The acute respiratory distress syndrome (ARDS) is characterised by diffuse impairment in gas exchange that can result from heterogenous aetiologies. ARDS causes 10% of intensive care unit admissions worldwide with inpatient mortality rates ranging from 35% for mild cases to 46% for severe cases.1 Despite being a common and frequently fatal process, there are no widely accepted pharmacological therapies available to treat ARDS, the management of which primarily rests on appropriate mechanical ventilation and supportive care.2 Unfortunately, numerous promising pharmacological therapies that demonstrated benefit in preclinical models or early clinical investigation have failed to demonstrate reliable improvement in clinical outcomes.3–7 In the context of a persistent clinical problem that has vexed state-of-the art investigative therapies, there have been thoughtful proposals on how to improve the investigation of potential ARDS therapies in experimental animal models of acute lung injury (ALI).8–10 A 2011 American Thoracic Society (ATS) statement defined experimental ALI as an acute process (ie, sequelae develop within 24 hours of exposure) with increased permeability of the alveolar-capillary membrane, frequently with histopathological correlation, leading to impairments in lung physiology.8 Building on these earlier proposals, Oakley and colleagues11 propose in this issue of Thorax two broad, fundamental changes in the philosophical framework for the investigation of novel therapeutics in preclinical ARDS models. The first fundamental change to the 2011 ATS definition proposed by Oakley et al 11 is that experimental animal models used to assess the clinical efficacy of proposed ARDS therapeutics should be clinically relevant. Specifically, the authors highlight three criteria to define an effective model based on the notion that the clinical conditions of animal models should reflect as best as possible the clinical conditions of human patients that would receive the experimental therapy. First, ARDS therapies should be tested in lungs with pre-existing injury …

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我们是否应该改变 ARDS 治疗的临床前模型范式？

急性呼吸窘迫综合征 (ARDS) 的特征是气体交换的弥漫性障碍，这可能是由异质性病因引起的。ARDS 导致全球 10% 的重症监护病房入院，住院死亡率从轻度病例的 35% 到重症病例的 46%。1 尽管是一个常见且经常致命的过程，但没有广泛接受的药物疗法可用于治疗 ARDS，其管理主要取决于适当的机械通气和支持性护理。2 不幸的是，许多在临床前模型或早期临床研究中证明有益的有希望的药物疗法未能证明临床结果的可靠改善。 3-7 在持续的背景下困扰最先进研究疗法的临床问题，Oakley 等人 11 提出的 2011 年 ATS 定义的第一个根本性变化是，用于评估提议的 ARDS 疗法的临床疗效的实验动物模型应该具有临床相关性。具体而言，作者强调了定义有效模型的三个标准，即基于动物模型的临床状况应尽可能最好地反映将接受实验治疗的人类患者的临床状况的概念。首先，应在已有损伤的肺中测试 ARDS 疗法…… 作者强调了定义有效模型的三个标准，其基础是动物模型的临床状况应尽可能最好地反映将接受实验治疗的人类患者的临床状况。首先，应在已有损伤的肺中测试 ARDS 疗法…… 作者强调了定义有效模型的三个标准，其基础是动物模型的临床状况应尽可能最好地反映将接受实验治疗的人类患者的临床状况。首先，应在已有损伤的肺中测试 ARDS 疗法……