Center for Clean Air Research

The University of Washington Center for Clear Air Research (UW CCAR) is focused on the cardiovascular health effects of near-roadway pollution, a complex mixture of components that come from vehicle emissions and the road surface, and vary by physical aging, atmospheric conditions, and photochemical reactions. UW CCAR is funded by the U.S. Environmental Protection Agency (RD-83479601).

This exposure scenario is not only known to be of considerable health importance, it also serves as a prototypical case for developing research approaches to dealing with multipollutant exposure-effect relationships. Near-roadway pollution is 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. Improvements in our understanding of near-roadway exposure effects from taking a more realistic and sophisticated multi-pollutant perspective would be expected to translate into more effective air pollution policies to reduce the public health burden of these exposures.

Our immediate aim in this Center is to integrate exposure, epidemiological, toxicological, clinical, and statistical sciences (a five-pronged approach) to both examine the cardiovascular effects of fresh and aged roadway emissions and, simultaneously, to advance our understanding of the components and reaction products that cause the effects. The general notion underlying our approach is that exposure, especially long-term exposure, to specific but as yet poorly characterized traffic-derived primary (fresh) and/or secondary (aged) organic particles and gases (and mixtures of these) cause or hasten development of cardiovascular disease. We maintain that this can be rigorously tested and putative causal components can be identified using an interlinked, multidisciplinary investigational strategy and applying statistical methods aimed specifically at the multipollutant problem.

Our approach builds on insights gained from our work to date that: 1) fresh, whole vehicular emissions can drive the oxidation of lipids and inflammation in atherosclerotic regions, an effect that is dependent on both particulate and gaseous components of the emissions; 2) the combination of fresh gasoline engine emissions, which are relatively low in PM mass and high in volatile organic compounds, and the higher PM-containing diesel engine emissions lead to synergistic increases in vascular lipid peroxidation; 3) acute exposure to diesel exhaust increases vascular tone; and 4) long-term traffic exposure has important effects on cardiovascular health as reflected in cardiac structure and function, specifically left ventricular mass, and on microvascular disease, as reflected by retinal artery narrowing. These experimental and observational findings enable us to focus our biological hypotheses and choice of endpoints to take the next significant step forward in understanding this multi-pollutant conundrum and providing information useful in directing actions to mitigate the health burden associated with proximity to busy roadways. While obtaining a complete understanding of the near-roadway exposure cardiovascular disease relationship and identification of all causal pollutant species and their combinations is overly ambitious at this point, we have high confidence that the work we propose is an absolutely necessary and timely step toward that end.

Our Center is designed to address at least three of the six of research questions posed in the RFA [(i) pollutant health effects in a multi-pollutant context; (ii) biological mechanisms underlying health effects; (iii) exposure-response relationships] and has relevance for another two [(iv) susceptible subpopulations; and (v) origin, transportation and transformation of multi-pollutant constituents]. The goals, objectives and approaches to be used in this Center are described below.

Goal

The ultimate goal of the UW CCAR is to understand the physical and chemical features of exposures to near-roadway mixtures, including their interactions and concentration response relationship, that cause or exacerbate cardiovascular health effects.

Objectives and Approach

The University of Washington team, with its expertise in exposure assessment and estimation in clinical exposure studies, toxicology and air pollution epidemiology including major field studies, and in biostatistical methods development and application, is joining with the Lovelace Respiratory Research Institute (LRRI) and University of New Mexico team, with its well-developed and unique expertise in development and characterization of laboratory-generated exposure atmospheres and in toxicology, and with the Washington State University (WSU) team with its unique pollutant monitoring capabilities, to tackle the challenging problems entailed in taking a multi-pollutant approach to investigating air pollution health effects. The proposed research applies a highly-integrated, multi-disciplinary approach to the common theme of near-roadway exposures and cardiovascular health effects. While a multidisciplinary approach to air pollution health effects research is not original, our application of the highly interlinked five-pronged approach we propose is unique and is likely to make substantial progress in the use of a multi-pollutant approach to improving understanding of air pollution health effects.

The Center we propose is clearly an interdisciplinary enterprise, although the discipline oriented divisions (projects and cores) are somewhat arbitrarily defined because of the strongly interwoven nature of all of the projects. The use of a human clinical study in the experimental setting to extend and validate our exposure atmosphere-related toxicological findings is particularly noteworthy, but that is only one example. Health endpoints center on common themes across the animal and human experiments and the laboratory and population studies. The field characterization component informs the evolution of experimental exposure atmospheres. The Biostatistics Core develops methods for dealing with multivariate data of a nature common to all three health studies (projects 3, 4 and 5), methods that are intended to find ready application by the other centers created under this RFA and by other investigators attempting to unravel effects of mixed exposures.