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Rationale: We previously identified two acute respiratory distress syndrome (ARDS) subphenotypes in two separate randomized controlled trials with differential response to positive end-expiratory pressure.

Objectives: To identify these subphenotypes in a third ARDS cohort, to test whether subphenotypes respond differently to fluid management strategy, and to develop a practical model for subphenotype identification.

Methods: We used latent class analysis of baseline clinical and plasma biomarker data to identify subphenotypes in FACTT (Fluid and Catheter Treatment Trial; n = 1,000). Logistic regression was used to test for an interaction between subphenotype and treatment for mortality. We used stepwise modeling to generate a model for subphenotype identification in FACTT and validated its accuracy in the two cohorts in which we previously identified ARDS subphenotypes.

Measurements and Main …