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

Jonathan E Millar, Karin Wildi, Nicole Bartnikowski, Mahe Bouquet, Kieran Hyslop, Margaret R Passmore, Katrina K Ki, Louise E See Hoe, Nchafatso G Obonyo, Lucile Neyton, Sanne Pedersen, Sacha Rozencwajg, J Kenneth Baillie, Gianluigi Li Bassi, Jacky Y Suen, Daniel F McAuley, John F Fraser

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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.
Original languageEnglish
Article numbere15048
JournalPhysiological reports
Issue number19
Publication statusPublished - 07 Oct 2021


  • acute respiratory distress syndrome
  • phenotype
  • models
  • animal


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