Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures

EPA Grant Number: R832416C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R832416
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Harvard Particle Center
Center Director: Koutrakis, Petros
Title: Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
Investigators: Silverman, Frances , Gold, Diane R.
Current Investigators: Silverman, Frances , Gold, Diane R. , Urch, Bruce
Institution: University of Toronto
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
RFA: Particulate Matter Research Centers (2004) RFA Text |  Recipients Lists
Research Category: Health Effects , Air


Using our controlled particle exposure facility, we have demonstrated that short-term exposure to fine Concentrated Ambient Particles (CAPs) + ozone (O3) causes acute conduit artery vasoconstriction and is associated with increased diastolic blood pressure in healthy adults. Both of these findings were associated with the organic carbon component of the particulate matter (PM).

This proposal aims to further examine the components and sources of PM responsible for these cardiovascular physiologic responses. A new state-of-the-art ambient PM exposure facility (to be built at the University of Toronto in collaboration with Harvard School of Public Health) will allow us to examine responses to fine, ultrafine and coarse CAPs, in downtown Toronto, Canada. To gain insight into these responses, cardiovascular outcomes in the proposed study will include not only our more established physiologic outcomes (brachial artery diameter and blood pressure), but also complementary measurements including cardiovascular hemodynamics, autonomic function (e.g., HRV), markers of systemic inflammation (e.g., CBCs, IL-6, CRP) and endothelial dysfunction (endothelins).


We propose to expose 50 healthy adults to fine, ultrafine and coarse CAPs and particle-free (filtered) air. Each participant will receive 4 exposures in random order, separated by at least two weeks. Cardiovascular outcomes will be measured both pre-, post- and 24 hrs post-exposure and will include measures of: brachial artery diameter, flow- and nitroglycerin-mediated dilatation by ultrasonography; stroke volume (SV) and cardiac output (CO) by echocardiography; blood pressure (BP); and venous blood CBCs, IL-6, CRP and endothelins. Also, during exposures, continuous measurements of: beat-to-beat arterial BP by Finometer monitor, including calculated determinations of SV, CO and systemic vascular resistance; and HRV using 24 hr Holter monitoring will be performed. PM exposures will be characterized for particle mass, number, diameter, size and composition (inorganic ions, trace metals, organic and elemental carbon and black carbon). Gaseous co-pollutants (carbon monoxide, CO2, NO, NO2, SO2, O3), temperature and humidity will be monitored continuously during the exposure experiments. In addition, on the days before and after exposures, 24-hr measurements will be conducted for each participant using a multi-pollutant personal sampler. For each of the observed biological effects, repeated measures ANOVA models will be employed to assess differences among treatments. These models will contain a random effect for subject and a categorical variable for the four exposure treatments (fine, ultrafine, coarse, CAPs and particle-free air). To assess exposure-response relationships between biological outcomes and CAPs mass or individual components concentrations, single pollutant analyses will be conducted in which a separate linear mixed regression model will be used for each exposure parameter. These models will use biologic response as the dependent variable, subject as a random effect, and either particle mass, number, diameter or component as the exposure metric in the model. Hierarchical linear models will be developed to account for the multiple levels of data, including measurements taken at different time points within an exposure, for a subject.

Expected Results:

We expect to find physiologic responses consistent with vascular narrowing (increased BP, decreased brachial artery diameter) in response to all three CAPs size fractions, as compared to particle-free air. Also, we expect that the cardiovascular responses may vary by CAP treatment (fine, ultrafine, and coarse).

Publications and Presentations:

Publications have been submitted on this subproject: View all 8 publications for this subprojectView all 200 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 5 journal articles for this subprojectView all 194 journal articles for this center

Supplemental Keywords:

Air pollution,, RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, ambient air quality, atmospheric particulate matter, chemical characteristics, human health effects, cardiovascular vulnerability, automobile exhaust, airborne particulate matter, chemical composition, biological mechanisms, biological mechanism , traffic related particulate matter, human exposure, mobile sources, ambient particle health effects, autonomic dysfunction, human health risk

Progress and Final Reports:

  • 2006 Progress Report
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R832416    Harvard Particle Center

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832416C001 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
    R832416C002 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
    R832416C003 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
    R832416C004 Cardiovascular Effects of Mobile Source Exposures: Effects of Particles and Gaseous Co-pollutants
    R832416C005 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions