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

Abstract

Background

Bronchial thermoplasty (BT) is an endoscopic therapy used for the treatment of refractory asthma. Some predictive factors, for example the number of activations and severity of disease at baseline, have been used to determine the effectiveness of BT in treating patients with asthma. The aim of the present study was to comprehensively analyze RNA samples from the airway bronchial tissues of patients with severe asthma treated by BT, and to characterize each patient as a BT responder or non-responder.

Methods

Eight patients with severe asthma scheduled to undergo BT and bronchus biopsies were recruited before the procedures were conducted. Extracted RNA samples from bronchial tissues were sequenced and differential gene expression analysis was carried out.

Results/discussion: Subjects with Asthma Quality of Life Questionnaire score changes ≥0.5 for a period of 12 months were considered BT responders. Non-responders had score changes <0.5 for 12 months. Histopathology findings were similar to those reported previously, and no significant differences in the expression of α-smooth muscle actin and protein gene product 9.5 were observed between responders and non-responders. Transcriptome analysis at baseline identified 67 genes that were differentially expressed between responders and non-responders, including SLPI, MMP3, and MUC19, which were upregulated in responders. Although the differentially expressed gene products may have conflicting effects, genes in the airway epithelium and extracellular matrix of patients with severe asthma may determine the BT response. Our results identified possible transcriptomic changes that could be used to identify BT responders.

Keywords:

• Bronchial tissue
• gene expression
• histopathology
• severe asthma
• airway smooth muscle

Acknowledgements

We thank Sarah Williams, PhD and Margaret Biswas, PhD from Edanz Group (https://en-author-services.edanzgroup.com/ac) for editing a draft of this manuscript.

Declaration of interest

The authors declare that they have no competing interests.

Authors’ contributions

Concept and design: Satoshi Ano, Norihiro Kikuchi, Masashi Matsuyama, Yukio Ishii; Acquisition, analysis, and interpretation of data: Satoshi Ano, Norihiro Kikuchi, Masashi Matsuyama, Masayuki Nakajima, Yuzuru Kondo, Michiko Masuda, Hajime Osawa, Yukio Ishii; Drafting and revising critically for important intellectual content: Satoshi Ano, Masashi Matsuyama, Yukio Ishii; Supervision and validation: Yukio Ishii, Nobuyuki Hizawa

Additional information

Funding

This work was supported by JSPS KAKENHI grant number 18H03173 (to Y.I.). The funding source had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.