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Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults

Eugene H Chang1, Nima Pouladi2, Stefano Guerra3

  • 1Department of Otolaryngology, Tucson, Ariz; College of Medicine, Tucson, Ariz; Asthma/Airway Disease Research Center, Tucson, Ariz; University of Arizona BIO5 Institute, University of Arizona, Tucson, Ariz.

The Journal of Allergy and Clinical Immunology
|April 3, 2022
PubMed

Insights

Adult asthmatics with childhood persistent wheeze (PW+) show distinct rhinovirus (RV) responses. These RV-A-activated pathways in PW+ individuals suggest targeted therapies to slow asthma progression.

Area of Science:

  • Immunology
  • Respiratory Medicine
  • Genomics

Background:

  • Adult asthma pathogenesis is unclear due to limited natural history data.
  • Children with early-onset persistent wheeze (PW+) are more prone to rhinovirus (RV) infections and adult asthma.

Purpose of the Study:

  • To investigate distinct biomechanistic processes in nasal epithelial cells of adult asthmatics with (PW+) versus without (PW-) a history of childhood persistent wheeze upon RV exposure.

Main Methods:

  • Nasal epithelial cells from adult asthmatics (10 PW+, 20 PW-) were cultured at air-liquid interface.
  • Cells were challenged with rhinovirus-A (RV-A16) or control, followed by RNA sequencing.

Main Results:

  • 35 differentially expressed genes in extracellular remodeling and angiogenesis distinguished PW+ from PW- groups.
  • 22 transcriptomic pathways showed PW-by-RV interactions, predominantly overactivated in PW+ patients.
  • These pathways involved Toll-like receptor, cytokine responses, remodeling, and angiogenesis.

Conclusions:

  • Adult asthmatics with a history of early-life persistent wheeze exhibit unique biomolecular responses to RV-A.
  • Targeting these specific RV-A-induced mechanisms may offer a strategy to mitigate asthma progression in this patient group.
Abstract

Keywords:
Early-onset childhood asthmaRNA sequencingToll-like receptor pathwaysairway remodelingapoptosisblood vessel remodelinginterleukin responsepersistent wheezeprotein processingrhinovirustranscriptome

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