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. 2020 Apr 7;21(1):81.
doi: 10.1186/s12931-020-01337-9.

Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis

Adrien Carla  1 , Bruno Pereira  2 , Hanifa Boukail  1 , Jules Audard  1   3 , Nathalie Pinol-Domenech  4 , Manuela De Carvalho  4 , Raiko Blondonnet  1   3 , Ruoyang Zhai  3 , Dominique Morand  1 , Céline Lambert  2 , Vincent Sapin  3   5 , Lorraine B Ware  6   7 , Carolyn S Calfee  8 , Julie A Bastarache  6   7   9 , John G Laffey  10   11 , Nicole P Juffermans  12 , Lieuwe D Bos  12 , Antonio Artigas  13 , Patricia R M Rocco  14 , Michael A Matthay  8 , Daniel F McAuley  15 , Jean-Michel Constantin  16 , Matthieu Jabaudon  17   18   19 ; ESICM Translational Biology Group of the Acute Respiratory Failure section
Affiliations

Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis

Adrien Carla et al. Respir Res. .

Abstract

Background: Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits.

Methods: We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects.

Discussion: This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation.

Systematic review registration: PROSPERO (ID: CRD42019157236).

Keywords: Acute respiratory distress syndrome; Preclinical; Subphenotypes; Systematic review protocol.

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Conflict of interest statement

The authors declare that they have no competing interests.

References

    1. Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;377:562–572. - PubMed
    1. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800. - PubMed
    1. Definition Task Force ARDS, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND. Caldwell E, et al. acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–2533. - PubMed
    1. Prescott HC, Calfee CS, Thompson BT, Angus DC, Liu VX. Toward smarter lumping and smarter splitting: rethinking strategies for Sepsis and acute respiratory distress syndrome clinical trial design. Am J Respir Crit Care Med. 2016;194:147–155. - PMC - PubMed
    1. Seymour CW, Kennedy JN, Wang S, Chang C-CH, Elliott CF, Xu Z, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. JAMA. 2019;321(20):2003–2017. - PMC - PubMed

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