title: 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.
authors.affiliation: Gradient, Cambridge, MA , USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Goodman
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Prueitt
authors.forename: Sonja N
authors.initials: SN
authors.lastname: Sax
authors.forename: Daniella M
authors.initials: DM
authors.lastname: Pizzurro
authors.forename: Heather N
authors.initials: HN
authors.lastname: Lynch
authors.forename: Ke
authors.initials: K
authors.lastname: Zu
authors.forename: Ferdinand J
authors.initials: FJ
authors.lastname: Venditti
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D004784:Environmental Monitoring; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D010126:Ozone / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D018675:Toxicity Tests
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D010126:Ozone
keywords: air pollution; biomarkers; causal framework; epidemiology; inflammation; mode of action; ozone; risk assessment; weight of evidence