Airway Transcriptome Networks Identify Susceptibility to Frequent Asthma Exacerbations in Children.

BACKGROUND: Frequent asthma exacerbators, defined as those experiencing >1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children.

OBJECTIVE: To determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency.

METHODS: We performed RNA-sequencing of upper airway cells from both frequent and non-frequent exacerbators enrolled in the Ohio Pediatric Asthma Repository.

RESULTS: Through molecular network analysis, we found non-frequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth.

CONCLUSION: These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.