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Airway Remodeling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction

Lung Pathology, Department of Gene Therapy, and Respiratory Pediatrics, Imperial College London at the Royal Brompton Hospital, London, United Kingdom; Department of Allergology, and Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland

Correspondence and requests for reprints should be addressed to Peter K. Jeffery, D.Sci., Ph.D., Lung Pathology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. E-mail: p.jeffery{at}imperial.ac.uk

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.

Key Words: asthma • inflammation • pathology • pediatric • remodeling

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