2014 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, Chris , 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: December 1, 2013 through July 31,2014
Project Amount: $8,000,000
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

Each of the four individual EPA Clean Air Research Centers aims to advance understanding of the human health effects of exposures to complex (multipollutant) air pollution mixtures. The University of Washington (UW) Center for Clean Air Research (CCAR) specifically is examining how pollution from roadways affects cardiovascular health. The research integrates exposure, epidemiological, toxicological, clinical, and statistical sciences to study the cardiovascular hazards of recent and aged roadway emissions.

The 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 not only is 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
  6. To develop a statistical and methodological framework for studying health effects of multipollutant mixtures

Research Projects and Core Groups:

  • Administrative Core
  • Biostatistics Core
  • Project 1: Exposure Mapping—Characterization of Gases and Particles for Exposure Assessment in Health Effects and Laboratory Studies
  • Project 2: Simulated Roadway Exposure Atmospheres for Laboratory Animal and Human Studies
  • Project 3: Cardiovascular Consequences of Immune Modification by Traffic-Related Emissions
  • Project 4: Vascular Response to Traffic-Derived Inhalation in Humans
  • Project 5: Effects of Long-Term Exposure to Traffic-Derived Aerosols and Gases on Subclinical Measures of Cardiovascular Disease and DNA Methylation in a Multiethnic Cohort

Progress Summary:

With support from the administrative and biostatistics cores, significant progress was made on all CCAR projects in Year 5 of the grant.

Administrative Core

The Administrative Core supported all CCAR projects through coordinating meetings, managing IT resources, leading QA/QC activities, preparing reports, tracking manuscripts, and coordinating Institutional Review Board and Human Subjects and Institutional Animal Care and Use Committee activities. 

Biostatistics Core

This Core has continued to support Project 1’s data management and compilation.

The Core has provided extensive input to Project 1 analyses, both through staff support and through consultation of additional ongoing analyses by other members of the Project 1 team. Dr. Sheppard has collaborated with Matt Campen on the paper Ozone Inhalation Enhances Coronary Artery Constriction and Impairs Dilation via Superoxide-Dependent Mechanisms, which is being finalized for submission. This work quantifies the constrictive and dilatory responses in the coronary vascular bed to known agonists following O3 exposure in order to better elucidate underlying pathophysiological mechanisms driving extrapulmonary toxicity. Dr. Sheppard collaborated with co-authors on the statistical and presentation aspects of the paper, specifically the approach to conducting the repeated measures ANOVA and refinements to the data display.

The Biostatistics Core has supported the redesign of Project 4, which is poised to begin collecting data. 

Project 5 will be the main thrust of activities for the Core in Year 5. In the past year, we constructed preliminary spatial models of the Project 1 multipollutant badge data for the summer of 2013 collected in Baltimore, Maryland, with the goal of formulating a strategy for predicting multipollutant profiles based on Project 1 data at Multi-Ethnic Study of Atherosclerosis (MESA) Air study subject locations. In this analysis, we had data for 14 pollutants measured at 43 monitoring locations: O3, NO2, NOx, SO2, pentane, isoprene, nonane, decane, undecane, dodecane, benzene, toluene, meta-xylene and ortho-xylene. Our goal was to understand the spatial predictability of each pollutant using GIS covariates at each location via cross-validation. To address the problem we considered two different approaches. First, we used a combination of partial least squares (PLS) and universal kriging (UK) in pollutant-specific prediction models. In this approach, PLS scores calculated for each pollutant were a lower dimensional representation of the GIS covariates that we then used to model the mean structure in UK. Second, as an alternative to PLS with UK, we did a two-step variable selection of GIS covariates, again treating each pollutant separately. We used elastic-net penalized regression in the first step of this selection algorithm. Given the selected variables from the first step (i.e., all variables with non-zero coefficients from the penalized regression), in the second step we further selected the best subset of variables with the highest adjusted R-squared out of the set of variables identified in the first step. The best subset of GIS covariates was then fed into the UK algorithm as the mean structure. Based on results from the Baltimore dataset, the second approach (two-step variable selection followed by UK) resulted in high cross-validated R-squared (indicating good spatial predictability) and performed better than PLS followed by UK. As a next step in this work, we plan to apply our predictive (sparse) principal component analysis (PCA) approaches to multipollutant data from Project 1. Based on the results of our preliminary comparison, we plan to predict the principal scores at the MESA Air subject locations using the second approach. Ultimately, our goal is to use the predicted scores in a health analysis to understand the health effects of multipollutant mixtures.

Our goal is to develop a statistical framework for assessing health effects of long-term exposure to multipollutant mixtures when health data and monitoring data are spatially misaligned. To deal with spatial misalignment, we initially tried a sequential approach where we reduce the dimension of the exposure data by sparse PCA (sparse PCA) at monitoring locations and use spatial modeling to predict component scores at subject locations. This did not work well because some of the PC loadings included pollutants that are not well-predicted by GIS covariates and/or spatial smoothing. To resolve this issue, we then developed new methods, termed predictive (sparse) PCA for spatially misaligned data. These methods identify (sparse) principal component loading vectors that explain as much variability in the observed data as possible, while also ensuring the corresponding principal component scores can be predicted accurately by means of spatial statistics at locations where observations are not available. This will make it possible to identify important mixtures of air pollutants and to quantify their health effects in cohort studies, where currently available methods cannot be used.

We demonstrated the utility of predictive (sparse) PCA in simulated data and in an application to annual averages of particulate matter speciation data from national Environmental Protection Agency (EPA) regulatory monitors (CSN and IMPROVE monitors). A manuscript based on this work is nearly complete and will be submitted to the Journal of the American Statistical Association: Applications and Case Studies. The current version of predictive (sparse) PCA is based on spatial prediction by unpenalized regression splines (i.e., low-rank splines combined with GIS covariates), with separate unlinked prediction models for each PC score. Future extensions of this work will include penalized and linked multivariate prediction models for different scores. In a complementary project, we are developing methods for predictive k-means clustering.

Using our recently developed framework, we are currently working on understanding the health effects of multipollutant mixtures derived from our predictive (sparse) PCA approaches on systolic blood pressure (SBP) in the National Institute of Environmental Health Sciences Sisters Study. This builds on previous work in which we found an association between SBP and PM2.5 in this cohort. Based on our preliminary results, we are finding that using IMPROVE monitors in addition to CSN for spatial prediction could introduce substantial bias in health estimates. We believe this is because the compatibility condition between monitoring and subject locations, a key condition for valid measurement error corrections when the exposure model is misspecified, is violated by the IMPROVE monitoring network design.

After completing our method refinement and analyses in the Sisters Study and CSN/IMPROVE setting where long-term exposure measurements are available (albeit spatially misaligned), we will take on the more challenging task of incorporating spatio-temporal mobile monitoring data from Project 1. This effort will culminate in analyses of associations between long-term exposure to PM2.5 components and gases and cardiovascular disease outcomes in the MESA cohort (CCAR Project 5), with intra-urban exposure contrasts derived from Project 1 monitoring data.

The Core has been supporting and leading efforts to publish and otherwise disseminate UW CCAR research. 

Progress of Projects

Project 1 made considerable progress on data quality assurance and data management tasks and began data analysis. In the previous year, Project 2 conducted subchronic inhalation studies with several mixed atmospheres in collaboration with Project 3. The primary accomplishment of this past year for Project 3 was an investigation into the role of blood-borne ligands and bioactivity in terms of driving endothelial cell activation or dysfunction. Researchers for Project 4 completed their revised study design and obtained human subjects approval. For Project 5, data collection continued and data analysis began.

Future Activities:

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. 

Project 1 
Activities in the next year will focus on analyzing final QC data from the field sampling campaigns and 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 are underway.  

Project 2
The next round of studies will continue the new short-term bioassays to include the atmospheric reaction chamber and urban background studies.
 
Project 3
 
Aim 1
 
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.
 
Collaborative Studies
 
Interactions with the GLACIER program are two-fold. First, we have obtained serum samples from Rob Brook at the University of Michigan from his human exposures to coarse particulate matter. With these samples we currently are testing a battery of inflammatory potential assays. Data from these studies should be forthcoming in the fourth year of funding. Second, we will be sending tissues to Jesus Araujo to analyze HDL dysfunction and oxidized lipids in serum and bronchoalveolar lavage fluid. Plans for this are still being prepared, in terms of which pollutant atmospheres and which specific animal models to use, but studies will again be undertaken in Year 4. These will provide important clues into the nature and origin of the circulating vasoactive species.
 
We have identified a biological chemist at Virginia Commonwealth University, Dr. Andrew Ottens, who has been examining the proteomic changes in serum following exposures. In the coming year, we will publish his findings related to peptide fragmentation in parallel with bioactivity related to vascular dysfunction, loss of endothelial barrier integrity and neuroinflammation.

Project 4
We will launch the Center-sponsored study protocol and complete procedures as proposed. 

Project 5
The final field campaign in the “non-heating” season in Los Angeles currently is underway and will be complete by August 1, 2014. We have complete IRB approval at the University of Washington, Wake Forest University, and University of California, Los Angeles for all of these activities.
 
In addition to focusing a significant amount of effort on these field campaigns, our immediate next goals are to continue analyzing the data collected in the first three sampling campaigns to understand the relative importance of time spent in transit to total personal exposure. This will help us determine how to generate individual exposure estimates for all MESA Air participants, for use in epidemiological analyses. We also are in the process of preparing three manuscripts on the study design and methods, a comparison of the three time-location measurement methods utilized in this study, and an analysis of the relative contributions of each microenvironment to overall exposure to ambient-source nitrogen dioxide.
 
The next project year will see effort transition primarily to Aim 3: Epidemiological analyses incorporating the exposure information gained through Aims 1 and 2.

 


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 (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 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 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, Drton M, Larson T, Kaufman JD, Sandler DP, Szpiro AA. Covariate-adaptive clustering of exposures for air pollution epidemiology cohorts. Annals of Applied Statistics 2017;11(1):93-113. 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, 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, 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)
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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)
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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 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, PM, subclinical, volatile organic compounds, VOCs, 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:

    UW Center for Clean Air Research (CCAR) | University of Washington, DEOHS Exit
    Research Centers & Institutes | Department of Environmental & Occupational Health Sciences | UW School of Public Health Exit

    Progress and Final Reports:

    Original Abstract
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2015 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