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

James G Williams1,2, Akhilesh Kaushal1,2, Nirmeen Elmadany1,2

  • 1Division of Critical Care Medicine and Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Research Square
|February 6, 2026
PubMed

Insights

Pediatric acute respiratory distress syndrome (PARDS) patients can be divided into two epigenetic subgroups based on gene methylation patterns. This discovery may lead to new targeted therapies for this critical pediatric intensive care unit (PICU) condition.

Area of Science:

  • Epigenetics
  • Pediatric Critical Care Medicine
  • Immunology

Background:

  • Pediatric acute respiratory distress syndrome (PARDS) is a leading cause of mortality in pediatric intensive care units (PICUs).
  • The biological heterogeneity of PARDS presents a challenge for developing effective treatments.
  • Epigenetic modifications, specifically DNA methylation, are implicated in gene expression regulation and disease variability.

Purpose of the Study:

  • To investigate whether differential methylation patterns can classify pediatric acute respiratory distress syndrome (PARDS) patients into distinct subgroups.
  • To explore the relationship between methylation profiles and clinical outcomes in pediatric patients with PARDS.

Main Methods:

  • A prospective, single-center cohort study involving pediatric patients with PARDS and control subjects under 18 years of age.
  • Methylomic analysis of nasal brushings collected on day 1 of intensive care unit admission.
  • Application of Principal Component Analysis (PCA) and hierarchical clustering to identify patient subgroups based on methylation patterns.

Main Results:

  • Two distinct subgroups of PARDS patients were identified based on differential methylation patterns.
  • These subgroups were characterized by variations in the methylation of genes involved in immune, repair, and regeneration processes.
  • One identified subgroup showed a trend toward worse clinical outcomes compared to the other, which exhibited methylation patterns similar to control subjects.

Conclusions:

  • Pediatric acute respiratory distress syndrome (PARDS) patients can be stratified into at least two subgroups defined by differential gene methylation.
  • These methylation patterns are associated with genes critical for immune function, tissue repair, and regeneration.
  • The identified subgroups and their associated methylation profiles may offer potential targets for future therapeutic interventions in PARDS.

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