Dataset Information

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

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.

SUBMITTER: Chang EH

PROVIDER: S-EPMC9463086 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chang Eugene H EH Pouladi Nima N Guerra Stefano S Jandova Jana J Kim Alexander A Li Haiquan H Li Jianrong J Morgan Wayne W Stern Debra A DA Willis Amanda L AL Lussier Yves A YA Martinez Fernando D FD

The Journal of allergy and clinical immunology 20220331 3

<h4>Background</h4>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<sup>+</sup>) 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<sup>-</sup>).<h4>Objective</h4>Our aim was to d ...[more]

PMID: 35367470

Similar Datasets

Project description:Prevention strategies that delay the onset of asthma may improve clinical outcomes. To identify early life environmental exposures associated with asthma age-of-onset and potential genetic modifiers of these exposures, we studied 1085 subjects with physician-diagnosed asthma and disease onset at or after age two. Subjects reported retrospectively on their exposure to 17 environmental factors before the age of two. The presence of individual or combinations of these early life exposures was then tested for association with variation in asthma age-of-onset. For exposures significantly associated with age-of-onset, we tested if 26 single nucleotide polymorphisms (SNP) with an established association with allergic disease significantly modified the effect of the exposure. Five environmental exposures were significantly associated with variation in asthma age-of-onset after correction for multiple testing: carpet at home (P = 6 × 10(-5)), a serious chest illness (P = 10(-4)), father a cigarette smoker (P = 6 × 10(-4)) and direct exposure to father's smoking (P = 3 × 10(-4)). Individuals with early childhood asthma onset, between the ages of two and six, were 1.4-fold (CI 1.1-1.9) more likely to report having lived in a house with carpet and 2.1-fold (CI 1.3-3.5) more likely to report suffering a serious chest illness before the age of two, than asthmatics with later disease onset. We further found these individual risks to increase to 3.2-fold (CI 1.7-6.0) if carpet exposure and suffering a serious chest illness co-occurred before age two. Paternal smoking exposures were less likely to be reported by asthmatics with early when compared to later disease onset (OR 0.5, CI 0.3-0.7). There were no significant SNP interactions with these environmental exposures after correction for multiple testing. Our results suggest that disease onset in individuals at a high-risk of developing asthma can potentially be delayed by avoiding exposure to carpet at home and preventing serious chest illnesses during the first 2 years of life.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets