Autonomic Effects of Controlled Fine Particulate Exposure in Young Healthy Adults: Effect Modification by Ozone

Fakhri, Asghar; Ilic, Ljubomir M.; Wellenius, Gregory A.; Urch, Bruce; Silverman, Frances; Gold, Diane R.; Mittleman, Murray A.

doi:10.1289/ehp.0900541

Cited by 64 publications

(54 citation statements)

References 38 publications

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“…Controlled-exposure studies have shown altered HRV after combined exposure to particles and ozone. 29,30 We also observed an increase in the duration of the QT interval immediately after exposure. A prolonged QT interval is a risk factor for ventricular tachyarrhythmias and sudden death.…”

Section: Discussionmentioning

confidence: 50%

“…We observed a decrease in the HF component of HRV immediately after ozone exposure, which is consistent with findings in multiple PM studies (PM Integrated Science Assessment). A previous controlled-exposure study 29 did not find significant ozone-induced changes in HRV. However, in this study, the participants were exposed to a smaller concentration of ozone (0.12 ppm) and did not exercise during exposure, which would have resulted in a smaller dose of ozone delivered to their airways.…”

Section: Discussionmentioning

confidence: 56%

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Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects

et al. 2012

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Background— Recent epidemiology studies have reported associations between short-term ozone exposure and mortality. Such studies have previously reported associations between airborne particulate matter pollution and mortality, and support for a causal relationship has come from controlled-exposure studies that describe pathophysiological mechanisms by which particulate matter could induce acute mortality. In contrast, for ozone, almost no controlled-human-exposure studies have tested whether ozone exposure can modulate the cardiovascular system. Methods and Results— Twenty-three young healthy individuals were exposed in a randomized crossover fashion to clean air and to 0.3-ppm ozone for 2 hours while intermittently exercising. Blood was obtained immediately before exposure, immediately afterward, and the next morning. Continuous Holter monitoring began immediately before exposure and continued for 24 hours. Lung function was performed immediately before and immediately after exposure, and bronchoalveolar lavage was performed 24 hours after exposure. Immediately after ozone exposure, we observed a 98.9% increase in interleukin-8, a 21.4% decrease in plasminogen activator inhibitor-1, a 51.3% decrease in the high-frequency component of heart rate variability, and a 1.2% increase in QT duration. Changes in interleukin-1B and plasminogen activator inhibitor-1 were apparent 24 hours after exposure. In agreement with previous studies, we also observed ozone-induced drops in lung function and an increase in pulmonary inflammation. Conclusions— This controlled-human-exposure study shows that ozone can cause an increase in vascular markers of inflammation and changes in markers of fibrinolysis and markers that affect autonomic control of heart rate and repolarization. We believe that these findings provide biological plausibility for the epidemiology studies that associate ozone exposure with mortality. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01492517.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 56%

Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects

et al. 2012

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“…Despite experimental support for cardiovascular effects of ozone (such as vascular oxidative stress and/or inflammation, increased heart rate, increased diastolic pressure, decreased heart rate variability and decreased nitric oxide bioavailability, for 2-hour to multi-day exposures to 500-800 ppb ozone) from animal models (Chuang et al, 2009;Perepu et al, 2010;Tankersley et al, 2010), results from controlled human studies remain ambiguous (Kusha et al, 2012;Fakhri et al, 2009). Similarly, investigation of blood biomarkers (reflecting haemostasis and inflammation) of cardiovascular risk in panel studies have provided inconsistent associations with ozone, complicated by the different averaging times and lag structures examined (Rudez et al, 2009;Thompson et al, 2010;Chuang et al, 2007;Liao et al, 2005;Steinvil et al 2008).…”

Section: Experimental and Panel Studiesmentioning

confidence: 99%

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

Broome¹,

Johnston

Horsley

et al. 2016

Medical Journal of Australia

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This document presents answers to 24 questions relevant to reviewing European policies on air pollution and to addressing health aspects of these policies. The answers were developed by a large group of scientists engaged in the WHO project "Review of evidence on health aspects of air pollution -REVIHAAP". The experts reviewed and discussed the newly accumulated scientific evidence on the adverse effects on health of air pollution, formulating science-based answers to the 24 questions. Extensive rationales for the answers, including the list of key references, are provided. The review concludes that a considerable amount of new scientific information on the adverse effects on health of particulate matter, ozone and nitrogen dioxide, observed at levels commonly present in Europe, has been published in recent years. This new evidence supports the scientific conclusions of the WHO air quality guidelines, last updated in 2005, and indicates that the effects in some cases occur at air pollution concentrations lower than those serving to establish these guidelines. It also provides scientific arguments for taking decisive actions to improve air quality and reduce the burden of disease associated with air pollution in Europe.This publication arises from the project REVIHAAP and has been co-funded by the European Union. Keywords AIR POLLUTANTS AIR POLLUTION -ADVERSE EFFECTS ENVIRONMENT AND PUBLIC HEALTH EVIDENCE BASED PRACTICE GUIDELINES HEALTH POLICYAddress requests about publications of the WHO Regional Office for Europe to: Publications WHO Regional Office for Europe Scherfigsvej 8 DK-2100 Copenhagen Ø, Denmark Alternatively, complete an online request form for documentation, health information, or for permission to quote or translate, on the Regional Office web site (http://www.euro.who.int/pubrequest). © World Health Organization 2013All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full.The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate borderlines for which there may not yet be full agreement.The mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. ...

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“…This may be associated with the biomarker changes observed by the authors, because other studies using ozone exposure regimens that likely produced a lower pulmonary response have not reported changes in heart rate variability. 4 Finally, Devlin et al suggest that their findings provide support for cardiovascular effects reported in some epidemiology studies. Exposures in epidemiology studies are generally an order of magnitude lower and the effects far more extreme (eg, death).…”

mentioning

confidence: 80%

Letter by Goodman and Sax Regarding Article, “Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects”

Goodman

Sax

2013

Circulation

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We read with interest the study by Devlin et al. 1 In this study, 23 healthy individuals were exposed once to clean air or to 300 ppb ozone for 2 hours while exercising intermittently. Several biomarkers of inflammation, thrombosis, and heart rate variability were evaluated before exposure, immediately after exposure, for 24 hours, or at 24 hours. Measurements of some of these biomarkers were statistically significantly different after ozone exposure, and the authors observed a decrease in lung function.Devlin et al evaluated statistical significance, but they did not evaluate the clinical significance of the results. Although the biomarkers they measured may be on the causal pathway to cardiovascular effects, it is our opinion that they are of small enough magnitude that they are more likely indicative of homeostatic processes and thus do not provide information on the potential for adverse effects.2 For example, small changes in heart rate variability can occur as a result of lifestyle factors and should not be considered adverse. 3In addition, not all of the biomarkers changed after ozone exposure. If ozone causes cardiovascular effects, coherent changes in biomarkers should occur, rather than changes in certain biomarkers at certain times. Although it is possible that the mode of action of ozone acts only through a subset of biomarkers at certain time points, there is insufficient evidence to date to support this hypothesis.There was only 1 exposure level in this study, which was 4 times higher than the ozone National Ambient Air Quality Standard (75 ppb). Thus, it is unknown whether these effects occur at the lower concentrations to which the general population is exposed. In addition, exposure-response, which is critical for addressing causation, cannot be evaluated on the basis of only 1 exposure level.It is notable that study subjects were exercising at high multiples of normal breathing levels, resulting in a significant group decrease in pulmonary function (as expected on the basis of previous studies). This may be associated with the biomarker changes observed by the authors, because other studies using ozone exposure regimens that likely produced a lower pulmonary response have not reported changes in heart rate variability. 4 Finally, Devlin et al suggest that their findings provide support for cardiovascular effects reported in some epidemiology studies. Exposures in epidemiology studies are generally an order of magnitude lower and the effects far more extreme (eg, death). In addition, results among epidemiology studies are inconsistent; most find no association between ozone and cardiovascular mortality. 5Devlin et al demonstrated that high levels of ozone are associated with small changes in biomarkers. Their work adds to the body of knowledge on this topic, which is currently limited. Still, there is no known biologically plausible mechanism by which ambient ozone could cause cardiovascular effects. In fact, because ozone is so reactive, effects tend to be restricted to the point of exposure (i...

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Autonomic Effects of Controlled Fine Particulate Exposure in Young Healthy Adults: Effect Modification by Ozone

Cited by 64 publications

References 38 publications

Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects

Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

Letter by Goodman and Sax Regarding Article, “Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects”

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