Measuring and managing pulmonary edema in ARDS: a narrative review

Despite significant advancements in the understanding of pulmonary vascular permeability and the preclinical development of compounds targeting pulmonary vascular permeability, their translation into clinical therapies for acute respiratory distress syndrome (ARDS) has remained unsuccessful. Among others, this translational gap can be attributed to limitations in measuring pulmonary vascular permeability in the clinical setting. This review aims to evaluate current and near-future modalities for quantifying pulmonary edema and their potential application in research settings. We first outline the definition of ARDS and the pathophysiology of pulmonary edema, focusing on pulmonary vascular mechanisms and therapeutic targets to reducing vascular leakage. Next, we examine techniques for assessing pulmonary edema, including gravimetry (the preclinical gold standard), transpulmonary thermodilution (the clinical gold standard), as well as newer modalities such as lung ultrasound and chest CT. Finally, we discuss how pulmonary edema measurements may serve as meaningful endpoints in early-phase clinical trials. The use of pulmonary edema as a primary endpoint in clinical trials may carry significant advantages, including more direct parameters for translation of pre-clinical studies on vascular leakage into clinical application, and possibly a higher success rate for transition to large phase III trials. Amidst the era of personalized medicine, the quantification of pulmonary edema holds promise in guiding clinical pharmacological trials for ARDS.