Increased airway smooth muscle mass in children with asthma, cystic fibrosis, and non-cystic fibrosis bronchiectasis.

Regamey N, Ochs M, Hilliard TN, Mühlfeld C, Cornish N, Fleming L, Saglani S, Alton EW, Bush A, Jeffery PK, Davies JC

American Journal Of Respiratory And Critical Care Medicine

Am J Respir Crit Care Med. 2008 Apr 15;177(8):837-43. doi: 10.1164/rccm.200707-977OC. Epub 2008 Jan 24.

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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 mm(2) 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 (mum(3)) 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.

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