Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma

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.

Effect of budesonide combined with montelukast sodium on pulmonary function parameters and immunoglobulin levels in children with bronchial asthma

“…As confirmed by clinical practice, effective treatments for children with bronchial asthma mainly include drug therapy, traditional Chinese medicine treatment, anti-IgE monoclonal antibodies, anti-tumor necrosis factor, and bronchial thermoplasty. 17,18 Drug therapy remains the dominant treatment employed in clinical practice. The optimal drugs in drug therapy are glucocorticoids.…”

S100 A alarmins and Thymic stromal lymphopoietin (TSLP) regulation in severe asthma following bronchial thermoplasty

“…BT also seems to modulate epithelial metabolic pro le leading to a shift from a glycolysis-biased gene expression pro le to an oxidative phosphorylation-based pro le (22). BT further seems to modulate the in ammatory pro le of the airway epithelium (17,20,23).…”