Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy

作者：Katie R. Famous, Kevin Delucchi, Lorraine B. Ware, Kirsten N. Kangelaris, Kathleen D. Liu, Bruce Thompson, Carolyn S. Calfee · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2016 · DOI：10.1164/rccm.201603-0645oc · 被引用次数：865 · 研究领域：Respiratory Support and Mechanisms、Sepsis Diagnosis and Treatment、Hemodynamic Monitoring and Therapy

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 RESULTS: We confirmed that a two-class (two-subphenotype) model best described the study population. Subphenotype 2 was again characterized by higher inflammatory biomarkers and hypotension. Fluid management strategy had significantly different effects on 90-day mortality in the two subphenotypes (P = 0.0039 for interaction); mortality in subphenotype 1 was 26% with fluid-liberal strategy versus 18% with fluid-conservative, whereas mortality in subphenotype 2 was 40% with fluid-liberal strategy versus 50% in fluid-conservative. A three-variable model of IL-8, bicarbonate, and tumor necros...