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

## TL;DR

This study identifies two distinct subgroups of pediatric acute respiratory distress syndrome based on methylation patterns in nasal brushings, which may help guide future treatments.

## Contribution

The study demonstrates that PARDS patients can be classified into two subgroups based on methylation patterns of immune-related genes.

## Key findings

- Two PARDS subgroups were identified through differential methylation of genes related to immune, repair, and regeneration processes.
- One subgroup showed a methylation pattern similar to controls, while the other had worse clinical outcomes.
- These methylation patterns could represent potential therapeutic targets if validated further.

## Abstract

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.