Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction

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Abstract
Rationale: We hypothesized that the epithelial reticular basement membrane (RBM) thickening and eosinophilic inflammation characteristic of asthma would be present in symptomatic infants with reversible airflow obstruction. Methods: RBM thickness and numbers of inflammatory cells were determined in ultrathin sections of endobronchial biopsies obtained from 53 infants during clinical bronchoscopy for severe wheeze and/or cough. Group A: 16 infants with a median age of 12 months (range 3.4–26 months), with decreased specific airway conductance (sGaw) and bronchodilator reversibility; Group B: 22 infants with a median age of 12.4 months (5.1–25.9 months), with decreased sGaw but without bronchodilator reversibility; and Group C: 15 infants with a median age of 11.5 months (3.4–24.3 months) with normal sGaw. Additional comparisons were made with the following groups. Group D: 17 children, median age 10.3 years (6–16 years), with difficult asthma; Group E: 10 pediatric control subjects without asthma, median age 10 years (6–16 years); and Group F: nine adult normal, healthy control subjects, median age 27 years (21–42 years). Main Results: There were no significant differences in RBM thickness or inflammatory cell number between the infant groups. RBM thickness was similar in the infants and Groups E and F. However, the RBM in all infant groups (Group A: median 4.3 μm [range 2.8–9.2 μm]; Group B: median 4.15 μm [range 2.7–5.8 μm]; Group C: median 3.8 μm [range 2.7–5.5 μm]) was significantly less thick than that in the older children with asthma (Group D: median 8.3 μm [range 5.3–12.7 μm]; p < 0.001). Conclusion: RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults are not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.