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Early Detection of Airway Wall Remodeling and Eosinophilic Inflammation in Preschool Wheezers

¹ Departments of Respiratory Paediatrics and ² Lung Pathology, Imperial College London; and ³ Department of Histopathology, Royal Brompton Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Professor Peter K. Jeffery F.R.C. Path., D.Sc. (Med.), Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. E-mail: p.jeffery{at}imperial.ac.uk

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) µm; RWs: median, 3.5 (2.1–5.4) µm; control subjects: median, 3.8 (2.5–4.7) µm. 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 1 and 3 years, a time when intervention may modify the natural history of asthma.

Key Words: asthma • pediatrics • pathology

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Eosinophilic inflammation and reticular basement membrane thickening, the pathologic hallmarks of asthma, are not present in infant wheezers but are seen in schoolchildren with asthma. What This Study Adds to the Field The reticular basement membrane thickening and eosinophilic inflammation seen in adults are present in wheezy preschool children.

 

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