Liang Ya-Ru, Chang Chuan-Hsin, Huang Shiang-Yu, Wu Yao-Kuang, Yang Mei-Chen, Huang Kuo-Liang, Tzeng I-Shiang, Hsieh Po-Chun, Lan Chou-Chin
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.
J Asthma Allergy. 2025 Jun 5;18:941-954. doi: 10.2147/JAA.S511885. eCollection 2025.
Asthma causes airway inflammation, leading to symptoms that impair patients' quality of life, making it a significant global public health issue. Inhaled corticosteroids (ICS) with long-acting beta-agonists therapy (LABA) is commonly used to manage moderate to severe asthma. For patients unresponsive to ICS with LABA, omalizumab may be added to improve asthma control. Understanding transcriptomic expressions is crucial as it provides insights into the molecular mechanisms underlying treatment. However, the impact of omalizumab on transcriptomic expressions remains unclear. Therefore, this study aims to investigate the transcriptomic expression profiles and clinical outcomes between patients receiving ICS with LABA therapy and those adding omalizumab.
This is a prospective, real-world study that enrolled 26 participants, divided into three groups: Group 1, ICS with LABA (n=10); Group 2, ICS with LABA plus omalizumab (n=12); and Group 3, healthy controls (n=4). Assessments included transcriptomic expression profiles, and bioinformatics analysis, IgE, airborne allergen test, pulmonary function test, blood tests, and asthma control test (ACT).
ACT scores were significantly higher in Group 1 and 2 compared to Group 3. IgE levels, dust mite sensitivity, and dynamic pulmonary function changes after bronchodilator administration were notably higher in Group 2. In these patients, down-regulated genes included those related to immune response, NOD-like receptor signaling, RIG-I signaling, IL-17 signaling, and antioxidant activity. Conversely, up-regulated genes were found in the cGMP-PKG signaling pathway, cardiomyopathy-related pathways, and voltage-gated calcium channel activity.
Patients receiving ICS with LABA plus omalizumab still exhibited more dynamic airway changes and higher IgE levels. Downregulation of immune and inflammatory pathways suggests its potential as an add-on treatment for severe asthma. However, upregulated genes were observed in the cGMP-PKG signaling pathway, cardiomyopathy-related pathways, and voltage-gated calcium channel activity.
哮喘会引发气道炎症，导致一系列影响患者生活质量的症状，使其成为一个重大的全球公共卫生问题。吸入性糖皮质激素（ICS）联合长效β受体激动剂疗法（LABA）常用于治疗中度至重度哮喘。对于对ICS联合LABA治疗无反应的患者，可添加奥马珠单抗以改善哮喘控制情况。了解转录组表达至关重要，因为它能为治疗背后的分子机制提供见解。然而，奥马珠单抗对转录组表达的影响仍不明确。因此，本研究旨在调查接受ICS联合LABA治疗的患者与添加奥马珠单抗的患者之间的转录组表达谱及临床结果。
这是一项前瞻性的真实世界研究，纳入了26名参与者，分为三组：第1组，ICS联合LABA（n = 10）；第2组，ICS联合LABA加奥马珠单抗（n = 12）；第3组，健康对照（n = 4）。评估内容包括转录组表达谱、生物信息学分析、免疫球蛋白E（IgE）、空气过敏原检测、肺功能测试、血液检测以及哮喘控制测试（ACT）。
与第3组相比，第1组和第2组的ACT评分显著更高。第2组的IgE水平、尘螨敏感性以及支气管扩张剂给药后的动态肺功能变化明显更高。在这些患者中，下调的基因包括与免疫反应、NOD样受体信号传导、RIG - I信号传导、白细胞介素 - 17信号传导以及抗氧化活性相关的基因。相反，在环磷酸鸟苷 - 蛋白激酶G（cGMP - PKG）信号通路、心肌病相关通路以及电压门控钙通道活性方面发现了上调的基因。
接受ICS联合LABA加奥马珠单抗治疗的患者仍表现出更多的动态气道变化和更高的IgE水平。免疫和炎症通路的下调表明其作为重度哮喘附加治疗的潜力。然而，在cGMP - PKG信号通路、心肌病相关通路以及电压门控钙通道活性方面观察到了上调的基因。
