Divide and conquer:identifying acute respiratory distress syndrome subphenotypes

The acute respiratory distress syndrome (ARDS) definition identifies patients with acute onset hypoxaemia and respiratory failure, who have bilateral opacities on chest radiograph that are not fully explained by cardiac failure or fluid overload.1 ARDS is a common illness that accounts for approximately 10% of critical care admissions and 20% of patients requiring mechanical ventilation.2 The hospital mortality in patients with ARDS remains high, increasing from approximately 35% for those with mild disease to 46% for those with severe ARDS.2 This high mortality has remained relatively unchanged in the last 20 years.3 To date, despite decades of research, there is no pharmacological treatment that can modify the underlying biological mechanisms implicated in ARDS and improve patient outcomes.4 Within ARDS populations, there is substantial biological and outcome heterogeneity, with observed differences in dominant pathogenic mechanisms, treatment responses and outcomes.5–7 Identifying ARDS subphenotypes based on pathogenic mechanisms that determine treatment responses irrespective of ARDS severity is defined as predictive enrichment.7 8 The identification of such ARDS subphenotypes will enable improved trial design in ARDS by selecting patients based on responder characteristics to therapeutic interventions, hopefully resulting in improved outcomes.6 In Thorax, Bos et al report a cohort study in 700 ARDS patients, testing the hypothesis that ARDS subgroups exist due to differences in biological characteristics.9 In this retrospective analysis of a prospectively collected cohort, 20 biomarkers were