LaKind Associates, LLC, Catonsville, MD, USA.
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Crit Rev Toxicol. 2021 Jul;51(6):467-508. doi: 10.1080/10408444.2021.1965086. Epub 2021 Sep 27.
We utilized a practical, transparent approach for systematically reviewing a chemical-specific evidence base. This approach was used for a case study of ozone inhalation exposure and adverse metabolic effects (overweight/obesity, Type 1 diabetes [T1D], Type 2 diabetes [T2D], and metabolic syndrome). We followed the basic principles of systematic review. Studies were defined as "Suitable" or "Supplemental." The evidence for Suitable studies was characterized as strong or weak. An overall causality judgment for each outcome was then determined as either causal, suggestive, insufficient, or not likely. Fifteen epidemiologic and 33 toxicologic studies were Suitable for evidence synthesis. The strength of the human evidence was weak for all outcomes. The toxicologic evidence was weak for all outcomes except two: body weight, and impaired glucose tolerance/homeostasis and fasting/baseline hyperglycemia. The combined epidemiologic and toxicologic evidence was categorized as weak for overweight/obesity, T1D, and metabolic syndrome,. The association between ozone exposure and T2D was determined to be insufficient or suggestive. The streamlined approach described in this paper is transparent and focuses on key elements. As systematic review guidelines are becoming increasingly complex, it is worth exploring the extent to which related health outcomes should be combined or kept distinct, and the merits of focusing on critical elements to select studies suitable for causal inference. We recommend that systematic review results be used to target discussions around specific research needs for advancing causal determinations.
我们采用了一种实用、透明的方法来系统地评估特定化学物质的证据基础。这种方法用于臭氧吸入暴露和不良代谢效应（超重/肥胖、1 型糖尿病[T1D]、2 型糖尿病[T2D]和代谢综合征）的案例研究。我们遵循系统评价的基本原则。研究被定义为“合适”或“补充”。合适研究的证据被描述为强或弱。然后，根据每个结果的因果关系判断，将其确定为因果关系、提示性、证据不足或不太可能。有 15 项流行病学研究和 33 项毒理学研究适合进行证据综合。所有结果的人体证据都很薄弱。毒理学证据除了两个结果（体重和葡萄糖耐量/稳态受损以及空腹/基线高血糖）外，其他结果都很薄弱。超重/肥胖、T1D 和代谢综合征的流行病学和毒理学综合证据被归类为弱。臭氧暴露与 T2D 的关联被确定为证据不足或提示性。本文描述的简化方法是透明的，重点关注关键要素。随着系统评价指南变得越来越复杂，值得探讨的是，相关健康结果应该合并还是保持区别，以及关注关键要素以选择适合因果推断的研究的优点。我们建议将系统评价结果用于针对特定研究需求的讨论，以推进因果关系的确定。
