Final 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. , 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
Epidemiological studies have demonstrated strong and consistent associations between ambient PM exposure and increased short- and long-term morbidity and mortality from cardiopulmonary diseases. Current thinking suggests that the cardiopulmonary effects of PM inhalation are attributable to pulmonary/systemic inflammation, oxidative stress, endothelial activation/dysfunction, or autonomic dysfunction. The main objective of this project was to carry out controlled human exposures to fine, ultrafine and coarse concentrated ambient particles (CAPs) and to examine acute changes in cardiopulmonary outcomes to further our understanding of biological mechanisms of cardiopulmonary diseases attributed to PM. In the design phase of the project it was agreed to focus on coarse and fine CAPs and not to include ultrafine CAPs exposures.
Controlled Human Exposures: To facilitate these studies, a CAPs exposure facility for humans was established and characterized in Toronto, Ontario, Canada from 2006 to 2007. The facility was funded through a Canadian infrastructure grant to the Southern Ontario Centre for Atmospheric Aerosol Research, University of Toronto. Healthy non-smokers 19-60 years of age were recruited from the University of Toronto and Greater Toronto Area. Thirty-four subjects met inclusion criteria and were enrolled. Using a randomized block design, subjects had five 130 min exposures at rest with a minimum 2-week wash-out period between. Exposures included: one fine CAPs (PM2.5-0.1), two coarse CAPs (PM10-2.5), one HEPA filtered ambient air (HFAA) and one HEPA filtered medical air (HFMA). The target and maximum levels were as follows: fine CAPs (target 250 µg/m3; max 500 µg/m3); and coarse CAPs (target 200 µg/m3; max 400 µg/m3). A total of 141 exposures were completed. Cardiovascular and respiratory health outcomes were measured before, during and after exposures.
Health Outcomes: Cardiovascular outcomes included: i) vascular dysfunction (brachial artery diameter and reactivity) by ultrasonography; ii) cardiac output by echocardiography; iii) blood pressure (BP) by automated arm cuff; iv) arterial pressure waveforms measures of large arterial compliance, central aortic BP and hemodynamics by SphygmoCor device; v) markers of systemic inflammation (CBCs, blood IL-6 and CRP); and vi) markers of oxidative stress in blood and urine. Respiratory outcomes included: i) pulmonary function by spirometry; ii) respiratory inflammation by induced sputum; and iii) respiratory and nasal symptomotology. In a subset of 11 subjects, DNA methylation was analyzed on candidate genes (TLR4, IL-12, IL-6, iNOS) and repeated elements (Alu, LINE-1) via bisulfite-pyrosequencing. Mortara Holter (ECG) monitors were worn by the subjects over 24 hours (started at ~8 am, prior to the pre-exposure ultrasound measures), as a measure of cardiac autonomic dysfunction (heart rate variability [HRV] analyses).
Exposure Characterization: Exposures were characterized using continuous measures of particle mass (TEOM) and black carbon (PSAP) as well as integrated measurements (filter samples) of particle mass, sulfate, nitrate, ammonium, trace elements, organic and elemental carbon and biological material including airborne endotoxin and markers of fungi (β-(1,3)-D-glucan). On-site daily measures included vehicle counts, meteorological data, TEOM PM2.5, gaseous air pollutants (NO, NO2, SO2, CO, O3), as well as pollen characterization (GRIPST-2000 pollen sampler) and fungal spores/pollen (Burkard sampler). Daily stationary central site monitoring data (gaseous and PM criteria pollutants) were obtained to statistically adjust for potential effects on baseline pre-exposure data.
- Acute human exposures to CAPs of coarse and fine size fractions result in cardiovascular responses including increased blood pressure, vascular narrowing of the brachial artery diameter (BAD), vascular/autonomic dysfunction (impaired flow-mediated dilatation [FMD]), inflammation (respiratory and systemic), and oxidative stress, compared to filtered air (control) exposures;
- Respiratory inflammatory responses (induced sputum), pulmonary function (flow-volume curves) and nasal/respiratory symptom responses are greater for coarse CAPs than fine CAPs; and
- Associations between CAPs and cardiovascular responses differ by particle size fraction and PM composition.
Brook RD, Urch B, Dvonch JT, Bard RL, Speck M, Keeler G, Morishita M, Marsik FJ, Kamil AS, Kaciroti N, Harkema J, Corey P, Silverman F, Gold D, Wellenius G, Mittleman MA, Rajagopalan S, Brook JR. Insights into the mechanisms and mediators of the effects of air pollution exposure on blood pressure and vascular function in healthy humans. Hypertension 2009;54:659-667.
Fakhri AA, Ilic LM, Wellenius GA, Urch B, Silverman F, Gold DR, Mittleman MA. Autonomic effects of controlled fine particulate exposure in young healthy adults: effect modification by ozone. Environ Health Perspect 2009;117(8):1287-1292.
Sivagangabalan G, Spears D, Masse S, Urch B, Brook RD, Silverman S, Gold DR, Lukic KZ, Speck M, Kusha M, Farid T, Poku K, Shi E, Floras J, Nanthakumar K. The Effect of air pollution on spatial dispersion of myocardial repolarization in healthy human volunteers. J Am Coll Cardiol 2011;57(2):198-206.
Thompson AMS, Zanobetti A, Silverman F, Schwartz J, Coull B, Urch B, Speck M, Brook JR, Manno M, Gold DR. Baseline repeated-measures from controlled human exposure studies: associations between ambient air pollution exposure and systemic inflammatory biomarkers IL-6 and fibrinogen. Environ Health Perspect 2010;118(1):120-124.
Urch RB. Controlled Human Exposures to Concentrated Ambient Fine Particles and Ozone: Individual and Combined Effects on Cardiorespiratory Outcomes. PhD Thesis. University of Toronto, Department of Medicine. Archived in University of Toronto T-Space, 2010a. http://hdl.handle.net/1807/26250
Urch B, Speck M, Corey P, Wasserstein D, Manno M, Lukic KZ, Brook JR, Liu L, Coull B, Schwartz J, Gold DR, Silverman F. Concentrated ambient fine particles and not ozone induce a systemic interleukin-6 response in humans. Inhal Toxicol 2010b;22(3):210-218.
Kusha M, Masse S, Farid T, Sivagangabalan G, Urch B, Silverman F, Brook RD, Gold DR, Lukic KZ, Mangat I, Speck M, Nair K, Poku K, Mittleman M, Wellenius GA, Nanthakumar K. The effect of air pollution on temporal dispersion of repolarization under basal conditions in volunteers with no pre-existing cardiovascular disease. Re-submitted to Environmental Health Perspectives (September 2011). Resubmitted October 14, 2011 (under review).
Watkins A, Spears D, Urch B, Kusha M, Quadros K, Danilewitz M, Farid T, Chauhan V, Nanthakumar K. Air pollution and arrhythmic risk: The smog is yet to clear. Canadian Journal of Cardiology (September 2011). Currently being revised for resubmission.
Liu L, Poon R, Szyszkowicz M, Urch B, Speck M, Silverman F, Brook JR, Gold D. 2011. Controlled human exposure to fine and coarse ambient particles and effects on systemic biomarkers. Extended abstract. Air & Waste Management Association Conference Proceedings, June 21-24, 2011, Orlando, FL (conference proceedings, on-line).
Speck M, Urch RB, Fritscher L, Corey P, Brook JR, Gold DR, Silverman F. 2009. Exposure to coarse but not fine concentrated ambient particles increases airway leukocytes in humans. Am J Respir Crit Care Med 2009;179:A3153 (poster presentation).
Urch B, Speck M, Corey P, Brook JR, Brook RD, Gold DR, Behbod B, Silverman F. 2010b. Blood pressure changes during and after controlled exposures to Toronto concentrated ambient coarse and fine particles in healthy subjects. Poster presented at the NIEHS-EPA Symposium on Air Pollution and Cardiovascular Disease. Seattle, WA, June 2010.
Urch B, Speck M, Scott J, Ewaze J, Brook JR, Gold DR, Behbod B, Silverman F. 2010c. Associations between inhaled endotoxin/β-(1,3)-D-glucan levels and airway/systemic neutrophils after controlled exposures to coarse and fine particles: effect of atopy on responses. Poster presented at the American Association for Aerosol Research's Air Pollution and Health: Bridging the Gap from Sources to Health Outcomes. San Diego, CA, March 2010.
B, Speck M, Corey P, Brook JR, Brook RD, Gold DR, Silverman F. Changes in blood pressure and vascular responses with controlled exposures to fine and coarse concentrated ambient particles (CAPs). Am J Respir Crit Care Med 2011;183:A5615.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
|Other subproject views:||All 8 publications||5 publications in selected types||All 5 journal articles|
|Other center views:||All 200 publications||194 publications in selected types||All 194 journal articles|
||Sivagangabalan G, Spears D, Masse S, Urch B, Brook RD, Silverman F, Gold DR, Lukic KZ, Speck M, Kusha M, Farid T, Poku K, Shi E, Floras J, Nanthakumar K. The effect of air pollution on spatial dispersion of myocardial repolarization in healthy human volunteers. Journal of the American College of Cardiology 2011;57(2):198-206.||
||Thompson AM, Zanobetti A, Silverman F, Schwartz J, Coull B, Urch B, Speck M, Brook JR, Manno M, Gold DR. Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen. Environmental Health Perspectives 2010;118(1):120-124.||
||Urch B, Speck M, Corey P, Wasserstein D, Manno M, Lukic KZ, Brook JR, Liu L, Coull B, Schwartz J, Gold DR, Silverman F. Concentrated ambient fine particles and not ozone induce a systemic interleukin-6 response in humans. Inhalation Toxicology 2010;22(3):210-218.||
Supplemental Keywords:concentrated air particles, acute cardiovascular effects, coarse particles, fine particles, vascular dysfunction, inflammation, oxidative stress, 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