Precision Medicine in Critical Illness: Sepsis and Acute Respiratory Distress Syndrome

Abstract

Sepsis and the acute respiratory distress syndrome (ARDS) each cause substantial morbidity and mortality. In contrast to other lung diseases, the entire course of disease in these syndromes is measured in days to weeks rather than months to years, which raises unique challenges in achieving precision medicine. We review advances in sepsis and ARDS resulting from omics studies, including those involving genome-wide association, gene expression, targeted proteomics, and metabolomics approaches. We focus on promising evidence of biological subtypes in both sepsis and ARDS that consistently display high risk for death. In sepsis, a gene expression signature with dysregulated adaptive immune signaling has evidence for a differential response to systemic steroid therapy, whereas in ARDS, a hyperinflammatory pattern identified in plasma using targeted proteomics responded more favorably to randomized interventions including high positive end-expiratory pressure, volume conservative fluid therapy, and simvastatin therapy. These early examples suggest heterogeneous biology that may be challenging to detect by clinical factors alone and speak to the promise of a precision approach that targets the right treatment at the right time to the right patient.