A cross-disciplinary evaluation of evidence for multipollutant effects on cardiovascular disease.

BACKGROUND: The current single-pollutant approach to regulating ambient air pollutants is effective at protecting public health, but efficiencies may be gained by addressing issues in a multipollutant context since multiple pollutants often have common sources and individuals are exposed to more than one pollutant at a time. OBJECTIVE: We performed a cross-disciplinary review of the effects of multipollutant exposures on cardiovascular effects. METHODS: A broad literature search for references including at least two criteria air pollutants (particulate matter [PM], ozone [O3], oxides of nitrogen, sulfur oxides, carbon monoxide) was conducted. References were culled based on scientific discipline then searched for terms related to cardiovascular disease. Most multipollutant epidemiologic and experimental (i.e., controlled human exposure, animal toxicology) studies examined PM and O3 together. DISCUSSION: Epidemiologic and experimental studies provide some evidence for O3 concentration modifying the effect of PM, although PM did not modify O3 risk estimates. Experimental studies of combined exposure to PM and O3 provided evidence for additivity, synergism, and/or antagonism depending on the specific health endpoint. Evidence for other pollutant pairs was more limited. CONCLUSIONS: Overall, the evidence for multipollutant effects was often heterogeneous, and the limited number of studies inhibited making a conclusion about the nature of the relationship between pollutant combinations and cardiovascular disease.

Framework for assessing causality of air pollution-related health effects for reviews of the National Ambient Air Quality Standards.

To inform regulatory decisions on the risk due to exposure to ambient air pollution, consistent and transparent communication of the scientific evidence is essential. The United States Environmental Protection Agency (U.S. EPA) develops the Integrated Science Assessment (ISA), which contains evaluations of the policy-relevant science on the effects of criteria air pollutants and conveys critical science judgments to inform decisions on the National Ambient Air Quality Standards. This article discusses the approach and causal framework used in the ISAs to evaluate and integrate various lines of scientific evidence and draw conclusions about the causal nature of air pollution-induced health effects. The framework has been applied to diverse pollutants and cancer and noncancer effects. To demonstrate its flexibility, we provide examples of causality judgments on relationships between health effects and pollutant exposures, drawing from recent ISAs for ozone, lead, carbon monoxide, and oxides of nitrogen. U.S. EPA's causal framework has increased transparency by establishing a structured process for evaluating and integrating various lines of evidence and uniform approach for determining causality. The framework brings consistency and specificity to the conclusions in the ISA, and the flexibility of the framework makes it relevant for evaluations of evidence across media and health effects.

Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study.

OBJECTIVE: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. METHODS: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. RESULTS: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.

Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead.

The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants.

Traffic-related air pollutants and exhaled markers of airway inflammation and oxidative stress in New York City adolescents.

Exposures to ambient diesel exhaust particles have been associated with respiratory symptoms and asthma exacerbations in children; however, epidemiologic evidence linking short-term exposure to ambient diesel exhaust particles with airway inflammation is limited. We conducted a panel study with asthmatic and nonasthmatic adolescents to characterize associations between ambient diesel exhaust particle exposures and exhaled biological markers of airway inflammation and oxidative stress. Over four weeks, exhaled breath condensate was collected twice a week from 18 asthmatics and 18 nonasthmatics (ages 14-19 years) attending two New York City schools and analyzed for pH and 8-isoprostane as indicators of airway inflammation and oxidative stress, respectively. Air concentrations of black carbon, a diesel exhaust particle indicator, were measured outside schools. Air measurements of nitrogen dioxide, ozone, and fine particulate matter were obtained for the closest central monitoring sites. Relationships between ambient pollutants and exhaled biomarkers were characterized using mixed effects models. Among all subjects, increases in 1- to 5-day averages of black carbon were associated with decreases in exhaled breath condensate pH, indicating increased airway inflammation, and increases in 8-isoprostane, indicating increased oxidative stress. Increases in 1- to 5-day averages of nitrogen dioxide were associated with increases in 8-isoprostane. Ozone and fine particulate matter were inconsistently associated with exhaled biomarkers. Associations did not differ between asthmatics and nonasthmatics. The findings indicate that short-term exposure to traffic-related air pollutants may increase airway inflammation and/or oxidative stress in urban youth and provide mechanistic support for associations documented between traffic-related pollutant exposures and respiratory morbidity.

Traffic density and stationary sources of air pollution associated with wheeze, asthma, and immunoglobulin E from birth to age 5 years among New York City children.

Exposures to ambient air traffic-related pollutants and their sources have been associated with respiratory and asthma morbidity in children. However, longitudinal investigation of the effects of traffic-related exposures during early childhood is limited. We examined associations of residential proximity and density of traffic and stationary sources of air pollution with wheeze, asthma, and immunoglobulin (Ig) E among New York City children between birth and age 5 years. Subjects included 593 Dominican and African American participants from the Columbia Center for Children's Environmental Health cohort. Prenatally, through age 5 years, residential and respiratory health data were collected every 3-6 months. At ages 2, 3, and 5 years, serum IgE was measured. Spatial data on the proximity and density of roadways and built environment were collected for a 250 m buffer around subjects' homes. Associations of wheeze, asthma, total IgE, and allergen-specific IgE with prenatal, earlier childhood, and concurrent exposures to air pollution sources were analyzed using generalized estimating equations or logistic regression. In repeated measures analyses, concurrent residential density of four-way intersections was associated significantly with wheeze (odds ratio: 1.26; 95% confidence interval [CI]: 1.01, 1.57). Age 1 exposures also were associated with wheeze at subsequent ages. Concurrent proximity to highway was associated more strongly with total IgE (ratio of the geometric mean levels: 1.25; 95% CI: 1.09, 1.42) than were prenatal or earlier childhood exposures. Positive associations also were observed between percent commercial building area and asthma, wheeze, and IgE and between proximity to stationary sources of air pollution and asthma. Longitudinal investigation suggests that among Dominican and African American children living in Northern Manhattan and South Bronx during ages 0-5 years, residence in neighborhoods with high density of traffic and industrial facilities may contribute to chronic respiratory morbidity, and concurrent, prenatal, and earlier childhood exposures may be important. These findings may have broad implications for other urban populations that commonly have high asthma prevalence and exposure to a high density of traffic and stationary air pollution sources.

Effects of Heating Season on Residential Indoor and Outdoor Polycyclic Aromatic Hydrocarbons, Black Carbon, and Particulate Matter in an Urban Birth Cohort.

Exposure to air pollutants has been associated with adverse health effects. However, analyses of the effects of season and ambient parameters such as ozone have not been fully conducted. Residential indoor and outdoor air levels of polycyclic aromatic hydrocarbons (PAH), black carbon (measured as absorption coefficient [Abs]), and fine particulate matter <2.5 µm (PM)(2.5) were measured over two-weeks in a cohort of 5-6 year old children (n=334) living in New York City's Northern Manhattan and the Bronx between October 2005 and April 2010. The objectives were to: 1) characterize seasonal changes in indoor and outdoor levels and indoor/outdoor (I/O) ratios of PAH (gas + particulate phase; dichotomized into Σ(8)PAH(semivolatile) (MW 178-206), and Σ(8)PAH(nonvolatile) (MW 228-278)), Abs, and PM(2.5); and 2) assess the relationship between PAH and ozone. Results showed that heating compared to nonheating season was associated with greater Σ(8)PAH(nonvolatile) (p<0.001) and Abs (p<0.05), and lower levels of Σ(8)PAH(semivolatile) (p<0.001). In addition, the heating season was associated with lower I/O ratios of Σ(8)PAH(nonvolatile) and higher I/O ratios of Σ(8)PAH(semivolatile) (p<0.001) compared to the nonheating season. In outdoor air, Σ(8)PAH(nonvolatile) was correlated negatively with community-wide ozone concentration (p<0.001). Seasonal changes in emission sources, air exchanges, meteorological conditions and photochemical/chemical degradation reactions are discussed in relationship to the observed seasonal trends.

Traffic-related particulate matter and acute respiratory symptoms among New York City area adolescents.

BACKGROUND: Exposure to traffic-related particulate matter (PM) has been associated with adverse respiratory health outcomes in children. Diesel exhaust particles (DEPs) are a local driver of urban fine PM [aerodynamic diameter < or = 2.5 microm (PM(2.5))]; however, evidence linking ambient DEP exposure to acute respiratory symptoms is relatively sparse, and susceptibilities of urban and asthmatic children are inadequately characterized. OBJECTIVES: We examined associations of daily ambient black carbon (BC) concentrations, a DEP indicator, with daily respiratory symptoms among asthmatic and nonasthmatic adolescents in New York City (NYC) and a nearby suburban community. METHODS: BC and PM(2.5) were monitored continuously outside three NYC high schools and one suburban high school for 4-6 weeks, and daily symptom data were obtained from 249 subjects (57 asthmatics, 192 nonasthmatics) using diaries. Associations between pollutants and symptoms were characterized using multilevel generalized linear mixed models, and modification by urban residence and asthma status were examined. RESULTS: Increases in BC were associated with increased wheeze, shortness of breath, and chest tightness. Multiple lags of nitrogen dioxide (NO(2)) exposure were associated with symptoms. For several symptoms, associations with BC and NO(2) were significantly larger in magnitude among urban subjects and asthmatics compared with suburban subjects and nonasthmatics, respectively. PM(2.5) was not consistently associated with increases in symptoms. CONCLUSIONS: Acute exposures to traffic-related pollutants such as DEPs and/or NO(2) may contribute to increased respiratory morbidity among adolescents, and urban residents and asthmatics may be at increased risk. The findings provide support for developing additional strategies to reduce diesel emissions further, especially in populations susceptible because of environment or underlying respiratory disease.

Ambient metals, elemental carbon, and wheeze and cough in New York City children through 24 months of age.

RATIONALE: The effects of exposure to specific components of ambient fine particulate matter (PM(2.5)), including metals and elemental carbon (EC), have not been fully characterized in young children. OBJECTIVES: To compare temporal associations among PM(2.5); individual metal constituents of ambient PM(2.5), including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal reports of respiratory symptoms through 24 months of age. METHODS: Study participants were selected from the Columbia Center for Children's Environmental Health birth cohort recruited in New York City between 1998 and 2006. Respiratory symptom data were collected by questionnaire every 3 months through 24 months of age. Ambient pollutant data were obtained from state-operated stationary monitoring sites located within the study area. For each subject, 3-month average inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM(2.5) were calculated for each symptom-reporting period based on the questionnaire date and the preceding 3 months. Associations between pollutants and symptoms were characterized using generalized additive mixed effects models, adjusting for sex, ethnicity, environmental tobacco smoke exposure, and calendar time. MEASUREMENTS AND MAIN RESULTS: Increases in ambient Ni and V concentrations were associated significantly with increased probability of wheeze. Increases in EC were associated significantly with cough during the cold/flu season. Total PM(2.5) was not associated with wheeze or cough. CONCLUSIONS: These results suggest that exposure to ambient metals and EC from heating oil and/or traffic at levels characteristic of urban environments may be associated with respiratory symptoms among very young children.

Air pollution and childhood asthma: recent advances and future directions.

PURPOSE OF REVIEW: Current levels of air pollution are consistently associated with asthma development and morbidity among children, suggesting that current regulatory policies may be insufficient. This review will describe recent studies that have examined specific emission sources or components of pollutants that may be associated with pediatric asthma and identify subpopulations that may be particularly susceptible to the effects of air pollution exposure. RECENT FINDINGS: Important advances include new characterizations of the effects of traffic-related air pollution in urban areas. They also include the application of novel exposure and outcome measures such as pollution estimates derived from land use regression modeling and biological markers of airway inflammation. Additionally, studies have identified host susceptibility characteristics that may modify responses to air pollution exposure, including polymorphisms in oxidative stress genes and epigenetic alterations. SUMMARY: Identifying specific sources and toxic constituents of air pollution and accurately assessing air pollutant-related asthma outcomes are needed to better direct control strategies. Further research is needed to identify additional host factors that confer increased susceptibility to air pollution exposure. Future therapy to reduce the adverse effects of air pollution on respiratory disease will likely depend on targeting susceptible populations for intervention.

Spatial and Temporal Variations in Traffic-related Particulate Matter at New York City High Schools.

Relatively little is known about exposures to traffic-related particulate matter at schools located in dense urban areas. The purpose of this study was to examine the influences of diesel traffic proximity and intensity on ambient concentrations of fine particulate matter (PM(2.5)) and black carbon (BC), an indicator of diesel exhaust particles, at New York City (NYC) high schools. Outdoor PM(2.5) and BC were monitored continuously for 4-6 weeks at each of 3 NYC schools and 1 suburban school located 20 kilometers upwind of the city. Traffic count data were obtained using an automated traffic counter or video camera. BC concentrations were 2-3 fold higher at urban schools compared with the suburban school, and among the 3 urban schools, BC concentrations were higher at schools located adjacent to highways. PM(2.5) concentrations were significantly higher at urban schools than at the suburban school, but concentrations did not vary significantly among urban schools. Both hourly average counts of trucks and buses and meteorological factors such as wind direction, wind speed, and humidity were significantly associated with hourly average ambient BC and PM(2.5) concentrations in multivariate regression models. An increase of 443 trucks/buses per hour was associated with a 0.62 mug/m(3) increase in hourly average BC at a NYC school located adjacent to a major interstate highway. Car traffic counts were not associated with BC. The results suggest that local diesel vehicle traffic may be important sources of airborne fine particles in dense urban areas and consequently may contribute to local variations in PM(2.5) concentrations. In urban areas with higher levels of diesel traffic, local, neighborhood-scale monitoring of pollutants such as BC, which compared to PM(2.5), is a more specific indicator of diesel exhaust particles, may more accurately represent population exposures.

Differential oxidant potential of carcinogenic and weakly carcinogenic estrogens: Involvement of metabolic activation and cytochrome P450.

Different estrogens vary in their carcinogenic potential despite having similar hormonal potencies; however, mechanisms of estrogen-induced carcinogenesis remain to be fully elucidated. It has been hypothesized that generation of reactive estrogen-quinones and oxidative stress, both of which result from metabolic activation of estrogens, play an essential role in estrogen-induced carcinogenesis. This hypothesis was tested using the estrogen-receptor (ER)-alpha-positive hamster kidney tumor (H301) and the human breast cancer (MCF-7) cell lines. Estrogens with differing carcinogenic potentials were compared in terms of their capacities to induce 8-iso-prostaglandin F(2alpha) (8- iso-PGF(2alpha)), a marker of oxidative stress. Tumor cells were treated with either 17beta-estradiol (E2), a carcinogenic estrogen or 17-alpha-ethinylestradiol (EE), a weakly-carcinogenic estrogen. Tumor cells were also treated with alpha-naphthoflavone, a cytochrome P450 inhibitor, or a combination of alpha-naphthoflavone and E2 to study the effect of metabolic activation of E2 on E2-induced oxidative stress. H301 cells treated with E2 displayed time- and dose-dependent increases in 8-iso-PGF(2alpha), compared to controls; treatment with 10 nM E2 resulted in a maximal 4-fold induction following 48 h of treatment. In contrast, H301 cells treated with EE did not display an increase in 8-iso-PGF(2alpha) compared with controls. In H301 cells cotreated with alpha-naphthoflavone and E2, alpha-naphthoflavone inhibited the E2-induced increase in 8-iso-PGF(2alpha). These data indicate that a carcinogenic estrogen shows strong oxidant potential, whereas a weakly-carcinogenic estrogen shows poor oxidant potential. Furthermore, inhibiting metabolic activation of a carcinogenic estrogen blocks its oxidant potential. Our data support the hypothesis that metabolic activation and subsequent generation of oxidative stress may play critical roles in estrogen-induced carcinogenesis.