Bronchial thermoplasty in severe asthma: a real-world study on efficacy and gene profiling

Menzella, Francesco

doi:10.1186/s13223-022-00680-4

Cited by 10 publications

(5 citation statements)

References 45 publications

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“…suggest that BT might act on mediators involved in broader pathophysiological mechanisms rather than targeting a speci c endotype (42,51,52). This is supported by other studies reporting better asthma control post-BT in patients with and without T2 in ammation (4,5). This might be a downstream effect of the BT-induced renewal of the epithelium and subsequent improved integrity (20,21).…”

Section: Discussionmentioning

confidence: 64%

“…An alternative to biologics therapy lays in bronchial thermoplasty (BT) which has been preconized in severe asthma patients unresponsive or ineligible to biologics, and therefore has been utilized in patients harboring features of T2-high and T2-low in ammation (2,4,5). This approach consists in a single delivery of radiofrequency thermal energy in airways of 3-10 mm in diameter.…”

Section: Introductionmentioning

confidence: 99%

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

Gagnon,

Klein,

Vos

et al. 2023

Preprint

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Rationale: Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. Success of the recently approved anti-TSLP and BT in improving asthma control regardless of asthma inflammatory endotype reemphasize the role of bronchial epithelium and its secreted mediators in severe asthma pathophysiology. Objectives: Identifying new potential pathophysiological pathways relevant to severe asthma and modulated by bronchial thermoplasty. Methods: In this study we evaluated the transcriptome of cultured bronchial epithelial cells (BECs) of severe asthmatics obtained pre- and post-BT treatment using microarrays. We further validated gene and protein expressions in BECs and in bronchial biopsies with immunohistochemistry pre- and post-BT treatment. Measurements and main results: Transcriptomics analysis revealed that a large portion of differentially expressed genes (DEG) was involved in anti-viral response, anti-microbial response and pathogen induced cytokine storm signaling pathway. S100A gene family stood out as five members of this family where consistently downregulated post-BT. Further validation revealed that S100A7, S100A8, S100A9 and their receptor (RAGE, TLR4, CD36) expressions were highly enriched in severe asthmatic BECs. Further, these S100A family members were downregulated at the gene and protein levels in BECs and in bronchial biopsies of severe asthmatics post-BT. TLR4 and CD36 protein expression were also reduced in BECs post-BT. Thymic stromal lymphopoietin (TSLP) and human b-defensin 2 (hBD2) were significantly decreased while no significant change was observed in IL-25 and IL-33. Conclusions: These data suggest that BT might improve asthma control by downregulating epithelial derived S100A family expression and related downstream signaling pathways.

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Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

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

Gagnon,

Klein,

Vos

et al. 2023

Preprint

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“…However, an increase in CD68 transcripts after BT is reported with an association to response. 44 One of the strengths of this study is that bronchial brushes and BALF were obtained without increasing oral corticosteroids before the bronchoscopy. This is in contrast to other studies in which bronchial samples were generally taken during the BT procedure in conjunction with pre-treatment OCS for 3 days, per treatment protocol.…”

Section: Dovepressmentioning

confidence: 99%

Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma

Wijsman¹,

Goorsenberg²,

Ravi³

et al. 2022

JAA

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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.

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“…Among increased ASM mass as a hallmark of asthma related airway remodeling, extra cellular matrix (ECM), including the reticular basement membrane (RBM), contributes to airway remodelling as well ( 11 ). Research has shown BT impacts on the gene expression related to this airway remodeling ( 12 ). In addition, histopathological studies have reported a reduction in thickness of the RBM after BT ( 6 , 7 ) which correlated with the asthma control score ( 7 , 8 ).…”

mentioning

confidence: 99%