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

Eugene H Chang; Nima Pouladi; Stefano Guerra; Jana Jandova; Alexander Kim; Haiquan Li; Jianrong Li; Wayne Morgan; Debra A Stern; Amanda L Willis; Yves A Lussier; Fernando D Martinez

doi:10.1016/j.jaci.2022.03.020

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

J Allergy Clin Immunol. 2022 Sep;150(3):604-611. doi: 10.1016/j.jaci.2022.03.020. Epub 2022 Mar 31.

Authors

Affiliations

¹ Department 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. Electronic address: echang@oto.arizona.edu.
² Department of Biomedical Informatics, the University of Utah School of Medicine, Salt Lake City, Utah.
³ College of Medicine, Tucson, Ariz; Asthma/Airway Disease Research Center, Tucson, Ariz; University of Arizona BIO5 Institute, University of Arizona, Tucson, Ariz.
⁴ Department of Otolaryngology, Tucson, Ariz.
⁵ University of Arizona BIO5 Institute, University of Arizona, Tucson, Ariz.

Abstract

Background: The study of pathogenic mechanisms in adult asthma is often marred by a lack of precise information about the natural history of the disease. Children who have persistent wheezing (PW) during the first 6 years of life and whose symptoms start before age 3 years (PW⁺) are much more likely to have wheezing illnesses due to rhinovirus (RV) in infancy and to have asthma into adult life than are those who do not have PW (PW^-).

Objective: Our aim was to determine whether nasal epithelial cells from PW⁺ asthmatic adults as compared with cells from PW^- asthmatic adults show distinct biomechanistic processes activated by RV exposure.

Methods: Air-liquid interface cultures derived from nasal epithelial cells of 36-year old participants with active asthma with and without a history of PW in childhood (10 PW⁺ participants and 20 PW^- participants) from the Tucson Children's Respiratory Study were challenged with a human RV-A strain (RV-A16) or control, and their RNA was sequenced.

Results: A total of 35 differentially expressed genes involved in extracellular remodeling and angiogenesis distinguished the PW⁺ group from the PW^- group at baseline and after RV-A stimulation. Notably, 22 transcriptomic pathways showed PW-by-RV interactions; the pathways were invariably overactivated in PW⁺ patients, and were involved in Toll-like receptor- and cytokine-mediated responses, remodeling, and angiogenic processes.

Conclusions: Asthmatic adults with a history of persistent wheeze in the first 6 years of life have specific biomolecular alterations in response to RV-A that are not present in patients without such a history. Targeting these mechanisms may slow the progression of asthma in these patients.

Keywords: Early-onset childhood asthma; RNA sequencing; Toll-like receptor pathways; airway remodeling; apoptosis; blood vessel remodeling; interleukin response; persistent wheeze; protein processing; rhinovirus; transcriptome.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Asthma* / diagnosis
Child
Child, Preschool
Enterovirus Infections*
Epithelial Cells
Humans
Phenotype
Picornaviridae Infections*
Respiratory Sounds
Rhinovirus / genetics

Abstract

Publication types

MeSH terms

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