Gradient, Cambridge, MA , USA.
Crit Rev Toxicol. 2015 May;45(5):412-52. doi: 10.3109/10408444.2015.1031371.
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.
美国环境保护署（EPA）最近得出结论，短期（<30 天）臭氧暴露与心血管（CV）效应之间可能存在因果关系；然而，将短暂效应与慢性心血管疾病（CVD）联系起来的生物学机制尚未建立。一些研究评估了臭氧暴露后与炎症、氧化应激、凝血、血管反应性、脂质学和葡萄糖代谢相关的循环生物标志物水平的变化，以阐明生物学机制。我们进行了证据权重（WoE）分析，以确定是否有证据支持这些生物标志物与短期臭氧暴露之间的关联，这表明在臭氧国家环境空气质量标准（NAAQS）为 75 十亿分之一（ppb）以下，CVD 存在生物学机制。所有生物标志物类别中的流行病学发现均不一致，只有少数研究报告了统计学上显著的变化，并且报告的影响方向没有一致性。在臭氧浓度高于 75 ppb 的情况下进行的 2 至 5 小时的人体受控暴露研究报告称，炎症和氧化应激的生物标志物略有升高，但具有不确定的临床相关性。实验动物研究报告了某些生物标志物之间更一致的结果，尽管这些研究也是在臭氧暴露远高于 75 ppb 的情况下进行的，并且提供的有关臭氧暴露-反应关系的信息有限。总体而言，目前的 WoE 并不能令人信服地证明短期臭氧暴露低于 NAAQS 与生物标志物水平的不良变化之间存在因果关系，但由于研究的局限性，它们不能提供缺乏因果关系的明确证据。
