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

被引：14

作者：

Millar, Jonathan E. ^{[1
,2
,3
]}

Wildi, Karin ^{[1
,2
,4
]}

Bartnikowski, Nicole ^{[1
,5
]}

Bouquet, Mahe ^{[1
,2
]}

Hyslop, Kieran ^{[1
,2
]}

Passmore, Margaret R. ^{[1
,2
]}

Ki, Katrina K. ^{[1
,2
]}

Hoe, Louise E. See ^{[1
,2
]}

Obonyo, Nchafatso G. ^{[1
,6
]}

Neyton, Lucile ^{[3
]}

Pedersen, Sanne ^{[1
]}

Rozencwajg, Sacha ^{[1
,7
]}

Baillie, J. Kenneth ^{[3
]}

Bassi, Gianluigi Li ^{[1
,2
]}

Suen, Jacky Y. ^{[1
,2
]}

McAuley, Daniel F. ^{[8
]}

Fraser, John F. ^{[1
,2
]}

机构：

[1] Prince Charles Hosp, Crit Care Res Grp, Brisbane, Qld, Australia

[2] Univ Queensland, Fac Med, Brisbane, Qld, Australia

[3] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland

[4] Cardiovasc Res Inst Basel, Basel, Switzerland

[5] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia

[6] Imperial Coll London, Wellcome Trust Ctr Global Hlth Res, London, England

[7] Sorbonne Univ, UPMC Univ Paris 06, INSERM,Med ICU,Pitie Salpetriere Univ Hosp, UMRS 1166,ICAN Inst Cardiometab & Nutr, Paris, France

[8] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland

来源：

PHYSIOLOGICAL REPORTS | 2021年 / 9卷 / 19期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

acute respiratory distress syndrome; animal; models; phenotype; ANIMAL-MODELS; SUBPHENOTYPES; VALIDATION; LUNG;

D O I：

10.14814/phy2.15048

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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.

引用

页数：11