Intensive Care MedIntensive Care MedIntensive Care MedClinically, the Berlin ARDS definition describes acute respiratory distress syndrome (ARDS) as acute hypoxaemic respiratory failure that is not fully explained by cardiac failure or fluid overload, that develops within 7 days of clinical recognition of a known risk factor, with bilateral radiographic opacities that are not fully explained by effusions, lobar/lung collapse, or nodules. Three risk strata were defined on the basis of the severity of hypoxaemia represented by the ratio of partial pressure of oxygen in arterial blood to inspired oxygen concentration (PaO2/FiO2 ratio), assessed at a minimum positive end-expiratory pressure (PEEP) of 5 cmH2O [1]. Hospital mortality worsens with severity of hypoxaemia and thus grade of ARDS (from 35% in mild ARDS to 46% in severe ARDS)[1, 2].

The ARDS consensus definitions to date have mainly relied on feasible clinical criteria, which helps to group patients together for inclusion in clinical trials and for clinical management [1, 3]. This generates clinical and biological differences in observable patient characteristics. These differences are associated with inter-individual variation in the risk of illness, risk of outcomes from the illness, response to treatments administered for the illness and combinations thereof (referred to as heterogeneity)[4, 5]. For example, pneumonia is a common risk factor for ARDS [2, 3, 6]. However, not every patient admitted with pneumonia develops ARDS. One possible explanation is that there are differences in host responses between patients, as observed by variation in biomarker profiles for the same risk factor [7]. Amongst patients