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Zhong J.,Harvard University | Urch B.,University of Toronto | Speck M.,Li Ka Shing Knowledge Institute | Coull B.A.,Harvard University | And 13 more authors.
Hypertension | Year: 2015

Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) in epidemiological studies. Understanding the impact of specific PM components on BP is essential in developing effective risk-reduction strategies. We investigated the association between endotoxin and β-1,3-d-Glucan - two major biological PM components - and BP. We also examined whether vascular endothelial growth factor, a vasodilatory inflammatory marker, modified these associations. We conducted a single-blind, randomized, crossover trial of controlled human exposure to concentrated ambient particles with 50 healthy adults. Particle-associated-endotoxin and β-1,3-d-Glucan were sampled using polycarbonate-membrane-filters. Supine resting systolic BP and diastolic BP were measured pre-, 0.5-hour post-, and 20-hour postexposure. Urine vascular endothelial growth factor concentration was determined using enzyme-linked immunosorbant assay and creatinine-corrected. Exposures to endotoxin and β-1,3-d-Glucan for 130 minutes were associated with increases in BPs: at 0.5-hour postexposure, every doubling in endotoxin concentration was associated with 1.73 mm Hg higher systolic BP (95% confidence interval, 0.28, 3.18; P=0.02) and 2.07 mm Hg higher diastolic BP (95% confidence interval, 0.74, 3.39; P=0.003); every doubling in β-1,3-d-Glucan concentration was associated with 0.80 mm Hg higher systolic BP (95% confidence interval, -0.07, 1.67; P=0.07) and 0.88 mm Hg higher diastolic BP (95% confidence interval, 0.09, 1.66; P=0.03). Vascular endothelial growth factor rose after concentrated ambient particle endotoxin exposure and attenuated the association between endotoxin and 0.5-hour postexposure diastolic BP (Pinteraction=0.02). In healthy adults, short-term endotoxin and β-1,3-d-Glucan exposures were associated with increased BP. Our findings suggest that the biological PM components contribute to PM-related cardiovascular outcomes, and postexposure vascular endothelial growth factor elevation might be an adaptive response that attenuates these effects. Source

Liu L.,Healthy Environments and Consumer Safety Branch | Urch B.,University of Toronto | Urch B.,Southern Ontario Center for Atmospheric Aerosol Research | Poon R.,Healthy Environments and Consumer Safety Branch | And 13 more authors.
Environmental Health Perspectives | Year: 2015

Background: Ambient coarse, fine, and ultrafine particles have been associated with mortality and morbidity. Few studies have compared how various particle size fractions affect systemic biomarkers. Objectives: We examined changes of blood and urinary biomarkers following exposures to three particle sizes. Methods: Fifty healthy nonsmoking volunteers, mean age of 28 years, were exposed to coarse (2.5–10 μm; mean, 213 μg/m3) and fine (0.15–2.5 μm; mean, 238 μg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (< 0.3 μm; mean, 136 μg/m3) and filtered medical air. Exposures lasted 130 min, separated by ≥ 2 weeks. Blood/urine samples were collected preexposure and 1 hr and 21 hr postexposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF; vascular mediators), and malondialdehyde (lipid peroxidation); as well as urinary VEGF, 8-hydroxy-deoxy-guanosine (DNA oxidation), and malondialdehyde. Mixed-model regressions assessed pre- and postexposure differences. results: One hour postexposure, for every 100-μg/m3 increase, coarse CAP was associated with increased blood VEGF (2.41 pg/mL; 95% CI: 0.41, 4.40) in models adjusted for O3, fine CAP with increased urinary malondialdehyde in single- (0.31 nmol/mg creatinine; 95% CI: 0.02, 0.60) and two-pollutant models, and ultrafine CAP with increased urinary 8-hydroxydeoxyguanosine in single- (0.69 ng/mg creatinine; 95% CI: 0.09, 1.29) and two-pollutant models, lasting < 21 hr. Endotoxin was significantly associated with biomarker changes similar to those found with CAPs. conclusions: Ambient particles with various sizes/constituents may influence systemic biomarkers differently. Endotoxin in ambient particles may contribute to vascular mediator changes and oxidative stress. © 2015, Public Health Services, US Dept of Health and Human Services. All rights reserved. Source

Ramanathan G.,University of California at Los Angeles | Yin F.,University of California at Los Angeles | Speck M.,University of Toronto | Tseng C.-H.,University of California at Los Angeles | And 9 more authors.
Particle and Fibre Toxicology | Year: 2016

Background: Exposures to ambient particulate matter (PM) are associated with increased morbidity and mortality. PM2.5 (<2.5 μm) and ozone exposures have been shown to associate with carotid intima media thickness in humans. Animal studies support a causal relationship between air pollution and atherosclerosis and identified adverse PM effects on HDL functionality. We aimed to determine whether brief exposures to PM2.5 and/or ozone could induce effects on HDL anti-oxidant and anti-inflammatory capacity in humans. Methods: Subjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 μg/m3, ozone targeted at 240 μg/m3 (120 ppb), PM2.5 plus ozone targeted at similar concentrations, and filtered air (FA) for 2 h, on 4 different occasions, at least two weeks apart, in a randomized, crossover study. Blood was obtained before exposures (baseline), 1 h after and 20 h after exposures. Plasma HDL anti-oxidant/anti-inflammatory capacity and paraoxonase activity were determined. HDL anti-oxidant/anti-inflammatory capacity was assessed by a cell-free fluorescent assay and expressed in units of a HDL oxidant index (HOI). Changes in HOI (ΔHOI) were calculated as the difference in HOI from baseline to 1 h after or 20 h after exposures. Results: There was a trend towards bigger ΔHOI between PM2.5 and FA 1 h after exposures (p = 0.18) but not 20 h after. This trend became significant (p <0.05) when baseline HOI was lower (<1.5 or <2.0), indicating decreased HDL anti-oxidant/anti-inflammatory capacity shortly after the exposures. There were no significant effects of ozone alone or in combination with PM2.5 on the change in HOI at both time points. The change in HOI due to PM2.5 showed a positive trend with particle mass concentration (p = 0.078) and significantly associated with the slope of systolic blood pressure during exposures (p = 0.005). Conclusions: Brief exposures to concentrated PM2.5 elicited swift effects on HDL anti-oxidant/anti-inflammatory functionality, which could indicate a potential mechanism for how particulate air pollution induces harmful cardiovascular effects. © 2016 Ramanathan et al. Source

Akhtar U.S.,University of Toronto | Akhtar U.S.,Southern Ontario Center for Atmospheric Aerosol Research | Rastogi N.,University of Toronto | Rastogi N.,Southern Ontario Center for Atmospheric Aerosol Research | And 16 more authors.
Toxicology Reports | Year: 2014

Epidemiological and toxicological studies have suggested that the health effects associated with exposure to particulate matter (PM) are related to the different physicochemical properties of PM. These effects occur through the initiation of differential cellular responses including: the induction of antioxidant defenses, proinflammatory responses, and ultimately cell death. The main objective of this study was to investigate the effects of size-fractionated ambient PM on epithelial cells in relation to their physicochemical properties. Concentrated ambient PM was collected on filters for three size fractions: coarse (aerodynamic diameter [AD] 2.5-10. μm), fine (0.15-2.5. μm), and quasi-ultrafine (<0.2. μm), near a busy street in Toronto, Ontario, Canada. Filters were extracted and analyzed for chemical composition and redox activity. Chemical analyses showed that the coarse, fine, and quasi-ultrafine particles were comprised primarily of metals, water-soluble species, and organic compounds, respectively. The highest redox activity was observed for fine PM. After exposure of A549 cells to PM (10-100. μg/ml) for 4. h, activation of antioxidant, proinflammatory and cytotoxic responses were assessed by determining the expression of heme oxygenase (HMOX-1, mRNA), interleukin-8 (IL-8, mRNA), and metabolic activity of the cells, respectively. All three size fractions induced mass-dependent antioxidant, proinflammatory, and cytotoxic responses to different degrees. Quasi-ultrafine PM caused significant induction of HMOX-1 at the lowest exposure dose. Correlation analyses with chemical components suggested that the biological responses correlated mainly with transition metals and organic compounds for coarse and fine PM and with organic compounds for quasi-ultrafine PM. Overall, the observed biological responses appeared to be related to the combined effects of size and chemical composition and thus both of these physicochemical properties should be considered when explaining PM toxicity. © 2014 The Authors. Source

Behbod B.,Harvard University | Urch B.,University of Toronto | Urch B.,Southern Ontario Center for Atmospheric Aerosol Research | Speck M.,University of Toronto | And 10 more authors.
Occupational and Environmental Medicine | Year: 2013

Background: Knowledge of the inhalable particulate matter components responsible for health effects is important for developing targeted regulation. Objectives: In a double-blind randomised cross-over trial of controlled human exposures to concentrated ambient particles (CAPs) and their endotoxin and (1→3)-β-D-glucan components, we evaluated acute inflammatory responses. Methods: 35 healthy adults were exposed to five 130-min exposures at rest: (1) fine CAPs (∼250 μg/m3); (2) coarse CAPs (∼200 mg/m3); (3) second coarse CAPs (∼200 mg/m3); (4) filtered air; and (5) medical air. Induced sputum cell counts were measured at screening and 24 h postexposure. Venous blood total leucocytes, neutrophils, interleukin-6 and high-sensitivity C reactive protein (CRP) were measured pre-exposure, 3 and 24 h postexposure. Results Relative to filtered air, an increase in blood leucocytes 24 h (but not 3 h) postexposure was significantly associated with coarse (estimate=0.44×109 cells/L (95% CI 0.01 to 0.88); n=132) and fi ne CAPs (0.68×109 cells /L (95% CI 0.19 to 1.17); n=132), but not medical air. Similar associations were found with neutrophil responses. An interquartile increase in endotoxin (5.4 ng/m 3) was signi ficantly associated with increased blood leucocytes 3 h postexposure (0.27×109 cells/L (95% CI 0.03 to 0.51); n=98) and 24 h postexposure (0.37×109 cells/L (95% CI 0.12 to 0.63); n=98). This endotoxin effect did not differ by particle size. There were no associations with glucan concentrations or interleukin-6, CRP or sputum responses. Conclusions In healthy adults, controlled coarse and fine ambient particle exposures independently induced acute systemic inflammatory responses. Endotoxin contributes to the inflammatory role of particle air pollution. Source

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