Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma

Pieta C Wijsman; Annika W M Goorsenberg; Abilash Ravi; Julia N S d'Hooghe; Barbara S Dierdorp; Tamara Dekker; Charlotte C L M van Schaik; Nick H T Ten Hacken; Pallav L Shah; Els J M Weersink; Elisabeth H Bel; Jouke T Annema; René Lutter; Peter I Bonta

doi:10.2147/JAA.S383418

Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma

J Asthma Allergy. 2022 Dec 16:15:1783-1794. doi: 10.2147/JAA.S383418. eCollection 2022.

Authors

Pieta C Wijsman^#¹, Annika W M Goorsenberg^#¹, Abilash Ravi^#^{1

2}, Julia N S d'Hooghe¹, Barbara S Dierdorp², Tamara Dekker², Charlotte C L M van Schaik¹, Nick H T Ten Hacken³, Pallav L Shah^{4

5

6}, Els J M Weersink¹, Elisabeth H Bel¹, Jouke T Annema¹, René Lutter^{1

2}, Peter I Bonta¹

Affiliations

¹ Department of Pulmonary Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
² Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
³ Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
⁴ Department of Pulmonology, Royal Brompton Hospital, London, UK.
⁵ National Heart & Lung Institute, Imperial College, London, UK.
⁶ Department of Pulmonology, Chelsea & Westminster Hospital, London, UK.

^# Contributed equally.

Abstract

Background: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response.

Methods: In this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders.

Results: Gene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders.

Conclusion: Local differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.

Keywords: airway inflammation; bronchial thermoplasty; bronchoalveolar lavage fluid cells; cytokines; epithelial transcriptome.

Grants and funding

This study was supported by the Lung Foundation Netherlands (Grant number: 5.2.13.064JO), Stichting Astma Bestrijding (SAB): grant nr. 1018/041 and The Dutch Lung Foundation for Health Research and Development (ZonMw grant number: 90713477) and Boston Scientific Corporation. All had no role in the design of the study.