Characterizing preclinical sub‐phenotypic models of acute respiratory distress syndrome: An experimental ovine study

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Millar, Jonathan | Wildi, Karin | Bartnikowski, Nicole | Bouquet, Mahe | Hyslop, Kieran | Passmore, Margaret | Ki, Katrina | See Hoe, Louise | Obonyo, Nchafatso | Neyton, Lucile | Pedersen, Sanne | Rozencwajg, Sacha | Baillie, J. Kenneth | Li Bassi, Gianluigi | Suen, Jacky | Mcauley, Daniel | Fraser, John

Edité par CCSD ; Wiley -

International audience. The acute respiratory distress syndrome (ARDS) describes a heterogenous population of patients with acute severe respiratory failure. However, contemporary advances have begun to identify distinct sub-phenotypes that exist within its broader envelope. These sub-phenotypes have varied outcomes and respond differently to several previously studied interventions. A more precise understanding of their pathobiology and an ability to prospectively identify them, may allow for the development of precision therapies in ARDS. Historically, animal models have played a key role in translational research, although few studies have so far assessed either the ability of animal models to replicate these sub-phenotypes or investigated the presence of sub-phenotypes within animal models. Here, in three ovine models of ARDS, using combinations of oleic acid and intravenous, or intratracheal lipopolysaccharide, we investigated the presence of sub-phenotypes which qualitatively resemble those found in clinical cohorts. Principal Component Analysis and partitional clustering identified two clusters, differentiated by markers of shock, inflammation, and lung injury. This study provides a first exploration of ARDS phenotypes in preclinical models and suggests a methodology for investigating this phenomenon in future studies.

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