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Published ahead of print on January 24, 2008, doi:10.1164/rccm.200707-977OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 8, April 2008, 837-843

A more recent version of this article appeared on April 15, 2008
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Submitted on July 3, 2007
Accepted on January 24, 2008

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

Nicolas Regamey1*, Matthias Ochs2, Tom N Hilliard1, Christian Muhlfeld2, Nikki Cornish3, Louise Fleming4, Sejal Saglani4, Eric WFW Alton3, Andrew Bush4, Peter K Jeffery3, and Jane C Davies1

1 Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom; Department of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, United Kingdom, 2 Institute of Anatomy, University of Berne, Berne, Switzerland, 3 Department of Gene Therapy, National Heart and Lung Institute, Imperial College London, London, United Kingdom, 4 Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, United Kingdom

* To whom correspondence should be addressed. 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. Objective: We investigated whether increase in ASM mass is already present in children with chronic inflammatory lung disease. Methods: Fibreoptic bronchoscopy was performed in 78 children (median age (IQR): 11.3 years (8.5-13.8)): 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 to controls (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 8204 (5270-11749; p<0.05) in asthma, 4504 (2838-8962; n.s.) in CF, 4971 (3476-10057; n.s.) in BX, and 1944 (1596-6318) in controls. Mean (SD) myocyte size (µm3) was 3344 (801; p<0.01) in asthma, 3264 (809; p<0.01) in CF, 3177 (873; p<0.05) in BX and 1927 (386) in controls. 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 non-CF bronchiectasis.
Key words: asthma, cystic fibrosis, children, biopsy, smooth muscle






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