Targeted treatment of acute respiratory distress syndrome with statins—a commentary on two phenotype stratified re-analysis of randomized controlled trials

No immunomodulatory pharmacological interventions have been found effective for the acute respiratory distress syndrome (ARDS) despite identification of potentially effective drugs in preclinical studies (1,2). A frequently mentioned reason is the clinical and biological heterogeneity of ARDS (2). In attempts to quantify this heterogeneity, etiological, physiological-, and biological phenotypes have been explored (2-4). A classification based on a physiological phenotype by PaO2/FiO2 ratio, is included in the Berlin definition as ‘oxygenation criterion’ and discriminates between mild, moderate and severe ARDS (2). Recently, two biological phenotypes have been identified: ‘hyper-inflammatory’ and ‘hypo-inflammatory’, depending on levels of; pro-inflammatory markers, coagulopathy, severe shock, and metabolic derangement (4). These two biological phenotypes, also called “subphenotypes”, have different outcomes with a high mortality in the ‘hyper-inflammatory’ phenotype and a low mortality in the ‘hypo-inflammatory’ phenotype. Furthermore, the biological phenotypes show a differential treatment responses to PEEP-strategies and fluid management (4,5). There is no data on a differential response to immunomodulatory treatments