2015 Progress Report: University of Washington Center for Clean Air Research (UW CCAR)

EPA Grant Number: R834796
Center: University of Washington Center for Clean Air Research
Center Director: Vedal, Sverre
Title: University of Washington Center for Clean Air Research (UW CCAR)
Investigators: Vedal, Sverre , Campen, Matthew J. , Gassett, Amanda , Jobson, B. Thomas , Kaufman, Joel D. , Larson, Timothy V. , McDonald, Jacob D. , Rosenfeld, Michael , Sampson, Paul , Sheppard, Lianne (Elizabeth) A. , Simpson, Christopher , Spalt, Elizabeth , Szpiro, Adam , VanReken, Timothy M. , Yost, Michael
Current Investigators: Vedal, Sverre , Campen, Matthew J. , Jobson, Thomas , Kaufman, Joel D. , Larson, Timothy V. , McDonald, Jacob D. , Rosenfeld, Michael , Sampson, Paul , Sheppard, Lianne (Elizabeth) A. , Simpson, Christopher , Szpiro, Adam , VanReken, Timothy M. , Yost, Michael
Institution: University of Washington , Lovelace Respiratory Research Institute , University of New Mexico , Washington State University
EPA Project Officer: Callan, Richard
Project Period: December 1, 2010 through November 30, 2015 (Extended to November 30, 2017)
Project Period Covered by this Report: August 1, 2014 through July 31,2015
Project Amount: $8,000,000
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

The University of Washington Center for Clean Air Research (UW CCAR) is focused on the cardiovascular health effects of near-roadway pollution, a complex mixture of particle, vapor and gas phase components that vary by vehicle emission source, road surface, extent of physical aging and the type and degree of atmospheric processing and photochemical reactions. This exposure scenario is not only known to be of considerable health importance but also serves as a prototypical case for developing research approaches to dealing with multipollutant exposure-effect relationships. Our aim is to integrate exposure, epidemiological, toxicological, clinical and statistical sciences to study cardiovascular hazards of fresh and aged roadway emissions and significantly advance our understanding of the components and reaction products that cause these effects.

The Center consists of five highly integrated research projects and two facility cores that together are pursuing the following six aims:

  1. To characterize real-world near-roadway pollutant concentrations, particle size distributions and chemical composition;
  2. To simulate realistic, contrasting, near-roadway multipollutant exposure atmospheres for laboratory animal and human studies;
  3. To identify cardiovascular and immunologic effects and the pathogenic mechanisms of near-roadway exposures using animal models;
  4. To identify cardiovascular and immunologic effects of near-roadway exposures in human clinical studies;
  5. To identify effects of long-term exposure to traffic-derived particles and gases on subclinical measures of cardiovascular disease and DNA methylation in a multiethnic population; and
  6. To develop a statistical and methodological framework for studying health effects of multipollutant mixtures.

Project 1: Exposure Mapping——Characterization of Gases and Particles for Exposure Assessment in Health Effects and Laboratory Studies

The main project objectives are:

  1. Characterize spatial and temporal gradients of selected air pollutants along roadways and within neighborhoods in Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) cities using a mobile platform.
  2. Measure spatial variation in concentrations of selected air pollutants at 2‑week average stationary sites in coordination with the mobile measurements.
  3. Characterize aging of air pollutant components as they are transported from roadway sources to neighborhood receptor locations.
  4. Provide detailed characterization of laboratory exposure conditions available for toxicology testing, and identify likely conditions that mimic those found in urban settings.

Project 2: Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies

Traffic-related emissions are associated with the incidence and progression of acute and chronic cardiovascular sequelae in human population studies; however, the causal components, subsequent chemical transformation of these components and their associated toxicity on the cardiovascular system have not yet been determined. Project 2 is in progress to develop atmospheres with the primary objective of simulating environments containing key components of roadway emissions and the products of environmental factors that transform them.

Project 3: Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions

Traffic-related emissions are associated with the incidence and progression of acute and chronic cardiovascular sequelae in human population studies. Such phenomena of near-roadway health effects have yet to be characterized toxicologically. Because of overlapping issues related to noise, socioeconomic status, ethnicity, etc., there is a need to better understand the biological plausibility that fresh mixtures of vehicular emissions have a more potent than expected impact on human health. We hypothesize that the complex mixtures produced by traffic are inherently more toxic due to the combined presence of both particulates and volatile organic emissions. Furthermore, we hypothesize that emissions-induced oxidation of certain endogenous phospholipids, presumably from the pulmonary surfactant, can stimulate the activity of immune cells through such receptors and in turn promote the invasion of existing vascular lesions.

Project 4: Effect of Commute Traffic on Vascular Function

Project 4 examines the acute vascular effects of commute traffic exhaust exposures in human subjects in a multipollutant context. This double-blind, randomized, controlled crossover trial will test whether traffic-derived mixed pollution atmospheres of diesel exhaust and gasoline engine exhaust, experienced through travel on roadways in a passenger car, causes an increased vascular response (brachial artery vasoconstriction, increased blood pressure, reduced retinal arteriolar diameter) compared with filtered air (FA) in healthy subjects. Nested aims include: whether specific exhaust-related monocytic gene expression effects are mediated by lipid peroxidation; whether traffic-related pollutants'’ vasoconstrictive effects are increased in subjects with a common SNP variant in the gene coding for TRPV1; and whether monocyte DNA methylation in specific genes is modified with exposure to typical, roadway-derived exposures.

Project 5: Effects of Long-Term Exposure to Traffic-Derived Aerosols and Gases on Subclinical Measures of Cardiovascular Disease and DNA Methylation in a Multi-Ethnic Cohort

Project 5 has three primary objectives:

  1. Employ the small-scale gradient data acquired as part of the mobile monitoring campaign in Project 1 in conjunction with central fixed site data, regulatory monitoring data and geographic covariates to build a multipollutant exposure model for traffic-derived air pollutants. This model will incorporate complex spatial information on primary and secondary traffic-derived particles and gases.
  2. Develop and validate individual-level exposure estimates for traffic-derived air pollutants, integrating (1) the outdoor residential concentration estimates from the multipollutant model; (2) estimates of residential infiltration rates; (3) road class–– and traffic condition––specific estimates of on-roadway concentrations; and (4) individual-level, questionnaire-derived time-location information. These individual-level exposure estimates will also utilize personal monitoring data designed to clarify the in-transit component of total exposure.
  3. Estimate the effect of individual-level exposure to traffic-derived air pollution on subclinical cardiovascular disease using these exposure models. Health outcomes will include left ventricular myocardial mass, as ascertained by MRI; arteriolar diameters, as measured by retinal photography; coronary artery calcium (CAC), as ascertained by CT; intima-medial thickness, as measured by ultrasound; and DNA methylation.

Biostatistics Core

The overall objective is to support the statistical needs of all Center projects. This will be achieved through five specific objectives:

  1. Advise Center projects on data management and compilation.
  2. Ensure quality statistical design and analysis of Center research.
  3. Implement novel statistical methods that are required for Center projects: develop an analytical framework for quantifying the health effects of different mixtures of air pollution components in a cohort study (Project 1 and Project 5).
  4. Identify additional statistical methodological research that will advance Center projects.
  5. Communicate and disseminate Center findings.

Progress Summary:

Project 1: Exposure Mapping——Characterization of Gases and Particles for Exposure Assessment in Health Effects and Laboratory Studies

Data collection related to aims 1 and 2 has been completed and provided the main focus of activities up to the beginning of this project. Field sampling in four cities in the MESA Air cohort was completed: Minneapolis/St. Paul, MN; Baltimore, MD; Los Angeles, CA; and Winston-Salem, NC. Mobile monitoring and passive sampling measurements were conducted for both heating and nonheating seasons. Due to financial constraints, Winston-Salem only was monitored with passive samplers. During this reporting period, we have focused on data analysis of final QC data sets and providing data for use by investigators in our project and other Center investigators. This process has been completed for data collected in Baltimore; Los Angeles; Albuquerque, NM; and the 2-week passive sample data for these cities. We also completed a collaborative measurement campaign in Atlanta, GA, with the SCAPE Center and have provided preliminary data for this activity. The final QC data set from this collaborative campaign is under review and being analyzed by both Centers.

Project 2: Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies

Over the past year, we have focused on continuing to evaluate the endothelial cell and myography assays with Project 3 and to extend additional endpoints to confirm the cardiovascular response of putative pollutants. These results are described in Project 3. Project 2 developed novel atmospheres that continue to evaluate the role of gas-particle interactions and the particle size on the toxicity of inhaled mixtures. This was done by developing novel atmospheres that focus on better understanding the gaseous-particle and size components of motor vehicle exhaust (MVE). Atmospheres included:

  • MVE minus gases: A denuder that removes gas phase organics was employed.
  • MVE minus semi-volatile organics-catalytic stripper with catalyst that removes gaseous and semi-volatile organics from the aerosol was applied to the test atmosphere to evaluate gases/organic particles versus solid particle residuals.
  • MVE benchmark
  • Woodsmoke

Project 3: Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions

Following up on the previous year'’s observation of the role of blood-borne ligands and bioactivity in terms of driving endothelial cell activation or dysfunction following ozone exposure, we identified a potential for altered serum biochemicals to scavenge nitric oxide, which was associated with lower levels of circulating nitrites/nitrates and also elevated nitrosothiols. This finding offers a complementary mechanism to previous observations of ligand-receptor dependent alterations impacting vasodilation. Ongoing research into the chemical changes in the blood have offered paradigm-shifting insights. For one, we typically see minimal, if any, changes in cytokine levels following even moderately high levels of pollutants. However, we routinely observe increases in fragmented and adducted proteins, and metabolomics studies suggest small molecule changes may also be numerous and contributory. A recent observation with serum from woodsmoke-exposed mice suggests that it is, in fact, a loss of some factor, rather than induction of higher levels of some mediator or mediators, that leads to indirect vascular pathology.

Project 4: Effect of Commute Traffic on Vascular Function

Project 4 was launched in Year 4 of the Center. In this project, we use a "“typical commute"” study design and pertinent experience in human exposure studies to advance the Center'’s research agenda with a double-blind, controlled exposure crossover clinical trial in 16 subjects, randomized to order. Using an innovative approach in which contrasts of in-vehicle exposure and potential participant susceptibility by genotype are nested in the experiment, we can address several hypotheses in this study. Building on our prior work, we will use a typical commute model to confirm or determine whether traffic- (e.g., mixed on-road environment with diesel and gasoline engine exhaust components) derived aerosols exert demonstrable and important acute vascular effects in human subjects and whether traffic-derived aerosols acutely induce increased lipid peroxidation, respond to oxidized phospholipids and result in measurable impacts on gene expression and DNA methylation in pathways that are related not only to the triggering of acute cardiovascular events but also to the development and progression of atherosclerosis. Of course, all of the outcomes we measure are completely transient and reversible, and exposures are designed to be those of a typical urban commute path.

Project 5: Effects of Long-Term Exposure to Traffic-Derived Aerosols and Gases on Subclinical Measures of Cardiovascular Disease and DNA Methylation in a Multi-Ethnic Cohort

Aim 1——Developing spatial exposure model: For Aim 1 of Project 5, we are working closely with Project 1 and Biostatistics Core personnel to develop approaches to their high-dimensional data, which can be applied to epidemiological analyses. We plan to use cluster membership as an effect modifier for the health analyses of the association between NO2 exposure and measurements of CAC. We have assigned clusters using predictive k-means clustering for each of the four cities sampled as part of Project 1.

Aim 2——Understanding in-vehicle contribution to individual level multipollutant exposures: A major effort has been in the field work portion of this project, which will address significant portions of the second aim of this project. Specifically, through a combination of personal, residential and in-vehicle sampling paired with intensive location tracking, we are seeking to understand the influence of time spent in transit on personal exposure, which will improve our individual-level exposure estimates and contribute to our epidemiological analysis.

Aim 3——Epidemiological Analyses: Several analyses relating to Aim 3 of Project 5 are in progress. These include analyses using the following outcomes: left ventricular myocardial mass, as ascertained by MRI; arteriolar diameters, as measured by retinal photography; coronary artery calcium (CAC), as ascertained by CT; intima-medial thickness, as measured by ultrasound; and DNA methylation. Cluster membership will be used as an effect modifier of the association between NOx exposure and measurements of CAC to determine whether or not the association varies by multipollutant profile (as identified by cluster).

Biostatistics Core

  1. Advise Center projects on data management and compilation: This Core has continued to support Project 1 with extensive work compiling datasets from multiple monitoring instruments in each campaign, ensuring they are properly aligned temporally, running quality control checks and maintaining documentation throughout all stages of the process.
  2. Ensure quality statistical design and analysis of Center research: The Core has provided extensive input to Project 1 analyses, both through staff support and through consultation with members of the Project 1 team. The Core has supported the redesign of Project 4. Project 5 has been an important thrust of activities for the Core in Year 5.
  3. Implement novel statistical methods that are required for Center projects: Develop an analytical framework for quantifying the health effects of different mixtures of air pollution components in a cohort study (Project 1 and Project 5): Our activities in the past year have expanded to consider predictive k-means clustering.
  4. Identify additional statistical methodological research that will advance Center projects: Many fresh ideas are generated during discussions at our weekly Environmental (Bio)statistics Working Group meetings, often while we are critiquing progress and results from ongoing projects.
  5. Communicate and disseminate Center findings: The Core has been supporting and leading efforts to publish and otherwise disseminate UW CCAR research.

CCAR Clean Air Research Center (CLARC) Program Collaborations

CCAR is committed to participating in four of the five CLARC collaborative projects that have been proposed:

  • Collaborative Project 1: Circulating Inflammatory Potential of Inhaled Coarse PM
  • Collaborative Project 2: Mobile and Fixed-Site Characterization of Vehicle Emission Impacts in Atlanta
  • Collaborative Project 3: Measurement Error for Air Pollution Cohort Studies: Application and Comparison of Several Statistical Methods to Georgia Birth Cohort Data
  • Collaborative Project 4: Inter-comparison of ambient PM2.5 estimation models in NC

 

Future Activities:

Project 1: Exposure Mapping——Characterization of Gases and Particles for Exposure Assessment in Health Effects and Laboratory Studies

Activities in the next year will focus on analysis of final QC data from the field sampling campaigns, completing the chamber characterization studies. We have completed most of the field work on target and will be assisting Project 4 in scripted commute studies for CCAR using instruments from the mobile platform. Data QC and review are underway for the cities that already have been sampled working with the Biostatistics Core. Work on publications and dissemination of results is underway.

Project 2: Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies

The next round of studies will continue the follow up on long-term assays, confirming the effect differentials related to surface area and gas-particle interactions.

Project 3: Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions

Compare potency of mixed emissions and photochemically transformed emissions in terms of serum inflammatory potential. This will be the focus of the remainder of the study, interacting closely with Dr. McDonald and Project 2. We will examine the relative systemic inflammatory potential following exposures to complex emissions.

Project 4: Effect of Commute Traffic on Vascular Function

We plan to continue the commute exposure study in Year 5 and complete it during the no-cost extension year and will conduct all health analyses in the no-cost extension year.

Project 5: Effects of Long-Term Exposure to Traffic-Derived Aerosols and Gases on Subclinical Measures of Cardiovascular Disease and DNA Methylation in a Multi-Ethnic Cohort

We are in the process of preparing three manuscripts related to Aim 2: (1) a comparison of the three time-location measurement methods utilized in this study (draft in review by co-authors), (2) an analysis of the relative contributions of each microenvironment to overall exposure to ambient-source nitrogen dioxide and (3) a manuscript discussing the results of all of traffic-related air pollutant sampling. For the remainder of Year 5 and the no-cost extension year, effort will focus on Aim 3: epidemiological analyses incorporating the exposure information gained through Aims 1 and 2.

Biostatistics Core

Our plans for the remaining funding period include publishing work currently in progress, wrapping up our collaborative projects, and focusing on developing spatial models of the mobile monitoring data for application to Project 5 analyses. We will continue Core activities to support all projects on an as-needed basis.

 


Journal Articles: 87 Displayed | Download in RIS Format

Other center views: All 187 publications 87 publications in selected types All 86 journal articles
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Journal Article Adar SD, D'Souza J, Mendelsohn-Victor K, Jacobs DR, Cushman M, Sheppard L, Thorne PS, Burke GL, Daviglus ML, Szpiro AA, Diez Roux AV, Kaufman JD, Larson TV. Markers of inflammation and coagulation after long-term exposure to coarse particulate matter: a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis. Environmental Health Perspectives 2015;123(6):541-548. R834796 (2014)
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  • Journal Article Aragon MJ, Chrobak I, Brower J, Roldan L, Fredenburgh LE, McDonald JD, Campen MJ. Inflammatory and vasoactive effects of serum following inhalation of varied complex mixtures. Cardiovascular Toxicology 2016;16(2):163-171. R834796 (2015)
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  • Journal Article Bergen S, Sheppard L, Sampson PD, Kim SY, Richards M, Vedal S, Kaufman JD, Szpiro AA. A national prediction model for PM2.5 component exposures and measurement error-corrected health effect inference. Environmental Health Perspectives 2013;121(9):1017-1025. R834796 (2013)
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  • Journal Article Bergen S, Szpiro AA. Mitigating the impact of measurement error when using penalized regression to model exposure in two-stage air pollution epidemiology studies. Environmental and Ecological Statistics 2015;22(3):601-631. R834796 (2014)
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  • Journal Article Bergen S, Sheppard L, Kaufman JD, Szpiro AA. Multipollutant measurement error in air pollution epidemiology studies arising from predicting exposures with penalized regression splines. Journal of the Royal Statistical Society Series C-Applied Statistics 2016;65(5):731-753. R834796 (Final)
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  • Journal Article Brower JB, Doyle-Eisele M, Moeller B, Stirdivant S, McDonald JD, Campen MJ. Metabolomic changes in murine serum following inhalation exposure to gasoline and diesel engine emissions. Inhalation Toxicology 2016;28(5):241-250. R834796 (2016)
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  • Journal Article Campen MJ, Lund A, Rosenfeld M. Mechanisms linking traffic-related air pollution and atherosclerosis. Current Opinion in Pulmonary Medicine 2012;18(2):155-160. R834796 (2012)
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  • Journal Article Campen M, Robertson S, Lund A, Lucero J, McDonald J. Engine exhaust particulate and gas phase contributions to vascular toxicity. Inhalation Toxicology 2014;26(6):353-360. R834796 (2014)
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  • Journal Article Chan SH, Van Hee VC, Bergen S, Szpiro AA, DeRoo LA, London SJ, Marshall JD, Kaufman JD, Sandler DP. Long-term air pollution exposure and blood pressure in the Sister Study. Environmental Health Perspectives 2015;123(10):951-958. R834796 (2015)
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  • Journal Article Chi GC, Liu Y, MacDonald JW, Barr RG, Donohue KM, Hensley MD, Hou L, McCall CE, Reynolds LM, Siscovick DS, Kaufman JD. Long-term outdoor air pollution and DNA methylation in circulating monocytes: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Environmental Health 2016;15(1):119 (12 pp.). R834796 (2016)
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  • Journal Article Chi GC, Hajat A, Bird CE, Cullen MR, Griffin BA, Miller KA, Shih RA, Stefanick ML, Vedal S, Whitsel EA, Kaufman JD. Individual and neighborhood socioeconomic status and the association between air pollution and cardiovascular disease. Environmental Health Perspectives 2016;124(12):1840-1847. R834796 (Final)
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  • Journal Article Cosselman KE, Krishnan RM, Oron AP, Jansen K, Peretz A, Sullivan JH, Larson TV, Kaufman JD. Blood pressure response to controlled diesel exhaust exposure in human subjects. Hypertension 2012;59(5):943-948. R834796C004 (Final)
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  • Journal Article Cosselman KE, Navas-Acien A, Kaufman JD. Environmental factors in cardiovascular disease. Nature Reviews Cardiology 2015;12(11):627-642. R834796 (2015)
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  • Journal Article Erickson MH, Gueneron M, Jobson BT. Measuring long chain alkanes in diesel engine exhaust by thermal desorption PTR-MS. Atmospheric Measurement Techniques. 2014;7(1):225-239. R834796 (2013)
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  • Journal Article Erickson MH, Gueneron M, Jobson BT. Measuring long chain alkanes in diesel engine exhaust by thermal desorption PTR-MS. Atmospheric Measurement Techniques 2014;7(1):225-239. R834796 (2014)
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  • Journal Article Erickson MH, Gueneron M, Jobson BT. Measuring long chain alkanes in diesel engine exhaust by thermal desorption PTR-MS. Atmospheric Measurement Techniques. 2014;7(1):225-239. R834796 (2013)
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  • Journal Article Fann N, Kim S-Y, Olives C, Sheppard L. Estimated changes in life expectancy and adult mortality resulting from declining PM2.5 exposures in the contiguous United States:1980-2010. Environmental Health Perspectives 2017;125(9):097003 (8 pp.). R834796 (2016)
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  • Journal Article Fox JR, Cox DP, Drury BE, Gould TR, Kavanagh TJ, Paulsen MH, Sheppard L, Simpson CD, Stewart JA, Larson TV, Kaufman JD. Chemical characterization and in vitro toxicity of diesel exhaust particulate matter generated under varying conditions. Air Quality, Atmosphere & Health 2015;8(5):507-519. R834796 (2014)
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  • Journal Article Galaviz VE, Yost MG, Simpson CD, Camp JE, Paulsen MH, Elder JP, Hoffman L, Flores D, Quintana PJE. Traffic pollutant exposures experienced by pedestrians waiting to enter the U.S. at a major U.S.-Mexico border crossing. Atmospheric Environment 2014;88:362-369. R834796 (2014)
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  • Journal Article Galaviz VE, Quintana PJE, Yost MG, Sheppard L, Paulsen MH, Camp JE, Simpson CD. Urinary metabolites of 1-nitropyrene in US-Mexico border residents who frequently cross the San Ysidro Port of Entry. Journal of Exposure Science and Environmental Epidemiology 2017;27(1):84-89. R834796 (2016)
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  • Journal Article Gueneron M, Erickson MH, VanderSchelden GS, Jobson BT. PTR-MS fragmentation patterns of gasoline hydrocarbons. International Journal of Mass Spectrometry 2015;379:97-109. R834796 (2014)
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  • Journal Article Hazlehurst MF, Spalt EW, Curl CL, Davey ME, Vedal S, Burke GL, Kaufman JD. Integrating data from multiple time-location measurement methods for use in exposure assessment: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Journal of Exposure Science and Environmental Epidemiology 2017;27(6):569-574. R834796 (2016)
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  • Journal Article Hazlehurst MF, Spalt EW, Nicholas TP, Curl CL, Davey ME, Burke GL, Watson KE, Vedal S, Kaufman JD. Contribution of the in-vehicle microenvironment to individual ambient-source nitrogen dioxide exposure: the Multi-Ethnic Study of Atherosclerosis and Air Pollution. Journal of Exposure Science & Environmental Epidemiology 2018;28(4):371-380. R834796 (Final)
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  • Journal Article Herring CL, Faiola CL, Massoli P, Sueper D, Erickson MH, McDonald JD, Simpson CD, Yost MG, Jobson BT, VanReken TM. New methodology for quantifying polycyclic aromatic hydrocarbons (PAHs) using high-resolution aerosol mass spectrometry. Aerosol Science and Technology 2015;49(11):1131-1148. R834796 (2015)
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  • Journal Article Hooper LG, Young MT, Keller JP, Szpiro A, O’Brien K M, Sandler DP, Vedal S, Kaufman J, London S. Ambient air pollution exposure and chronic bronchitis in a cohort of U.S. women. Environmental Health Perspectives 2018;126(2):027005 (9 pp.). R834796 (Final)
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  • Journal Article Hudda N, Gould T, Hartin K, Larson TV, Fruin SA. Emissions from an international airport increase particle number concentrations 4-fold at 10 km downwind. Environmental Science & Technology 2014;48(12):6628-6635. R834796 (2014)
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  • Journal Article Jandarov RA, Sheppard LA, Sampson PD, Szpiro AA. A novel principal component analysis for spatially misaligned air pollution data. Journal of the Royal Statistical Society: Series C, Applied Statistics 2017,66(1):3-28. R834796 (Final)
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  • Journal Article Keller JP, Olives C, Kim S-Y, Sheppard L, Sampson PD, Szpiro AA, Oron AP, Lindstrom J, Vedal S, Kaufman JD. A unified spatiotemporal modeling approach for predicting concentrations of multiple air pollutants in the Multi-Ethnic Study of Atherosclerosis and Air Pollution. Environmental Health Perspectives 2015;123(4):301-309. R834796 (2014)
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  • Journal Article Keller JP, Chang HH, Strickland MJ, Szpiro AA. Measurement error correction for predicted spatiotemporal air pollution exposures. Epidemiology 2017;28(3):338-345. R834796 (Final)
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  • Journal Article Keller JP, Chang HH, Strickland MJ, Szpiro AA. Measurement error correction for predicted spatiotemporal air pollution exposures. Epidemiology 2017;28(3):338-345. R834796 (2016)
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  • Journal Article Keller JP, Larson TV, Austin E, Barr RG, Sheppard L, Vedal S, Kaufman JD, Szpiro AA. Pollutant composition modification of the effect of air pollution on progression of coronary artery calcium:the Multi-Ethnic Study of Atherosclerosis. Environmental Epidemiology 2018;2:e024. R834796 (Final)
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  • Journal Article Kim SY, Dutton SJ, Sheppard L, Hannigan MP, Miller SL, Milford JB, Peel JL, Vedal S. Erratum to: The short-term association of selected components of fine particulate matter and mortality in the Denver Aerosol Sources and Health (DASH) study. Environmental Health 2016;15(1):85. R834796 (Final)
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  • Journal Article Kim S-Y, Dutton SJ, Sheppard L, Hannigan MP, Miller SL, Milford JB, Peel JL, Vedal S. The short-term association of selected components of fine particulate matter and mortality in the Denver Aerosol Sources and Health (DASH) study. Environmental Health 2015;14:49 (11 pp.). R834796 (2014)
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  • Journal Article Kim S-Y, Sheppard L, Bergen S, Szpiro AA, Sampson PD, Kaufman JD, Vedal S. Prediction of fine particulate matter chemical components with a spatio-temporal model for the Multi-Ethnic Study of Atherosclerosis cohort. Journal of Exposure Science & Environmental Epidemiology 2016;26(5):520-528. R834796 (2016)
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  • Journal Article Kim S-Y, Olives C, Sheppard L, Sampson PD, Larson TV, Kaufman JD. Historical prediction modeling approach for estimating long-term concentrations of PM2.5 in cohort studies before 1999 implementation of widespread monitoring. Environmental Health Perspectives 2017;125(1):38-46. R834796 (2016)
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  • Journal Article Kim S-Y, Sheppard L, Larson TV, Kaufman JD, Vedal S. Combining PM2.5 component data from multiple sources: data consistency and characteristics relevant to epidemiological analyses of predicted long-term exposures. Environmental Health Perspectives 2015;123(7):651-658. R834796 (2014)
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  • Journal Article Larson T, Gould T, Riley EA, Austin E, Fintzi J, Sheppard L, Yost M, Simpson C. Ambient air quality measurements from a continuously moving mobile platform: estimation of area-wide, fuel-based, mobile source emission factors using absolute principal component scores. Atmospheric Environment 2017;152:201-211. R834796 (2016)
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  • Journal Article Lee A, Szpiro A, Kim SY, Sheppard L. Impact of preferential sampling on exposure prediction and health effect inference in the context of air pollution epidemiology. Environmetrics 2015;26(4):255-267. R834796 (2015)
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  • Journal Article Lindstrom J, Szpiro AA, Sampson PD, Oron AP, Richards M, Larson TV, Sheppard L. A flexible spatio-temporal model for air pollution with spatial and spatio-temporal covariates. Environmental and Ecological Statistics 2014;21(3):411-433. R834796 (2013)
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  • Journal Article Lund AK, Doyle-Eisele M, Lin Y-H, Arashiro M, Surratt JD, Holmes T, Schilling KA, Seinfeld JH, Rohr AC, Knipping EM, McDonald, JD. The effects of α-pinene versus toluene-derived secondary organic aerosol exposure on the expression of markers associated with vascular disease. Inhalation Toxicology 2013;25(6):309-324. R834796 (2013)
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  • Journal Article Mauderly JL, Kracko D, Brower J, Doyle-Eisele M, McDonald JD, Lund AK, Seilkop SK. The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: IV. Vascular effects of repeated inhalation exposure to a mixture of five inorganic gases. Inhalation Toxicology 2014;26(11):691-696. R834796 (2014)
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  • Journal Article McDonald JD, Chow JC, Peccia J, Liu Y, Chand R, Hidy GM, Mauderly JL. Influence of collection region and site type on the composition of paved road dust. Air Quality, Atmosphere and Health 2013;6(3):615-628. R834796 (2013)
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  • Journal Article Olives C, Sheppard L, Lindstrom J, Sampson PD, Kaufman JD, Szpiro AA. Reduced-rank spatio-temporal modeling of air pollution concentrations in the Multi-Ethnic Study of Atherosclerosis and Air Pollution. Annals of Applied Statistics 2014;8(4):2509-2537. R834796 (2014)
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  • Journal Article Oppenheim HA, Lucero J, Guyot A-C, Herbert LM, McDonald JD, Mabondzo A, Lund AK. Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice. Particle and Fibre Toxicology 2013;10:62. R834796 (2014)
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  • Journal Article Paffett ML, Zychowski KE, Sheppard L, Robertson S, Weaver JM, Lucas SN, Campen MJ. Ozone inhalation impairs coronary artery dilation via intracellular oxidative stress: evidence for serum-borne factors as drivers of systemic toxicity. Toxicological Sciences 2015;146(2):244-253. R834796 (2014)
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  • Journal Article Riley EA, Banks L, Fintzi J, Gould TR, Hartin K, Schaal L, Davey M, Sheppard L, Larson T, Yost MG, Simpson CD. Multi-pollutant mobile platform measurements of air pollutants adjacent to a major roadway. Atmospheric Environment 2014;98:492-499. R834796 (2014)
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  • Journal Article Riley EA, Gould T, Hartin K, Fruin SA, Simpson CD, Yost MG, Larson T. Ultrafine particle size as a tracer for aircraft turbine emissions. Atmospheric Environment 2016;139:20-29. R834796 (2016)
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  • Journal Article Riley EA, Schaal L, Sasakura M, Crampton R, Gould TR, Hartin K, Sheppard L, Larson T, Simpson CD, Yost MG. Correlations between short-term mobile monitoring and long-term passive sampler measurements of traffic-related air pollution. Atmospheric Environment 2016;132:229-239. R834796 (2016)
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  • Journal Article Robertson S, Colombo ES, Lucas SN, Hall PR, Febbraio M, Paffett ML, Campen MJ. CD36 mediates endothelial dysfunction downstream of circulating factors induced by O3 exposure. Toxicological Sciences 2013;134(2):304-311. R834796 (2013)
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  • Journal Article Sampson PD, Richards M, Szpiro AA, Bergen S, Sheppard L, Larson TV, Kaufman JD. A regionalized national universal kriging model using Partial Least Squares regression for estimating annual PM2.5 concentrations in epidemiology. Atmospheric Environment 2013;75:383-392. R834796 (2013)
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  • Journal Article Schisler JC, Ronnebaum SM, Madden M, Channell M, Campen M, Willis MS. Endothelial inflammatory transcriptional responses to an altered plasma exposome following inhalation of diesel emissions. Inhalation Toxicology 2015;27(5):272-280. R834796 (2015)
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  • Journal Article Sheppard L, Burnett RT, Szpiro AA, Kim S-Y, Jerrett M, Pope III CA, Brunekreef B. Confounding and exposure measurement error in air pollution epidemiology. Air Quality, Atmosphere & Health 2012;5(2):203-216. R834796 (2012)
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  • Journal Article Spalt EW, Curl CL, Allen RW, Cohen M, Williams K, Hirsh JA, Adar SD, Kaufman JD. Factors influencing time-location patterns and their impact on estimates of exposure: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Journal of Exposure Science & Environmental Epidemiology 2016;26(4):341-348. R834796 (2014)
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  • Journal Article Spalt EW, Curl CL, Allen RW, Cohen M, Adar SD, Stukovsky KH, Avol E, Castro-Diehl C, Nunn C, Mancera-Cuevas K, Kaufman JD. Time-location patterns of a diverse population of older adults:the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Journal of Exposure Science & Environmental Epidemiology 2016;26(4):349-355. R834796 (2014)
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  • Journal Article Sun M, Kaufman JD, Kim S-Y, Larson TV, Gould TR, Polak JF, Budoff MJ, Diez Roux AV, Vedal S. Particulate matter components and subclinical atherosclerosis:common approaches to estimating exposure in a Multi-Ethnic Study of Atherosclerosis cross-sectional study. Environmental Health 2013;12:39. R834796 (2013)
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  • Journal Article Suwannasual U, Lucero J, McDonald JD, Lund AK. Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet. Environmental Research 2018;160:449-461. R834796 (Final)
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  • Journal Article Szpiro AA, Sheppard L, Lumley T. Efficient measurement error correction with spatially misaligned data. Biostatistics 2011;12(4):610-623. R834796 (2012)
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  • Journal Article Szpiro AA, Paciorek CJ, Sheppard L. Does more accurate exposure prediction necessarily improve health effect estimates? Epidemiology 2011;22(5):680-685. R834796 (2012)
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  • Journal Article Szpiro AA, Paciorek CJ. Measurement error in two-stage analyses, with application to air pollution epidemiology. Environmetrics 2013;24(8):501-517. R834796 (2013)
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  • Journal Article Szpiro AA, Sheppard L, Adar SD, Kaufman JD. Estimating acute air pollution health effects from cohort study data. Biometrics 2014;70(1):164-174. R834796 (2013)
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  • Journal Article Tessum MW, Larson T, Gould TR, Simpson CD, Yost MG, Vedal S. Mobile and fixed-site measurements to identify spatial distributions of traffic-related pollution sources in Los Angeles. Environmental Science & Technology 2018;52(5):2844-2853. R834796 (Final)
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  • Journal Article Tyler CR, Zychowski KE, Sanchez BN, Rivero V, Lucas S, Herbert G, Liu J, Irshad H, McDonald JD, Bleske BE, Campen MJ. Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes. Particle and Fibre Toxicology 2016;13(1):64 (18 pp.). R834796 (2016)
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  • Journal Article Vedal S, Kaufman JD. What does multi-pollutant air pollution research mean? American Journal of Respiratory and Critical Care Medicine 2011;183(1):4-6. R834796 (2012)
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  • Journal Article Wang M, Keller JP, Adar SD, Kim S-Y, Larson TV, Olives C, Sampson PD, Sheppard L, Szpiro AA, Vedal S, Kaufman JD. Development of long-term spatiotemporal models for ambient ozone in six metropolitan regions of the United States: the MESA Air Study. Atmospheric Environment 2015;123(A):79-87. R834796 (2016)
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  • Journal Article Wang M, Brunekreef B, Gehring U, Szpiro A, Hoek G, Beelen R. A new technique for evaluating land-use regression models and their impact on health effect estimates. Epidemiology 2016;27(1):51-56. R834796 (2015)
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  • Journal Article Wang M, Sampson PD, Hu J, Kleeman M, Keller JP, Olives C, Szpiro AA, Vedal S, Kaufman JD. Combining land-use regression and chemical transport modeling in a spatiotemporal geostatistical model for ozone and PM2.5. Environmental Science & Technology 2016;50(10):5111-5118. R834796 (2016)
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  • Journal Article Weuve J, Kaufman JD, Szpiro AA, Curl C, Puett RC, Beck T, Evans DA, Mendes de Leon CF. Exposure to traffic-related air pollution in relation to progression in physical disability among older adults. Environmental Health Perspectives 2016;124(7):1000-1008. R834796 (Final)
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  • Journal Article Xu W, Riley EA, Austin E, Sasakura M, Schaal L, Gould TR, Hartin K, Simpson CD, Sampson PD, Yost MG, Larson TV, Xiu G, Vedal S. Use of mobile and passive badge air monitoring data for NOx and ozone air pollution spatial exposure prediction models. Journal of Exposure Science and Environmental Epidemiology 2017;27(2):184-192. R834796 (Final)
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  • Journal Article Yin F, Lawal A, Ricks J, Fox JR, Larson T, Navab M, Fogelman AM, Rosenfeld ME, Araujo JA. Diesel exhaust induces systemic lipid peroxidation and development of dysfunctional pro-oxidant and pro-inflammatory high-density lipoprotein. Arteriosclerosis, Thrombosis, and Vascular Biology 2013;33(6):1153-1161. R834796 (2013)
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  • Journal Article Young MT, Sandler DP, DeRoo LA, Vedal S, Kaufman JD, London SJ. Ambient air pollution exposure and incident adult asthma in a nationwide cohort of U.S. women. American Journal of Respiratory and Critical Care Medicine 2014;190(8):914-921. R834796 (2015)
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  • Journal Article Zychowski KE, Lucas SN, Sanchez B, Herbert G, Campen MJ. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure. Toxicology and Applied Pharmacology 2016;305:40-45. R834796 (2016)
    R834796 (Final)
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  • Journal Article Chi GC, Hajat A, Bird CE, Cullen MR, Griffin BA, Miller KA, Shih RA, Stefanick ML, Vedal S, Whitsel EA, Kaufman JD. Individual and neighborhood socioeconomic status and the association between air pollution and cardiovascular disease. Environmental Health Perspectives 2016; doi:10.1289/EHP199 (Epub ahead of print]. R834796C005 (2015)
    R834796C005 (2016)
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  • Full-text: EHP-Full Text PDF (advance publication)
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  • Journal Article Herring CL, Faiola CL, Massoli P, Sueper D, Erickson MH, McDonald JD, Simpson CD, Yost MG, Jobson BT, VanReken TM:New Methodology for Quantifying Polycyclic Aromatic Hydrocarbons (PAHs) Using High-Resolution Aerosol Mass Spectrometry. Aerosol Science and Technology. 2015, 49(11):1131-1148. R834796C001 (2016)
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    Journal Article Peroxidation and Development of Dysfunctional Pro-Oxidant and Pro-Inflammatory High-Density Lipoprotein. Arterioscler Thromb Vasc Biol. 2013, 33(6):1153-61. R834796C003 (2016)
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    Journal Article Galaviz V, Yost M, Simpson C, Camp J, Paulsen M, Elder J, Hoffman L, Flores D, Quintana P:Traffic pollutant exposures experienced by pedestrians waiting to enter the US at a major US–Mexico border crossing. Atmospheric Environment. 2014, 88:362-369. R834796C001 (2016)
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    Journal Article Erickson M, Gueneron M, Jobson B:Measuring long chain alkanes in diesel engine exhaust by thermal desorption PTR-MS. Atmospheric Measurement Techniques. 2014, 7(1):225-239. R834796C001 (2016)
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    Journal Article Aragon MJ, Chrobak I, Brower J, Roldan L, Fredenburgh LE, McDonald JD, Campen MJ:Inflammatory and Vasoactive Effects of Serum Following Inhalation of Varied Complex Mixtures. Cardiovascular toxicology. 2016, 16(2):163-171. R834796C003 (2016)
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    Journal Article Campen MJ, Lund A, Rosenfeld M:Mechanisms linking traffic-related air pollution and atherosclerosis. Current opinion in pulmonary medicine. 2012, 18(2):155. R834796C003 (2016)
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    Journal Article Hudda N, Gould T, Hartin K, Larson TV, Fruin SA:Emissions from an international airport increase particle number concentrations 4-fold at 10 km downwind. Environmental science & technology. 2014, 48(12):6628-6635. R834796C001 (2016)
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    Journal Article Campen M, Robertson S, Lund A, Lucero J, McDonald J:Engine exhaust particulate and gas phase contributions to vascular toxicity. Inhalation toxicology. 2014, 26(6):353-360. R834796C003 (2016)
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    Journal Article Gueneron M, Erickson MH, VanderSchelden GS, Jobson BT:PTR-MS fragmentation patterns of gasoline hydrocarbons. International Journal of Mass Spectrometry. 2015, 379:97-109. R834796C001 (2016)
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    Journal Article Paffett ML, Sheppard L, Robertson S, Weaver J, Lucas SN, Campen MJ. Ozone inhalation enhances coronary artery constriction and impairs dilation via superoxide-dependent mechanisms. Toxicol Appl Pharmacol. 2015, In press. R834796C003 (2016)
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    Journal Article Lund AK, Doyle-Eisele M, Lin Y-H, Arashiro M, Surratt JD, Holmes T, Schilling KA, Seinfeld JH, Rohr AC, Knipping EM, McDonald, JD. The Effects of α-Pinene-vs. Toluene-Derived Secondary Organic Aerosol Exposure on the Expression of Markers Associated with Vascular Disease. Inhalation Toxicology. 2013, 25(6):309-324. R834796C002 (2016)
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    Journal Article Schisler J, Campen MJ, Madden M, and Willis MS. Transcriptional Endothelial Biosensor Response to Diesel-Induced Plasma Compositional Changes. Inhalation Toxicology. 2015, 27(5):272–280. R834796C003 (2016)
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    Supplemental Keywords:

    Air pollution exposure, atherosclerosis, carbon monoxide, cardiovascular disease, chemical transport, community exposures, coronary artery disease, diesel, environmental policy, epidemiologic inference, exposure modeling, exposure science, gasoline engine, health effects, inhalation toxicology, measurement error, mobile monitoring, multipollutant, oxidized phospholipids, ozone, particulate matter, subclinical, volatile organic compounds, Health, Scientific Discipline, Health Risk Assessment, Risk Assessments, Biochemistry, Environmental Monitoring, Atmospheric Sciences, particulate matter, airway disease, bioavailability, air pollution, particle exposure, ambient particle health effects, vascular dysfunction, cardiotoxicity

    Relevant Websites:

    University of Washington Center for Clear Air Research (UW CCAR) Exit
    Research Centers & Institutes | University of Washington Exit

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • 2016 Progress Report
  • Final Report
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834796C001 Exposure Mapping – Characterization of Gases and Particles for ExposureAssessment in Health Effects and Laboratory Studies
    R834796C002 Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies
    R834796C003 Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions
    R834796C004 Vascular Response to Traffic-Derived Inhalation in Humans
    R834796C005 Effects of Long-Term Exposure to Traffic-Derived Particles and Gases on Subclinical Measures of Cardiovascular Disease in a Multi-Ethnic Cohort