2006 Progress Report: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans: The Role of Oxidative Stress

EPA Grant Number: R830954
Title: Effect of Diesel Exhaust Particulate Exposures on Endothelial Function in Humans: The Role of Oxidative Stress
Investigators: Kaufman, Joel D. , Gill, Edward , Larson, Timothy V. , Leotta, Daniel , Sheppard, Lianne (Elizabeth) A. , Sullivan, Jeff
Current Investigators: Kaufman, Joel D. , Chandler, Wayne , Gill, Edward , Koenig, Jane Q. , Larson, Timothy V. , Leotta, Daniel , Sheppard, Lianne (Elizabeth) A. , Sullivan, Jeff , Trenga, Carol , Yost, Michael
Institution: University of Washington
EPA Project Officer: Chung, Serena
Project Period: August 15, 2003 through August 14, 2006 (Extended to August 14, 2008)
Project Period Covered by this Report: August 15, 2005 through August 14,2006
Project Amount: $1,036,972
RFA: Airborne Particulate Matter Health Effects: Cardiovascular Mechanisms (2002) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air , Health Effects

Objective:

Diesel exhaust particulate is a substantial and biologically active fraction of urban ambient fine particulate air pollution, which is associated with increases in cardiovascular morbidity and mortality. This project addresses the overall hypothesis that ambient fine particulate matter exerts cardiovascular health effects via alteration of endothelial homeostasis, through a mechanism mediated by oxidative stress. These studies use a controlled human inhalation exposure to diesel exhaust as an experimental model exposure for ambient fine particulate, to address the following objectives: 1) Determine whether exposure to inhaled diesel exhaust (DE) is associated with endothelial dysfunction in a concentration-related manner; 2) Determine whether exposure to inhaled DE is associated with evidence of systemic oxidative stress; and 3) Determine whether antioxidant supplementation blunts the DE effect on endothelial function.

Progress Summary:

The diesel exposure facility is functioning according to specifications. Between September 2005 and April 2006, 11 individuals with metabolic syndrome completed the study, resulting in a total of 23 participants in experiments 1 and 2. We completed data analyses for these two experiments, and concluded that exposure to diesel exhaust impacts both brachial artery diameter and plasma concentrations of endothelin-1. In addition, we began experiment 3, during which we will examine whether supplementation with antioxidant can alter the effect of DE on endothelial function and oxidative stress. Between May 2006 and August 2006, 13 individuals were enrolled in experiment 3, and 20 exposure sessions were carried out.

Future Activities:

Completion of experiment 3 to evaluate whether antioxidant supplementation can alter the effect of diesel exhaust on endothelial function and oxidative stress. Completion of data analysis from this experiment, and full reporting from all three experiments.

Journal Articles:

No journal articles submitted with this report: View all 33 publications for this project

Supplemental Keywords:

ambient air, human health, dose-response, mobile sources, RFA, Health, Scientific Discipline, Air, HUMAN HEALTH, particulate matter, air toxics, Environmental Chemistry, Health Risk Assessment, Exposure, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, mobile sources, genetic susceptability, Biology, copollutant exposures, sensitive populations, engine exhaust, atmospheric particulate matter, cardiopulmonary responses, fine particles, morbidity, PM 2.5, airway epithelial cells, diesel engines, inhaled pollutants, acute lung injury, air pollution, automotive exhaust, diesel exhaust, susceptible subpopulations, endothelial function, cardiopulmonary response, chronic health effects, lung inflammation, oxidant gas, particulate exposure, heart rate, ambient particle pollution, Acute health effects, highrisk groups, inhaled, chronic obstructive pulmonary disease, human susceptibility, diesel exhaust particles, cardiopulmonary, cardiotoxicity, mortality, diesel exhaust particulate, acute exposure, air quality, cardiovascular disease, biomarker, toxics, concentrated particulate matter, environmental hazard exposures, air contaminant exposure, co-pollutants, airborne urban contaminants

Relevant Websites:

http://depts.washington.edu/envhlth/nlakeexplab/ Exit

Progress and Final Reports:

Original Abstract
  • 2004 Progress Report
  • 2005 Progress Report
  • 2007 Progress Report
  • Final Report