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

Abstract

Saglani S, Payne DN, Zhu J, et al. Am J Respir Crit Care Med. 2007;176(9):858–864 PURPOSE OF THE STUDY. Eosinophilic airway inflammation and epithelial reticular basement membrane (RBM) thickening, absent in wheezy infants, may be present in preschool-aged children with severe, recurrent wheeze. This study compared RBM thickness and inflammation in endobronchial biopsies from wheezy preschool-aged children and age-matched control subjects. STUDY POPULATION. Tissue for endobronchial biopsy was obtained from wheezy preschool-aged children (aged 3 months to 5 years) who were undergoing a clinically indicated fiber-optic bronchoscopy. Nonasthmatic controls were subjects undergoing fiber-optic bronchoscopy to investigate stridor. METHODS. There were 16 children (median age: 29 months) with wheezing confirmed by video questionnaire (confirmed wheezers), 14 children (median age: 17 months) with reported wheeze (reported wheeze), and 10 (median age: 10 months) control subjects. Biopsy specimens were examined to compare eosinophilic inflammation (volume fraction of immunologically distinct inflammatory cells) and RBM thickness between the groups. RESULTS. Median RBM thickness was 4.6 μm in children with confirmed wheezing compared with 3.5 μm in those with reported wheezing and 3.8 μm in controls. Median values for eosinophil density were 1.07% in confirmed wheezers, 0.72% in reported wheezers, and 0.0% in controls. Eosinophilic inflammation was significantly greater in confirmed wheezers compared with control subjects (P < .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-aged children with confirmed wheeze between the ages of 1 and 3 years, a time when intervention may modify the natural history of asthma. REVIEWER COMMENTS. This study reconfirms that pathologic evidence of asthma can be found as early as 1 to 3 years of age. This also seems to relate to the time when lung-function abnormalities appear in preschool-aged persistent wheezers. Treatment during this critical period may affect the natural history of asthma.