Ozone exposure and systemic biomarkers: Evaluation of evidence for adverse cardiovascular health impacts

Abstract

The US Environmental Protection Agency (EPA) recently concluded that there is likely to be a causal relationship between short-term (< 30 days) ozone exposure and cardiovascular (CV) effects; however, biological mechanisms to link transient effects with chronic cardiovascular disease (CVD) have not been established. Some studies assessed changes in circulating levels of biomarkers associated with inflammation, oxidative stress, coagulation, vasoreactivity, lipidology, and glucose metabolism after ozone exposure to elucidate a biological mechanism. We conducted a weight-of-evidence (WoE) analysis to determine if there is evidence supporting an association between changes in these biomarkers and short-term ozone exposure that would indicate a biological mechanism for CVD below the ozone National Ambient Air Quality Standard (NAAQS) of 75 parts per billion (ppb). Epidemiology findings were mixed for all biomarker categories, with only a few studies reporting statistically significant changes and with no consistency in the direction of the reported effects. Controlled human exposure studies of 2 to 5 hours conducted at ozone concentrations above 75 ppb reported small elevations in biomarkers for inflammation and oxidative stress that were of uncertain clinical relevance. Experimental animal studies reported more consistent results among certain biomarkers, although these were also conducted at ozone exposures well above 75 ppb and provided limited information on ozone exposure-response relationships. Overall, the current WoE does not provide a convincing case for a causal relationship between short-term ozone exposure below the NAAQS and adverse changes in levels of biomarkers within and across categories, but, because of study limitations, they cannot not provide definitive evidence of a lack of causation.

Keywords:

• air pollution
• biomarkers
• causal framework
• epidemiology
• inflammation
• mode of action
• ozone
• risk assessment
• weight of evidence

Acknowledgments

The authors appreciate the valuable comments provided by the reviewers of this paper who were selected by the Editor and anonymous to the authors. Their comments greatly assisted the revision and improvement of this paper.

Declaration of interest

The authors are employed by Gradient, a private environmental consulting firm, and by Albany Medical College, a private medical school. Julie E. Goodman, Robyn L. Prueitt, Sonja N. Sax, and Ke Zu have testified before the EPA Clean Air Scientific Advisory Committee (CASAC) and/or at EPA hearings and have offered written comments to the EPA ozone docket on the health effects of ozone and the setting of the ozone NAAQS. The authors conducted the work reported in this paper during the normal course of employment, with financial support provided by the Texas Commission on Environmental Quality (TCEQ). The authors have the sole responsibility for the writing, content, and conclusions in this paper. The conclusions are not necessarily those of the TCEQ.

Supplementary material available online

Supplementary Tables 1–12

Notes

¹ See Table 1 for search terms used for each biomarker.

² [ti] = title; [MeSH] = medical subject headings (PubMed search term).