Redox signaling and antioxidant therapies in acute respiratory distress syndrome: a systematic review and meta-analysis

Objectives: No pharmacologic treatment that targets the pathophysiologic alterations of acute respiratory distress syndrome (ARDS) has proven effective. Previous studies have revealed overactive oxidative stress as a potential therapeutic target. Thus we conducted this systematic review to assess the efficacyof antioxidant therapy on the clinical outcomes of ARDS patients.
Methods: We retrieved clinical trials from electronic databases. Articles and conference abstracts about antioxidant therapies for patients with ARDS were identified in which the overall effect of each antioxidant therapy on the mortality of ARDS patients was summarized.
Results: We identified 18 relevant studies that met the inclusion criteria, including 899 patients in the experimental group and 870 patients in the control group. The pooled results indicated that most antioxidant therapies could not improve all-cause mortality and might even be harmful in ARDS patients at low risk of death.
Conclusion: Unclassified patients could not benefit from the antioxidant therapies, and thus discretion must be exercised when using these therapies.
Abbreviations ARDS: Acute respiratory distress syndrome; ICU: Intensive care unit; NAC: N-acetylcysteine; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; RR: Relative risk; CI: Confidence interval; OTC: L-2-oxothiazolidine-4-carboxylic acid; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; GLA: Gamma-linolenic acid; NA: Not applicable; PaO2/FiO2 ratio: The ratio of partial pressure arterial oxygen and fraction of inspired oxygen; ALI: Acute lung injury.

研究背景与目的：目前尚无针对急性呼吸窘迫综合征（Acute respiratory distress syndrome, ARDS）病理生理改变的药物治疗方案被证实有效。既往研究显示过度激活的氧化应激可作为潜在治疗靶点。因此本研究开展此项系统综述，以评估抗氧化治疗对急性呼吸窘迫综合征患者临床结局的疗效。
研究方法：本研究从电子数据库中检索临床试验，筛选纳入针对急性呼吸窘迫综合征患者的抗氧化治疗相关文献及会议摘要，并汇总各抗氧化治疗方案对急性呼吸窘迫综合征患者死亡率的整体效应。
研究结果：本研究共纳入符合纳入标准的相关研究18项，涉及试验组患者899例、对照组患者870例。合并分析结果显示，多数抗氧化治疗方案无法改善急性呼吸窘迫综合征患者的全因死亡率，且在低死亡风险的急性呼吸窘迫综合征患者中甚至可能产生有害影响。
研究结论：未分层的急性呼吸窘迫综合征患者无法从抗氧化治疗中获益，因此临床应用此类治疗方案时需谨慎斟酌。
缩写：ARDS（急性呼吸窘迫综合征，Acute respiratory distress syndrome）；ICU（重症监护病房，Intensive care unit）；NAC（N-乙酰半胱氨酸，N-acetylcysteine）；ROS（活性氧簇，Reactive oxygen species）；RNS（活性氮簇，Reactive nitrogen species）；RR（相对风险，Relative risk）；CI（置信区间，Confidence interval）；OTC（L-2-氧代噻唑烷-4-羧酸，L-2-oxothiazolidine-4-carboxylic acid）；EPA（二十碳五烯酸，Eicosapentaenoic acid）；DHA（二十二碳六烯酸，Docosahexaenoic acid）；GLA（γ-亚麻酸，Gamma-linolenic acid）；NA（不适用，Not applicable）；PaO2/FiO2比值（氧合指数，The ratio of partial pressure arterial oxygen and fraction of inspired oxygen）；ALI（急性肺损伤，Acute lung injury）