This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200707-977OCv1 177/8/837    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Regamey, N. Articles by Davies, J. C. Search for Related Content PubMed PubMed Citation Articles by Regamey, N. Articles by Davies, J. C.

Increased Airway Smooth Muscle Mass in Children with Asthma, Cystic Fibrosis, and Non-Cystic Fibrosis Bronchiectasis

¹ Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom; ² Department of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, United Kingdom; and ³ Institute of Anatomy, University of Berne, Berne, Switzerland

Correspondence and requests for reprints should be addressed to Dr. Nicolas Regamey, M.D., Department of Gene Therapy, National Heart and Lung Institute, 1B Manresa Road, London SW3 6LR, UK. E-mail: n.regamey{at}imperial.ac.uk

Rationale: Structural alterations to airway smooth muscle (ASM) are a feature of asthma and cystic fibrosis (CF) in adults.

Objectives: We investigated whether increase in ASM mass is already present in children with chronic inflammatory lung disease.

Methods: Fiberoptic bronchoscopy was performed in 78 children (median age [IQR], 11.3 [8.5–13.8] yr): 24 with asthma, 27 with CF, 16 with non-CF bronchiectasis (BX), and 11 control children without lower respiratory tract disease. Endobronchial biopsy ASM content and myocyte number and size were quantified using stereology.

Measurements and Main Results: The median (IQR) volume fraction of subepithelial tissue occupied by ASM was increased in the children with asthma (0.27 [0.12–0.49]; P < 0.0001), CF (0.12 [0.06–0.21]; P < 0.01), and BX (0.16 [0.04–0.21]; P < 0.01) compared with control subjects (0.04 [0.02–0.05]). ASM content was related to bronchodilator responsiveness in the asthmatic group (r = 0.66, P < 0.01). Median (IQR) myocyte number (cells per mm² of reticular basement membrane) was 8,204 (5,270–11,749; P < 0.05) in children with asthma, 4,504 (2,838–8,962; not significant) in children with CF, 4,971 (3,476–10,057; not significant) in children with BX, and 1,944 (1,596–6,318) in control subjects. Mean (SD) myocyte size (µm³) was 3,344 (801; P < 0.01) in children with asthma, 3,264 (809; P < 0.01) in children with CF, 3,177 (873; P < 0.05) in children with BX, and 1,927 (386) in control subjects. In all disease groups, the volume fraction of ASM in subepithelial tissue was related to myocyte number (asthma: r = 0.84, P < 0.001; CF: r = 0.81, P < 0.01; BX: r = 0.95, P < 0.001), but not to myocyte size.

Conclusions: Increases in ASM (both number and size) occur in children with chronic inflammatory lung diseases that include CF, asthma, and BX.

Key Words: asthma • cystic fibrosis • children • biopsy • smooth muscle

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Increased airway smooth muscle mass is a functionally important feature of chronic inflammatory lung diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary disease in adults. What This Study Adds to the Field Increased airway smooth muscle mass is already present in children with chronic inflammatory lung disease.