Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines

Abstract

Background-The pathology of pediatric severe therapy-resistant asthma (STRA) is little understood.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…Similar to adults with severe asthma, an eosinophilic-dominated profile has been observed in children, but not in relation to measurable levels of Th2 cytokines in bronchoalveolar lavage fluid or biopsies [61]. In adults, a non-eosinophilic phenotype appears to form a large subgroup of asthma [18,175,176], with data from a mild-to-moderate cohort [176] showing relatively poor corticosteroid sensitivity.…”

“…However, a bronchoscopic study did not support a defining role for Th2 cytokines in children with severe asthma [61]. Furthermore, the clinical expression of severe asthma in children is highly variable and distinct severe asthma phenotypes are less well-defined in children than they are in adults [16].…”

“…Whether the Th2 profile is similar to that observed in corticosteroid-naïve patients awaits further study, but would be supported by studies demonstrating efficacy of an anti-IL-13 antibody in improving FEV1 in adult patients with moderate-to-severe asthma [59,60]. Evidence for a Th2 pattern in severe asthmatic children remains controversial [61,62]. Inflammation associated with high expression of Th2 cytokines has also been linked to mast cells [63].…”

“…While the eosinophilic or ''Th2 high'' asthma phenotype, characterised by high expression of Th2 cytokines, IL-5 and IL-13, identifies ICS responsiveness in patients with milder asthma, eosinophilic inflammation may persist in some severe asthma patients despite high dose ICS, and even systemic corticosteroids [18,61,141,155,175,176]. Similar to adults with severe asthma, an eosinophilic-dominated profile has been observed in children, but not in relation to measurable levels of Th2 cytokines in bronchoalveolar lavage fluid or biopsies [61].…”

Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach

“…All children with STRA 120 underwent our clinical protocol which includes bronchoscopy, as previously 121 described (3) , followed by a single intramuscular injection of triamcinolone acetonide to 122 determine steroid responsiveness. This was a clinical investigation protocol, not a 123 clinical trial.…”