Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects

Abstract

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.

Sarcoendoplasmic Reticulum Ca2+ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

“…Inhalation of oxidant gases and other pollutants can compromise cardiac function (28). Inhalation of environmentally persistent free radicals, potentially derived from combustion of chlorine-containing hydrocarbons in rats, also caused cardiac inflammation and loss of function (29).…”

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

“…In this trial, subjects were recruited under an Environmental Protection Agency contract with Westat Corporation (Rockville, MD). Cardiac and pulmonary function, and systemic effects of ozone on coagulation and inflammatory markers have been previously reported from this study (25). A total of 24 volunteers were involved in the study.…”

“…During each visit, the subjects were exposed to either 0.3 parts per million ozone or filtered air for 2 hours in the morning time in a blinded manner. During the exposure, subjects alternated between 15 minutes of rest and 15 minutes of exercise on a cycle ergometer (25). Exposures were conducted at the U.S. Environmental Protection Agency, Human Studies Facility on the campus of the University of North Carolina, Chapel Hill.…”

“…The exposure chambers were maintained at 40% relative humidity for all exposures. For more details of the exposure system, see online supplement 1 and Devlin and coworkers (25).…”

Air Pollution Exposure

“…3,4,34,35 Epidemiologic studies of short-term air pollution exposures have also consistently demonstrated relationships with both airway and systemic infl ammation in healthy individuals. [36][37][38] Whether longer-term exposures result in fi brosis in humans remains unknown.…”