Characterizing preclinical sub-phenotypic models of acute respiratory distress syndrome: An experimental ovine study
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Wildi, K
Bartnikowski, N
Bouquet, M
Hyslop, K
Passmore, MR
Ki, KK
See Hoe, LE
Obonyo, NG
Neyton, L
Pedersen, S
Rozencwajg, S
Baillie, JK
Li Bassi, G
Fraser, John F.
et al.
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Abstract
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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Physiological Reports
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9
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19
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© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Clinical sciences
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Millar, JE; Wildi, K; Bartnikowski, N; Bouquet, M; Hyslop, K; Passmore, MR; Ki, KK; See Hoe, LE; Obonyo, NG; Neyton, L; Pedersen, S; Rozencwajg, S; Baillie, JK; Li Bassi, G; Fraser, JF; et al., Characterizing preclinical sub-phenotypic models of acute respiratory distress syndrome: An experimental ovine study, Physiological Reports, 2021, 9 (19), pp. e15048