Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 139, Issue 4, Pages 1176-1185Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.08.009
Keywords
Refractory asthma; asthma control; airway smooth muscle; airway remodeling; epithelium neuroendocrine cells; mucosal nerves; bronchial epithelium
Categories
Funding
- Boston Scientific, Marlborough, Mass
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Background: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma, yet its effect on different bronchial structures remains unknown. Objective: We sought to examine the effect of BT on bronchial structures and to explore the association with clinical outcome in patients with severe refractory asthma. Methods: Bronchial biopsy specimens (n = 300) were collected from 15 patients with severe uncontrolled asthma before and 3 months after BT. Immunostained sections were assessed for airway smooth muscle (ASM) area, subepithelial basement membrane thickness, nerve fibers, and epithelial neuroendocrine cells. Histopathologic findings were correlated with clinical parameters. Results: BT significantly improved asthma control and quality of life at both 3 and 12 months and decreased the numbers of severe exacerbations and the dose of oral corticosteroids. At 3 months, this clinical benefit was accompanied by a reduction in ASM area (median values before and after BT, respectively: 19.7% [25th-75th interquartile range (IQR), 15.9% to 22.4%] and 5.3% [25th-75th IQR], 3.5% to 10.1%, P < .001), subepithelial basement membrane thickening (4.4 mu m [25th-75th IQR, 4.0-4.7 mu m] and 3.9 mu m [25th-75th IQR, 3.7-4.6 mu m], P = 0.02), submucosal nerves (1.0 parts per thousand [25th-75th IQR, 0.7-1.3 parts per thousand] immunoreactivity and 0.3 parts per thousand [25th-75th IQR, 0.1-0.5 parts per thousand] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm(2) and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm(2), P = .02), and epithelial neuroendocrine cells (4.9/mm(2) [25th-75th IQR, 0-16.4/mm(2)] and 0.0/mm(2) [25th-75th IQR, 0-0/mm(2)], P = .02). Histopathologic parameters were associated based on Asthma Control Test scores, numbers of exacerbations, and visits to the emergency department (all P < .02) 3 and 12 months after BT. Conclusion: BT is a treatment option in patients with severe therapy-refractory asthma that downregulates selectively structural abnormalities involved in airway narrowing and bronchial reactivity, particularly ASM, neuroendocrine epithelial cells, and bronchial nerve endings.
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