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

Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma

Pieta C Wijsman #  1 , Annika W M Goorsenberg #  1 , Abilash Ravi #  1   2 , Julia N S d'Hooghe  1 , Barbara S Dierdorp  2 , Tamara Dekker  2 , Charlotte C L M van Schaik  1 , Nick H T Ten Hacken  3 , Pallav L Shah  4   5   6 , Els J M Weersink  1 , Elisabeth H Bel  1 , Jouke T Annema  1 , René Lutter  1   2 , Peter I Bonta  1
Affiliations

Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma

Pieta C Wijsman et al. J Asthma Allergy. .

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.

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Conflict of interest statement

René Lutter and Peter I Bonta are co-last authors for this study. Prof. Dr. Elisabeth H Bel reports grants from Teva, GSK, AstraZeneca, Sanofi, Chiesi, and Teva, outside the submitted work. Dr Peter I Bonta reports grants from Boston Scientific, Stichting Asthma Bestrijding, and Dutch Lung Foundation for Health Research and Development, during the conduct of the study. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study design. Three weeks before BT treatment baseline data were collected: BALF from the lingula and brushes from the left lower lobe. Six months after BT treatment BALF and brushes were collected from the treated lingula and left lower lobe, and untreated middle lobe. (Figure created with BioRender.com).
Figure 2
Figure 2
Differentially expressed gene sets before and after BT treatment. (A) (upper panel: baseline (pre BT) versus after treatment (post BT)). Heatmaps of inflammatory genes for bronchial epithelial cells showing a non-significant difference between the baseline (pre BT) and treated airways (post BT). (A) (lower panel: untreated versus treated (after treatment)). Heatmaps of inflammatory genes for bronchial epithelial cells after BT showing a significant downregulation of the treated lobe compared to the untreated middle lobe. (B) (After treatment). Z-scores from heatmaps showing a significant difference between untreated middle lobe and treated lobes after BT (p<0.0001 = ****). There were no significant differences between responders (green dots) and non-responders (red dots). (C) (baseline versus after treatment). Z-scores from heatmaps showing a non-significant difference between the baseline (pre-BT) and treated airways (post-BT).
Figure 3
Figure 3
Differentially expressed inflammatory and glycolysis gene sets in the responder and non-responder groups. (A) After treatment: Heatmaps of inflammatory genes for bronchial epithelial cells are downregulated in treated airways compared to the untreated (middle) lobe. No differences between responders and non-responders were seen. (B and C) at baseline: Glycolysis gene expression in responders and non-responders. (B) Heatmaps of genes representing glycolysis showing that glycolysis genes are downregulated in responders. (C) Z-scores from glycolysis genes showing a significant difference between responders and non-responders.
Figure 4
Figure 4
Differences at baseline between responders and non-responders. Mann–Whitney U-test analyses showed (A) difference in blood eosinophil count (p=0.006), (B) difference in BALF eosinophil count (p=0.02) and (C) difference between serum IgE (p=0.02) between responders and non-responders. * = p < 0.05.
Figure 5
Figure 5
Proposed interaction between BT and inflammation. Inflammatory genes are downregulated after BT, whereas the expression of oxidative phosphorylation genes and glucocorticoid receptors is increased after BT, as described in other studies., *Described in study of Ravi et al **Described in study of Papakonstantinou et al (Figure created with BioRender.com).
See this image and copyright information in PMC

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