Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids (ICS). Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective.
To apply unsupervised analysis of lung lavage (BAL) variables to identify clusters of preschool children with treatment-refractory wheeze.
155 children ≤ 6 years of age underwent bronchoscopy with BAL for evaluation of airway structure, inflammatory markers, and pathogens. Variables were screened with factor analysis, sorted into clusters by Ward’s method, membership was confirmed by discriminant analysis. RESULTS: The model was repeatable in a 48 case validation sample and accurately classified 86% of cases. Cluster 1 (n=60) had early-onset wheeze, 85% with structural abnormalities, mostly tracheamalacia, with low total IgE and agranulocytic BAL. Cluster 2 (n=42) had later-onset wheeze, the highest prevalence of gastroesophageal reflux, little atopy, and 2/3 had increased BAL lipid-laden macrophages. Cluster 3 (n=46) had mid-onset wheeze, low total IgE, and 2/3 had BAL viral transcripts, predominately human rhinovirus (HRV), with BAL neutrophilia. Cluster 4 (n=7) was older, with high total IgE, blood eosinophilia, and mixed BAL eosinophils and neutrophils.
Preschool children with recurrent wheeze refractory to ICS treatment include four clusters: airway malacia, gastroesophageal reflux, indolent HRV bronchoalveolitis, and type-2 inflammation. The results support the risk and cost of invasive bronchoscopy to diagnose causes of treatment-refractory wheeze and develop novel therapies targeting airway malacia, HRV infection, and BAL neutrophilia in preschool children.

Copyright © 2021. Published by Elsevier Inc.