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Phenotypes in acute respiratory distress syndrome

moving towards precision medicine

Sinha, Pratika,b; Calfee, Carolyn S.a,b,c

Current Opinion in Critical Care: February 2019 - Volume 25 - Issue 1 - p 12–20
doi: 10.1097/MCC.0000000000000571
RESPIRATORY SYSTEM: Edited by Laurent J. Brochard and Tài Pham

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.

aDivision of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine

bDepartment of Anesthesia

cCardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA

Correspondence to Dr Pratik Sinha, MB ChB, PhD, FRCEM, FFICM, 505 Parnassus Avenue, Box 0111, San Francisco, CA 94143-0111, USA. Tel: +1 415 476 5756; e-mail:

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