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吸入长效β2-激动剂和皮质类固醇治疗后哮喘患者的转录组分析。

Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting β2-agonists and corticosteroids.

机构信息

Division of Respiratory Therapy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

出版信息

Int J Med Sci. 2022 Oct 3;19(12):1770-1778. doi: 10.7150/ijms.76013. eCollection 2022.

Abstract

Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.

摘要

哮喘是全球范围内重大的公共卫生问题之一,给社会、经济和医疗保健带来了巨大负担。哮喘严重影响患者的生活质量和日常活动。哮喘的治疗包括吸入皮质类固醇(ICS)和长效β-激动剂(LABA),主要目的是改善肺功能,减轻症状和加重。目前的治疗方案是基于症状的策略,治疗后气道炎症的状况尚不清楚。我们进行这项研究是为了通过 RNA 转录组分析了解 ICS-LABA 治疗后患者的全面炎症或气道重塑状况。

本研究纳入了 8 名新诊断的哮喘患者和 2 名健康受试者。哮喘患者在 ICS-LABA 治疗前后进行了血液检查、肺功能检查和 RNA 转录组分析。与健康受试者相比,治疗前哮喘患者的蛋白酪氨酸激酶和相关信号通路表达较高。ICS-LABA 治疗后,核受体转录共激活因子、N-乙酰转移酶、蛋白酪氨酸激酶、核受体和 RNA 聚合酶 II-激活转录因子的表达下调。然而,治疗后的哮喘患者的半胱氨酸内肽酶、内切核酸酶、载脂蛋白和未折叠蛋白的表达仍高于健康受试者。ICS/LABA 的联合使用降低了气道炎症和重塑途径。然而,ICS/LABA 治疗后患者的过敏原刺激相关途径仍上调。药物和过敏原去除的联合使用是哮喘的完整治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3b/9608042/97498c1e4bc9/ijmsv19p1770g001.jpg

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