Grantee Research Project Results

Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles

EPA Grant Number: R832415C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R832415
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Rochester PM Center
Center Director: Oberdörster, Günter
Title: Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
Investigators: Frampton, Mark W. , Zareba, Wojciech , Utell, Mark J. , Oakes, David , Phipps, Richard , Gelein, Robert
Current Investigators: Frampton, Mark W. , Utell, Mark J. , Zareba, Wojciech , Phipps, Richard , Gelein, Robert , Oakes, David
Institution: University of Rochester
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2012)
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air

Objective:

These studies will use controlled human clinical exposures to test the hypothesis that inhalation of ambient ultrafine and fine PM causes measurable changes in coagulation and cardiovascular function, that these effects are determined by PM-associated reactive oxygen species, and that subjects with Type II diabetes are at increased risk for these effects.

Approach:

Three human exposure protocols will be conducted using the Harvard ultrafine ambient particle concentrator, in collaboration with the Aerosol Generation and Analysis Facility Core. The first protocol will examine effects in healthy subjects, the second protocol will examine effects in age-matched subjects with type 2 diabetes, and the third protocol will assess the role of pretreatment with the cyclooxygenase inhibitor aspirin in preventing the cardiovascular effects of ultrafine/fine particle exposure. In collaboration with the Vascular and Inflammation Facility Core, we will determine particle effects on platelet function and release of endothelial and platelet microparticles into the circulation, and will examine effects on platelet-leukocyte adhesion, bone marrow stimulation, and changes in gene expression in blood mononuclear cells. Continuous ECG monitoring, in collaboration with the Cardiac Facility Core, will detect changes in cardiac repolarization, and noninvasive impedence cardiography will measure changes in cardiac output. Genomic DNA from exposed subjects will be analyzed for candidate gene polymorphisms identified in Research Core #2, Epidemiological Studies. Exposure studies will be designed and conducted in parallel with similar animal exposure studies conducted by Research Core #4, Animal Models. The impact of PM-associated reactive oxygen species, size, composition, and source will be examined in collaboration with Research Core #1, Characterization and Source Apportionment, and with the Biostatistics Facility Core.

Expected Results:

Confirmation of our hypothesis that exposure to ambient ultrafine and fine particles promotes coagulation and alters cardiac function will have important implications for air pollution regulatory efforts, and will provide new approaches for the prevention of cardiovascular health effects.

Publications and Presentations:

Publications have been submitted on this subproject: View all 57 publications for this subproject | View all 191 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 41 journal articles for this subproject | View all 144 journal articles for this center

Supplemental Keywords:

ultrafine particles; endothelial dysfunction; air pollution, cardiovascular health,, RFA, Health, PHYSICAL ASPECTS, Scientific Discipline, Air, particulate matter, Health Risk Assessment, Risk Assessments, Physical Processes, atmospheric particulate matter, acute cardiovascular effects, long term exposure, atmospheric particles, airway disease, exposure, ambient particle health effects, human exposure, ultrafine particulate matter, atmospheric aerosol particles, PM, aersol particles, cardiovascular disease

Progress and Final Reports:

Main Center Abstract and Reports:

R832415 Rochester PM Center

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832415C001 Characterization and Source Apportionment
R832415C002 Epidemiological Studies on Extra Pulmonary Effects of Fresh and Aged Urban Aerosols from Different Sources
R832415C003 Human Clinical Studies of Concentrated Ambient Ultrafine and Fine Particles
R832415C004 Animal models: Cardiovascular Disease, CNS Injury and Ultrafine Particle Biokinetics
R832415C005 Ultrafine Particle Cell Interactions In Vitro: Molecular Mechanisms Leading To Altered Gene Expression in Relation to Particle Composition

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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.