Bruce Urch - Academia.edu (original) (raw)

Papers by Bruce Urch

ACS Earth and Space Chemistry

Proceedings of the National Academy of Sciences of the United States of America, May 16, 2017

The aim of our small mechanistic study (1) was to test the biologic plausibility that ambient par... more The aim of our small mechanistic study (1) was to test the biologic plausibility that ambient particle pollution might have epigenetic effects on DNA methylation that could be modulated by methyl donor supplements. We acknowledge in this letter and in our paper that generalizability of our results is limited not only by study size, but also by the characteristics of healthy study participants. In contributing to the body of literature used for scientific assessment and consequent policy decision making, carefully controlled mechanistic studies like ours complement the large epidemiologic studies that, as Lucock et al. (2) suggest, show that reduction in ambient particle levels have led to improvement in health and reduction in morbidity and mortality (3-6). Studies like ours cannot diminish-nor be used to underemphasize-the urgent need to lower air pollution levels to-at a minimum-meet the air-quality standards set forth in the United States and other countries. We agree that in the ethical conduct of clinical trials, consideration of potential toxicity of a study medication is paramount (2). As investigators, we reviewed the available published peer-reviewed literature for evidence of toxicity of the supplements, consulted nutrition experts, and concluded that our protocol-with 4 wk of supplementation with a dose and formulation that had previously been used for a large 5-y clinical trial (7)-presented no clinical risks that we could anticipate for healthy adults not pregnant and on no other medications. The protocol, including the dosage, was reviewed and approved by two Canadian institutional review boards and Health Canada's Clinical Trials Therapeutic Product Directorate, was registered with https://ClinicalTrials.gov, and was reviewed before implementation and monitored for safety at regular intervals during the trial by our study's Data Safety Monitoring Board. There were no reports of intolerance to the methyl donor supplements and there were no adverse events during the study.

Scientific reports, Jan 3, 2017

Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level pr... more Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lympho...

Proceedings of the National Academy of Sciences of the United States of America, Mar 13, 2017

Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammatio... more Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4(+) T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (P...

Environment international, Apr 20, 2017

Epidemiological studies have reported associations between air pollution and neuro-psychological ... more Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear. We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles. Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10μm, mean 213μg/m(3)) and fine (0.15-2.5μm, mean 238μg/m(3)) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (mean size 59.6nm, range 47.0-69.8nm), mean (136μg/m(3)) and filtered medical air. Exposures lasted 130min, separated by ≥2weeks, and the biological constituents endotoxin and β-1,3-d-glucan of each particle size fraction were measured. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post-exposure to determine neural biomarker levels. Mixed-model regressions assessed asso...

Particle and fibre toxicology, May 24, 2016

Exposures to ambient particulate matter (PM) are associated with increased morbidity and mortalit... more 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. Subjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 μg/m(3), ozone targeted at 240 μg/m(3) (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 dete...

J Amer Coll Cardiol, 2002

S-Hypertension, Vascular Disease, and Prevention 219A marized in the graph below. Regression anal... more S-Hypertension, Vascular Disease, and Prevention 219A marized in the graph below. Regression analysis yielded a correlation coefficient R=0.824 (p = 0.003). CONCLUSIONS: These data demonstrate a strong correlation between mean diastolic/ systolic Doppler velocity ratio by contrast-enhanced renal ultrasound and estimated creatinine clearance.

The Health Fitness Journal of Canada, Jul 12, 2011

Circulation, Nov 23, 2010

Hypertension, 2015

Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) i... more 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 a...

D18. AIR POLLUTION AND CARDIOVASCULAR DISEASE, 2011

A49. AIR POLLUTION: RESPIRATORY AND NOVEL HEALTH EFFECTS, 2012

Biomedical engineering online, Jan 18, 2006

The objective was to determine the repeatability and stability of capnography interfaced with hum... more The objective was to determine the repeatability and stability of capnography interfaced with human exposure facility. Capnographic wave signals were obtained from five healthy volunteers exposed to particle-free, filtered air during two consecutive 5 min intervals, 10 min apart, within the open and then the sealed and operational human exposure facility (HEF). Using a customized setup comprised of the Oridion Microcap portable capnograph, DA converter and AD card, the signal was acquired and saved as an ASCII file for subsequent processing. The minute ventilation (VE), respiratory rate (RR) and expiratory tidal volume (VTE) were recorded before and after capnographic recording and then averaged. Each capnographic tracing was analyzed for acceptable waves. From each recorded interval, 8 to 19 acceptable waves were selected and measured. The following wave parameters were obtained: total length and length of phase II and III, slope of phase II and III, area under the curve and area u...

Journal of the American Heart Association, Jan 19, 2013

Short-term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate-matter (PM) ha... more Short-term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate-matter (PM) have been related with increased blood pressure (BP) in controlled-human exposure and community-based studies. However, whether coarse (2.5 to 10 μm) PM exposure increases BP is uncertain. Recent observational studies have linked PM exposures with blood DNA hypomethylation, an epigenetic alteration that activates inflammatory and vascular responses. No experimental evidence is available to confirm those observational data and demonstrate the relations between PM, hypomethylation, and BP. We conducted a cross-over trial of controlled-human exposure to concentrated ambient particles (CAPs). Fifteen healthy adult participants were exposed for 130 minutes to fine CAPs, coarse CAPs, or HEPA-filtered medical air (control) in randomized order with ≥2-week washout. Repetitive-element (Alu, long interspersed nuclear element-1 [LINE-1]) and candidate-gene (TLR4, IL-12, IL-6, iNOS) blood methylation,...

Environmental health perspectives, Jan 16, 2015

Ambient coarse, fine and ultrafine particles have been associated with mortality and morbidity. F... more Ambient coarse, fine and ultrafine particles have been associated with mortality and morbidity. Few studies compared how various particle size fractions affected systemic biomarkers. We examined changes of blood and urinary biomarkers following exposures to three particle sizes. Fifty healthy non-smoking volunteers, mean age 28 years, were exposed to coarse (2.5-10 µm, mean 213 µg/m(3)) and fine (0.15-2.5 µm, mean 238 µg/m(3)) 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/m(3)) and filtered medical air. Exposures lasted 130 minutes, separated by ≥2 weeks. Blood/urine samples were collected pre-exposure, 1-hour and 21-hour post exposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF, vascular mediators), and malondialdehyde (lipid peroxidation), and urinary VEGF, 8-hydroxy-deoxy-guanosine (...

Occupational and environmental medicine, 2013

Knowledge of the inhalable particulate matter components responsible for health effects is import... more Knowledge of the inhalable particulate matter components responsible for health effects is important for developing targeted regulation. 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. 35 healthy adults were exposed to five 130-min exposures at rest: (1) fine CAPs (~250 µg/m(3)); (2) coarse CAPs (200 µg/m(3)); (3) second coarse CAPs (~200 µg/m(3)); (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. Relative to filtered air, an increase in blood leucocytes 24 h (but not 3 h) postexposure was significantly associated with coarse (estimate=0.44×10(9) cells/L (95% CI 0.01 to 0.88); n=132) and fine CAPs (0.6...

Respiratory Research, 2011

Background Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Ar... more Background Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA) and challenged with nebulized PBS (OVA/PBS) or OVA (OVA/OVA) for three consecutive days (sub-acute model) or 12 weeks (chronic model), which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3)...

Journal of the American College of Cardiology, 2011

We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O 3)... more We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O 3) would increase dispersion of ventricular repolarization. Background Elevated levels of air pollution are associated with cardiac arrhythmias through mechanisms yet to be elucidated. Methods Each of 25 volunteers (18 to 50 years of age) had four 2-h exposures to 150 g/m 3 CAP; 120 parts per billion O 3 ; CAP ϩ O 3 ; and filtered air (FA). Exposure-induced changes (⌬ ϭ 5-min epochs at end-start) in spatial dispersion of repolarization were determined from continuous 12-lead electrocardiographic recording. Results Spatial dispersion of repolarization assessed by corrected ⌬T-wave peak to T-wave end interval increased significantly for CAP ϩ O 3 (0.17 Ϯ 0.03, p Ͻ 0.0001) exposure only, remaining significant when factoring FA (CAP ϩ O 3 Ϫ FA) as control (0.11 Ϯ 0.04, p ϭ 0.013). The influence on repolarization was further verified by a significant increase in ⌬QT dispersion (for CAP ϩ O 3 compared with FA (5.7 Ϯ 1.4, p ϭ 0.0002). When the lowfrequency to high-frequency ratio of heart rate variability (a conventional representation of sympatheticparasympathetic balances) was included as a covariate, the effect estimate was positive for both corrected ⌬T-wave peak to T-wave end interval (p ϭ 0.002) and ⌬QT dispersion (p ϭ 0.038). When the high-frequency component (parasympathetic heart rate modulation) was included as a covariate with corrected ⌬T-wave peak to T-wave end interval, the effect estimate for high frequency was inverse (p ϭ 0.02). Conclusions CAP ϩ O 3 exposure alters dispersion of ventricular repolarization in part by increasing sympathetic and decreasing parasympathetic heart rate modulation. Detection of changes in repolarization parameters, even in this small cohort of healthy individuals, suggests an underappreciated role for air pollutants in urban arrhythmogenesis.

Journal of Allergy and Clinical Immunology, 1992

ACS Earth and Space Chemistry

Proceedings of the National Academy of Sciences of the United States of America, May 16, 2017

The aim of our small mechanistic study (1) was to test the biologic plausibility that ambient par... more The aim of our small mechanistic study (1) was to test the biologic plausibility that ambient particle pollution might have epigenetic effects on DNA methylation that could be modulated by methyl donor supplements. We acknowledge in this letter and in our paper that generalizability of our results is limited not only by study size, but also by the characteristics of healthy study participants. In contributing to the body of literature used for scientific assessment and consequent policy decision making, carefully controlled mechanistic studies like ours complement the large epidemiologic studies that, as Lucock et al. (2) suggest, show that reduction in ambient particle levels have led to improvement in health and reduction in morbidity and mortality (3-6). Studies like ours cannot diminish-nor be used to underemphasize-the urgent need to lower air pollution levels to-at a minimum-meet the air-quality standards set forth in the United States and other countries. We agree that in the ethical conduct of clinical trials, consideration of potential toxicity of a study medication is paramount (2). As investigators, we reviewed the available published peer-reviewed literature for evidence of toxicity of the supplements, consulted nutrition experts, and concluded that our protocol-with 4 wk of supplementation with a dose and formulation that had previously been used for a large 5-y clinical trial (7)-presented no clinical risks that we could anticipate for healthy adults not pregnant and on no other medications. The protocol, including the dosage, was reviewed and approved by two Canadian institutional review boards and Health Canada's Clinical Trials Therapeutic Product Directorate, was registered with https://ClinicalTrials.gov, and was reviewed before implementation and monitored for safety at regular intervals during the trial by our study's Data Safety Monitoring Board. There were no reports of intolerance to the methyl donor supplements and there were no adverse events during the study.

Scientific reports, Jan 3, 2017

Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level pr... more Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lympho...

Proceedings of the National Academy of Sciences of the United States of America, Mar 13, 2017

Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammatio... more Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4(+) T-helper cells. PM2.5 induced methylation changes in genes involved in mitochondrial oxidative energy metabolism. B-vitamin supplementation prevented these changes. Likewise, PM2.5 depleted 11.1% [95% confidence interval (CI), 0.4%, 21.7%; P = 0.04] of mitochondrial DNA content compared with sham, and B-vitamin supplementation attenuated the PM2.5 effect by 102% (P...

Environment international, Apr 20, 2017

Epidemiological studies have reported associations between air pollution and neuro-psychological ... more Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear. We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles. Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10μm, mean 213μg/m(3)) and fine (0.15-2.5μm, mean 238μg/m(3)) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (mean size 59.6nm, range 47.0-69.8nm), mean (136μg/m(3)) and filtered medical air. Exposures lasted 130min, separated by ≥2weeks, and the biological constituents endotoxin and β-1,3-d-glucan of each particle size fraction were measured. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post-exposure to determine neural biomarker levels. Mixed-model regressions assessed asso...

Particle and fibre toxicology, May 24, 2016

Exposures to ambient particulate matter (PM) are associated with increased morbidity and mortalit... more 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. Subjects were exposed to fine concentrated ambient fine particles (CAP) with PM2.5 targeted at 150 μg/m(3), ozone targeted at 240 μg/m(3) (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 dete...

J Amer Coll Cardiol, 2002

S-Hypertension, Vascular Disease, and Prevention 219A marized in the graph below. Regression anal... more S-Hypertension, Vascular Disease, and Prevention 219A marized in the graph below. Regression analysis yielded a correlation coefficient R=0.824 (p = 0.003). CONCLUSIONS: These data demonstrate a strong correlation between mean diastolic/ systolic Doppler velocity ratio by contrast-enhanced renal ultrasound and estimated creatinine clearance.

The Health Fitness Journal of Canada, Jul 12, 2011

Circulation, Nov 23, 2010

Hypertension, 2015

Short-term exposure to particulate matter (PM) is associated with increased blood pressure (BP) i... more 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 a...

D18. AIR POLLUTION AND CARDIOVASCULAR DISEASE, 2011

A49. AIR POLLUTION: RESPIRATORY AND NOVEL HEALTH EFFECTS, 2012

Biomedical engineering online, Jan 18, 2006

The objective was to determine the repeatability and stability of capnography interfaced with hum... more The objective was to determine the repeatability and stability of capnography interfaced with human exposure facility. Capnographic wave signals were obtained from five healthy volunteers exposed to particle-free, filtered air during two consecutive 5 min intervals, 10 min apart, within the open and then the sealed and operational human exposure facility (HEF). Using a customized setup comprised of the Oridion Microcap portable capnograph, DA converter and AD card, the signal was acquired and saved as an ASCII file for subsequent processing. The minute ventilation (VE), respiratory rate (RR) and expiratory tidal volume (VTE) were recorded before and after capnographic recording and then averaged. Each capnographic tracing was analyzed for acceptable waves. From each recorded interval, 8 to 19 acceptable waves were selected and measured. The following wave parameters were obtained: total length and length of phase II and III, slope of phase II and III, area under the curve and area u...

Journal of the American Heart Association, Jan 19, 2013

Short-term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate-matter (PM) ha... more Short-term exposures to fine (<2.5 μm aerodynamic diameter) ambient particulate-matter (PM) have been related with increased blood pressure (BP) in controlled-human exposure and community-based studies. However, whether coarse (2.5 to 10 μm) PM exposure increases BP is uncertain. Recent observational studies have linked PM exposures with blood DNA hypomethylation, an epigenetic alteration that activates inflammatory and vascular responses. No experimental evidence is available to confirm those observational data and demonstrate the relations between PM, hypomethylation, and BP. We conducted a cross-over trial of controlled-human exposure to concentrated ambient particles (CAPs). Fifteen healthy adult participants were exposed for 130 minutes to fine CAPs, coarse CAPs, or HEPA-filtered medical air (control) in randomized order with ≥2-week washout. Repetitive-element (Alu, long interspersed nuclear element-1 [LINE-1]) and candidate-gene (TLR4, IL-12, IL-6, iNOS) blood methylation,...

Environmental health perspectives, Jan 16, 2015

Ambient coarse, fine and ultrafine particles have been associated with mortality and morbidity. F... more Ambient coarse, fine and ultrafine particles have been associated with mortality and morbidity. Few studies compared how various particle size fractions affected systemic biomarkers. We examined changes of blood and urinary biomarkers following exposures to three particle sizes. Fifty healthy non-smoking volunteers, mean age 28 years, were exposed to coarse (2.5-10 µm, mean 213 µg/m(3)) and fine (0.15-2.5 µm, mean 238 µg/m(3)) 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/m(3)) and filtered medical air. Exposures lasted 130 minutes, separated by ≥2 weeks. Blood/urine samples were collected pre-exposure, 1-hour and 21-hour post exposure to determine blood interleukin-6 and C-reactive protein (inflammation), endothelin-1 and vascular endothelial growth factor (VEGF, vascular mediators), and malondialdehyde (lipid peroxidation), and urinary VEGF, 8-hydroxy-deoxy-guanosine (...

Occupational and environmental medicine, 2013

Knowledge of the inhalable particulate matter components responsible for health effects is import... more Knowledge of the inhalable particulate matter components responsible for health effects is important for developing targeted regulation. 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. 35 healthy adults were exposed to five 130-min exposures at rest: (1) fine CAPs (~250 µg/m(3)); (2) coarse CAPs (200 µg/m(3)); (3) second coarse CAPs (~200 µg/m(3)); (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. Relative to filtered air, an increase in blood leucocytes 24 h (but not 3 h) postexposure was significantly associated with coarse (estimate=0.44×10(9) cells/L (95% CI 0.01 to 0.88); n=132) and fine CAPs (0.6...

Respiratory Research, 2011

Background Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Ar... more Background Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA) and challenged with nebulized PBS (OVA/PBS) or OVA (OVA/OVA) for three consecutive days (sub-acute model) or 12 weeks (chronic model), which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3)...

Journal of the American College of Cardiology, 2011

We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O 3)... more We tested the hypothesis that exposure to concentrated ambient particles (CAP) and/or ozone (O 3) would increase dispersion of ventricular repolarization. Background Elevated levels of air pollution are associated with cardiac arrhythmias through mechanisms yet to be elucidated. Methods Each of 25 volunteers (18 to 50 years of age) had four 2-h exposures to 150 g/m 3 CAP; 120 parts per billion O 3 ; CAP ϩ O 3 ; and filtered air (FA). Exposure-induced changes (⌬ ϭ 5-min epochs at end-start) in spatial dispersion of repolarization were determined from continuous 12-lead electrocardiographic recording. Results Spatial dispersion of repolarization assessed by corrected ⌬T-wave peak to T-wave end interval increased significantly for CAP ϩ O 3 (0.17 Ϯ 0.03, p Ͻ 0.0001) exposure only, remaining significant when factoring FA (CAP ϩ O 3 Ϫ FA) as control (0.11 Ϯ 0.04, p ϭ 0.013). The influence on repolarization was further verified by a significant increase in ⌬QT dispersion (for CAP ϩ O 3 compared with FA (5.7 Ϯ 1.4, p ϭ 0.0002). When the lowfrequency to high-frequency ratio of heart rate variability (a conventional representation of sympatheticparasympathetic balances) was included as a covariate, the effect estimate was positive for both corrected ⌬T-wave peak to T-wave end interval (p ϭ 0.002) and ⌬QT dispersion (p ϭ 0.038). When the high-frequency component (parasympathetic heart rate modulation) was included as a covariate with corrected ⌬T-wave peak to T-wave end interval, the effect estimate for high frequency was inverse (p ϭ 0.02). Conclusions CAP ϩ O 3 exposure alters dispersion of ventricular repolarization in part by increasing sympathetic and decreasing parasympathetic heart rate modulation. Detection of changes in repolarization parameters, even in this small cohort of healthy individuals, suggests an underappreciated role for air pollutants in urban arrhythmogenesis.

Journal of Allergy and Clinical Immunology, 1992