Airway Remodeling in Preschool Children with Severe Recurrent Wheeze
American Journal of Respiratory and Critical Care Medicine
Rationale: Airway wall structure in preschoolers with severe recurrent wheeze is poorly described. Objectives: To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze. Methods: Flexible bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle
... , mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr). Measurements and Main Results: RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 mm; P = 0.02), was correlated with age (P , 0.01; r = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 mm; P , 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P , 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P , 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P , 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multipletrigger wheezers. Conclusions: In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development. Supported by a grant from Glaxo-Smith-Kline France. Author Contributions: G.L., analysis, interpretation, drafting and revising the work, and final approval of the version for publication. P.G., analysis, drafting and revising the work, and final approval of the version for publication. A.D., data acquisition, drafting the work, and final approval of the version submitted for publication. R.A.-T., B.M., and N.B., data acquisition and final approval of the version submitted for publication. J.d.B., conception, design, data acquisition, analysis, interpretation, drafting and revising the work, final approval of the version for publication, and accountability for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Definition of abbreviations: ASM = airway smooth muscle; RBM = reticular basement membrane. Data are expressed as the median (interquartile range). Group 1: preschoolers less than or equal to 36 months. Group 2: preschoolers, 36-59 months. Group 3: schoolchildren. *P , 0.05, versus group 2. † P , 0.05 versus group 3.