2012 Progress Report: Vascular Response to Traffic-Derived Inhalation in HumansEPA 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: University of Washington Center for Clean Air Research
Center Director: Vedal, Sverre
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 Respiratory 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, 2011 through November 30,2012
RFA: Clean Air Research Centers (2009) RFA Text | Recipients Lists
Research Category: Health Effects , Air
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.
Project 4 is planned to begin human studies in Year 3 of the Center grant. 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. Our External Scientific Advisory Committee suggested that we simplify our Project 4 protocol, and we are taking that suggestion seriously.
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 currently are conducting a different experimental protocol, with exposure to diesel exhaust, which we plan to have completed by Center Year 3. This 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.
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. We modified our consent process slightly to reflect the International Agency for Research on Cancer determination that diesel exhaust emissions represented a human carcinogen. We briefly suspended our exposures while awaiting approval of the new language. Our IRB approved the modification, and participants are being recruited and exposed again using the revised materials. We anticipate moving forward with IRB approval for the CCAR Project 4 protocol shortly, so that it is ready to proceed in Center Year 3.
During Year 3 of this project, we will 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, VOCs, blood pressure, Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, Air Quality, air toxics, Health Risk Assessment, Risk Assessments, mobile sources, Biochemistry, Risk Assessment, ambient air quality, particulate matter, atmospheric particulate matter, air pollutants, vehicle emissions, aerosol particles, motor vehicle emissions, air quality models, airway disease, bioavailability, motor vehicle exhaust, air pollution, particle exposure, atmospheric aerosols, ambient particle health effects, vascular dysfunction, cardiotoxicity, atmospheric chemistry, cardiovascular disease
Progress and Final Reports:Original Abstract
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