Potential Impact of Subphenotyping in Pharmacologic Management of Acute Respiratory Distress Syndrome

Abstract

Background: Acute respiratory distress syndrome (ARDS) is an acute inflammatory process in the lungs associated with high morbidity and mortality. Previous research has studied both nonpharmacologic and pharmacologic interventions aimed at targeting this inflammatory process and improving ventilation. Hypothesis: To date, only nonpharmacologic interventions including lung protective ventilation, prone positioning, and high positive end-expiratory pressure ventilation strategies have resulted in significant improvements in patient outcomes. Given the high mortality associated with ARDS despite these advancements, interest in subphenotyping has grown, aiming to improve diagnosis and develop personalized treatment approaches. Data Collection: Previous trials evaluating pharmacologic therapies in heterogeneous populations have primarily demonstrated no positive effect, but hope to show benefit when targeting specific subphenotypes, thus increasing their efficacy, while simultaneously decreasing adverse effects. Results: Although most studies evaluating pharmacologic therapies for ARDS have not demonstrated a mortality benefit, there is limited data evaluating pharmacologic therapies in ARDS subphenotypes, which have found promising results. Neuromuscular blocking agents, corticosteroids, and simvastatin have resulted in a mortality benefit when used in patients with the hyper-inflammatory ARDS subphenotype. Therapeutic Opinion: The use of subphenotyping could revolutionize the way ARDS therapies are applied and therefore improve outcomes while also limiting the adverse effects associated with their ineffective use. Future studies should evaluate ARDS subphenotypes and their response to pharmacologic intervention to advance this area of precision medicine.