Methylomic Analysis of Nasal Brushings Reveals Two Subgroups in Pediatric Acute Respiratory Distress Syndrome

Pediatric acute respiratory distress syndrome (PARDS) is a significant cause of mortality in the pediatric intensive care unit (PICU), and supportive care remains the mainstay of treatment. The biological heterogeneity of PARDS hampers the development of new therapies. One source of heterogeneity is the epigenetic regulation of gene expression via methylation. We hypothesized that PARDS patients could be classified into at least two subgroups defined by differential methylation of immune-related genes. We conducted a prospective, single-center cohort study of PARDS and control patients under 18 years of age admitted to the PICU. Nasal brushings were obtained on day 1 for methylomic analysis, and clinical information and outcomes were recorded until discharge. We identified two groups of PARDS subjects using PCA and hierarchical clustering, which were defined by the differential methylation of promoters and bodies of genes involved in immune, repair, and regeneration processes. One group trended toward worse clinical outcomes. The other group had a methylation pattern very similar to control subjects. PARDS patients can be divided into two subgroups based on patterns of differential methylation around genes involved in immune, repair, and regeneration processes. These findings, if confirmed, could represent potential targets for future therapies.