Phenotypes in acute respiratory distress syndrome: moving towards precision medicine

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

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.

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.