Grantee Research Project Results

2005 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 , Rutgers , University of Medicine and Dentistry of New Jersey
Current 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, 2004 through September 30, 2005
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: (1) determine if exposure of healthy, young, nonsmoking volunteers for 2 hours to freshly generated aerosols will lead to abnormalities in endothelial and platelet function that are independent of pulmonary inflammation; and (2) 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:

During Year 1 of the project, we have developed standardized assays of platelet activation at our laboratories. It is critical that antibody labeling of the platelets occur within minutes of phlebotomy, and thus we have duplicated this sensitive assay in our own laboratory. Assays have been performed in our National Institute of Environmental Health Sciences (NIEHS) Center Analytical Cytometry/Image Analysis Facility Core, which is directed by co-investigator Dr. Debra Laskin. All assays to date have been performed on blood samples obtained before and after a clean air exposure to establish a stable baseline before commencing experimental exposures. Based on intraclass correlations (ICCs), all four activation markers that we are using (PAC1, CD42, CD36, and CD62) were in the very good to excellent range with ICCs ranging from 0.74-0.95.

Endothelial Function Measures

At this point we have insufficient data on flow mediated dilation (FMD) to permit calculation of reliability measures. However, this is in part due to scheduling limitations for the brachial ultrasound technician to be present at our facility. We currently are exploring options to increase efficiency by making arrangements for more technician time. We also are exploring laboratory assays to replace FMD. We propose to more directly assess pre- and postexposure endothelial function with a direct measure of NO production rather than using the functional measure of brachial artery reactivity.

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 single nucleotide polymorphism (SNP) analysis. We have submitted cheek swab specimens on nine test subjects, but results are pending as of this writing.

Subject Recruitment

Advertisements have been developed to recruit subjects for the pilot phases of platelet and brachial artery standardization, and we have successfully recruited from these.

Future Activities:

During Year 2 of the study, we will: (1) conduct pilot exposure sessions with diesel exhaust and secondary organic aerosols; (2) conduct gene screening using cheek swabs on a large scale in the community; (3) implement the nitrite assay and explore it as an adjunct to FMD if ultrasound availability continues to be limited; and (4) perform preliminary statistical analyses on pilot data.

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.