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Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children

Kieran J Phelan1, Kimberly A Dill-McFarland2, Arjun Kothari3

  • 1Divison of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio.

The Journal of Allergy and Clinical Immunology
|March 14, 2023
PubMed

Insights

Frequent asthma exacerbations in children are linked to nervous system changes. This study reveals peripheral nervous system remodeling in the upper airway of frequent exacerbators, offering new insights into pediatric asthma.

Area of Science:

  • Pediatric Pulmonology
  • Molecular Biology
  • Asthma Pathogenesis

Background:

  • Frequent asthma exacerbators are understudied in children.
  • Defining this subgroup is crucial for targeted therapies.
  • Asthma exacerbations significantly impact quality of life.

Purpose of the Study:

  • To elucidate molecular mechanisms of asthma pathogenesis.
  • To understand factors contributing to exacerbation frequency.
  • To identify distinct molecular profiles of frequent vs. nonfrequent exacerbators.

Main Methods:

  • RNA sequencing of upper airway cells.
  • Analysis of pediatric asthma patients from the Ohio Pediatric Asthma Repository.
  • Molecular network analysis to identify enriched biological processes.

Main Results:

  • Nonfrequent exacerbators showed immune system enrichment (Type 2 inflammation, response to infection).
  • Frequent exacerbators exhibited enrichment in nervous system processes (synaptic formation, axonal outgrowth).
  • Distinct molecular signatures differentiate exacerbator phenotypes.

Conclusions:

  • Frequent pediatric asthma exacerbators exhibit peripheral nervous system remodeling in the upper airway.
  • This remodeling represents a novel mechanism contributing to asthma exacerbations.
  • Findings suggest a potential new therapeutic target for severe pediatric asthma.
Abstract

Keywords:
Asthmaexacerbationfrequent exacerbatorneuronalpediatrictranscriptomics

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