Research Program Area: Health & Exposure
Ozone (O3) is a major gaseous component of air pollution in urban environments. Recent epidemiological evidence suggests that O3 exposure may increase cardiovascular morbidity, but the specific biological mechanisms mediating O3-associated cardiovascular effects remain to be elucidated. We designed a controlled human exposure study to address the question of whether short-term exposures to ambient levels of O3 cause acute cardiovascular responses as assessed by heart rate variability (HRV) and systemic biomarkers of inflammation and coagulability. Twenty five subjects (15 healthy and 10 asthmatic subjects) were recruited to participate in the study. The subjects were exposed to three conditions (filtered air, 100 ppb O3, and 200 ppb O3) in random order. Exposures were for 4 hours with intermittent exercise (30 min of each hour) at a minute ventilation of 20 L/kg/m2 body surface area. Exercise is used in controlled human exposure studies to simulate outdoor activity levels that involve higher ventilation rates that increase the effective dose of the pollutant. Heart rate variability was measured and blood samples were obtained immediately prior to, immediately after, and 20 h after each exposure period. Bronchoscopy to obtain bronchoalveolar lavage (BAL) fluid was performed at 20 h after exposure. We found that intermittent moderate-intensity exercise induced a pro-inflammatory systemic response characterized by increases in peripheral blood leukocyte counts, and C-reactive protein (CRP), monocyte chemotactic protein, and interleukin-6 concentrations. Exercise did not substantially alter levels of fibrinogen, angiotensin-converting enzyme, markers of coagulability, or HRV. We also found that exposure to 200 ppb O3 induced a decrease in lung function, airway injury as manifested by an increase in total BAL protein, and airway inflammation as evidenced by increases in BAL neutrophils, eosinophils, and several pro-inflammatory cytokines (all as compared to control exposure to filtered air with intermittent exercise). Exposure to 100 ppb O3 caused no decrease in lung function and only mild airway inflammation. Despite the induction of a local lung inflammatory response at 200 ppb, there was little evidence of a systemic inflammatory response to O3, with the exception of a trend toward an increase in serum CRP at 24 h after exposure. Moreover, no evidence of a pro-coagulatory response to O3 exposure was found. Despite this lack of a systemic response, we did find that exposure to 200 ppb O3 induced a significant decrease in the normalized high frequency (HF) domain of HRV at both 4 and 24 h after exposure. We also observed non-significant decreases in the HF domain with 100 ppb exposure at both the 4-h and 24-h time points. The presence of an exposure-relationship when the HF data at all concentrations and time points were analyzed in a linear regression also supports the role of O3 exposure in the observed increase in HF HRV. To our knowledge this is the first controlled exposure study to find an effect on HRV with O3 alone. The results suggest that short-term exposures to O3 can have acute cardiovascular effects.
For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753
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