Prevention or Treatment of Ards With Aspirin: A Review of Preclinical Models and Meta-Analysis of Clinical Studies.
Prevention or Treatment of Ards With Aspirin: A Review of Preclinical Models and Meta-Analysis of Clinical Studies.
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DOI：
10.1097/shk.0000000000000745
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发表时间：
2017-01
期刊：
影响因子：
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通讯作者：
Tuinman PR
中科院分区：
文献类型：
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作者：
Panka BA;de Grooth HJ;Spoelstra-de Man AM;Looney MR;Tuinman PR
急性呼吸窘迫综合征（ARDS）是一种危及生命的疾病，是危重病的重要原因。没有针对肺损伤本身的特异性药物干预已被证明可有效改善ARDS患者的结局。血小板活化被认为是ARDS病理生理学的关键组成部分，并可能为预防和治疗策略提供机会。我们假设使用乙酰水杨酸（ASA）可以预防和/或减轻肺损伤。我们对临床前研究进行了系统综述，并对研究ASA在肺损伤背景下疗效的临床研究进行了荟萃分析。检索MEDLINE、EMBASE和科克伦数据库。文献检索得到了1314篇唯一文献。15项临床前研究和8项临床研究符合入选和排除标准。在动物研究中，ASA的总体效果是积极的，例如，ASA改善了生存率，减轻了炎症和肺水肿。所涉及的作用机制包括干扰嗜中性粒细胞-血小板相互作用、减少白三烯、中性粒细胞胞外陷阱和白细胞生成素。大剂量ASA可能是首选药物。3项临床研究的荟萃分析显示，ASA使用与ARDS发生率降低相关（OR 0.59，95%CI 0.36 - 0.98），尽管研究间存在显著异质性。所有研究在方法学质量上都有各自的缺点。临床前研究的系统综述和临床研究的荟萃分析表明ASA在ARDS预防和治疗中具有有益作用。然而，目前可用的数据不足以证明ASA在ARDS中的适应症。大量的文献确实支持在人类中进行进一步的研究。我们建议在前瞻性随机试验之前，进行临床试验，评估ASA在肺损伤模型中的作用机制，以指导最佳时机和剂量。
The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself, have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury. We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. MEDLINE, EMBASE AND COCHRANE databases were searched. The literature search yielded 1314 unique articles. Fifteen pre-clinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g. ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps and prostaglandins. High dose ASA may be the drug of choice. A meta-analysis of 3 clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36–0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality. This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models is being evaluated to guide optimal timing and dose, before prospective randomized trials.