阿司匹林预防或治疗急性呼吸窘迫综合征：临床前模型综述及临床研究的荟萃分析。
Prevention or Treatment of Ards With Aspirin: A Review of Preclinical Models and Meta-Analysis of Clinical Studies.
作者信息
Panka Bernardo Amisa, de Grooth Harm-Jan, Spoelstra-de Man Angélique Maria Elisabeth, Looney Mark R, Tuinman Pieter-Roel
机构信息
*Department of Intensive Care Medicine, VU University Medical Centre, Amsterdam, The Netherlands †Department of Intensive Care Medicine, s' Lands Hospitaal Paramaribo, Paramaribo, Suriname ‡Research VUmc Intensive Care (REVIVE) and Institute for Cardiovascular Research (ICAR-VU), Amsterdam, The Netherlands §Department of Medicine, University of California, San Francisco; San Francisco, California.
出版信息
Shock. 2017 Jan;47(1):13-21. doi: 10.1097/SHK.0000000000000745.
BACKGROUND
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.
METHODS
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.
RESULTS
The literature search yielded 1,314 unique articles. Fifteen preclinical 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 three 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.
CONCLUSION
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 are being evaluated to guide optimal timing and dose, before prospective randomized trials.
背景
急性呼吸窘迫综合征（ARDS）是一种危及生命的疾病，在危重症中占很大比例。目前尚无针对肺损伤本身的特异性药物干预措施被证明能有效改善ARDS患者的预后。血小板活化被认为是ARDS病理生理学的关键组成部分，这可能为预防和治疗策略提供契机。我们假设使用阿司匹林（ASA）可能预防和/或减轻肺损伤。
方法
我们对临床前研究进行了系统评价，并对研究ASA在肺损伤中的疗效的临床研究进行了荟萃分析。检索了Medline、embase和Cochrane数据库。
结果
文献检索共得到1314篇独特的文章。15项临床前研究和8项临床研究符合纳入和排除标准。在动物研究中，ASA的总体效果是积极的，例如，ASA提高了生存率，减轻了炎症和肺水肿。其作用机制包括干扰中性粒细胞与血小板的相互作用、减少白三烯、中性粒细胞胞外陷阱和前列腺素。高剂量ASA可能是首选药物。对三项临床研究的荟萃分析显示，使用ASA与ARDS发病率降低之间存在关联（OR 0.59，95%CI 0.36-0.98），尽管研究之间存在很大的异质性。所有研究在方法学质量上都有自身的不足。
结论
这项临床前研究的系统评价和临床研究的荟萃分析表明，ASA在ARDS的预防和治疗中具有有益作用。然而，目前可得的数据不足以证明在ARDS中使用ASA的合理性。现有文献确实支持在人体中进行进一步研究。我们建议在进行前瞻性随机试验之前，先进行临床试验，评估ASA在肺损伤模型中的作用机制，以指导最佳的给药时机和剂量。
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