From preclinical to clinical models of acute respiratory distress syndrome

Various preclinical models that mimic the clinical causes of acute respiratory distress syndrome (ARDS) have been used to better understand the mechanisms of acute lung injury and its repair and to investigate novel therapies targeting such mechanisms. Despite important preclinical and clinical research efforts in recent decades, few candidate therapies with promising preclinical effects have been successfully translated into the clinical scenario, which could be attributable to the intrinsic limitations of the models as well as to the incorrect identification of appropriate phenotypes of patients to target with novel therapies that have proven beneficial in select preclinical models. However, current translational research strategies based on the use of multiple complementary preclinical and clinical models hold the promise of revolutionizing intensive care by using granular knowledge that should allow for a better diagnosis, greater predictability of the disease course, and the development of targeted therapies while ensuring patient safety through reduced adverse effects. Our goal was to summarize the strengths and limitations of the available models of ARDS, including animal, in vitro, and clinical models, and to discuss the current challenges and perspectives for research.