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. 2019 Feb 18;5(1):00123-2018.
doi: 10.1183/23120541.00123-2018. eCollection 2019 Feb.

Airway transcriptomic profiling after bronchial thermoplasty

Shu-Yi Liao  1   2   3 , Angela L Linderholm  1   3 , Ken Y Yoneda  1   2 , Nicholas J Kenyon  1   2 , Richart W Harper  1   2
Affiliations

Airway transcriptomic profiling after bronchial thermoplasty

Shu-Yi Liao et al. ERJ Open Res. .

Abstract

Background: Bronchial thermoplasty is a nonpharmacological, device-based treatment option for a specific population of severe asthmatic subjects, but the underlying mechanisms are largely unknown. The purpose of this study is to identify potential altered pathways by bronchial thermoplasty using a transcriptomic approach.

Methods: Patients undergoing bronchial thermoplasty were recruited to the study, and a bronchial brushing sample was obtained before each bronchial thermoplasty session and sent for RNA sequencing. A variance component score test was performed to identify those genes whose expression varied after bronchial thermoplasty sessions. Differential gene expression meta-analysis of severe asthmatic subjects versus controls was performed using public repositories. Overlapping genes were included for downstream pathway and network analyses.

Results: 12 patients were enrolled in our study. A total of 133 severe asthma cases and 107 healthy controls from the public repositories were included in the meta-analysis. Comparison of differentially expressed genes from our study patients with the public repositories identified eight overlapping genes: AMIGO2, CBX7, NR3C2, SETBP1, SHANK2, SNTB1, STXBP1 and ZNF853. Network analysis of these overlapping genes identified pathways associated with neurophysiological processes.

Conclusion: We have shown that bronchial thermoplasty treatment alters several gene networks that are important in asthma pathogenesis. These results potentially elucidate the disease-modifying mechanisms of bronchial thermoplasty and provide several targets for further investigation.

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Conflict of interest statement

Conflict of interest: S-Y. Liao has no conflicts of interest. Conflict of interest: A.L. Linderholm has no conflicts of interest. Conflict of interest: K.Y. Yoneda has no conflicts of interest. Conflict of interest: N.J. Kenyon has no conflicts of interest. Conflict of interest: R.W. Harper has no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Schematic of the analysis workflow. DEG: differentially expressed genes; BT: bronchial thermoplasty.
FIGURE 2
FIGURE 2
CONSORT flow diagram. BT: bronchial thermoplasty.
FIGURE 3
FIGURE 3
Number of unique and common genes in each analysis. BT: bronchial thermoplasty.
FIGURE 4
FIGURE 4
Network built from overlapping genes and Rho GTPase (SNTB1 and ZNF853 were not found to interact with other genes in the network), modified from the MetaCore network. Circled: overlapping genes; green arrow: activation; red arrow: inhibition; grey arrow: unspecified.
See this image and copyright information in PMC

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