Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults.
J Allergy Clin Immunol
; 150(3): 604-611, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-35367470
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Child
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Child, preschool
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article