Cookie Notice

This site uses cookies. By continuing to browse this site, you are agreeing to our use of cookies. Review our cookies information for more details.

OK
skip to main content

Nasal transcriptomics characterize an early-onset asthma subtype after rhinovirus infections

Published: March 31, 2022

Persistent wheezing in early life is highly associated with rhinovirus (RV) infections and represents a significant risk factor for the development of early-onset asthma. We hypothesized that adult patients who had persistent wheezing in early life would have a specific altered molecular response to RV infections that might elucidate mechanisms of disease.
 
In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Chang et al. tested this hypothesis in a study of adult asthmatics enrolled in the Tucson Children’s Respiratory Study. Subjects were divided into those with a history of persistent wheeze in childhood, defined as having wheezing episodes during the first three years of life and are still having such episodes at age 6 years (PW+), and those that did not have persistent wheeze (PW-). All subjects had a physician-diagnosis of asthma by age 36 years and reported asthma symptoms or episodes at least once between the ages of 22 and 36 years. Nasal biopsies from each subject were obtained and in vitro air-liquid-interface (ALI) cultures developed. A human strain of RV-A16 was used to challenge these differentiated cultures and compare with mock control. RNA was extracted and gene ontology analyses were compared between PW+ and PW- asthmatics at baseline and after RV-A infection.
 
At baseline, PW+ cultures showed increased expression of gene ontology pathways relevant to airway remodeling. After RV-A infection, PW+ cultures expressed upregulation of both excessive inflammatory responses to RV and overactive airway remodeling mechanisms.
 
This study suggests that specific airway epithelial responses both at baseline and after RV infection persist up to adult life in patients with asthma who had persistent wheezing in early life. The strengths of this study include: 1) the use of a longitudinal cohort in which subjects could be phenotyped without recall bias and 2) RNA-Seq comparisons of epithelial transcriptomic responses to define a molecular endotype of PW+ cultures at baseline and after RV infection. These findings suggest that therapeutic approaches to target airway remodeling and RV immune responses early in life may slow the progression of asthma in children with persistent wheeze.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

Full Article