Grantee Research Project Results
2007 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, 2006 through September 30,2007
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 healthy, young, non-smoking volunteers for two hours to freshly generated aerosols will lead to abnormalities in endothelial, and platelet function that are independent of pulmonary inflammation.
- Detemrine 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:
- Overall Progress
As of the end of the third year, we have completed running three 2-hour exposure sessions each for 38 subjects, although not all subjects were studied for all outcome measures due to scheduling. In addition, 3 subjects have completed 2 sessions without the SOA condition (e.g., we have 41 subjects who have completed a diesel exhaust and a clean air exposure). - Platelet Activation Analysis
As of year three of the project, we have collected data on 41 subjects by conducting standardized assays of platelet activation at EOHSI. These assays have been performed in our NIEHS Center Analytical Cytometry Core Facility. All assays to date have been performed on blood samples obtained before and after each exposure condition, namely diesel exhaust (DE), secondary organic aerosols (SOA) and a clean air (CA) exposure. Based on pre-post comparisons there is little suggestion of any effect of the diesel condition on platelet activation. In the fourth year we are almost exclusively focused on recruiting eNOS homozygotes, as to date we have studied only five. We also are making arrangements to introduce platelet aggregation assays as an alternative to the platelet activation, continuing our search for a clear diesel effect on coagulation. - Endothelial Function Measures
a. Brachial Artery Ultrasound Scanning (BAUS) Procedure -
We are measuring endothelial function by flow mediated dilation (FMD %) of the brachial artery. All brachial artery ultrasounds to date have been performed on 11 subjects at EOHSI Clinical Center before and after a diesel exhaust and a clean air exposure. Due to unavailability of an ultrasound technician between November 2006 and July 2007, brachial artery ultrasound data was not collected during this period. Since July 2007, we have collected BAUS data on 7 additional subjects using a new ultrasound technician, newly trained by our ultrasound consultant, Jason Allen of Duke University . Results from these tests are pending. Because of the these logistical problems with the BAUS we have added two alternative measures of endothelial function, blood nitrite / nitrate, and Endo-PAT arterial tonometry. Final analysis on blood nitrite and on EndoPAT tonometry is pending, but preliminary analyses are shown in the full report. - Genetic Screening For eNOS Polymorphisms
Buccal swab specimens from 346 volunteers have been collected from various campus locations, using the Isohelix DNA cheek swab. These clinical samples are immediately transferred to the EOHSI Bionomics Research and Technology Center (BRTC) for registration and processing. To date we have identified 23 individuals, 6.6% of those studied, who are homozygous for the polymorphism of interest, and 5 have completed the protocol.
Future Activities:
We are continuing to run subjects, focusing as much as possible on those homozygous for the eNOS Glu298Asp polymorphism. We will attempt to approach the 25 homozygous subjects in our initial plan. We are continuing to collect BAUS and nitrite data, but are initiating analytic work to maintain our planned schedule. If necessary, a no cost extension will be requested.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other project views: | All 17 publications | 10 publications in selected types | All 9 journal articles |
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Rich DQ, Freudenberger RS, Ohman-Strickland P, Cho Y, Kipen HM. Right heart pressure increases after acute increases in ambient particulate concentration. Environmental Health Perspectives 2008;116(9):1167-1171. |
R832144 (2007) R832144 (Final) |
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Sunil VR, Laumbach RJ, Patel KJ, Turpin BJ, Lim H-J, Kipen HM, Laskin JD, Laskin DL. Pulmonary effects of inhaled limonene ozone reaction products in elderly rats. Toxicology and Applied Pharmacology 2007;222(2):211-220. |
R832144 (2007) R832144 (Final) |
Exit Exit |
Supplemental 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.