Severe preschool asthmatics have altered cytokine and anti-viral responses during exacerbation.

Abstract

Preschool asthma/recurrent wheeze is a heterogeneous condition. Different clinical phenotypes have been described, including episodic viral wheeze (EVW), severe intermittent wheeze (SIW), and multiple-trigger wheeze (MTW). To compare clinical, viral, and inflammatory/immune profiling at exacerbation between MTW, SIW, and EVW phenotypes. Multicenter, prospective, observational cohort (VIRASTHMA-2). Children (1-5years) with preschool asthma were enrolled during hospitalization for a severe exacerbation. History and anamnestic data, plasma, and nasal samples were collected at exacerbation (T1) and at steady state, 8weeks later (T2), and sputum samples were collected at T1. A total of 147 children were enrolled, 37 (25%) had SIW, 18 (12.2%) EVW, and 92 (63%) MTW. They were atopic (47%), exposed to mold (22%) and cigarette smoke (50%), and prone to exacerbations (≥2 in the previous year in 70%). At exacerbation, at least one virus was isolated in 94% and rhinovirus in 75%, with no difference between phenotypes. Children with MTW and SIW phenotypes displayed lower plasma concentrations of IFN-γ (P=.002), IL-5 (P=.020), TNF-α (P=.038), IL-10 (P=.002), IFN-β (P=.036), and CXCL10 (P=.006) and lower levels of IFN-γ (P=.047) in sputum at exacerbation than children with EVW. At T2, they also displayed lower plasma levels of IFN-γ (P=.045) and CXCL10 (P=.013). Among preschool asthmatic children, MTW and SIW, prone to exacerbations, display lower systemic levels of Th1, Th2 cytokines, pro- and anti-inflammatory cytokines, and antiviral responses during severe virus-induced exacerbation.