Nerve ablation after bronchial thermoplasty and sustained improvement in severe asthma

N Facciolongo, A Di Stefano, V Pietrini, C Galeone, F Bellanova, F Menzella, N Scichilone, R Piro, G L Bajocchi, B Balbi, L Agostini, P P Salsi, D Formisano, M Lusuardi, N Facciolongo, A Di Stefano, V Pietrini, C Galeone, F Bellanova, F Menzella, N Scichilone, R Piro, G L Bajocchi, B Balbi, L Agostini, P P Salsi, D Formisano, M Lusuardi

Abstract

Background: Bronchial thermoplasty (BT) is a non-pharmacological intervention for severe asthma whose mechanism of action is not completely explained by a reduction of airway smooth muscle (ASM). In this study we analyzed the effect of BT on nerve fibers and inflammatory components in the bronchial mucosa at 1 year.

Methods: Endobronchial biopsies were obtained from 12 subjects (mean age 47 ± 11.3 years, 50% male) with severe asthma. Biopsies were performed at baseline (T0) and after 1 (T1), 2 (T2) and 12 (T12) months post-BT, and studied with immunocytochemistry and microscopy methods. Clinical data including Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores, exacerbations, hospitalizations, oral corticosteroids use were also collected at the same time points.

Results: A statistically significant reduction at T1, T2 and T12 of nerve fibers was observed in the submucosa and in ASM compared to T0. Among inflammatory cells, only CD68 showed significant changes at all time points. Improvement of all clinical outcomes was documented and persisted at the end of follow up.

Conclusions: A reduction of nerve fibers in epithelium and in ASM occurs earlier and persists at one year after BT. We propose that nerve ablation may contribute to mediate the beneficial effects of BT in severe asthma.

Trial registration: Registered on April 2, 2013 at ClinicalTrials.gov Identifier: NCT01839591 .

Keywords: Bronchial biopsies; Bronchial thermoplasty; Bronchoscopy; Nerve fibers; Severe asthma.

Conflict of interest statement

Ethics approval and consent to participate

The study conformed to the Declaration of Helsinki and was approved by the institutional ethics committee of Azienda Ospedaliera Arcispedale S. Maria Nuova/IRCCS and Azienda USL di Reggio Emilia, Italy (protocol n°2331, Reggio Emilia, February 18, 2013). Written informed consent was obtained from each participant prior to enrolment in the study. All authors reviewed the manuscript and approved the final version to publish.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Trend of individual data (AQLQ, panels a and b, ACQ, panels c and d, exacerbations, panel e and f) at different time points: T0 vs T3, panels a, c, and e, T0 vs T12, panels b, d and f. Note that seven lines are representative of 12 patients due to overlap of data
Fig. 2
Fig. 2
a-b X axis: time points. Y axis: nerve fiber score, 0–3 scale a) Trend of nerve fibers–PGP9.5 in submucosa (panel a): median and range values, T0 vs. T1 p = 0.002, T0 vs. T2 p = 0.003, T0 vs T12 p = 0.008 and T2 vs T12 p = 0.59 b) Trend of nerve fibers–PGP9.5 in the smooth muscle (panel b): median and range values, T0 vs. T1 p = 0.004, T0 vs. T2 p = 0.003, T0 vs T12 p = 0.025, and T2 vs T12 p = 0.024
Fig. 3
Fig. 3
a) Overall picture of the nerve endings/fibers (arrows) immunodetected with PGP9.5 at time T0 in bronchial biopsies of a patient with asthma. e: Bronchial Epithelium (green); S: Bronchial Submucosa (blue); M: Bronchial Muscle (red). b) Bronchial biopsy at T1. c) Bronchial biopsy at T2. d) Bronchial biopsy at T12. Note the scarcity of nerve fibers in the submucosa and muscle bundles at T1 to T12

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