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Review
. 2019 Feb;25(1):12-20.
doi: 10.1097/MCC.0000000000000571.

Phenotypes in acute respiratory distress syndrome: moving towards precision medicine

Pratik Sinha  1   2 , Carolyn S Calfee  1   2   3
Affiliations
Review

Phenotypes in acute respiratory distress syndrome: moving towards precision medicine

Pratik Sinha et al. Curr Opin Crit Care. 2019 Feb.

Abstract

Purpose of review: To provide an overview of the current research in identifying homogeneous subgroups and phenotypes in ARDS.

Recent findings: In recent years, investigations have used either physiology, clinical data, biomarkers or a combination of these to stratify patients with ARDS into distinct subgroups with divergent clinical outcomes. In some studies, there has also been evidence of differential treatment response within subgroups. Physiologic approaches include stratification based on P/F ratio and ventilatory parameters; stratification based on P/F ratio is already being employed in clinical trials. Clinical approaches include stratification based on ARDS risk factor or direct vs. indirect ARDS. Combined clinical and biological data has been used to identify two phenotypes across five cohorts of ARDS, termed hyperinflammatory and hypoinflammatory. These phenotypes have widely divergent clinical outcomes and differential response to mechanical ventilation, fluid therapy, and simvastatin in secondary analysis of completed trials. Next steps in the field include prospective validation of inflammatory phenotypes and integration of high-dimensional 'omics' data into our understanding of ARDS heterogeneity.

Summary: Identification of distinct subgroups or phenotypes in ARDS may impact future conduct of clinical trials and can enhance our understanding of the disorder, with potential future clinical implications.

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Figures

Figure 1.
Figure 1.
Standardized values for continuous class-predicting variables in FACTT. The variables are sorted from left to right in descending order for the difference in values between the hypo-inflammatory subphenotype (1) and hyper-inflammatory subphenotype (2). Values were standardized using z-scale. BMI = body mass index, ICAM-1 = intercellular adhesion molecule-1, PAI-1 plasminogen activator inhibitor-1, PEEP positive end-expiratory pressure, TNFr1 = tumor necrosis factor receptor-1, SPD = Surfactant protein D, RAGE = receptor for advanced glycation end-products, Min Vent = minute ventilation. This figure has been previously published (Famous et al, Am J Respir Crit Care Med. 2017;195(3):331–8).[50]
Figure 2.
Figure 2.
90-day survival in patients in the HARP-2 trial. Patients were stratified by subphenotype and randomized treatment groups (simvastatin vs placebo). Simvastatin was associated with significantly higher survival rates than placebo (p=0.03). This figure has been previously published (Calfee et al Lancet Respir Med. 2018;6(9):691–8).[51]
See this image and copyright information in PMC

References

    1. Force ADT, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33. - PubMed
    1. Matthay MA, McAuley DF, Ware LB. Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Lancet Respir Med. 2017;5(6):524–34. - PubMed
    1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818–24. - PubMed
    1. Acute Respiratory Distress Syndrome N, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–8. - PubMed
    1. National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564–75. - PubMed

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