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

Marina Pretolani; Anders Bergqvist; Gabriel Thabut; Marie-Christine Dombret; Dominique Knapp; Fatima Hamidi; Loubna Alavoine; Camille Taillé; Pascal Chanez; Jonas S Erjefält; Michel Aubier

doi:10.1016/j.jaci.2016.08.009

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

J Allergy Clin Immunol. 2017 Apr;139(4):1176-1185. doi: 10.1016/j.jaci.2016.08.009. Epub 2016 Sep 5.

Authors

Affiliations

¹ Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France; Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France.
² Unit of Airway Inflammation, Lund University, Lund, Sweden.
³ Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France; Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France; Unit of Airway Inflammation, Lund University, Lund, Sweden; Department of Pneumology B, Bichat-Claude Bernard University Hospital, Paris, France; Assistance Publique des Hôpitaux de Paris, Paris, France.
⁴ Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France; Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France; Department of Pneumology A, Bichat-Claude Bernard University Hospital, Paris, France; Assistance Publique des Hôpitaux de Paris, Paris, France.
⁵ Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France; Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France; Assistance Publique des Hôpitaux de Paris, Paris, France.
⁶ Clinical Investigation Center, Bichat-Claude Bernard University Hospital, Paris, France.
⁷ Inserm U1067 and CNRS UMR7733, Department of Respiratory Diseases, APHM Aix-Marseille University, Marseille, France.
⁸ Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France; Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France; Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France; Department of Pneumology A, Bichat-Claude Bernard University Hospital, Paris, France; Assistance Publique des Hôpitaux de Paris, Paris, France. Electronic address: michel.aubier@aphp.fr.

PMID: 27609656
DOI: 10.1016/j.jaci.2016.08.009

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 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.

Keywords: Refractory asthma; airway remodeling; airway smooth muscle; asthma control; bronchial epithelium; epithelium neuroendocrine cells; mucosal nerves.

Publication types

Clinical Trial

MeSH terms

Adult
Aged
Asthma / pathology
Asthma / therapy*
Bronchi / pathology
Bronchi / radiation effects
Bronchoscopy / methods
Female
Humans
Hyperthermia, Induced / methods*
Male
Middle Aged
Quality of Life
Respiratory Function Tests
Treatment Outcome