阿奇霉素增强未控制哮喘患者气道上皮抗病毒免疫：AZIMUNE随机对照试验结果
2026/05/29
摘要
背景：病毒性呼吸道感染是哮喘急性加重的主要原因，哮喘患者气道上皮I 型和 Ⅲ 型干扰素反应减弱，可能导致急性加重更为严重。尽管临床研究已经显示阿奇霉素可减少哮喘急性加重，但其是否通过调节气道上皮抗病毒免疫发挥作用仍不明确。本研究旨在探讨阿奇霉素治疗能否增强未控制哮喘患者气道上皮的抗病毒反应，并调节警报素的水平。
方法：本项为研究者发起的、双盲、安慰剂对照AZIMUNE试验，共纳入40例未控制哮喘成人患者，按1:1随机分配至阿奇霉素组（500 mg，每周 3 次）或安慰剂组（500mg，每周1次），疗程12周。研究者在基线和治疗12周后分别通过支气管镜获取支气管上皮细胞，体外培养后以鼻病毒感染，并定量检测IFN-β、IFN-λ、警报素（IL-33和TSLP）以及促炎性细胞因子的蛋白水平。
结果：与基线相比，阿奇霉素组（n=16）经鼻病毒诱导的IFN-β（p=0.047）和IFN-λ（p=0.013）浓度显著升高，而安慰剂组（n=16）未见明显变化。阿奇霉素组的IL-33（p=0.001）浓度显著下降，但TSLP水平无明显改变。阿奇霉素组的临床结局在数值上有所改善，但差异未达到统计学显著性。
结论：在未控制哮喘患者中，阿奇霉素可增强气道上皮对鼻病毒感染的抗病毒免疫反应，并降低 IL-33水平。这一双重免疫调节作用提示，阿奇霉素可作为预防病毒诱导的哮喘急性加重的辅助治疗药物。
背景：病毒性呼吸道感染是哮喘急性加重的主要原因，哮喘患者气道上皮I 型和 Ⅲ 型干扰素反应减弱，可能导致急性加重更为严重。尽管临床研究已经显示阿奇霉素可减少哮喘急性加重，但其是否通过调节气道上皮抗病毒免疫发挥作用仍不明确。本研究旨在探讨阿奇霉素治疗能否增强未控制哮喘患者气道上皮的抗病毒反应，并调节警报素的水平。
方法：本项为研究者发起的、双盲、安慰剂对照AZIMUNE试验，共纳入40例未控制哮喘成人患者，按1:1随机分配至阿奇霉素组（500 mg，每周 3 次）或安慰剂组（500mg，每周1次），疗程12周。研究者在基线和治疗12周后分别通过支气管镜获取支气管上皮细胞，体外培养后以鼻病毒感染，并定量检测IFN-β、IFN-λ、警报素（IL-33和TSLP）以及促炎性细胞因子的蛋白水平。
结果：与基线相比，阿奇霉素组（n=16）经鼻病毒诱导的IFN-β（p=0.047）和IFN-λ（p=0.013）浓度显著升高，而安慰剂组（n=16）未见明显变化。阿奇霉素组的IL-33（p=0.001）浓度显著下降，但TSLP水平无明显改变。阿奇霉素组的临床结局在数值上有所改善，但差异未达到统计学显著性。
结论：在未控制哮喘患者中，阿奇霉素可增强气道上皮对鼻病毒感染的抗病毒免疫反应，并降低 IL-33水平。这一双重免疫调节作用提示，阿奇霉素可作为预防病毒诱导的哮喘急性加重的辅助治疗药物。
（南方医科大学南方医院 凌嘉骏 赵海金）
(Ghanizada M, Malm Tillgren S, Menzel M, Praeger-Jahnsen L, Said NM, Ditlev S, Sverrild A, Porsbjerg C, Uller L, Lapperre T; AZIMUNE Study Group. Azithromycin enhances epithelial antiviral immunity in uncontrolled asthma: results from the AZIMUNE randomized controlled trial. Eur Respir J. 2026 May 7:2502441. doi: 10.1183/13993003.02441-2025. Epub ahead of print. PMID: 42097684.)
Abstract
Background: Viral respiratory infections are the leading trigger of asthma exacerbations and impaired epithelial type I and Ⅲ interferon responses may contribute to more severe exacerbations. Azithromycin reduces exacerbations clinically, but its effects on epithelial antiviral immunity remain unclear. This study investigated whether azithromycin treatment enhances airway epithelial antiviral responses and modulates alarmin concentration in patients with uncontrolled asthma.
Methods: In the investigator-initiated, double-blind, placebo-controlled AZIMUNE trial, 40 adults with uncontrolled asthma were randomized (1:1) to azithromycin (500 mg, three times/week) or placebo (500 mg/week) for 12 weeks. Bronchial epithelial cells were obtained via bronchoscopy at baseline and after week 12, and cultured and infected ex vivo with rhinovirus. Protein levels of IFN-β, IFN-λ, alarmins (IL-33 and thymic stromal lymphopoietin (TSLP)), and proinflammatory cytokines were quantified.
Results: Azithromycin significantly increased rhinovirus-induced concentration of IFN-β (p=0.047) and IFN-λ (p=0.013) in azithromycin group (n=16) compared with baseline, whereas no change was seen in the placebo group (n=16). Azithromycin treatment also reduced IL-33 concentration (p=0.001), while TSLP levels were unaffected. Clinical outcomes improved numerically in the azithromycin group, but differences versus placebo were not statistically significant.
Conclusions: Azithromycin enhances epithelial antiviral immunity and attenuates IL-33 concentration in response to rhinoviral infection in asthma. The dual immunomodulatory effect of azithromycin supports its role as adjunctive therapy to prevent virus-induced exacerbations.
Abstract
Background: Viral respiratory infections are the leading trigger of asthma exacerbations and impaired epithelial type I and Ⅲ interferon responses may contribute to more severe exacerbations. Azithromycin reduces exacerbations clinically, but its effects on epithelial antiviral immunity remain unclear. This study investigated whether azithromycin treatment enhances airway epithelial antiviral responses and modulates alarmin concentration in patients with uncontrolled asthma.
Methods: In the investigator-initiated, double-blind, placebo-controlled AZIMUNE trial, 40 adults with uncontrolled asthma were randomized (1:1) to azithromycin (500 mg, three times/week) or placebo (500 mg/week) for 12 weeks. Bronchial epithelial cells were obtained via bronchoscopy at baseline and after week 12, and cultured and infected ex vivo with rhinovirus. Protein levels of IFN-β, IFN-λ, alarmins (IL-33 and thymic stromal lymphopoietin (TSLP)), and proinflammatory cytokines were quantified.
Results: Azithromycin significantly increased rhinovirus-induced concentration of IFN-β (p=0.047) and IFN-λ (p=0.013) in azithromycin group (n=16) compared with baseline, whereas no change was seen in the placebo group (n=16). Azithromycin treatment also reduced IL-33 concentration (p=0.001), while TSLP levels were unaffected. Clinical outcomes improved numerically in the azithromycin group, but differences versus placebo were not statistically significant.
Conclusions: Azithromycin enhances epithelial antiviral immunity and attenuates IL-33 concentration in response to rhinoviral infection in asthma. The dual immunomodulatory effect of azithromycin supports its role as adjunctive therapy to prevent virus-induced exacerbations.
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