2006 Progress Report: Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human ExposuresEPA 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 , Harvard University
Current Institution: University of Toronto
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
Project Period Covered by this Report: October 1, 2005 through September 30, 2006
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Health Effects , Air
The proposed project will examine the acute cardiovascular effects of fine, ultrafine and coarse CAPs in healthy adults, using a controlled particle exposure facility, in Toronto. Fifty subjects will each receive three CAPs exposures (3 size fractions) and a particle-free air exposure, in random order. Cardiac vascular/physiologic outcomes will be measured pre-, post- and 24 hrs post-exposure, and will include measures of: i) vascular dysfunction (brachial artery diameter, flow- and nitroglycerin-mediated dilatation by ultrasonography; stroke volume and cardiac output by Doppler, 2-D echocardiography); ii) blood pressure; and iii) markers of systemic inflammation (CBCs, IL-6, CRP, endothelins) in blood taken pre-, post- and 24 hrs post-exposure. We will also perform continuous (in-exposure) measurements of: beat-to-beat arterial BP using a Finometer monitor, including calculated determinations of cardiac output, stroke volume and systemic vascular resistance (SVR); and measures of cardiac autonomic dysfunction (HRV using 24 hr Holter monitoring). The specific hypotheses to be addressed by this proposed research are the following:
- Acute human exposures to CAPs of ultrafine, fine and coarse size fractions result in cardiovascular responses consistent with vascular narrowing, vascular/autonomic dysfunction, inflammation, and/or endothelial activation compared to filtered air (control) exposures.
- Associations between CAPs and cardiovascular responses differ by particle size fraction and composition.
Human Ethics Approval. The study protocol was submitted to St. Michael’s Hospital, Human Research Ethics Board, Office of Research Administration in two stages: first for approval of study work in the 1st year, not involving human testing (approval date Dec 19, 2005); and second for the entire study, including human testing (approval date April 27, 2006). Subsequent to this, human ethics approval and supporting documentation was forwarded to Harvard for human ethics approval from the U.S. Environmental Protection Agency (EPA). This approval is pending. No human exposure testing for this project will be carried out until official approval is received from the U.S. EPA and the human CAPs exposure facility has been fully tested and characterized.
New Harvard PM Concentrator Facility. Construction of our human CAPs (fine, ultrafine, coarse) exposure facility, funded through a Canadian infrastructure grant (CFI), began at the end of July, 2006. However, over the previous year numerous meetings/discussions have been held to plan the facility, including GOEHU, University of Toronto, Harvard and the Southern Ontario Centre for Atmospheric Aerosol Research. The facility is due to be completed in 3 months. After this, it will be tested and characterized before human studies start.
Subaward Agreement. A subaward agreement between Harvard and St. Michael’s Hospital was signed July 11, 2006. Subsequent to this an account was set up for ordering equipment and supplies. As well, a sub-contract is being setup between St. Michael’s Hospital and the University of Michigan (Rob Brook), for analyses of ultrasound and echocardiography.
Training. Bruce Urch, the study coordinator and Research Assistant, traveled to Rochester in May, 2006 for training/familiarization with the use of the Harvard ultrafine concentrator (at the Rochester PM Centre). In June, 2006 he also had training on the Finometer at a local University research lab using the same device for a cardiac nutrition study. Mary Speck, the Laboratory Technologist at GOEHU currently doing ultrasound measurements will be trained in Michigan to do the echo cardiac measures. She has been in contact with the Michigan group and will travel there to be trained by an echo technologist under the supervision of Drs. Robert Brook and Julie Kovach. Subsequently, she will perfect echo testing using our Terason system, sending echo images of GOEHU staff to Michigan for review.
Collaborations. There have been regular scientific communications/meetings between the study investigators (GOEHU, Michigan and Harvard), mostly by teleconference but also in-person, which have proven to be both fruitful and beneficial to the development/progress of this project, thus will continue throughout to its completion.
Two pieces of major equipment will be purchased for this study including echocardiograph (echo) and a Finometer. The echo is a separate module of our current Terason ultrasound system, which will be upgraded to the Terason 3000 system to facilitate operation of both the ultrasound and echo. Quotes have been obtained and the echo and Finometer will be ordered in August, 2006.
Also, final modifications to the study design and protocols will be made. Installation and testing of the particle concentrator will be completed, as will study questionnaires. Once completed, study participant recruitment and screening will begin.
Journal Articles:No journal articles submitted with this report: View all 8 publications for this subproject
Supplemental Keywords:concentrated air particles, acute cardiovascular effects, coarse particles, fine particles, vascular dysfunction,, RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, ambient air quality, atmospheric particulate matter, human health effects, chemical characteristics, automobile exhaust, airborne particulate matter, cardiovascular vulnerability, traffic related particulate matter, chemical composition, biological mechanism , biological mechanisms, human exposure, ambient particle health effects, mobile sources, autonomic dysfunction, oxidative stress
Progress and Final Reports:Original Abstract
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