Grantee Research Project Results

2006 Progress Report: Responses to Fresh Aerosol in Susceptible Subjects

EPA Grant Number: R832144
Title: 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: Particulate Matter , Air Quality and Air Toxics , 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.

We are also collecting plasma and sputum specimens, however analysis of these stored specimens is pending

Journal Articles:

No journal articles submitted with this report: View all 17 publications for this project

Supplemental Keywords:

Ambient air, genetic polymorphisms, susceptibility, human health;, RFA, Health, Scientific Discipline, Air, HUMAN HEALTH, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Risk Assessments, particulate matter, Biology, genetic susceptability, mobile sources, Exposure, Biochemistry, air toxics, inhaled, air quality, environmental hazard exposures, inhaled pollutants, sensitive populations, diesel exhaust, fine particles, lung inflammation, oxidant gas, acute lung injury, human exposure, DEP, engine exhaust, cardiopulmonary responses, particulate exposure, Nitric Oxide Synase, Acute health effects, airway epithelial cells, copollutant exposures, cardiotoxicity, acute exposure, diesel exhaust particulate, chronic health effects, susceptible subpopulations, concentrated particulate matter, air contaminant exposure, toxics, atmospheric particulate matter, heart rate, air pollution, highrisk groups, human susceptibility, airborne urban contaminants, cardiovascular disease, cardiopulmonary, human health risk, ambient particle pollution, cardiopulmonary response, automotive exhaust, diesel engines

Progress and Final Reports:

Original Abstract

The 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.