Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers

Rationale: It is unclear when the pathologic features of asthma first appear. We hypothesized that eosinophilic airway inflammation and epithelial reticular basement membrane (RBM) thickening, absent in wheezy infants, would be present in preschool children with severe, recurrent wheeze. Objectives: To compare RBM thickness and inflammation in endobronchial biopsies (EBs) from wheezy preschool children and age-matched control subjects. Methods: EBs were obtained from wheezy preschool children (aged 3 mo to 5 yr), undergoing a clinically indicated fiberoptic bronchoscopy. Subjects undergoing fiberoptic bronchoscopy to investigate stridor acted as nonasthmatic controls. RBM thickness was measured and the density of subepithelial, immunologically distinct inflammatory cells was determined and expressed as a volume fraction (%). EBs from 16 children (median age, 29 [7-57] mo) with wheeze confirmed by video questionnaire (confirmed wheezers [CWs]), 14 with reported wheeze (reported wheezers [RWs]) (median age, 17 [8-58] mo), and 10 control subjects (median age, 19 [5-42] mo) were assessed. Measurements and Main Results: RBM thickness in the three groups was as follows: CWs: median, 4.6 (range, 2.9-8.0) mu m; RWs: median, 3.5 (2.1-5.4) mu m; control subjects: median, 3.8 (2.8-4.7) mu m. RBM was significantly thicker in CWs than in control subjects (P < 0.05). Eosinophil density was as follows: CWs: median, 1.07% (range, 0.0-3.52%); RWs: median, 0.72% (0.0-2.04%); control subjects: median, 0.0% (0.0-1.05%). Eosinophilic inflammation was significantly greater in CWs compared with control subjects (P < 0.05). There were no between-group differences for any other inflammatory cell phenotype. Conclusions: The characteristic pathologic features of asthma in adults and school-aged children develop in preschool children with confirmed wheeze between the ages of I and 3 years, a time when intervention may modify the natural history of asthma.