Liao Shu-Yi, Linderholm Angela L, Yoneda Ken Y, Kenyon Nicholas J, Harper Richart W
Division of Pulmonary, Critical Care and Sleep Medicine, University of California Davis, Sacramento, CA, USA.
VA Northern California Health Care System, Mather, CA, USA.
ERJ Open Res. 2019 Feb 18;5(1). doi: 10.1183/23120541.00123-2018. eCollection 2019 Feb.
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.
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 controls was performed using public repositories. Overlapping genes were included for downstream pathway and network analyses.
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: , , , , , , and . Network analysis of these overlapping genes identified pathways associated with neurophysiological processes.
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.
支气管热成形术是一种针对特定严重哮喘患者群体的非药物、基于设备的治疗选择,但其潜在机制很大程度上尚不清楚。本研究的目的是使用转录组学方法确定支气管热成形术可能改变的途径。
招募接受支气管热成形术的患者参加本研究,在每次支气管热成形术之前获取支气管刷检样本并送去进行RNA测序。进行方差成分评分测试以识别那些在支气管热成形术后表达发生变化的基因。使用公共数据库对严重哮喘患者与对照进行差异基因表达荟萃分析。将重叠基因纳入下游途径和网络分析。
12名患者纳入我们的研究。荟萃分析纳入了来自公共数据库的总共133例严重哮喘病例和107名健康对照。将我们研究患者的差异表达基因与公共数据库进行比较,确定了8个重叠基因: 、 、 、 、 、 、 和 。对这些重叠基因进行网络分析,确定了与神经生理过程相关的途径。
我们已经表明,支气管热成形术治疗改变了几个在哮喘发病机制中重要的基因网络。这些结果可能阐明支气管热成形术的疾病修饰机制,并为进一步研究提供几个靶点。