Age-dependent differences in airway inflammation and function in severe uncontrolled asthma.

Abstract

Endobronchial biopsy studies have deepened our understanding of airway inflammation and remodeling in severe asthma, but direct comparisons between pediatric and adult populations remain scarce. We compared the histopathologic and clinical characteristics of children and adults with severe uncontrolled asthma. Demographic, clinical, and laboratory data, lung function, fractional exhaled nitric oxide, and endobronchial biopsy samples were evaluated from 13 children and 36 adults with severe uncontrolled asthma. The pediatric group had a higher proportion of boys, while girls predominated in adults. Children exhibited better lung function than adults (median percentage predicted forced expiratory volume in 1 second 82% vs 55%). In contrast, inflammatory cell densities were significantly higher in children across multiple airway compartments: elevated levels of eosinophils, chymase-positive mast cells, and CD8⁺ T cells in the intraepithelial layer; neutrophils, tryptase-positive mast cells, and chymase-positive mast cells in the airway smooth muscle layer; and eosinophils, tryptase-positive mast cells, and chymase-positive mast cells in the submucosal layer. In contrast, CD4⁺ T-cell density in the submucosal layer was higher in adults. Structural parameters, including basement membrane and epithelial thickness, collagen deposition, and airway smooth muscle/total tissue area, were similar between groups. Children with severe asthma exhibit greater airway inflammation yet maintain better lung function compared to adults with similar structural remodeling. These findings highlight a potential therapeutical window in the pediatric population, emphasizing the need for age-tailored management approaches in severe asthma.