Comparative Analysis of ICS Combined with LABA versus Addition of Omalizumab on Transcriptomic Expression Profiles in Patients with Allergic Asthma

Ya-Ru Liang,1,* Chuan-Hsin Chang,2,* Shiang-Yu Huang,1 Yao-Kuang Wu,3,4 Mei-Chen Yang,3,4 Kuo-Liang Huang,3,4 I-Shiang Tzeng,2 Po-Chun Hsieh,5,6,* Chou-Chin Lan3,4,* 1Division of Respiratory Therapy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 3Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 4School of Medicine, Tzu-Chi University, Hualien, Taiwan; 5Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 6School of Chinese Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Chou-Chin Lan, Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian City, New Taipei City, 23142, Taiwan, Tel +886-2-6628-9779 ext. 2259, Fax +886-2-6628-9009, Email [email protected]: 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.Materials and Methods: 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).Results: 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.Conclusion: 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.Keywords: asthma, airway inflammation, omalizumab, RNA transcriptome