Research Horizons


Airway Remodeling Creates Susceptibility to Frequent Asthma Exacerbations in Children

Asthma Research | Top Scientific Achievement
2023 Research Discoveries Graphic abstract describes how researchers at Cincinnati Children’s used RNA sequencing to show that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling.

Asthma is a common allergic respiratory disease found in both children and adults. Yet the mechanisms underlying asthma pathogenesis and exacerbation frequency have been understudied, despite the high healthcare costs and morbidity rates associated with frequent asthma exacerbators in both populations.

In a study led by first author Kieran Phelan and senior author Gurjit “Neeru” Khurana Hershey, MD, PhD, researchers for the first time implicated the nervous system as having a role in recurrent exacerbation pathology in children with asthma. They also highlighted frequent asthma exacerbators—patients hospitalized two or more times in a year for a severe asthma event—as a biologically distinct endotype in children.

For the study, researchers studied biospecimens, including nasal epithelial cells and blood, and health outcomes data collected by the Ohio Pediatric Asthma Repository from 132 pediatric asthma exacerbators—both frequent and non-frequent—who were treated at one of Ohio’s major children’s hospitals, including those in Cincinnati, Cleveland, Columbus and Dayton. Their goal was to identify the clinical and molecular features specific to children prone to recurrent severe asthma exacerbations, also known as frequent exacerbators (FEs).

Among their findings, researchers discovered that FEs displayed a unique increase in gene signatures associated with nervous system processes, while the airways of non-FEs were characterized by the expression of allergic inflammation previously known to be involved in asthma.

The study’s results suggest that more frequent asthma exacerbations don’t lead to more severe exacerbations. Instead, repeated exacerbations result in neuronal airway remodeling that prime it to react the same way it has in the past.

“Our findings highlight fundamental differences in these exacerbations and suggest that therapy targeting neuronal pathways may be necessary to adequately prevent and/or treat frequent exacerbations,” Khurana Hershey says.

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Publication Information
Original title: Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children
Published in: The Journal of Allergy & Clinical Immunology
Publish date: Mar 12, 2023
Read the study

Research By

Kieran Phelan, MD
Kieran Phelan, MD
University of Cincinnati College of Medicine
Gurjit Khurana Hershey, MD, PhD
Gurjit Khurana Hershey, MD, PhD
Director, Division of Asthma Research

My lab combines epidemiologic, basic, translational and clinical research approaches to answer fundamental questions related to childhood asthma, atopic dermatitis, food allergy and allergic rhinitis.