Research in context
Evidence before this study
Previous studies of patients with acute respiratory distress syndrome (ARDS), using data from US-based randomised controlled trials, have identified two distinct subphenotypes with differential responses to mechanical ventilation and fluid therapy. Whether these subphenotypes can be identified in non-US patient populations by use of different datasets and, more importantly, whether these subphenotypes respond differently to pharmacotherapies is unknown. We searched PubMed for any study reporting differential responses to pharmacotherapy by ARDS subphenotype published from database inception to March 7, 2018, using the terms (“ARDS” or “acute lung injury”) AND (subtype OR subphenotype OR endotype) and no language restrictions. We identified no previous studies.
Added value of this study
Our study reports the identification of two distinct ARDS subphenotypes in a secondary analysis of a UK-based randomised controlled trial of simvastatin for ARDS treatment. The hyperinflammatory subphenotype of ARDS had a survival benefit from simvastatin. To our knowledge, our study is the first to report a differential response to pharmacotherapy by molecular subphenotype in ARDS.
Implications of all the available evidence
Although other areas of medicine (eg, cancer and asthma) have made substantial progress through identification of biologically distinct subtypes of disease with differential treatment responses, critical care medicine has lagged behind. Our findings suggest that targeting specific biological subtypes of critical illness syndromes in clinical trials might yield progress after decades of negative pharmacotherapy trials in the intensive care unit.