Transcriptome genetic differences between responders and non-responders before bronchial thermoplasty

Ano, Satoshi; Kikuchi, Norihiro; Matsuyama, Masashi; Nakajima, Masayuki; Kondo, Yoshitaka; Masuda, Masahiro; Osawa, Hajime; Ishii, Yukio; Hizawa, Nobuyuki

doi:10.1080/02770903.2021.1945088

Cited by 6 publications

(9 citation statements)

References 44 publications

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“…The study expands the knowledge regarding the mechanisms of action of BT using gene expression profiling in bronchial biopsy samples. Genes to be investigated were selected through a hypothesis-driven approach based on and expanding data available in the literature [ 6 , 13 – 17 , 20 – 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…SLPI gene expression has emerged as the most promising marker at baseline to predict response to BT in the work by Ano S et al [ 24 ]. SLPI can inhibit leukocyte elastase, cathepsin G, trypsin and mast cell chymase.…”

Section: Discussionmentioning

confidence: 99%

“…Based on Fig. 3 shown in that manuscript [ 24 ], it seems even possible to define a cut-off in SLPI expression in bronchial specimens which could distinguish responders from non-responders to BT [ 24 ]. We were not able to confirm the usefulness of the quantification of SLPI gene expression at baseline to predict response to BT.…”

Section: Discussionmentioning

confidence: 99%

“…The aims of this study were to determine efficacy of BT, to identify genes modulated by BT and associations between gene expression levels in bronchial biopsy specimens and clinical outcomes. We investigated the expression of 20 genes, selected following a hypothesis-driven approach starting from and expanding literature data [ 6 , 13 – 17 , 20 – 24 ]. In particular, we analyzed expression of genes reflecting airway remodelling: alpha smooth muscle actin (ACTA2) marker of airway smooth muscle cells, cadherin 1 (CDH1) marker of epithelial cells, connective tissue growth factor (CTGF), fibroblast activation protein alpha (FAP), alpha-1 and alpha-2 chain type I collagen (COL1A1, COL1A2), galectin-3 (LGAL3) markers of stroma.…”

Section: Introductionmentioning

confidence: 99%

“…We investigated genes coding high temperature receptors (transient receptor potential cation channel subfamily V member 1 and member 2: TRPV1 and TRPV2) [ 22 , 23 ] because BT is based on heat delivery. Finally we analyzed the expression of SLPI which has emerged as the most promising potential marker of response to BT in the work by Ano S et al [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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

Menzella

2022

Allergy Asthma Clin Immunol

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Background Bronchial thermoplasty (BT) is an effective treatment in severe asthma. How to select patients who more likely benefit from BT is an unmet clinical need. Moreover, mechanisms of BT efficacy are still largely unknown. We sought to determine BT efficacy and to identify potential mechanisms of response. Methods This retrospective cohort study evaluated clinical outcomes in 27 patients with severe asthma: 13 with T2-high and 14 with T2-low endotype. Expression levels of 20 genes were compared by real-time PCR in bronchial biopsies performed at the third BT session versus baseline. Clinical response was measured based on Asthma Control Questionnaire (ACQ) score < 1.5, asthma exacerbations < 2, oral corticosteroids reduction of at least 50% at 12 months post-BT. Patients were classified as responders when they had at least 2 of 3 outcome measures. Results 81% of patients were defined as responders. BT induced a reduction in alpha smooth muscle actin (ACTA2) and an increase in CD68, fibroblast activation protein-alpha (FAP), alpha-1 and alpha-2 type I collagen (COL1A1, COL1A2) gene expression in the majority of patients. A higher reduction in ubiquitin carboxy-terminal-hydrolase L1 (PGP9.5) mRNA correlated with a better response based on Asthma Quality of Life Questionnaire (AQLQ). Lower changes in CD68 and FAP mRNAs correlated with a better response based on ACQ. Lower levels of occludin (OCLN), CD68, connective tissue growth factor (CTGF), higher levels of secretory leukocyte protease inhibitor (SLPI) and lower changes in CD68 and CTGF mRNAs were observed in patients who had less than 2 exacerbations post-BT. Lower levels of COL1A2 at baseline were observed in patients who had ACQ < 1.5 at 12 months post-BT. Conclusions BT is effective irrespective of the asthma endotypes and seems associated with airway remodelling. Quantification of OCLN, CD68, CTGF, SLPI, COL1A2 mRNAs could be useful to identify patients with better results. Trial registration: The study protocol was approved by the Local Ethics Committee (Azienda USL-IRCCS of Reggio Emilia—Comitato Etico Area Vasta Nord of Emilia Romagna; protocol number: 2019/0014076) and all the patients provided written informed consent before participating in the study.

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