Department of Anesthesia, University of California San Francisco, San Francisco, CA, USA.
Cardiovascular Research Institute, University of California, San Francisco, USA.
Intensive Care Med. 2020 Dec;46(12):2136-2152. doi: 10.1007/s00134-020-06296-9. Epub 2020 Nov 18.
Although the acute respiratory distress syndrome (ARDS) is well defined by the development of acute hypoxemia, bilateral infiltrates and non-cardiogenic pulmonary edema, ARDS is heterogeneous in terms of clinical risk factors, physiology of lung injury, microbiology, and biology, potentially explaining why pharmacologic therapies have been mostly unsuccessful in treating ARDS. Identifying phenotypes of ARDS and integrating this information into patient selection for clinical trials may increase the chance for efficacy with new treatments. In this review, we focus on classifying ARDS by the associated clinical disorders, physiological data, and radiographic imaging. We consider biologic phenotypes, including plasma protein biomarkers, gene expression, and common causative microbiologic pathogens. We will also discuss the issue of focusing clinical trials on the patient's phase of lung injury, including prevention, administration of therapy during early acute lung injury, and treatment of established ARDS. A more in depth understanding of the interplay of these variables in ARDS should provide more success in designing and conducting clinical trials and achieving the goal of personalized medicine.
虽然急性呼吸窘迫综合征(ARDS)的定义明确为急性低氧血症、双侧浸润和非心源性肺水肿的发展,但在临床危险因素、肺损伤生理学、微生物学和生物学方面,ARDS 具有异质性,这可能解释了为什么药物治疗在治疗 ARDS 方面大多不成功。通过识别 ARDS 的表型并将这些信息整合到临床试验患者选择中,可以增加新治疗方法的疗效机会。在这篇综述中,我们专注于通过相关临床疾病、生理数据和影像学来对 ARDS 进行分类。我们考虑了生物学表型,包括血浆蛋白生物标志物、基因表达和常见的因果微生物病原体。我们还将讨论将临床试验集中在患者肺损伤阶段的问题,包括预防、早期急性肺损伤期间的治疗以及已建立的 ARDS 的治疗。更深入地了解 ARDS 中这些变量的相互作用,应该能够在设计和进行临床试验以及实现个体化医疗目标方面取得更大的成功。