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Combustion related particulate matter air pollution (PM) is associated with an increased risk of respiratory infections in adults. The exact mechanism underlying this association has not been determined. We hypothesized that increased concentrations of combustion related PM would result in dysregulation of the innate immune system. This epidemiological study includes 111 adult patients hospitalized with respiratory infections who underwent transcriptional analysis of their peripheral blood. We examined the association between gene expression at the time of hospitalization and ambient measurements of particulate air pollutants in the 28 days prior to hospitalization. For each pollutant and time lag, gene-specific linear models adjusting for infection type were fit using LIMMA (Linear Models For Microarray Data), and pathway/gene set analyses were performed using the CAMERA (Correlation Adjusted Mean Rank) program. Comparing patients with viral and/or bacterial infection, the expression patterns associated with air pollution exposure differed. Adjusting for the type of infection, increased concentrations of Delta-C (a marker of biomass smoke) and other PM were associated with upregulation of iron homeostasis and protein folding. Increased concentrations of black carbon (BC) were associated with upregulation of viral related gene pathways and downregulation of pathways related to antigen presentation. The pollutant/pathway associations differed by lag time and by type of infection. This study suggests that the effect of air pollution on the pathogenesis of respiratory infection may be pollutant, timing, and infection specific.

Background Inflammation may contribute to cognitive difficulties in patients with breast cancer. We tested 2 hypotheses: inflammation is elevated in patients with breast cancer vs noncancer control participants and inflammation in patients is associated with worse attention and processing speed over the course of chemotherapy. Methods Serum cytokines (interleukin [IL]–4, 6, 8, 10; tumor necrosis factor [TNF]–α) and soluble receptors [sTNFRI, II]) were measured in 519 females with breast cancer before and after chemotherapy and 338 females without cancer serving as control participants. Attention and processing speed were measured by Rapid Visual Processing (RVP), Backward Counting (BCT), and Trail Making-A (TMT-A) tests. Linear regression models examined patient vs control cytokines and receptor levels, adjusting for covariates. Linear regression models also examined relationships between patient cytokines and receptor levels and test performance, adjusting for age, body mass index, anxiety, depression, cognitive reserve, and chemotherapy duration. Statistical tests were 2-sided (α = .05). Results sTNFRI and sTNFRII increased over time in patients relative to controls, whereas IL-4, IL-6, and IL-10 decreased. Prechemotherapy, higher IL-8 associated with worse BCT (β = 0.610, SE = 0.241, P = .01); higher IL-4 (β = −1.098, SE = 0.516, P = .03) and IL-10 (β = −0.835, SE = 0.414, P = .04) associated with better TMT-A. Postchemotherapy, higher IL-8 (β = 0.841, SE = 0.260, P = .001), sTNFRI (β = 6.638, SE = 2.208, P = .003), and sTNFRII (β = 0.913, SE = 0.455, P = .045) associated with worse BCT; higher sTNFRII also associated with worse RVP (β = −1.316, SE = 0.587, P = .03). At prechemotherapy, higher IL-4 predicted RVP improvement over time (β = 0.820, SE = 0.336, P = .02); higher sTNFRI predicted worse BCT over time (β = 5.566, SE = 2.367, P = .02). Longitudinally, increases in IL-4 associated with BCT improvement (β = −0.564, SE = 0.253, P = .03). Conclusions Generally, worse attention and processing speed were associated with higher inflammatory cytokines and receptors and lower anti-inflammatory cytokines in patients; future confirmatory studies are needed.

Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth.To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US.Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included.Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated.Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth.The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian,1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively.Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.

Effect estimates of prenatal exposure to ambient PM

The effectiveness of implantable cardioverter-defibrillators (ICDs) on reducing mortality has not been well studied in patients with long QT syndrome (LQTS).This study aimed to assess the survival benefits of ICDs in the overall LQTS population and in subgroups defined by ICD indications.This study included 3,035 patients (597 with ICD) from the Rochester LQTS Registry with a QTc ≥470 milliseconds or confirmed LQTS mutation. Using multivariable Cox proportional hazards models, the risk of all-cause mortality, all-cause mortality before age 50 years, and sudden cardiac death (SCD) were estimated as functions of time-dependent ICD therapy. Indication subgroups examined included patients with: 1) nonfatal cardiac arrest; 2) syncope while on beta-blockers; and 3) a QTc ≥500 milliseconds and syncope while off beta-blockers.During the 118,837 person-years of follow-up, 389 patients died (137 before age 50 years, and 116 experienced SCD). In the entire population, patients with ICDs had a lower risk of death (HR: 0.54; 95% CI: 0.34-0.86), death before age 50 years (HR: 0.29; 95% CI: 0.14-0.61), and SCD (HR: 0.22; 95% CI: 0.09-0.55) than patients without ICDs did. Patients with ICDs also had a lower risk of mortality among the 3 indication subgroups (HR: 0.14; 95% CI: 0.06-0.34; HR: 0.27; 95% CI: 0.10-0.72; and HR: 0.42; 95% CI: 0.19-0.96, respectively).ICD therapy was associated with a lower risk of all-cause mortality, all-cause mortality before age 50 years, and SCD in the LQTS population, as wells as with a lower risk of all-cause mortality in indication subgroups. This study provides evidence supporting ICD implantation in patients with high-risk LQTS.

Background: Previous work reported increased rates of acute cardiovascular hospitalizations associated with increased PM2.5 concentrations in the previous few days across urban centers in New York State from 2005 to 2016. These relative rates were higher after air quality policies and economic changes resulted in decreased PM2.5 concentrations and changes in PM composition (e.g. increased secondary organic carbon), compared to before and during these changes. Changes in PM composition and sources may explain this difference. Objectives: To estimate the rate of acute cardiovascular hospitalizations associated with increases in source specific PM2.5 concentrations. Methods: Using source apportioned PM2.5 concentrations at the same NYS urban sites, a time-stratified case-crossover design, and conditional logistic regression models adjusting for ambient temperature and relative humidity, we estimated the rate of these acute cardiovascular hospitalizations associated with increases in mean source specific PM2.5 concentrations in the previous 1, 4, and 7 days. Results: Interquartile range (IQR) increases in spark-ignition emissions (GAS) concentrations were associated with increased excess rates of cardiac arrhythmia hospitalizations (2.3%; 95% CI = 0.4%, 4.2%; IQR = 2.56 μg/m3) and ischemic stroke hospitalizations (3.7%; 95% CI = 1.1%, 6.4%; 2. 73 μg/m3) over the next day. IQR increases in diesel (DIE) concentrations were associated with increased rates of congestive heart failure hospitalizations (0.7%; 95% CI = 0.2% 1.3%; 0.51 μg/m3) and ischemic heart disease hospitalizations (0.8%; 95% CI = 0.3%, 1.3%; 0.60 μg/m3) over the next day, as hypothesized. However, secondary sulfate PM2.5 (SS) was not. Increased acute cardiovascular hospitalization rates were also associated with IQR increases in concentrations of road dust (RD), residual oil (RO), and secondary nitrate (SN) over the previous 1, 4, and 7 days, but not other sources. Conclusions: These findings suggest a role of several sources of PM2.5 in New York State (i.e. traffic emissions, non-traffic emissions such as brake and tire wear, residual oil, and nitrate that may also reflect traffic emissions) in the triggering of acute cardiovascular events. Keywords: Cardiovascular hospitalizations, Air pollution, Source apportionment, Traffic emissions

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. This trend was also observed in male and female mice in which thrombin-mediated platelet calcium mobilization was augmented coincident with platelet activation in males and attenuated in females 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.

PURPOSE: Long-term exposure to ambient fine particle (PM(2.5)) concentrations has been associated with an increased rate or risk of neurodegenerative conditions but individual PM sources have not been previously examined in relation to neurodegenerative diseases. METHODS: Using the Statewide Planning and Research Cooperative System database, we studied 63,287 hospital admissions with a primary diagnosis of either Alzheimer’s disease (AD), dementia, or Parkinson’s disease (PD) for New York State (NYS) residents living within 15 miles from six PM(2.5) monitoring sites. In addition to PM(2.5) concentrations, we studied seven specific PM(2.5) sources: secondary sulfate, secondary nitrate, biomass burning, diesel, spark-ignition emissions, pyrolyzed organic rich, and road dust. We estimated the rate of neurodegenerative hospital admissions associated with increased concentration of PM(2.5) and individual PM(2.5) sources average concentrations in the previous 0–29, 0–179, and 0–364 days. RESULTS: Increases in ambient PM(2.5) concentrations were not consistently associated with increased hospital admissions rates. Increased source-specific PM2.5 concentrations were associated with both increased (e.g., secondary sulfates and diesel emissions) and decreased rates (e.g., secondary nitrate and spark-ignition vehicular emissions) of neurodegenerative admissions. CONCLUSIONS: We did not observe clear associations between overall ambient PM(2.5) concentrations or source apportioned ambient PM(2.5) contributions and rates of neurologic disease hospitalizations.

Rationale: In a previous trial (MOSES [Multicenter Ozone Study of oldEr Subjects]), 3 hours of controlled ozone (O3) exposure caused concentration-related reductions in lung function with evidence ...

Acute respiratory effects of low-level ozone exposure are not well defined in older adults.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.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.The mean (95% confidence interval) FEVExposure 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).

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.

Increased ambient air pollutant concentrations during pregnancy have been associated with reduced birth weight, but the etiologically relevant pregnancy time window(s) is/are unclear. In 76,500 singleton births in Monroe County, NY (2005-2016), who were 37-42 gestational weeks at delivery, we used generalized linear models to regress term birth weight against mean gestational month pollutant concentrations, adjusting for mean temperature, and maternal, infant, and medical service use characteristics. Overall, there were no clear patterns of term birth weight change associated with increased concentrations of any pollutant across gestational months. However, among Hispanic women only, increases in all pollutants, except O

Prior studies reported that exposure to increased concentrations of fine particulate matter (PM

Rationale: Fine particulate matter air pollution of 2.5 μm or less in diameter (PM2.5) has been associated with an increased risk of respiratory disease, but assessments of specific respiratory infections in adults are lacking. Objectives: To estimate the rate of respiratory infection healthcare encounters in adults associated with acute increases in PM2.5 concentrations. Methods: Using case–crossover methods, we studied 498,118 adult New York State residents with a primary diagnosis of influenza, bacterial pneumonia, or culture-negative pneumonia upon hospitalization or emergency department (ED) visit (2005–2016). We estimated the relative rate of healthcare encounters associated with increases in PM2.5 in the previous 1–7 days and explored differences before (2005–2007), during (2008–2013), and after (2014–2016) implementation of air quality policies and economic changes. Results: Interquartile range increases in PM2.5 over the previous 7 days were associated with increased excess rates (ERs) of culture-negative pneumonia hospitalizations (2.5%; 95% confidence interval [CI], 1.7–3.2%) and ED visits (2.5%; 95% CI, 1.4–3.6%), and increased ERs of influenza ED visits (3.9%; 95% CI, 2.1–5.6%). Bacterial pneumonia hospitalizations, but not ED visits, were associated with increases in PM2.5 and, though imprecise, were of a similar magnitude to culture-negative pneumonia (Lag Day 6 ER, 2.3%; 95% CI, 0.3–4.3). Increased relative rates of influenza ED visits and culture-negative pneumonia hospitalizations were generally larger in the “after” period (P

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p

Previous studies have reported increased risks of myocardial infarction in association with elevated ambient particulate matter (PM) in the previous hour(s). However, whether PM can trigger mechanisms that act on this time scale is still unclear. We hypothesized that increases in PM are associated with rapid changes in measures of heart rate variability and repolarization. We used data from panel studies in Augsburg, Germany, and Rochester, New York, USA, and two controlled human exposure studies in Rochester. Data included ECG recordings from all four studies, controlled exposures to (concentrated) ultrafine particles (UFP; particles with an aerodynamic diameter 2.5, aerodynamic diameter 2.5 concentrations in the preceding six hours in both panel studies. We did not find consistent associations between particle metrics and T-wave complexity. This study provided consistent evidence that recent exposures to UFP and PM2.5 can induce acute pathophysiological responses.

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

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,≤2.5 μm in aerodynamic diameter), accumulation mode particle (AMP, 100-500 nm) and ultrafine particle (UFP, 10-100 nm) 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 6-120 h (e.g. change in SBP associated with each interquartile range (IQR) increase in PM2.5 lagged 0-5 h was 1.27 mmHg [95%CI: 0.09, 2.46 mmHg]). 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 0-5 h for the low, medium and high TAC tertile groups were 1.93 mmHg [95%CI: 0.23, 3.63 mmHg], -0.31 mmHg [95%CI: -2.62, 2.01 mmHg], and 1.29 mmHg [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 6-120 h.

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.

Background Perchlorate and similar anions compete with iodine for uptake into the thyroid by the sodium iodide symporter (NIS). This may restrict fetal growth via impaired thyroid hormone production. Methods We collected urine samples from 107 pregnant women and used linear regression to estimate differences in newborn size and gestational age associated with increases in perchlorate, thiocyanate, nitrate, and perchlorate equivalence concentrations (PEC; measure of total NIS inhibitor exposure). Results NIS inhibitor concentrations were not associated with newborn weight, length, or gestational age. Each 2.62 ng/μg creatinine increase in perchlorate was associated with smaller head circumference (0.32 cm; 95% CI: −0.66, 0.01), but each 3.38 ng/μg increase in PEC was associated with larger head circumference (0.48 cm; −0.01, 0.97). Conclusions These anions may have effects on fetal development (e.g. neurocognitive) that are not reflected in gross measures. Future research should focus on other abnormalities in neonates exposed to NIS inhibitors.

BACKGROUND: Previous studies have reported associations between ambient fine particle (PM(2.5)) concentrations and hypertensive disorders of pregnancy (HDP). However, none have examined whether ultrafine particles (UFP

IntroductionIschemic stroke treatment is time-sensitive, and barriers to providing prehospital care encountered by Emergency Medical Services (EMS) providers have been under-studied.Hypothesis/ProblemThis study described barriers to providing prehospital care, identified predictors of these barriers, and assessed the impact of these barriers on EMS on-scene time and administration of tissue plasminogen activator (tPA) in the emergency department (ED).MethodsA retrospective cohort study was performed using the Get With The Guidelines-Stroke (GWTG-S; American Heart Association [AHA]; Dallas, Texas USA) registry at two hospitals to identify ischemic stroke patients arriving by EMS. Variables were abstracted from prehospital and hospital medical records and merged with registry data. Barriers to care were grouped into themes. Logistic regression was used to identify predictors of barriers to care, and bi-variate tests were used to assess differences in EMS on-scene time and the proportion of patients receiving tPA between patients with and without barriers.ResultsBarriers to providing prehospital care were documented for 15.5% of patients: 29.6% related to access, 26.7% communication, 23.0% extrication and transportation, 20.0% refusal, and 14.1% assessment/management. Non-white and non-black race (OR: 3.69; 95% CI, 1.63-8.36) and living alone (OR: 1.53; 95% CI, 1.05-2.23) were associated with greater odds of barriers to providing care. The EMS on-scene time was ≥15 minutes for 70.4% of patients who had a barrier to care, compared with 49.0% of patients who did not (PConclusionsBarriers to providing prehospital care were documented for a sizable proportion of ischemic stroke patients, with the majority related to patient access and communication, and occurred more frequently among non-white and non-black patients and those living alone. Although EMS on-scene time was longer for patients with barriers to care, the proportion of patients receiving tPA in the ED did not differ.LiT, CushmanJT, ShahMN, KellyAG, RichDQ, JonesCMC. Barriers to providing prehospital care to ischemic stroke patients: predictors and impact on care. Prehosp Disaster Med.2018;33(5):501–507.

Background Previous studies reported triggering of acute cardiovascular events by short-term increasedPM2.5 concentrations. From 2007 to 2013, national and New York state air quality policies and economic influences resulted in reduced concentrations of PM2.5 and other pollutants across the state. We estimated the rate of cardiovascular hospital admissions associated with increased PM2.5 concentrations in the previous 1–7 days, and evaluated whether they differed before (2005–2007), during (2008–2013), and after these concentration changes (2014–2016). Methods Using the Statewide Planning and Research Cooperative System (SPARCS) database, we retained all hospital admissions with a primary diagnosis of nine cardiovascular disease (CVD) subtypes, for residents living within 15 miles of PM2.5 monitoring sites in Buffalo, Rochester, Albany, Queens, Bronx, and Manhattan from 2005 to 2016 (N = 1,922,918). We used a case-crossover design and conditional logistic regression to estimate the admission rate for total CVD, and nine specific subtypes, associated with increased PM2.5 concentrations. Results Interquartile range (IQR) increases in PM2.5 on the same and previous 6 days were associated with 0.6%–1.2% increases in CVD admission rate (2005–2016). There were similar patterns for cardiac arrhythmia, ischemic stroke, congestive heart failure, ischemic heart disease (IHD), and myocardial infarction (MI). Ambient PM2.5 concentrations and annual total CVD admission rates decreased across the period. However, the excess rate of IHD admissions associated with each IQR increase in PM2.5 in previous 2 days was larger in the after period (2.8%; 95%CI = 1.5%–4.0%) than in the during (0.6%; 95%CI = 0.0%–1.2%) or before periods (0.8%; 95%CI = 0.2%–1.3%), with similar patterns for total CVD and MI, but not other subtypes. Conclusions While pollutant concentrations and CVD admission rates decreased after emission changes, the same PM2.5 mass was associated with a higher rate of ischemic heart disease events. Future work should confirm these findings in another population, and investigate whether specific PM components and/or sources trigger IHD events.

Background To date, there have been relatively few studies of acute cardiovascular responses to controlled ozone inhalation, although a number of observational studies have reported significant positive associations between both ambient ozone levels and acute cardiovascular events and long-term ozone exposure and cardiovascular mortality. Objectives We hypothesized that short-term controlled exposure to low levels of ozone in filtered air would induce autonomic imbalance, repolarization abnormalities, arrhythmia, and vascular dysfunction. Methods This randomized crossover study of 87 healthy volunteers 55–70 years of age was conducted at three sites using a common protocol, from June 2012 to April 2015. Subjects were exposed for 3 h in random order to 0 ppb (filtered air), 70 ppb ozone, and 120 ppb ozone, alternating 15 min of moderate exercise with 15 min of rest. A suite of cardiovascular endpoints was measured the day before, the day of, and up to 22 h after each exposure. Mixed effect linear and logit models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. Site and time were included in the models. Results We found no significant effects of ozone exposure on any of the primary or secondary measures of autonomic function, repolarization, ST segment change, arrhythmia, or vascular function (systolic blood pressure and flow-mediated dilation). Conclusions In this multicenter study of older healthy women and men, there was no convincing evidence for acute effects of 3-h, relatively low-level ozone exposures on cardiovascular function. However, we cannot exclude the possibility of effects with higher ozone concentrations, more prolonged exposure, or in subjects with underlying cardiovascular disease. Further, we cannot exclude the possibility that exposure to ambient ozone and other pollutants in the days before the experimental exposures obscured or blunted cardiovascular biomarker response to the controlled ozone exposures.

It is assumed that platelets in diseased conditions share similar properties to platelets in healthy conditions, although this has never been examined in detail for myocardial infarction (MI). We examined platelets from patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) compared with platelets from healthy volunteers to evaluate for differences in platelet phenotype and function. Platelet activation was examined and postreceptor signal transduction pathways were assessed. Platelet-derived plasma biomarkers were evaluated by receiver operator characteristic curve analysis. Maximum platelet activation through the thromboxane receptor was greater in STEMI than in NSTEMI but less through protease-activated receptor 1. Extracellular-signal related-kinase 5 activation, which can activate platelets, was increased in platelets from subjects with STEMI and especially in platelets from patients with NSTEMI. Matrix metalloproteinase 9 (MMP9) protein content and enzymatic activity were several-fold greater in platelets with MI than in control. Mean plasma MMP9 concentration in patients with MI distinguished between STEMI and NSTEMI (area under curve [AUC] 75% [confidence interval (CI) 60-91], P = 0.006) which was superior to troponin T (AUC 66% [CI 48-85, P = 0.08), predicting STEMI with 80% sensitivity (95% CI 56-94), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P 0.0001), and NSTEMI with 50% sensitivity (CI 27-70), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P = 0.03). Platelets from patients with STEMI and NSTEMI show differences in platelet surface receptor activation and postreceptor signal transduction, suggesting the healthy platelet phenotype in which antiplatelet agents are often evaluated in preclinical studies is different from platelets in patients with MI.

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.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 diameter100 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.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 with3% 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.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.

We previously reported an increased risk of stillbirth associated with increases in trimester-specific ambient air pollutant concentrations. Here, we consider whether sudden increase in the mean ambient air pollutant concentration immediately before delivery triggers stillbirth.We used New Jersey linked fetal death and hospital discharge data and hourly ambient air pollution measurements from particulate matter ≤ 2.5 mm (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), and sulfur dioxide (SO2) monitors across New Jersey for the years 1998-2004. For each stillbirth, we assigned the concentration of air pollutants from the closest monitoring site within 10 km of the maternal residence. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the relative odds of stillbirth associated with interquartile range (IQR) increases in the mean pollutant concentrations on lag day 2 and lag days 2 through 6 before delivery, and whether these associations were modified by maternal risk factors.The relative odds of stillbirth increased with IQR increases in the mean concentrations of CO (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.05-1.37), SO2 (OR = 1.11, 95% CI = 1.02-1.22), NO2 (OR = 1.11, 95% CI = 0.97-1.26), and PM2.5 (OR = 1.07, 95% CI = 0.93-1.22) 2 days before delivery. We found similar associations with increases in pollutants 2 through 6 days before delivery. These associations were not modified by maternal risk factors.Short-term increases in ambient air pollutant concentrations immediately before delivery may trigger stillbirth.

Background Laboratory findings have suggested that systemic and vascular inflammation can impair the antiatherogenic function of high-density lipoproteins (HDLs). However, evidence from population studies is sparse. Objective The objective of the study was to assess if blood inflammatory markers modify the risk of recurrent coronary events associated with apolipoprotein A-I (apoA-I) and HDL cholesterol (HDL-C) among postinfarction patients. Methods ApoA-I, HDL-C, and inflammatory markers (C-reactive protein [CRP], serum amyloid A (SAA), fibrinogen, von Willebrand factor [vWF], and D-dimer) were measured from blood samples of 1028 patients drawn 2 months after an index myocardial infarction (MI). Patients were followed up for the composite coronary endpoint (nonfatal MI, coronary death, or unstable angina) for an average of 26 months. Cox proportional hazard models were used to assess effect modifications for the association of apoA-I and HDL-C with coronary risk by each inflammatory marker. Results CRP significantly modified the risk of recurrent coronary events associated with apoA-I. Among the entire population, multivariable-adjusted hazard ratios associated with each standard deviation increase in apoA-I for those with low and high CRP levels were 0.89 and 1.35, respectively ( P value for interaction = .008). vWF was a significant effect modifier of the apoA-I/coronary risk association only among diabetic patients (hazard ratios were 0.56 and 1.43, for diabetic patients with low and high vWF levels, respectively; P value for interaction = .002). No effect modification was observed for the HDL-C/coronary risk association. Conclusion Among stable post-MI patients, CRP modified the risk of recurrent coronary events associated with apoA-I. VWF modified this association only among the diabetic subgroup.

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 (PM 2.5 ) 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 (10–100 nm; UFP), accumulation mode (100–500 nm; AMP), and fine particles ( 2.5 ). Using linear regression models, we estimated the change in each biomarker associated with increased pollutant concentrations at intervals between 1 and 96 h preceding blood collection. Results Each 0.13 µg/m 3 increase in Delta-C concentration in the prior 12 h was associated with a 0.91% increase in fibrinogen levels (95% CI=0.23%, 1.59%), but unexpectedly in the prior 48 h, each 0.17 µg/m 3 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 PM 2.5, 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 PM 2.5 , BC, AMP, and UFP concentrations in the previous 96 h were also associated with adverse changes in markers of systemic inflammation and coagulation, but not with markers of endothelial cell dysfunction or platelet activation.

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/cm3 increase in AMP, and a –1.7 ohm reduction in collagen-induced aggregation (95% CI = –3.1, –0.3) associated with each 2097-particles/cm3 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.

Taking advantage of the natural experiment of the 2008 Beijing Olympics (August 8 to September 24), when air pollution levels decreased by 13% to 60%, the authors assessed whether having ≥1 pregnancy month during the Olympics was associated with decreased risks of hypertensive disorders (HDs) and/or fetal-placental conditions (FPCs). Singleton births to mothers with ≥1 pregnancy month in 2008 or 2009 (N = 56,155) were included. Using generalized additive models, the authors estimated the risk of HDs and FPCs associated with (1) the 2008 Olympics compared with the same dates in 2009, and (2) increased mean ambient PM10 (particulate matter with an aerodynamic diameter

Background: Mechanisms underlying previously reported air pollution and cardiovascular (CV) morbidity associations remain poorly understood. Objectives: We examined associations between markers of pathways thought to underlie these air pollution and CV associations and ambient particle concentrations in postinfarction patients. Methods: We studied 76 patients, from June 2006 to November 2009, who participated in a 10-week cardiac rehabilitation program following a recent (within 3 months) myocardial infarction or unstable angina. Ambient ultrafine particle (UFP; 10–100 nm), accumulation mode particle (AMP; 100–500 nm), and fine particle concentrations (PM2.5; ≤ 2.5 μm in aerodynamic diameter) were monitored continuously. Continuous Holter electrocardiogram (ECG) recordings were made before and during supervised, graded, twice weekly, exercise sessions. A venous blood sample was collected and blood pressure was measured before sessions. Results: Using mixed effects models, we observed adverse changes in rMSSD [square root of the mean of the sum of the squared differences between adjacent normal-to-normal (NN) intervals], SDNN (standard deviation of all NN beat intervals), TpTe (time from peak to end of T-wave), heart rate turbulence, systolic and diastolic blood pressures, C-reactive protein, and fibrinogen associated with interquartile range increases in UFP, AMP, and PM2.5 at 1 or more lag times within the previous 5 days. Exposures were not associated with MeanNN, heart-rate–corrected QT interval duration (QTc), deceleration capacity, and white blood cell count was not associated with UFP, AMP, and PM2.5 at any lag time. Conclusions: In cardiac rehabilitation patients, particles were associated with subclinical decreases in parasympathetic modulation, prolongation of late repolarization duration, increased blood pressure, and systemic inflammation. It is possible that such changes could increase the risk of CV events in this susceptible population.

The purpose of this study was to examine the trends in the rates of stillbirth by race and ethnicity and to determine the risk factors of stillbirth.We used New Jersey data (1997-2005) for live births and fetal deaths. Cox proportional hazards model was used to estimate the risk of stillbirth associated with maternal risk factors and pregnancy complications.The rate of stillbirth was 4.4/1000 total births (3.4 for white and 7.9 for black non-Hispanics and 4.4 for Hispanics/1000 total births). The rates of stillbirth decreased from 3.8 in 1997 to 2.7/1000 total births in 2005 for white non-Hispanics but remained unchanged for other race/ethnicity groups. Adjusted relative risks for the risk factors associated with stillbirth were 1.3 (95% CI, 1.2-1.4) for maternal age ≥ 35 years, 1.9 (95% CI, 1.7-2.1) for black non-Hispanics, 2.8 (95% CI, 2.4-3.3) for no prenatal care, 40.2 (95% CI, 36.9-43.9) for placental abruption, 5.3 (95% CI, 3.4-8.2) for eclampsia, 3.5 (95% CI, 2.8-4.3) for diabetes mellitus and 1.7 (95% CI, 1.3-2.2) for preeclampsia.There was a decline in the rate of stillbirth but there were persistent racial disparities with the highest rates of stillbirth for black non-Hispanics.

International audience; BACKGROUND: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design. OBJECTIVES: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach. METHODS: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter ≤ 10 μm in aerodynamic diameter (PM₁₀) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables. RESULTS: Among locations with data for the PM₁₀ analysis, ORs estimating the relative risk of term LBW associated with a 10-μg/m³ increase in average PM₁₀ concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30-1.35] for the Netherlands to 1.15 (95% CI, 0.61-2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations. CONCLUSIONS: Variability in PM₁₀-LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.

Background Epidemiologic studies consistently demonstrate an association between acute cardiopulmonary events and changes in air pollution; however, the mechanisms that underlie these associations are not completely understood. Oxidative stress and inflammation have been suggested to play a role in human responses to air pollution. The proteasome is an intracellular protein degradation system linked to both of these processes and may help mediate air pollution effects. Objectives In these studies, we determined whether acute experimental exposure to two different aerosols altered white blood cell (WBC) or red blood cell (RBC) proteasome activity in human subjects. One aerosol was fresh diesel exhaust (DE), and the other freshly generated secondary organic aerosol (SOA). Methods Thirty-eight healthy subjects underwent 2-hr resting inhalation exposures to DE and separate exposures to clean air (CA); 26 subjects were exposed to DE, CA, and SOA. CA responses were subtracted from DE or SOA responses, and mixed linear models with F-tests were used to test the effect of exposure to each aerosol on WBC and RBC proteasome activity. Results WBC proteasome activity was reduced 8% (p = 0.04) after exposure to either DE or SOA and decreased by 11.5% (p = 0.03) when SOA was analyzed alone. RBCs showed similar 8–10% declines in proteasome activity (p = 0.05 for DE alone). Conclusions Air pollution produces oxidative stress and inflammation in many experimental models, including humans. Two experimental aerosols caused rapid declines in proteasome activity in peripheral blood cells, supporting a key role for the proteasome in acute human responses to air pollution.

Background Skin cancer is the most common of all cancers and a public health concern of increasing magnitude in the U.S. Purpose A mid-year review of Healthy People 2010 found that the percentage of adults engaging in sun-safe practices increased from 59% in 2000 to 71% in 2005. This paper examines whether this increase in sun-safe practices in adults is an artifact caused by the change from 2000 to 2005 in the operational definition of "sun-safe practices" in the National Health Interview Survey (NHIS). Methods This study analyzed the 2000 and 2005 NHIS data sets in 2009 to examine changes in sun-safe practice prevalence estimates and to estimate the relative odds of practicing sun-safe behaviors associated with gender, age, race/ethnicity, education, and geographic region. Results Contrary to the Healthy People 2010 mid-year review, it was found that engaging in sun-safe practices by adults decreased from 59% (2000) to 55% (2005). A question order effect and use of images for use of sun-safe hats likely caused an artificial change in "cover-up" behavior estimates from 31% (2000) to 18% (2005) and wide-brim hat usage from 27% (2000) to 12% (2005). When eliminating data from these two questions added in 2005, the relative odds of practicing sun-safe behaviors was significantly lower for men in both 2000 and 2005 but were not different for other demographic characteristics. Conclusions The current analyses suggest that the increase in sun-safe behaviors in adults and a notable decrease in "hat use" may be due to methodologic artifacts. When operational definitions change, caution should be used in interpreting estimates over time.

Most previous studies (D’Ippoliti et al. 2003; Peters et al. 2001, 2005; Pope et al. 2006; Zanobetti and Schwartz 2005), but not all (Sullivan et al. 2005), that have investigated the triggering of myocardial infarction (MI) by particulate matter (PM) air pollution concentrations in the hours and days before MI onset have reported an association. Other studies have reported increased mortality due to MI or increased mortality or cardiovascular admissions among MI survivors associated with increases in PM over the previous few days (Braga et al. 2001; von Klot et al. 2005; Zanobetti and Schwartz 2007). Several studies have investigated whether certain subgroups are particularly susceptible and have reported increased cardiovascular effects among those with diabetes (Dubowsky et al. 2006; Goldberg et al. 2001; Liu et al. 2007; O’Neill et al. 2005; Zanobetti and Schwartz 2002) and among patients with chronic obstructive pulmonary disease (COPD) (Naess et al. 2007; Zanobetti and Schwartz 2005; Zanobetti et al. 2000). However, Zanobetti and Schwartz (2005) reported increased susceptibility among patients with COPD but not among persons with diabetes. Numerous researchers have reported that the percentage of infarctions that are nontransmural has been increasing (Goff et al. 2000; Hellermann et al. 2003; Kostis et al. 2007; Myerson et al. 2009; Roger et al. 2006, 2010; Rogers et al. 2008). More recently, Shao (2008) noted a similar secular trend in clinical presentation of MI to emergency departments (EDs) in New Jersey. In short, 72% of persons admitted to hospitals in New Jersey from 1990 through 1992 for MI had had transmural infarctions, and only 28% had had nontransmural infarctions. Since then, however, this pattern has reversed. From 2002 through 2004, most of the admissions for MI were for nontransmural infarctions (63%), with only 37% for transmural infarctions (Shao 2008). These changes may be due in part to improvements in preventive pharmacotherapies (statins, beta blockers, aspirin), interventional procedures [angioplasty, coronary artery bypass graft (CABG)], more sensitive diagnostic tests (troponins), and treatment of the MI upon ED arrival (reperfusion therapy, increased use of antiplatelet agents). It has not been reported whether PM with aerodynamic diameter ≤ 2.5 μm (PM2.5) triggers all infarctions, whether PM–MI associations differ in magnitude, or whether these associations are restricted to PM–transmural or PM–nontransmural infarctions alone. Such investigations may provide insight into the mechanisms by which PM may trigger cardiovascular events. Using the same data as Shao (2008), we attempted to replicate, in New Jersey, previous MI–PM2.5 studies that were conducted in other U.S. and European cities. We hypothesized that increases in mean PM2.5 concentration on the same day and a few days before ED arrival for MI may be associated with increased risk of MI and that these effect estimates would be greater for persons with diabetes and those with COPD than for individuals without these conditions. Further, we explored whether there were differences in risks associated with increases in ambient PM2.5 concentration between transmural and nontransmural infarctions.

Perchlorate is a commonly occurring environmental toxicant that may be transported across the placental barrier by the sodium-iodide symporter (NIS), possibly resulting in both increased perchlorate exposure and decreased iodide uptake by the fetus. Therefore, we measured levels of three physiologically relevant NIS-inhibitors (perchlorate, nitrate, and thiocyanate) and iodide in maternal and fetal fluids collected during cesarean-section surgeries on 150 U.S. women. Geometric means of perchlorate, thiocyanate, and nitrate levels in maternal urine (2.90, 947, and 47900 microg/L, respectively) were similar to previously published results, while urinary iodide levels (1420 microg/L) were significantly higher (p < 0.0001), likely because of prevalent prenatal vitamin use in the study population (74%). Thiocyanate levels were higher in the maternal serum, cord serum, and amniotic fluid of smokers compared to women with environmental tobacco smoke exposure and nonsmokers (p-values of 0.0006, 0.0011, and 0.0026, respectively). Perchlorate was detected in most samples: urine (100%), maternal serum (94%), cord serum (67%), and amniotic fluid (97%). Maternal urinary perchlorate levels were positively correlated with perchlorate levels in amniotic fluid (r = 0.57), indicating that maternal urine perchlorate is an effective biomarker of fetal perchlorate exposure. Maternal serum perchlorate was generally higher than cord serum perchlorate (median ratio 2.4:1 for paired samples), and maternal urine perchlorate was always higher than fetal amniotic fluid perchlorate levels (mean ratio 22:1); conversely, iodide levels were typically higher in fetal fluids compared to maternal fluids. We found no evidence of either disproportionate perchlorate accumulation or lack of iodide in the fetal compartment. In this panel of healthy infants, we found no association between cord blood levels of these anions and newborn weight length, and head circumference.

Objectives We explored the association between acute changes in daily mean pulmonary artery (PA) and right ventricular (RV) pressures and concentrations of ambient fine particulate matter [PM with aerodynamic diameter ≤2.5 μm (PM2.5)] as an explanation for previous associations between congestive heart failure (HF) hospital admissions and PM. Materials and methods In the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, to see whether management of ambulatory HF could be improved by providing continuous right heart pressure monitoring to physicians, the Chronicle Implantable Hemodynamic Monitor (Medtronic, Inc., Minneapolis, MN, USA) continuously measured multiple right heart hemodynamic parameters, heart rate, and activity trends in subjects with moderate/severe HF. Using these trial data, we calculated daily mean pressures, using only those time intervals where the subject was not physically active (n = 5,807 person-days; n = 11 subjects). We then studied the association between mean daily PA/RV pressures and mean ambient PM2.5 concentrations on the same day and previous 6 days. Results Each 11.62-μg/m3 increase in same-day mean PM2.5 concentration was associated with small but significant increases in estimated PA diastolic pressure [0.19 mmHg; 95% confidence interval (CI), 0.05–0.33] and RV diastolic pressure (0.23 mmHg; 95% CI, 0.11–0.34). Although we saw considerable differences in the magnitude of response by COMPASS-HF randomization group (total data access for physicians vs. blocked clinician access), season, left ventricular ejection fraction, and obesity, these effects were not significantly different. Conclusions These pilot study findings provide a potential mechanism for previous findings of increased risk of HF associated with ambient PM. However, because of the small number of subjects, a larger study is needed for confirmation.

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.

We previously observed increased odds of ST-elevation myocardial infarctions (STEMIs) associated with increased ambient fine particulate matter (PM2.5) in the previous hour. However, data are lacking on the effects of specific PM sources. Using data from 362 patients, a case-crossover design, and conditional logistic regression, we estimated the relative odds of STEMI associated with increased Delta-C (wood smoke), black carbon (BC; traffic), PM2.5, and gaseous pollutants in the previous 1-72 h. We did not observe increased odds of STEMIs associated with increased Delta-C or BC. We did observe increased odds associated with each 7.1 μg/m3 increase in PM2.5 (OR (95% CI): 1.17 (0.99, 1.39)) and each 19.9 p.p.b. increase in ozone (O3; 1.27 (1.00, 1.63)) in the previous hour, and each 0.22 p.p.m. increase in 48-h carbon monoxide (CO) concentrations (1.32 (1.00, 1.73]). Larger relative odds were associated with PM2.5 in May-October, and O3 and CO in November-April. Increased PM2.5, O3, and CO, but not wood smoke or BC, were associated with increased odds of STEMI, and effects may differ by season. Studies using spatially adjusted pollution estimates are needed, as well as studies further examining O3 and CO effects on the risk of STEMI.

1-Nitro-pyrene has been considered a compound specific to diesel combustion emission, while 1- and 2-nitro-napthalene are mainly produced through photochemical conversion of naphthalene released to the atmosphere. Metabolites of these compounds may serve as biomarkers of exposure to traffic related pollutants. We collected urine samples from 111 healthy and non-smoking subjects within (i.e., during the Beijing Olympics) and outside (i.e., before and after the Olympics) a traffic control regime to improve Beijing's air quality. Urines were analyzed for the sum of 1&2-amino-naphthalene (metabolites of 1- and 2-nitro-naphthalene) and 1-amino-pyrene (a metabolite of 1-nitro-pyrene), using an HPLC-fluorescence method. Within the same time periods, PM2.5 mass and constituents were measured, including elemental carbon, sulfate, nitrate, PAHs, carbon monoxide, nitrogen dioxide, sulfur dioxide, ozone, and particle number concentrations. The associations between the urinary metabolites and air pollutants were analyzed using linear mixed-effects models. From the pre- to during-Olympic period, 1&2-amino-naphthalene and 1-hydroxy-pyrene decreased by 23% (p = 0.066) and 16% (p = 0.049), respectively, while there was no change in 1-amino-pyrene (2% increase, p = 0.892). From during- to post-Olympic period, 1&2-amino-naphthalene, 1-amino-pyrene and 1-hydroxy-pyrene concentrations increased by 26% (p = 0.441), 37% (p = 0.355), and 3% (p = 0.868), respectively. Furthermore, 1&2-amino-naphthalene and 1-hydroxy-pyrene were associated with traffic related pollutants in a similar lag pattern. 1-amino-pyrene was associated more strongly with diesel combustion products (e.g. PN and elemental carbon) and not affected by season. Time-lag analyses indicate strongest/largest associations occurred 24–72 h following exposure. 1&2-amino-naphthalene and 1-hydroxy-pyrene can be used as a biomarker of exposure to general vehicle-emitted pollutants. More data are needed to confirm 1-amino-pyrene as a biomarker of exposure to diesel combustion emissions. Controlling creatinine as an independent variable in the models will provide a moderate adjusting effect on the biomarker analysis. Keywords: PAH metabolites, Biomarkers, Diesel exhaust particles, Exposure assessment, Traffic-emitted pollutants

Background Previously, we reported a 18% increased odds of ST-elevation myocardial infarction (STEMI) associated with each 7.1 µg/m3 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 24 h. Results When the air mass passed through the West-Southwest direction (WSW) any time in the past 24 h, the odds of STEMI associated with each 7.1 µg/m3 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 24 h, 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.

Objectives: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF. Design: We performed a case–crossover study. Participants: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n = 203) were followed until July 2002. Evaluations/Measurements: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects. Results: We found a statistically significant positive association between episodes of PAF and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio = 2.08; 95% confidence interval = 1.22, 3.54; p = 0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon. Conclusions: Increased ambient O3 pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events.

The authors evaluated the association between ventricular arrhythmias detected by implantable cardioverter defibrillators and ambient air pollution concentrations in the hours immediately before the arrhythmia. Patients given implantable cardioverter defibrillators at the New England Medical Center in Boston, Massachusetts, between mid-1995 and 1999 who lived within 40 km of a central monitoring site (n = 203) were followed until July 2002. The authors used a case-crossover design to study the association between ambient air pollution and up to 798 confirmed ventricular arrhythmias among 84 subjects. The authors found that interquartile range increases in 24-hour moving average particulate matter less than 2.5 mum in aerodynamic diameter and ozone were associated with 19% and 21% increased risks of ventricular arrhythmia, respectively. For each, there was evidence of a linear exposure response, and the associations appeared independent. These associations were stronger than associations with mean concentrations on the same calendar day and previous calendar days. The authors did not find associations with pollutant concentrations less than 24 hours before the arrhythmia. Cases with a prior ventricular arrhythmia within 72 hours had greater risk associated with air pollutants than did cases without a recent arrhythmia. These results confirm previous findings and suggest that matching of pollution periods to arrhythmias is important in detecting such associations.

Epidemiologic studies have demonstrated a consistent link between sudden cardiac deaths and particulate air pollution. We used implanted cardioverter defibrillator (ICD) records of ventricular tachyarrhythmias to assess the role of air pollution as a trigger of these potentially life-threatening events. The study cohort consisted of 203 cardiac patients with ICD devices in the Boston metropolitan area who were followed for an average of 3.1 years between 1995 and 2002. Fine particle mass and gaseous air pollution plus temperature and relative humidity were measured on almost all days, and black carbon, sulfate, and particle number on a subset of days. Date, time, and intracardiac electrograms of ICD-detected arrhythmias were downloaded at the patients' regular follow-up visits (about every 3 months). Ventricular tachyarrhythmias were identified by electrophysiologist review. Risk of ventricular arrhythmias associated with air pollution was estimated with logistic regression, adjusting for season, temperature, relative humidity, day of the week, patient, and a recent prior arrhythmia. We found increased risks of ventricular arrhythmias associated with 2-day mean exposure for all air pollutants considered, although these associations were not statistically significant. We found statistically significant associations between air pollution and ventricular arrhythmias for episodes within 3 days of a previous arrhythmia. The associations of ventricular tachyarrhythmias with fine particle mass, carbon monoxide, nitrogen dioxide, and black carbon suggest a link with motor vehicle pollutants. The associations with sulfate suggest a link with stationary fossil fuel combustion sources.

Background We and others have shown that increases in particulate air pollutant (PM) concentrations in the previous hours and days have been associated with increased risks of myocardial infarction, but little is known about the relationships between air pollution and specific subsets of myocardial infarction, such as ST-elevation myocardial infarction (STEMI) and non ST-elevation myocardial infarction (NSTEMI). Methods Using data from acute coronary syndrome patients with STEMI (n = 338) and NSTEMI (n = 339) and case-crossover methods, we estimated the risk of STEMI and NSTEMI associated with increased ambient fine particle (

Previous studies have reported an increased risk of myocardial infarction (MI) associated with acute increases in PM concentration. Recently, we reported that MI/fine particle (PM2.5) associations may be limited to transmural infarctions. In this study, we retained data on hospital discharges with a primary diagnosis of acute myocardial infarction (using International Classification of Diseases ninth Revision [ICD-9] codes), for those admitted January 1, 2004 to December 31, 2006, who were ≥ 18 years of age, and were residents of New Jersey at the time of their MI. We excluded MI with a diagnosis of a previous MI and MI coded as a subendocardial infarction, leaving n = 1563 transmural infarctions available for analysis. We coupled these health data with PM2.5 species concentrations predicted by the Community Multiscale Air Quality chemical transport model, ambient PM2.5 concentrations, and used the same case-crossover methods to evaluate whether the relative odds of transmural MI associated with increased PM2.5 concentration is modified by the PM2.5 composition/mixture (i.e., mass fractions of sulfate, nitrate, elemental carbon, organic carbon, and ammonium). We found the largest relative odds estimates on the days with the highest tertile of sulfate mass fraction (OR = 1.13; 95% CI = 1.00, 1.27), nitrate mass fraction (OR = 1.18; 95% CI = 0.98, 1.35), and ammonium mass fraction (OR = 1.13; 95% CI = 1.00 1.28), and the lowest tertile of EC mass fraction (OR = 1.17; 95% CI = 1.03, 1.34). Air pollution mixtures on these days were enhanced in pollutants formed through atmospheric chemistry (i.e., secondary PM2.5) and depleted in primary pollutants (e.g., EC). When mixtures were laden with secondary PM species (sulfate, nitrate, and/or organics), we observed larger relative odds of myocardial infarction associated with increased PM2.5 concentrations. Further work is needed to confirm these findings and examine which secondary PM2.5 component(s) is/are responsible for an acute MI response.

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent. Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association. Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates. Results: In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (–8.9 g; 95% CI: –13.2, –4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations. Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.