2011 Progress Report: Effects of Long-Term Exposure to Traffic-Derived Particles and Gases on Subclinical Measures of Cardiovascular Disease in a Multi-Ethnic Cohort

EPA Grant Number: R834796C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R834796
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: University of Washington Center for Clean Air Research
Center Director: Vedal, Sverre
Title: Effects of Long-Term Exposure to Traffic-Derived Particles and Gases on Subclinical Measures of Cardiovascular Disease in a Multi-Ethnic Cohort
Investigators: Vedal, Sverre , Kaufman, Joel D. , Larson, Timothy V. , Sampson, Paul , Sheppard, Lianne (Elizabeth) A. , Szpiro, Adam , Yost, Michael
Current Investigators: Kaufman, Joel D. , Larson, Timothy V. , Sampson, Paul , Sheppard, Lianne (Elizabeth) A. , Szpiro, Adam , Vedal, Sverre , Yost, Michael
Institution: University of Washington
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, 2010 through July 31,2011
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

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 multi-pollutant 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: i) the outdoor residential concentration estimates from the multi-pollutant model; ii) estimates of residential infiltration rates; iii) road class- and traffic condition-specific estimates of on-roadway concentrations; and iv) individual-level questionnaire-derived time-location information. These individual-level exposure estimates also will 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 as ascertained by CT, intima-medial thickness as measured by ultrasound, and DNA methylation.

Progress Summary:

The main activities of Project 5 relate to the epidemiologic health study that will begin only in subsequent years. Activities during the first year of the project have included project planning, including protocol development, participation in quality assurance planning, scheduling, coordination with the MESA field centers, and harmonization with the Collaborative Health Studies Coordinating Center (CHSCC). Planning work has included development of a sampling schedule in coordination with the MESA field centers; discussions with the CHSCC regarding strategies related to human subjects approvals; and coordination with Project 1 on sampling locations based on mapping characteristics of MESA participants’ residential locations.

One difficulty that has arisen has been related to the epigenetic analyses included in Aim 3. Our original proposal stated that genome-wide DNA methylation analysis would be conducted as part of the NIH Roadmap Initiative grant to Yongmei Liu at Wake Forest University (ES107650-01, “Epigenome-Wide Association Study of DNA Methylation and Atherosclerosis”), on specially prepared blood samples collected in all MESA participants at Exam 5. Due to funding limitations, the scope of the Epigenome-Wide Association Study was altered; at present, the DNA methylation analysis is occurring on 3800 participants from four field centers (in Baltimore, New York, St. Paul, and Winston-Salem), rather than the expected 5400 from all six field centers. Chicago and Los Angeles, both of which were originally included in Projects 1 and 5, are the two centers in which epigenetic testing is not occurring.

We are addressing this change in two ways. First, we have altered the cities included in air monitoring activities in this Center. As described in the Project 1 summary, the mobile monitoring campaign originally scheduled for Baltimore, Chicago, Los Angeles, and Winston-Salem will now occur in Baltimore, Los Angeles, St. Paul and Winston-Salem. The personal and residential monitoring included in Project 5 was originally planned for Chicago and LA; because of the change in the epigenetic testing, we now will include Winston-Salem and Los Angeles. While ideally these cities would be measuring all health outcomes of interest, retaining Los Angeles in the monitoring campaigns of both Projects 1 and 5 allows us to capture some of the highest air pollutant concentrations in the country, and substituting St. Paul for Chicago (in Project 1) and Winston-Salem for Chicago (in Project 5) maximizes the number of participants for which we have data on all proposed health outcomes.

Our second approach for dealing with this change is to work together with MESA and MESA Air investigators to process and store blood samples from a subset of approximately 150 Los Angeles participants to potentially allow for future epigenetic analyses. Specifically, we are proposing a modified protocol by which clinic staff would draw blood into PBMC isolation tubes, the blood would be centrifuged and the PBMC fraction washed and cryopreserved at the site, and then shipped frozen to Wake Forest University for storage. 

Overall, epidemiological analyses, including left ventricular myocardial mass as ascertained by MRI, arteriolar diameters as measured by retinal photography, coronary artery calcium as ascertained by CT, and intima-medial thickness as measured by ultrasound will occur for participants in Baltimore, Los Angeles, St. Paul, and Winston-Salem. The epidemiological analyses including DNA methylation outcomes will include participants in Baltimore, St. Paul, Winston-Salem, and likely a subset from Los Angeles.

There also has been one important change in the timeline for Project 5. Originally, it was expected that the personal monitoring and field work activities associated with this project would occur in Year 2. However, because it is critical that this project align with the activities in Project 1, and because the Project 1 mobile monitoring campaigns in Winston-Salem and Los Angeles do not begin until January 2013, the personal and residential monitoring associated with Project 5 will be delayed until Project Year 3.

There have been no other problems, delays, or adverse conditions that could impair the ability of this project to meet the results specified in the application. There also have been no absences or changes of key personnel, nor any costs significantly higher than originally estimated. While no data have been collected to date, Project 5 personnel are working closely with the Quality Assurance Manager to develop appropriate QA plans and policies. Because the residential monitoring and epidemiological analyses will not begin until Year 3, we have not yet begun application for Human Subject approval.

Future Activities:

During Year 2 of this project, we intend to work with the CHSCC and the MESA field centers at UCLA and Wake Forest University to acquire appropriate Human Subjects approvals for the personal and residential sampling included in this project. We also will develop Standard Operating Procedures and Quality Assurance Plans to govern these sampling efforts. We will collaborate with the MESA and MESA Air studies as the fifth and final clinic exam comes to a close, during which the health outcome data included in this project are being collected. We also will work with the MESA and MESA Air studies to attempt to collect blood samples from a subset of participants in Los Angeles to allow for future epigenetic analyses.

Journal Articles:

No journal articles submitted with this report: View all 17 publications for this subproject

Supplemental Keywords:

Cardiovascular health, epidemiology, volatile organic compounds, VOCs, subclinical, atherosclerosis;, Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Air Quality, air toxics, Health Risk Assessment, Risk Assessments, mobile sources, Risk Assessment, ambient air quality, atmospheric particulate matter, particulate matter, aerosol particles, air pollutants, motor vehicle emissions, vehicle emissions, air quality models, motor vehicle exhaust, airway disease, bioavailability, air pollution, particle exposure, atmospheric aerosols, ambient particle health effects, vascular dysfunction, cardiotoxicity, atmospheric chemistry, exposure assessment

Progress and Final Reports:

Original Abstract
2012 Progress Report
2013 Progress Report
2015 Progress Report


Main Center Abstract and Reports:

R834796    University of Washington Center for Clean Air Research

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