The long term goal of the candidate is to develop a patient oriented research program in Pulmonary Medicine and Environmental Health at the University of Washington that determines mechanisms of pulmonary and cardiovascular effect from environmental pollutants. The candidate will perform two studies to determine the effects of PM2.5 on cardiac function. The first study is a case-crossover study which will determine the association of sudden cardiac arrest to PM2.5 and co-pollutant levels. The second is a panel study in elderly individuals that will expand on the understanding of mechanism of cardiac effect by determining whether inflammatory cytokine and thrombotic responses to particulate matter (PM), CO or N02 occur in susceptible sub-populations. It hypothesizes that these air pollutants induce an inflammatory cascade within the lung that results in measurable elevations in local and systemic inflammatory mediators that induce a decompensation of cardiac function, especially in susceptible groups. These proposed studies of inflammatory markers will be coupled to measures of intra-individual changes in thrombotic proteins (D-dimer and fibrinogen) with varying levels of air pollution exposure in this cohort of elderly participants with and without lung and heart disease. The proposed study builds on an established project within the UW EPA PM Research Center repeatedly measuring personal PM exposures and health effects, in 108 elderly individuals with and without cardiac or respiratory diseases during a high and low pollution season. By assessing intra-individual differences, this project will: 1) Determine whether PM exposure-effect relationships can be detected for exhaled nitric oxide and for serum TNF-alpha and TNF-alpha receptors, IL-6 and IL-6 receptor, endothelin-1 and C-reactive protein (CRP) and whether these effects are associated with sub-clinical morbidity including a reduction in heart rate variability. 2) Determine whether elevated PM 2.5 is associated with increased susceptibility to thrombosis by measuring intra-individual variation of D-dimer and fibrinogen levels. Elucidating molecular mechanisms of susceptibility to air pollution induced morbidity will aid in designing public health policy to prevent morbidity and mortality from air pollution.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23ES011139-04
Application #
6919881
Study Section
Special Emphasis Panel (ZES1-LKB-E (K2))
Program Officer
Shreffler, Carol K
Project Start
2002-08-05
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2006-05-31
Support Year
4
Fiscal Year
2005
Total Cost
$105,007
Indirect Cost
Name
University of Washington
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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