Grantee Research Project Results

2011 Progress Report: Vascular Response to Traffic-Derived Inhalation in Humans

EPA Grant Number: R834796C004
Subproject: this is subproject number 004 , 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: Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials
Center Director: Faustman, Elaine
Title: Vascular Response to Traffic-Derived Inhalation in Humans
Investigators: Kaufman, Joel D. , Lund, Amie K. , MacDonald, Jacob
Current Investigators: Kaufman, Joel D. , Larson, Timothy V.
Institution: University of Washington , Lovelace Biomedical & Environmental Research Institute
Current 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 November 30,2011
RFA: Clean Air Research Centers (2009) RFA Text | Recipients Lists
Research Category: Human Health , Air

Objective:

Project 4 examines the acute vascular effects of model traffic-derived inhalation exposures in human subjects, in a multi-pollutant context. The project uses controlled clinical exposures to examine specific hypotheses based on the premise that traffic-related air pollutants acutely trigger increased arterial reactivity, vasoconstriction, and increased blood pressure in humans, and that these responses will vary depending on the components and sources of those exposures. We will test the hypothesis that traffic (e.g., diesel and gasoline engine) -derived aerosols exert vascular effects in human subjects, and provide insight into the most toxic components and mechanisms underlying epidemiological observations of cardiovascular disease events and mortality.

Progress Summary:

Project 4 is planned to begin human studies in year 3 of the Center. The experiments will be customized based on findings in Center Projects 1-3.

Building on data derived from animal studies and exposure characterization studies in Center years 1 and 2, and by customizing exposures to capitalize on those findings, we plan clinical experiments nested within a crossover trial to be primarily conducted in Center years 3 and 4. In healthy subjects, we will test whether a traffic-derived laboratory-generated high-potency pollution atmosphere, as suggested through other Center projects, causes an increased vascular response (brachial artery vasoconstriction and increased blood pressure) compared with both a roadway-derived exposure of hypothesized lower potency, and with filtered air.

Projects funded from other sources are ongoing in the human exposure facility, and we anticipate no new obstacles to completing the proposed Center-funded work. We have recently completed one experimental protocol, are conducting data analysis on those results, and are currently launching a new experimental protocol that we plan to have completed by Center year 3. The new protocol will permit us to conduct pilot evaluations of the proposed procedures to be used in Center Project 4, as we ramp up Center activities in the laboratory in anticipation of the launch of the Center-funded protocol in year 3. We are now conducting pilot scale investigations regarding DNA methylation procedures as proposed in the Center application.

The new experimental protocol (supported primarily by NIEHS 5P50ES015915) being launched has received IRB approval without controversy, and we do not anticipate difficulties with approval for the Center-funded activities that will follow this protocol. However, it remains premature to proceed with an IRB application for a Center-funded project as we can yet anticipate protocol modifications, nor define the to-be-used exposure situation, which will be an underpinning of that IRB application.

There are currently no changes to the aims or procedures as described in the grant application. In the 18 months subsequent to filing this report, we anticipate that we will need to adjust our planned approach to reflect the results of the animal experiments and interval scientific knowledge.

Future Activities:

During Year 2 of this project, we will continue to collaborate with Center investigators and staff from Projects 2 and 3 to refine our plans for the experimental protocol so that we can launch the Center-sponsored experimental protocol on time and with all procedures adequately pilot-tested.

Journal Articles:

No journal articles submitted with this report: View all 2 publications for this subproject

Supplemental Keywords:

Cardiovascular health, diesel exhaust, gasoline exhaust, fine particles, volatile organic compounds, blood pressure, Health, Air, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Risk Assessments, Air Quality, mobile sources, Biochemistry, air toxics, Risk Assessment, aerosol particles, vehicle emissions, bioavailability, atmospheric chemistry, motor vehicle emissions, particulate matter, motor vehicle exhaust, ambient particle health effects, cardiotoxicity, air quality models, air pollutants, atmospheric aerosols, atmospheric particulate matter, vascular dysfunction, ambient air quality, air pollution, cardiovascular disease, exposure assessment, airway disease

Relevant Websites:

http://depts.washington.edu/uwccar/

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R834796 Predictive Toxicology Center for Organotypic Cultures and Assessment of AOPs for Engineered Nanomaterials

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

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.