Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations - 19/04/17

Doi : 10.1016/j.jaci.2016.08.009

Marina Pretolani, PharmD, PhD ^a,^b,^c,^{^{∗
These authors contributed equally to this work.}}, Anders Bergqvist, PhD ^d,^{^{∗
These authors contributed equally to this work.}}, Gabriel Thabut, MD, PhD ^a,^b,^c,^d,^e,^g, Marie-Christine Dombret, MD ^a,^b,^c,^f,^g, Dominique Knapp, MS ^a,^b,^c,^g, Fatima Hamidi, MS ^a,^b,^c, Loubna Alavoine, MD ^h, Camille Taillé, MD, PhD ^a,^b,^c,^f,^g, Pascal Chanez, MD, PhD ⁱ, Jonas S. Erjefält, PhD ^d, Michel Aubier, MD ^a,^b,^c,^f,^g,^⁎
^a Inserm UMR1152, Physiopathology and Epidemiology of Respiratory Diseases, Paris, France
^b Paris Diderot University, Faculty of Medicine, Bichat campus, Paris, France
^c Laboratory of Excellence, INFLAMEX, Université Sorbonne Paris Cité, and DHU FIRE, Paris, France
^d Unit of Airway Inflammation, Lund University, Lund, Sweden
^e Department of Pneumology B, Bichat-Claude Bernard University Hospital, Paris, France
^f Department of Pneumology A, Bichat-Claude Bernard University Hospital, Paris, France
^h Clinical Investigation Center, Bichat-Claude Bernard University Hospital, Paris, France
^g Assistance Publique des Hôpitaux de Paris, Paris, France
ⁱ Inserm U1067 and CNRS UMR7733, Department of Respiratory Diseases, APHM Aix-Marseille University, Marseille, France

^∗Corresponding author: Michel Aubier, MD, Service de Pneumologie A, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France.Service de Pneumologie AHôpital Bichat-Claude Bernard46 rue Henri HuchardParis75018France

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.

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Key words : Refractory asthma, asthma control, airway smooth muscle, airway remodeling, epithelium neuroendocrine cells, mucosal nerves, bronchial epithelium

Abbreviations used : ACT, AQLQ, ASM, BT, FVC, ICU, IQR, OCS, PGP, SBM

Esquema

Methods

Subjects

BT procedure

Bronchoscopy and biopsy collection

Histopathologic studies

Statistical analyses

Results

Clinical effects of BT

Histopathologic effects of BT

Correlation analyses

Discussion

Supported in part by Boston Scientific, Marlborough, Mass.

Disclosure of potential conflict of interest: M. Pretolani receives grant support from MedImmune. G. Thabut serves as a consultant for GlaxoSmithKline and AstraZeneca and travel support from AstraZeneca. P. Chanez received an honorarium and personal fees from Boston Scientific; serves on the board for Chiesi, Novartis, AstraZeneca, GlaxoSmithKline, TEVA, Boston Scientific, ALK-Abelló, and Sanofi; receives grant support from Roche, AstraZeneca and Jannsen; and receives payments for lectures from Novartis, Boston Scientific, AstraZeneca, Chiesi, and ALK-Abelló. M. Aubier receives grant support from AstraZeneca, GlaxoSmithKline, Roche, and Boston Scientific. The rest of the authors declare that they have no relevant conflicts of interest.

Exportación

Vol 139 - N° 4

P. 1176-1185 - avril 2017 Regresar al número

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Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations - 19/04/17

Abstract

Background

Objective

Methods

Results

Conclusion

Esquema

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Contenido

Mi cuenta

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