Precision medicine in acute respiratory distress syndrome

Acute Respiratory Distress Syndrome (ARDS) is a severe form of respiratory failure that affects about 10% of intensive care unit patients worldwide and continues to have a high mortality rate. Despite decades of research, effective therapies remain limited, largely due to the biological and clinical heterogeneity within ARDS. This thesis explores ways to overcome this through subphenotyping, a precision medicine approach that identifies distinct and meaningful patient subgroups. The research focuses on three key mechanistic and clinically measurable domains: imaging, respiration, and inflammation. In the imaging domain, the thesis examines whether subgroups differing in lung recruitability can be identified, distinguishing between recruitable and non-recruitable subphenotypes with distinct physiological profiles. The prognostic value of radiographic edema scores in mechanically ventilated patients is also evaluated. In the respiratory domain, previously defined low-power and high-power subphenotypes were applied early in the disease course to assess their potential for guiding personalized ventilatory strategies and evaluating responses to immunomodulatory therapy. In the inflammatory domain, established Hypoinflammatory and Hyperinflammatory subphenotypes are examined in relation to responses to tocilizumab, an immunomodulatory drug. Additionally, the role of nucleosomes as biomarkers of immune activation and organ injury is explored. Together, this thesis demonstrates that clinically relevant ARDS subphenotypes can be identified using multivariate, longitudinal, and complex data. The findings provide exploratory evidence that these subphenotypes may help tailor interventions and improve patient outcomes. The next critical steps are prospective validation of these classifications and evaluation of targeted therapies in clinical trials to bring subphenotyping closer to routine clinical application.