Rhinovirus-infected preschool children with problematic wheeze have lung eosinophilic inflammation

Area of Science:

• Pediatric Respiratory Medicine
• Immunology
• Virology

Background:

• Rhinovirus (RV) infections are key triggers of childhood wheezing and are linked to later asthma development.
• Indolent RV infections in preschool children with refractory wheeze are associated with mixed lung inflammation, prompting investigation into RV's role in asthma inception via type 2 (T2) inflammatory pathways.

Purpose of the Study:

• To determine if indolent RV infection in infants is associated with eosinophilic airway inflammation and a T2 inflammatory signature.

Main Methods:

• Bronchoalveolar lavage (BAL) was performed on children (≤5 years) with and without RV infection.
• Eosinophils and eosinophil-derived neurotoxin (EDN) were quantified in BAL.
• T2 inflammation-associated proteins and gene expression were analyzed using proximity extension assays and RNA sequencing.

Main Results:

• RV infection was linked to higher EDN levels but not increased intact eosinophils in the airways.
• Elevated EDN did not correlate with transcripts or proteins indicative of a T2 high inflammatory phenotype.

Conclusions:

• In infants with severe wheeze, EDN presence without canonical T2 cytokines suggests lung eosinophils may mediate antiviral responses rather than typical T2 inflammation.
• RV-associated wheeze in infants may identify those at high risk for asthma, suggesting RV-targeted therapies could be more beneficial than T2-targeting treatments.