Cardiovascular Effects of Urban and Rural Coarse Particulate Matter in Obese and Lean AdultsEPA Grant Number: R833740
Title: Cardiovascular Effects of Urban and Rural Coarse Particulate Matter in Obese and Lean Adults
Investigators: Brook, Robert D. , Keeler, Gerald J. , Gold, Diane R. , Brook, Jeffrey R. , Dvonch, Joseph T. , Urch, Bruce , Silverman, Frances , Kaciroti, Niko
Institution: University of Michigan , Harvard University , University of Toronto
Current Institution: University of Michigan - Ann Arbor , Harvard University , University of Toronto
EPA Project Officer: Chung, Serena
Project Period: March 1, 2008 through February 28, 2011 (Extended to February 28, 2014)
Project Amount: $1,199,500
RFA: Sources, Composition, and Health Effects of Coarse Particulate Matter (2006) RFA Text | Recipients Lists
Research Category: Air , Air Quality and Air Toxics , Particulate Matter
Coarse particulate matter (PM10-2.5) is a heterogeneous mixture of crustal materials, trace metals/elements, and bio-aerosols. The components vary considerably due to location differences in primary sources. Despite fewer studies than for fine particulate matter (PM), epidemiological evidence suggests that coarse PM may also be associated with an increased risk for acute cardiovascular (CV) events. In order to support the biological plausibility that coarse PM exposure is causally linked to CV disease, it is essential to demonstrate that it can rapidly trigger adverse biological responses in humans capable of acutely promoting CV events. The overall hypothesis is that short-term exposure to both urban and rural coarse PM is capable of promoting pro-vasoconstrictive vascular dysfunctions and CV autonomic imbalance.
We will perform a series of coarse CAP exposures in both a rural (Dexter) and urban (Dearborn) setting in Michigan and aim to comprehensively link these experiments with our coarse PM study in urban Toronto (Harvard EPA PM Center). We will expose 25 lean (BMI<28 kg/m2) + 25 Obese (BMI>30 kg/m2) subjects (50 total subjects) to rural and urban coarse PM for 2 hours using a new mobile exposure laboratory. The experimental protocol will match that of Toronto and all results can thus be integrated. All 50 subjects will be crossed-over to receive randomized, blinded exposures to coarse CAP (150-300 μg/m3) at both sites and to filtered air (3 exposures each). Outcomes will be measured before, after, and 23 hrs post exposures. “Primary” outcomes include CAP-induced changes in autonomic balance (heart rate variability (HRV)), and pro-vasoconstrictive vascular dysfunctions [vasoconstriction (brachial artery diameter by ultrasound) and a pro-hypertensive reaction (within-exposure blood pressure (BP))]. Brachial artery endothelial-dependent vasodilatation will also be assessed (ultrasound). Complimentary/exploratory outcomes will include intra-exposure continuous BP/hemodynamic assessment (Finometer), cardiac output (echocardiography), microvascular endothelial function (endo-PAT), central aortic hemodynamics/compliance (SphygmoCor), and biomarkers of systemic oxidative stress/inflammation. The CAP exposures will be extensively characterized for mass, constituents, and sources and correlated to the biological outcome responses.
This proposal aims to demonstrate that short-term concentrated ambient coarse PM (CAP) inhalation (1) triggers pro-vasoconstrictive vascular dysfunctions related to (mediated by) CV autonomic imbalance; and (2) that these responses occur to a greater degree in obese than in lean adults; and (3) we aim to elucidate the constituents/sources responsible for the CV responses and to perform detailed characterizations of differences in rural vs. urban coarse PM to improve the epidemiological understanding of coarse PM.
This protocol will be the first to investigate the vascular effects of coarse PM. In addition, the susceptibility of different at-risk sub-populations and the relative CV toxicity of 3 coarse PM sources of differing constituents will be explored. It is expected that exposures to both rural and urban coarse PM will cause arterial vasoconstriction and raise BP and that obese individuals will have a greater adverse response via mechanisms involving autonomic imbalance. These results will provide biological plausibility that coarse PM, even of varying composition and sources, is capable of triggering CV events. Moreover, the extensive coarse PM characterization at 3 locations will in-itself significantly enhance our level of understanding of coarse PM epidemiology in rural and urban environments.