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Effectiveness of bronchial thermoplasty in patients with severe refractory asthma : Clinical and histopathologic correlations

Pretolani, Marina; Bergqvist, Anders LU ; Thabut, Gabriel; Dombret, Marie Christine; Knapp, Dominique; Hamidi, Fatima; Alavoine, Loubna; Taillé, Camille; Chanez, Pascal and Erjefält, Jonas S. LU , et al. (2017) In Journal of Allergy and Clinical Immunology 139(4). p.1176-1185
Abstract

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... (More)

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 μm [25th-75th IQR, 4.0-4.7 μm] and 3.9 μm [25th-75th IQR, 3.7-4.6 μm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P < .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm2 and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm2, P = .02), and epithelial neuroendocrine cells (4.9/mm2 [25th-75th IQR, 0-16.4/mm2] and 0.0/mm2 [25th-75th IQR, 0-0/mm2], 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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published
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keywords
Airway remodeling, Airway smooth muscle, Asthma control, Bronchial epithelium, Epithelium neuroendocrine cells, Mucosal nerves, Refractory asthma
in
Journal of Allergy and Clinical Immunology
volume
139
issue
4
pages
1176 - 1185
publisher
Elsevier
external identifiers
  • scopus:85006132133
  • wos:000398771800013
ISSN
0091-6749
DOI
10.1016/j.jaci.2016.08.009
language
English
LU publication?
yes
id
23b93d7a-c479-4a4d-bc13-cf158e4adcaa
date added to LUP
2016-12-30 10:52:48
date last changed
2018-07-29 04:23:03
@article{23b93d7a-c479-4a4d-bc13-cf158e4adcaa,
  abstract     = {<p>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 &lt; .001), subepithelial basement membrane thickening (4.4 μm [25th-75th IQR, 4.0-4.7 μm] and 3.9 μm [25th-75th IQR, 3.7-4.6 μm], P = 0.02), submucosal nerves (1.0 ‰ [25th-75th IQR, 0.7-1.3 ‰] immunoreactivity and 0.3 ‰ [25th-75th IQR, 0.1-0.5 ‰] immunoreactivity, P &lt; .001), ASM-associated nerves (452.6 [25th-75th IQR, 196.0-811.2] immunoreactive pixels per mm<sup>2</sup> and 62.7 [25th-75th IQR, 0.0-230.3] immunoreactive pixels per mm<sup>2</sup>, P = .02), and epithelial neuroendocrine cells (4.9/mm<sup>2</sup> [25th-75th IQR, 0-16.4/mm<sup>2</sup>] and 0.0/mm<sup>2</sup> [25th-75th IQR, 0-0/mm<sup>2</sup>], 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.</p>},
  author       = {Pretolani, Marina and Bergqvist, Anders and Thabut, Gabriel and Dombret, Marie Christine and Knapp, Dominique and Hamidi, Fatima and Alavoine, Loubna and Taillé, Camille and Chanez, Pascal and Erjefält, Jonas S. and Aubier, Michel},
  issn         = {0091-6749},
  keyword      = {Airway remodeling,Airway smooth muscle,Asthma control,Bronchial epithelium,Epithelium neuroendocrine cells,Mucosal nerves,Refractory asthma},
  language     = {eng},
  number       = {4},
  pages        = {1176--1185},
  publisher    = {Elsevier},
  series       = {Journal of Allergy and Clinical Immunology},
  title        = {Effectiveness of bronchial thermoplasty in patients with severe refractory asthma : Clinical and histopathologic correlations},
  url          = {http://dx.doi.org/10.1016/j.jaci.2016.08.009},
  volume       = {139},
  year         = {2017},
}