• Crit Care · Nov 2023

    Multicenter Study Observational Study

    Subphenotypes in patients with acute respiratory distress syndrome treated with high-flow oxygen.

    • Pierre-Louis Blot, Benjamin G Chousterman, Manel Santafè, Jérôme Cartailler, Andrés Pacheco, Mònica Magret, Joan R Masclans, Antoni Artigas, Oriol Roca, and Marina García-de-Acilu.
    • Département d'anesthésie-Réanimation, Hôpital Lariboisière, Paris, France.
    • Crit Care. 2023 Nov 1; 27 (1): 419419.

    BackgroundAcute respiratory distress syndrome (ARDS) subphenotypes differ in outcomes and treatment responses. Subphenotypes in high-flow nasal oxygen (HFNO)-treated ARDS patients have not been investigated.ObjectivesTo identify biological subphenotypes in HFNO-treated ARDS patients.MethodsSecondary analysis of a prospective multicenter observational study including ARDS patients supported with HFNO. Plasma inflammation markers (interleukin [IL]-6, IL-8, and IL-33 and soluble suppression of tumorigenicity-2 [sST2]) and lung epithelial (receptor for advanced glycation end products [RAGE] and surfactant protein D [SP-D]) and endothelial (angiopoietin-2 [Ang-2]) injury were measured. These biomarkers and bicarbonate were used in K-means cluster analysis to identify subphenotypes. Logistic regression was performed on biomarker combinations to predict clustering. We chose the model with the best AUROC and the lowest number of variables. This model was used to describe the HAIS (High-flow ARDS Inflammatory Subphenotype) score.ResultsAmong 41 HFNO patients, two subphenotypes were identified. Hyperinflammatory subphenotype (n = 17) showed higher biomarker levels than hypoinflammatory (n = 24). Despite similar baseline characteristics, the hyperinflammatory subphenotype had higher 60-day mortality (47 vs 8.3% p = 0.014) and longer ICU length of stay (22.0 days [18.0-30.0] vs 39.5 [25.5-60.0], p = 0.034). The HAIS score, based on IL-8 and sST2, accurately distinguished subphenotypes (AUROC 0.96 [95%CI: 0.90-1.00]). A HAIS score ≥ 7.45 was predictor of hyperinflammatory subphenotype.ConclusionARDS patients treated with HFNO exhibit two biological subphenotypes that have similar clinical characteristics, but hyperinflammatory patients have worse outcomes. The HAIS score may identify patients with hyperinflammatory subphenotype and might be used for enrichment strategies in future clinical trials.© 2023. The Author(s).

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