significant. Other source types showed inconsistent patterns of excess rates. For asthma ED visits, only biomass burning and road dust showed consistent positive associations with road dust having significant values for most lag times. Secondary nitrate also showed significant positive associations with asthma ED visits in the AFTER period compared to no associations in the prior periods. These results suggest that the relationships of asthma and COPD exacerbation with source-specific PM2.5 are not well defined and further work will be needed to determine the causes of the apparent increases in the per unit mass toxicity of PM2.5 in New York State in the 2014-16 period.

Ambient wintertime particulate air pollution and hypertensive disorders of pregnancy in Monroe County, New York.

BACKGROUND: Previous studies have reported associations between ambient fine particle (PM2.5) concentrations and hypertensive disorders of pregnancy (HDP). However, none have examined whether ultrafine particles (UFP; < 100 nm), accumulation mode particles (AMP; 100-500 nm), markers of traffic pollution (black carbon; BC), or wood burning (Delta-C; (30% of ambient wintertime PM2.5 in Monroe County, NY is from wood burning)) are associated with an increased odds of HDP. We estimated the odds of HDP associated with increased concentrations of PM2.5, UFP, AMP, BC, and Delta-C in each gestational month during winter months. METHODS: Electronic medical records and birth certificate data were linked with land-use regression models in Monroe County, New York in 2009-2013 to predict monthly pollutant concentrations during winter (November-April) based on maternal residential address for 16,637 births. Using multivariable logistic regression, we estimated the odds of HDP associated with each interquartile range (IQR) increase in PM2.5, UFP, AMP, BC, and Delta-C concentrations during each gestational month, adjusting for maternal characteristics, birth hospital, temperature, and relative humidity. RESULTS: Each 0.52 µg/m3 increase in Delta-C concentration during the 7th gestational month was associated with an increased odds of HDP (odds ratio (OR) = 1.21; 95% confidence interval (CI) = 1.01, 1.45), with a similar sized estimate in month 8 (OR = 1.18; 95%CI = 0.98, 1.43). Non-statistically significant increased odds of HDP associated with IQR increases in BC concentrations during months 3 (OR = 1.12; 95%CI = 0.98, 1.28) and 7 (OR = 1.12; 95%CI = 0.96, 1.29) were observed. Increased odds of HDP were not observed for PM2.5, UFP, or AMP. CONCLUSIONS: Our findings suggest that maternal exposure to wood smoke in Monroe County during winter is associated with an increased odds of HDP during late gestation. Additional studies are needed to evaluate the effect of wood smoke on HDP and to explore effects on other pregnancy outcomes.

Changes in triggering of ST-elevation myocardial infarction by particulate air pollution in Monroe County, New York over time: a case-crossover study.

BACKGROUND: Previous studies have reported that fine particle (PM2.5) concentrations triggered ST elevation myocardial infarctions (STEMI). In Rochester, NY, multiple air quality policies and economic changes/influences from 2008 to 2013 led to decreased concentrations of PM2.5 and its major constituents (SO42-, NO3-, elemental and primary organic carbon). This study examined whether the rate of STEMI associated with increased ambient gaseous and PM component concentrations was different AFTER these air quality policies and economic changes (2014-2016), compared to DURING (2008-2013) and BEFORE these polices and changes (2005-2007). METHODS: Using 921 STEMIs treated at the University of Rochester Medical Center (2005-2016) and a case-crossover design, we examined whether the rate of STEMI associated with increased PM2.5, ultrafine particles (UFP, < 100 nm), accumulation mode particles (AMP, 100-500 nm), black carbon, SO2, CO, and O3 concentrations in the previous 1-72 h was modified by the time period related to these pollutant source changes (BEFORE, DURING, AFTER). RESULTS: Each interquartile range (3702 particles/cm3) increase in UFP concentration in the previous 1 h was associated with a 12% (95% CI = 3%, 22%) increase in the rate of STEMI. The effect size was larger in the AFTER period (26%) than the DURING (5%) or BEFORE periods (9%). There were similar patterns for black carbon and SO2. CONCLUSIONS: An increased rate of STEMI associated with UFP and other pollutant concentrations was higher in the AFTER period compared to the BEFORE and DURING periods. This may be due to changes in PM composition (e.g. higher secondary organic carbon and particle bound reactive oxygen species) following these air quality policies and economic changes.

Respiratory Responses to Ozone Exposure. MOSES (The Multicenter Ozone Study in Older Subjects).

RATIONALE: Acute respiratory effects of low-level ozone exposure are not well defined in older adults. OBJECTIVES: MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults. METHODS: We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance. MEASUREMENTS AND MAIN RESULTS: The mean (95% confidence interval) FEV1 and FVC increased from preexposure values by 2.7% (2.0-3.4) and 2.1% (1.3-2.9), respectively, 15 minutes after exposure to filtered air (0 ppb). Exposure to ozone reduced these increases in a concentration-dependent manner. After 120-ppb exposure, FEV1 and FVC decreased by 1.7% (1.1-2.3) and 0.8% (0.3-1.3), respectively. A similar concentration-dependent pattern was still discernible 22 hours after exposure. At 4 hours after exposure, plasma CC16 increased from preexposure levels in an ozone concentration-dependent manner. Sputum neutrophils obtained 22 hours after exposure showed a marginally significant increase in a concentration-dependent manner (P = 0.012), but proinflammatory cytokines (IL-6, IL-8, and tumor necrosis factor-α) were not significantly affected. CONCLUSIONS: Exposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults. Clinical trial registered with www.clinicaltrials.gov (NCT01487005).

Hourly land-use regression models based on low-cost PM monitor data.

Land-use regression (LUR) models provide location and time specific estimates of exposure to air pollution and thereby improve the sensitivity of health effects models. However, they require pollutant concentrations at multiple locations along with land-use variables. Often, monitoring is performed over short durations using mobile monitoring with research-grade instruments. Low-cost PM monitors provide an alternative approach that increases the spatial and temporal resolution of the air quality data. LUR models were developed to predict hourly PM concentrations across a metropolitan area using PM concentrations measured simultaneously at multiple locations with low-cost monitors. Monitors were placed at 23 sites during the 2015/16 heating season. Monitors were externally calibrated using co-located measurements including a reference instrument (GRIMM particle spectrometer). LUR models for each hour of the day and weekdays/weekend days were developed using the deletion/substitution/addition algorithm. Coefficients of determination for hourly PM predictions ranged from 0.66 and 0.76 (average 0.7). The hourly-resolved LUR model results will be used in epidemiological studies to examine if and how quickly, increases in ambient PM concentrations trigger adverse health events by reducing the exposure misclassification that arises from using less time resolved exposure estimates.

Associations between ambient wood smoke and other particulate pollutants and biomarkers of systemic inflammation, coagulation and thrombosis in cardiac patients.

BACKGROUND: Increased particulate air pollution has been associated with both an increased risk of myocardial infarction (MI) and adverse changes in cardiac biomarkers. Up to 30% of ambient wintertime fine particles (PM2.5) in Rochester, NY are from wood burning. Our study examined associations between ambient levels of a marker of wood smoke (Delta-C) and other particulate air pollutants and biomarkers of inflammation, coagulation and thrombosis. METHODS: We measured blood concentrations of C-reactive protein (CRP), D-dimer, fibrinogen, P-selectin, platelet factor 4 (PF-4), von Willebrand factor (vWF), and myeloperoxidase (MPO) of 135 patients undergoing cardiac catheterization during the winters of 2011-2013. We coupled these data with hourly ambient concentrations of Delta-C, black carbon (BC; marker of traffic pollution), and ultrafine (10-100nm; UFP), accumulation mode (100-500nm; AMP), and fine particles (<2.5µm; PM2.5). Using linear regression models, we estimated the change in each biomarker associated with increased pollutant concentrations at intervals between 1 and 96h preceding blood collection. RESULTS: Each 0.13µg/m3 increase in Delta-C concentration in the prior 12h was associated with a 0.91% increase in fibrinogen levels (95% CI=0.23%, 1.59%), but unexpectedly in the prior 48h, each 0.17µg/m3 increase in Delta-C concentration was associated with a 2.75% decrease in MPO levels (95% CI=-5.13%,-0.37%). We did not see associations between Delta-C concentrations and any other biomarkers. Interquartile range (IQR) increases in PM2.5, BC, UFP, and AMP concentrations were generally associated with increased CRP and fibrinogen, but not PF4, D-dimer, vWF, or P-selectin. CONCLUSIONS: In a population of cardiac patients, we noted adverse changes in fibrinogen associated with increased concentrations of a marker of wood smoke. Increases in PM2.5, BC, AMP, and UFP concentrations in the previous 96h were also associated with adverse changes in markers of systemic inflammation and coagulation, but not with markers of endothelial cell dysfunction or platelet activation.

Estimating Hourly Concentrations of PM2.5 across a Metropolitan Area Using Low-Cost Particle Monitors.

There is concern regarding the heterogeneity of exposure to airborne particulate matter (PM) across urban areas leading to negatively biased health effects models. New, low-cost sensors now permit continuous and simultaneous measurements to be made in multiple locations. Measurements of ambient PM were made from October to April 2015-2016 and 2016-2017 to assess the spatial and temporal variability in PM and the relative importance of traffic and wood smoke to outdoor PM concentrations in Rochester, NY, USA. In general, there was moderate spatial inhomogeneity, as indicated by multiple pairwise measures including coefficient of divergence and signed rank tests of the value distributions. Pearson correlation coefficients were often moderate (~50% of units showed correlations >0.5 during the first season), indicating that there was some coherent variation across the area, likely driven by a combination of meteorological conditions (wind speed, direction, and mixed layer heights) and the concentration of PM2.5 being transported into the region. Although the accuracy of these PM sensors is limited, they are sufficiently precise relative to one another and to research grade instruments that they can be useful is assessing the spatial and temporal variations across an area and provide concentration estimates based on higher-quality central site monitoring data.

Fine Particulates, Preterm Birth, and Membrane Rupture in Rochester, NY.

BACKGROUND: It remains unclear whether fine particulate (PM2.5) exposure affects risk of preterm birth and prelabor rupture of membranes. Unmeasured, poorly measured, and undiscovered individual-level confounders might have introduced bias into past studies that relied on between-women comparisons. METHODS: This was a longitudinal study of preterm birth and prelabor rupture of membranes in Rochester, NY, 2004-2012 (N = 3,264 women, N = 7,121 singleton births). We used conditional logistic regression to match pregnancies to the same woman and estimate the odds of each outcome associated with average PM2.5 concentrations during each trimester and whole pregnancy. RESULTS: For preterm birth, adjusted odds ratios (95% confidence interval) for 1 µg/m increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.11 (1.04, 1.18), 1.09 (1.02, 1.16), 1.06 (1.00, 1.13), and 1.17 (1.07, 1.28), respectively. For prelabor rupture of membranes, corresponding odds ratios were 1.00 (0.97, 1.04), 0.99 (0.96, 1.02), 0.99 (0.96, 1.03), and 0.99 (0.94, 1.04), respectively. CONCLUSION: Risk of preterm birth was greater for pregnancies with elevated PM2.5 exposure than other pregnancies to the same women at lower exposure. We did not observe an association between PM2.5 concentrations and prelabor rupture of membranes.

Antidepressant use and risk of central nervous system metastasis.

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, were found to increase central nervous system (CNS) metastasis in mice. Our study investigated in humans whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis. We identified 189 cases of CNS metastasis amongst breast cancer, melanoma, and non-Hodgkin lymphoma subjects who were diagnosed with CNS metastasis or infiltration between January 1, 2005 and September 30, 2013 and 756 controls (patients without CNS metastasis or infiltration). Using logistic regression, we estimated the relative odds of CNS metastasis associated with antidepressant use adjusting for relevant covariates. The prevalence of antidepressants was 28.6 % in cases and 27.5 % in controls, whereas SSRIs were used in 16.9 % of cases and 17.3 % of controls. Among all patients, antidepressants were not associated with CNS metastasis or infiltration. No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures, with the possible exception of an increased risk of CNS metastasis associated with 'any SSRI use' among breast cancer patients (OR = 1.73, 95 % CI = 0.75, 4.04). We did not observe clear patterns of association, which may be due in part to the small sample size in many of our analyses.

Does total antioxidant capacity modify adverse cardiac responses associated with ambient ultrafine, accumulation mode, and fine particles in patients undergoing cardiac rehabilitation?

BACKGROUND: Previous studies suggest that pathways reducing oxidative stress may have a protective effect against adverse cardiac responses associated with ambient PM. However, few studies have directly assessed total antioxidant capacity (TAC) as a potential effect modifier of cardiac responses to increased ambient PM. OBJECTIVES: We examined if TAC modifies the association between ambient PM and markers of heart rate variability (HRV), repolarization, systemic inflammation, and systolic blood pressure (SBP) in post-infarction patients. METHODS: We recruited 76 patients with a recent coronary event (myocardial infarction or unstable angina) who participated in a cardiac rehabilitation program from June 2006 to November 2009 in Rochester, New York. Ambient fine particle (PM2.5,≤2.5µm in aerodynamic diameter), accumulation mode particle (AMP, 100-500nm) and ultrafine particle (UFP, 10-100nm) concentrations were measured continuously by fixed-site monitors. Markers of HRV and repolarization were measured by continuous Holter electrocardiogram (ECG) recordings before and during exercise sessions of the rehabilitation program. Blood pressure was measured and venous blood samples were collected before exercise to measure TAC and inflammation markers. We applied linear mixed models to assess changes in markers of HRV, repolarization, systemic inflammation, and SBP associated with increased PM concentrations in the low, medium and high TAC tertile groups, after adjusting for covariates including temperature, calendar time since the beginning of the study, visit number, month of year, and hour of day. RESULTS: Based on subject-visits with available TAC, we observed increases in SBP, C-reactive protein, and fibrinogen, and decreases in rMSSD (square root of the mean of the sum of the squared differences between adjacent normal to normal intervals) and SDNN (standard deviation of normal to normal beat intervals) associated with increased PM2.5, AMP and UFP in the previous 6-120h (e.g. change in SBP associated with each interquartile range (IQR) increase in PM2.5 lagged 0-5h was 1.27mmHg [95%CI: 0.09, 2.46mmHg]). However, we did not observe a consistent pattern of effect measure modification by TAC for any combination of pollutant and outcome (e.g. changes in SBP associated with each IQR increase in PM2.5 lagged 0-5h for the low, medium and high TAC tertile groups were 1.93mmHg [95%CI: 0.23, 3.63 mmHg], -0.31 mmHg [95%CI: -2.62, 2.01 mmHg], and 1.29mmHg [95%CI: -0.64, 3.21 mmHg], respectively. P for interaction=0.28). CONCLUSIONS: In a post-infarction population, total antioxidant capacity does not appear to modify the association between biomarkers of heart rate variability, repolarization, systemic inflammation, and systolic blood pressure and ambient PM concentrations in the previous 6-120h.

Increases in ambient particulate matter air pollution, acute changes in platelet function, and effect modification by aspirin and omega-3 fatty acids: A panel study.

Increased particulate matter (PM) air pollutant concentrations have been associated with platelet activation. It was postulated that elevated air pollutant concentrations would be associated with increases in measures of platelet function and that responses would be blunted when taking aspirin and/or fish oil. Data from a sequential therapy trial (30 subjects with type 2 diabetes mellitus), with 4 clinic visits (first: no supplements, second: aspirin, third: omega-3 fatty acid supplements, fourth: aspirin and omega-3 fatty acids) per subject, were utilized. Using linear mixed models, adjusted for relative humidity, temperature, visit number, and season, changes in three platelet function measures including (1) aggregation induced by adenosine diphosphate (ADP), (2) aggregation induced by collagen, and (3) thromboxane B2 production were associated with interquartile range (IQR) increases in mean concentrations of ambient PM2.5, black carbon, ultrafine particles (UFP; 10-100 nm), and accumulation mode particles (AMP; 100-500 nm) in the previous 1-96 h. IQR increases in mean UFP and AMP concentrations were associated with significant decreases in platelet response, with the largest being a -0.43 log(pg/ml) decrease in log(thromboxane B2) (95% CI = -0.8, -0.1) associated with each 582-particles/cm(3) increase in AMP, and a -1.7 ohm reduction in collagen-induced aggregation (95% CI = -3.1, -0.3) associated with each 2097-particles/cm(3) increase in UFP in the previous 72 h. This UFP effect on thromboxane B2 was significantly muted in diabetic subjects taking aspirin (-0.01 log[pg/ml]; 95% CI = -0.4, 0.3). The reason for this finding remains unknown, and needs to be investigated in future studies.

Ambient and Controlled Particle Exposures as Triggers for Acute ECG Changes.

INTRODUCTION: Previous studies have examined changes in heart rate variability (HRV*) and repolarization associated with increased particulate matter (PM) concentrations on the same and previous few days. However, few studies have examined whether these health responses to PM occur within a few hours or even less. Moreover, it is not clear whether exposure of subjects to ambient or-controlled PM concentrations both lead to similar health effects or whether any of the subjects' individual characteristics modify any of their responses to PM. The aims of the cur- rent study were to investigate whether exposure to PM was associated with rapid changes (< 60 minutes or con- current hour up to a delay of 6 hours) in markers of car- diac rhythni or changes in total antioxidant capacity (a marker of protection against oxidative stress) and whether any PM effects on cardiac rhythm markers were modified by total antioxidant capacity, age, obesity, smoking, hypertension, exertion, prior myocardial infarction (MI), or medication. METHODS: We obtained data from a completed study in Augsburg, Germany (a panel study in N= 109 subjects, including a group with type 2 diabetes or impaired glucose tolerance [IGT; also known as prediabetes]) and a group of other- wise healthy subjects with a potential genetic susceptibil- ity to detoxifying and inflammatory pathways (Hampel et al. 2012b), as well as three completed studies in Rochester, New York (the REHAB panel study of N= 76 postinfarction patients in a cardiac rehabilitation pro- gram [Rich et al. 2012b]; the UPDIABETES study of con- trolled exposure to ultrafine particles [UFPs, particles with an aerodynamic diameter < 100 nm] of N = 19 patients with type 2 diabetes [Stewart et al. 2010; Vora et al. 2014j; and the UPCON controlled-exposure study of concentrated UFP exposure in N = 20 young, healthy, life- time nonsmokers). Data included 5-minute and 1-hour values for HRV and repolarization parameters from elec- trocardiogram (ECG) recordings and total antioxidant capacity measured in stored blood samples. Ambient con- centrations of UFPs, accumulation-mode particles (AMP, particles with an aerodynamic diameter of 100-500 nm), fine PM (PM2.5, particles with an aerodynamic diameter 2.5 pm), and black carbon (BC) were also available. We first conducted factor analyses in each study to find subgroups of correlated ECG outcomes and to reduce the number of outcomes examined in our statistical models. We then restricted the statistical analyses to the factors and representative.outcomes that were common to all four studies, including total HRV (measured as the standard deviation of normal-to-normal [NN] beat intervals [SDNNj), parasympathetic modulation (measured as the root mean square of the successive differences [RMSSD between adjacent NN beat intervals), and T-wave morphol- ogy (measured as T-wave complexity). Next, we used addi- tive mixed models to estimate the change in each outcome associated with increased pollutant concentrations in the . concurrent and previous 6 hours and with 5-minute inter- vals up to the previous 60 minutes, accounting for the correlation of repeated outcome measures for each subject and adjusting for time trend, hour of the day, temperature, relative humidity, day of the week, month, and visit number. Because multiple comparisons were an issue in our. analyses, we used a discovery-and-replication approach to draw conclusions across studies for each research question. RESULTS: In the Augsburg study, interquartile range (IQR) increases in UFP concentrations lagged 2 to 5 hours were associated with 1%-3% decreases in SDNN (e.g., lagged 3 hours in the group with a genetic susceptibility: -2.26%; 95% confidence interval [CI], -3.98% to -0.53%). In the REHAB study, similarly, IQR increases in UFP concentra- tions in the previous 5 hours were associated with < 3% decreases in SDNN (e.g., lagged 1 hour: -2.69%; 95% CI, -5.13% to -0.26%). We also found decreases in SDNN associated with IQR increases in total particle count-(a surrogate for UFP) in the UPDIABETES study (lagged 1 hour: -13.22%; 95% CI, -24.11% to -2.33%) but not in the UPCON study. In the Augsburg study, IQR increases in PM2.5 concen- trations in the concurrent hour and lagged 1-5 hours, AMP concentrations lagged 1 and 3 hours, and BC con- centrations lagged 1-5 hours were associated with -1%-5% decreases in SDNN (e.g., PM2.5 lagged 2 hours in the group with diabetes or IGT: -4.59%; 95% CI, -7.44% to -1.75%). In the REHAB study, IQR increases in PM2.5 concentrations lagged 5 and 6 hours and AMP concentra- tions in the concurrent hour and lagged up to 5 hours were associated with 1%-2% decreases in SDNN (e.g., PM2.5 lagged 4 hours: -2.13%; 95% CI, -3.91% to -0.35%). In the Augsburg study, IQR increases in PM2.5 concen- trations in the concurrent hour and BC lagged 1 and 6 hours were associated with 3%-7% decreases in RMSSD (e.g., PM2.5 concurrent hour in the group with diabetes or IGT: -7.20%; 95% CI, -12.11% to -2.02%). In the REHAB study, similarly, increases in PM2.5 concen- trations lagged 4 to 6 hours-though not AMP or BC con- centrations at any lag hour-were associated with -2.5%-3.5% decreases in RMSSD (e.g., PM2.5 lagged 5 hours: -3.49%; 95% CI, -6.13% to -0.84%). We did not find consistent evidence of any pollutant effects on T-wave complexity in 1-hour recordings. For 5-minute record- ings, there was no consistent evidence of UFP effects on SDNN, RMSSD, or T-wave complexity at any 5-minute interval within 60 minutes. We further concluded that these replicated hourly effects of UFP and PM2.5 on short-term measures of SDNN and RMSSD generally did not differ between the groups in the studies (i.e., type 2 diabetes, pre-diabetes/IGT, post- infarction, and healthy subjects). Last, we found no con- sistent evidence of effects of any pollutant on total anti- oxidant capacity and no consistent evidence of modification of our PM2.5-outcome associations by any of the potential effect modifiers. ONCLUSIONS: Increased UFP concentrations were associated with decreased SDNN in both of the panel studies and one of the two controlled-exposure studies. We also found that decreased SDNN was associated with both increased PM2.5 and AMP concentrations in the previous 6 hours in the panel studies and that decreased RMSSD was associ- ated with increased PM2.5 concentrations in the previous 6 hours in the panel studies. We therefore concluded that the research questions were replicated. Our findings suggest that both UFPs and PM2.5 are associated with autonomic dysfunction within hours of exposure, which may in part. explain the previously reported risk of acute cardiovascular events associated with increased PM in the previous few hours. Despite the heterogeneity of the study populations,and protocols, our findings provided consistent evidence for the induction of rapid pathophysiological responses by UFPs and PM2.5- The absence of consistent associations between UFPs, PM2.5, and these outcomes when examining shorter time intervals indicates that the 5- to 60-minute responses may be less pronounced than the responses occurring within hours. However, the findings from the 5-minute intervals may have been affected by the variety of proto- cols and conditions from study to study as well as by the potential effects of underlying diseases (e.g., healthy indi- viduals versus individuals with diabetes or a recent cor- onary artery. event), physical activity, circadian rhythms, stress, and/or medications.

Triggering of myocardial infarction by increased ambient fine particle concentration: Effect modification by source direction.

BACKGROUND: Previously, we reported a 18% increased odds of ST-elevation myocardial infarction (STEMI) associated with each 7.1 µg/m(3) increase in PM2.5 concentration in the hour prior to MI onset. We found no association with non-ST elevation myocardial infarction (NSTEMI). We examined if this association was modified by PM2.5 source direction. METHODS: We used the NOAA HYbrid Single-Particle Lagrangian Trajectory (HYSPLIT) model to calculate each hourly air mass location for the 24 hours before each case or control time period in our previous PM2.5/STEMI case-crossover analysis. Using these data on patients with STEMI (n=338), hourly PM2.5 concentrations, and case-crossover methods, we evaluated whether our PM2.5/STEMI association was modified by whether the air mass passed through each of the 8 cardinal wind direction sectors in the previous 24h. RESULTS: When the air mass passed through the West-Southwest direction (WSW) any time in the past 24h, the odds of STEMI associated with each 7.1µg/m(3) increase in PM2.5 concentration in the previous hour (OR=1.27; 95% CI=1.08, 1.22) was statistically significantly (p=0.01) greater than the relative odds of STEMI associated with increased PM2.5 concentration when the wind arrived from any other direction (OR=0.99; 95% CI=0.80, 1.22). We found no other effect modification by any other source direction. Further, relative odds estimates were largest when the time spent in the WSW was 8-16 h, compared to ≤7 h or 17-24 h, suggesting that particles arising from sources in this direction were more potent in triggering STEMIs. CONCLUSIONS: Since relative odds estimates were higher when the air mass passed through the WSW octant in the past 24h, there may be specific components of the ambient aerosol that are more potent in triggering STEMIs. This direction is associated with substantial emissions from coal-fired power plants and other industrial sources of the Ohio River Valley, many of which are undergoing modifications to reduce their emissions.