Grantee Research Project Results
2006 Progress Report: Responses to Fresh Aerosol in Susceptible Subjects
EPA Grant Number: R832144Title: Responses to Fresh Aerosol in Susceptible Subjects
Investigators: Kipen, Howard , Lioy, Paul J. , Philipp, Claire , Shindler, Daniel , Laskin, Deborah , Zhang, Junfeng , Ohman-Strickland, Pamela , Laumbach, Robert , Fan, Tina
Institution: Robert Wood Johnson Medical School
EPA Project Officer: Chung, Serena
Project Period: October 1, 2004 through September 30, 2008
Project Period Covered by this Report: October 1, 2005 through September 30,2006
Project Amount: $1,521,398
RFA: The Role of Air Pollutants in Cardiovascular Disease (2003) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air
Objective:
The specific objectives of this research project are to:
- Determine if exposure of 50 healthy, young, non-smoking volunteers for two hours to freshly generated aerosols (fresh diesel exhaust, secondary organic aerosol, clean air) will lead to abnormalities in endothelial, and platelet function that are independent of pulmonary inflammation.
- Determine if individuals with genetically increased risk for atherosclerotic cardiovascular disease and endothelial dysfunction exhibit enhanced sensitivity to diesel exhaust or secondary organic aerosol.
Progress Summary:
1. Platelet Activation
During year 1 of the project, we have developed standardized assays of platelet activation at our laboratories. Intraclass correlations for the assays of the four different markers ranged from 0.7-0.9. As of this time we have run 13 subjects with exposure to diesel exhaust, secondary organic aerosol, and to clean air. There are no obvious differences (pre-exposure to immediately post) in the activation profiles after this small number of subjects. Only one subject with the variant (susceptible) genome has been run to date. Intensive efforts to recruit these subjects is being initiated.
2. Endothelial Function Measures
At this point our flow mediated dilation (FMD) data do not appear to be adequately reliable for analysis in relation to exposure, although they do show a small non-significant effects of the exposure. We are currently exploring options to improve both data collection and analysis of this endpoint. We are also exploring laboratory assays to replace FMD by a direct measure of NO production rather than using the functional measure of brachial artery reactivity.
3. Genetic Screening For eNOS Polymorphisms
Gene screening has been done using the Isohelix DNA cheek swab sample to identify subjects who are at genetically increased risk for atherosclerotic cardiovascular disease and endothelial dysfunction. Specimens from the swab have been determined in our Bionomics Research and Technology Facility to have good quality DNA for SNP analysis. We have successfully identified 5 subjects with the SNP of interest, although only one has been studied to date. We will be conducting intensive screenings to identify the relatively uncommon individuals with this SNP, and bring them into the study in greater numbers.
Future Activities:
During year 3 of the study, we will:
- Continue to run subjects with all three exposures for collection of platelet activation data.
- Continue to refine our FMD technique while developing alternative measures of acute change in endothelial function.
Journal Articles:
No journal articles submitted with this report: View all 17 publications for this projectSupplemental Keywords:
Ambient air, genetic polymorphisms, susceptibility, human health;, RFA, Scientific Discipline, Health, Air, HUMAN HEALTH, particulate matter, Health Risk Assessment, air toxics, Exposure, Susceptibility/Sensitive Population/Genetic Susceptibility, Risk Assessments, Biochemistry, mobile sources, genetic susceptability, Biology, copollutant exposures, sensitive populations, atmospheric particulate matter, engine exhaust, Nitric Oxide Synase, airway epithelial cells, cardiopulmonary responses, fine particles, inhaled pollutants, acute lung injury, diesel engines, air pollution, susceptible subpopulations, diesel exhaust, automotive exhaust, chronic health effects, lung inflammation, oxidant gas, particulate exposure, cardiopulmonary response, heart rate, human exposure, ambient particle pollution, Acute health effects, inhaled, highrisk groups, human susceptibility, diesel exhaust particles, cardiotoxicity, cardiopulmonary, diesel exhaust particulate, concentrated particulate matter, air contaminant exposure, air quality, environmental hazard exposures, toxics, airborne urban contaminants, cardiovascular disease, acute exposure, human health riskProgress and Final Reports:
Original AbstractThe 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.