生物制剂减少重度哮喘患者阻塞性黏液栓有效性的系统综述
2026/02/25
摘要
哮喘是一种以慢性气道炎症和可逆性气流阻塞为特征的异质性疾病。尤其在重度哮喘中，尽管使用了吸入性糖皮质激素和支气管扩张剂治疗，气道黏液栓仍可导致显著且持续的气流阻塞。因此，临床医生评估和处理黏液栓至关重要。由2型炎症引起的黏液分泌增加和气道嗜酸性粒细胞增多促进了黏液栓的形成和持续存在。目前已有多种靶向2型炎症的生物制剂可用于哮喘治疗，相关研究通过基于CT扫描的黏液栓评分描述了它们对气道黏液栓的影响。然而，这些研究的结果、设计和人群尚未得到全面总结。作者通过文献检索，筛选出探讨生物制剂对中重度哮喘患者黏液栓影响的主要研究，并按研究设计和人群进行归类。共发现三项安慰剂对照随机对照试验（RCT）：一项针对tezepelumab的研究纳入了不同基线血嗜酸性粒细胞计数和呼出气一氧化氮分数（FENO）水平的患者，两项针对dupilumab的研究则纳入了血嗜酸性粒细胞或痰嗜酸性粒细胞升高和/或FENO升高的患者。这些RCT结果显示，与安慰剂相比，生物制剂治疗降低了黏液栓评分。在tezepelumab的RCT中，2型高哮喘患者的疗效更为显著，凸显了黏液栓形成与2型炎症之间的关联。在2型高人群中，各生物制剂的疗效幅度相似。其他生物制剂（本瑞利珠单抗、美泊利珠单抗、奥马珠单抗和瑞利珠单抗）在无安慰剂对照的观察性研究中进行了评估，结果显示治疗后黏液栓评分有所降低。在多项研究中，生物制剂治疗后黏液栓的减少与功能指标的改善相关，包括支气管扩张剂前第1秒用力呼气容积（FEV1）、空气潴留、磁共振成像评估的通气缺陷、哮喘控制以及健康相关生活质量。所有研究均显示，生物制剂干预后仍存在残留栓子，这表明需要进一步了解如何最佳量化和表征黏液栓，以预测其对治疗的反应，并制定优化的个体化治疗策略。本综述强调了在临床实践中评估和处理黏液栓对于优化患者结局的重要性。
关键词： 贝那利珠单抗；生物制剂；度普利尤单抗；美泊利珠单抗；黏液栓；奥马珠单抗；重度哮喘；Tezepelumab
Asthma is a heterogeneous disease characterized by chronic airway inflammation and reversible airflow obstruction. Particularly in severe asthma, airway mucus plugs can contribute to substantial and persistent airflow obstruction, despite inhaled corticosteroid and bronchodilator treatment. Consequently, it is important that clinicians assess and treat mucus plugs. Increased mucus production and airway eosinophilia caused by type 2 (T2) inflammation contributes to mucus plug formation and persistence. Several biologics are available to target T2 inflammation in asthma and studies have described their effects on airway mucus plugs using mucus plug scoring derived from computed tomography scans. However, the outcomes, designs and populations of the various studies have not been comprehensively summarized. A literature search was performed to identify primary publications examining the effects of biologics on mucus plugs in patients with moderate-to-severe asthma, organizing studies by design and study population. Three placebo-controlled randomized controlled trials (RCTs) were identified; one RCT of tezepelumab in patients across baseline blood eosinophil counts (BECs) and fractional exhaled nitric oxide (FeNO) levels and two RCTs of dupilumab in those with elevated BECs or sputum eosinophils and/or elevated FeNO levels. Across these RCTs, biologic treatment decreased mucus plug scores compared with placebo. In the tezepelumab RCT, greater effects were observed in patients with T2-high asthma, highlighting the association between mucus plugging and T2 inflammation. Among T2-high populations, effects were of a similar magnitude across biologics studied. Other biologics (benralizumab, mepolizumab, omalizumab and reslizumab) were evaluated in observational studies without a placebo control, demonstrating reductions in mucus plug scores after treatment. In several studies, decreases in mucus plugs with biologic treatment were associated with improvements in functional outcomes, including pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), air trapping, ventilation defects assessed by magnetic resonance imaging, asthma control and health-related quality of life. All studies showed residual plugs after biologic intervention, demonstrating a need for further understanding of how best to quantify and characterize mucus plugs to predict their response to treatment and develop optimal, individualised treatment strategies. This review highlights the relevance of assessing and targeting mucus plugs in clinical practice to help optimise patient outcomes.
Keywords: Benralizumab; Biologics; Dupilumab; Mepolizumab; Mucus plugs; Omalizumab; Severe asthma; Tezepelumab.
哮喘是一种以慢性气道炎症和可逆性气流阻塞为特征的异质性疾病。尤其在重度哮喘中，尽管使用了吸入性糖皮质激素和支气管扩张剂治疗，气道黏液栓仍可导致显著且持续的气流阻塞。因此，临床医生评估和处理黏液栓至关重要。由2型炎症引起的黏液分泌增加和气道嗜酸性粒细胞增多促进了黏液栓的形成和持续存在。目前已有多种靶向2型炎症的生物制剂可用于哮喘治疗，相关研究通过基于CT扫描的黏液栓评分描述了它们对气道黏液栓的影响。然而，这些研究的结果、设计和人群尚未得到全面总结。作者通过文献检索，筛选出探讨生物制剂对中重度哮喘患者黏液栓影响的主要研究，并按研究设计和人群进行归类。共发现三项安慰剂对照随机对照试验（RCT）：一项针对tezepelumab的研究纳入了不同基线血嗜酸性粒细胞计数和呼出气一氧化氮分数（FENO）水平的患者，两项针对dupilumab的研究则纳入了血嗜酸性粒细胞或痰嗜酸性粒细胞升高和/或FENO升高的患者。这些RCT结果显示，与安慰剂相比，生物制剂治疗降低了黏液栓评分。在tezepelumab的RCT中，2型高哮喘患者的疗效更为显著，凸显了黏液栓形成与2型炎症之间的关联。在2型高人群中，各生物制剂的疗效幅度相似。其他生物制剂（本瑞利珠单抗、美泊利珠单抗、奥马珠单抗和瑞利珠单抗）在无安慰剂对照的观察性研究中进行了评估，结果显示治疗后黏液栓评分有所降低。在多项研究中，生物制剂治疗后黏液栓的减少与功能指标的改善相关，包括支气管扩张剂前第1秒用力呼气容积（FEV1）、空气潴留、磁共振成像评估的通气缺陷、哮喘控制以及健康相关生活质量。所有研究均显示，生物制剂干预后仍存在残留栓子，这表明需要进一步了解如何最佳量化和表征黏液栓，以预测其对治疗的反应，并制定优化的个体化治疗策略。本综述强调了在临床实践中评估和处理黏液栓对于优化患者结局的重要性。
关键词： 贝那利珠单抗；生物制剂；度普利尤单抗；美泊利珠单抗；黏液栓；奥马珠单抗；重度哮喘；Tezepelumab
（南方医科大学南方医院 欧阳文珊 赵文驱 赵海金）
（Aegerter H, et al.Effectiveness of biologics for reducing occlusive mucus plugs in patients with severe asthma: a systematic review Respir Res. 2026 Jan 21. doi: 10.1186/s12931-026-03501-z.）
Abstract（Aegerter H, et al.Effectiveness of biologics for reducing occlusive mucus plugs in patients with severe asthma: a systematic review Respir Res. 2026 Jan 21. doi: 10.1186/s12931-026-03501-z.）
Asthma is a heterogeneous disease characterized by chronic airway inflammation and reversible airflow obstruction. Particularly in severe asthma, airway mucus plugs can contribute to substantial and persistent airflow obstruction, despite inhaled corticosteroid and bronchodilator treatment. Consequently, it is important that clinicians assess and treat mucus plugs. Increased mucus production and airway eosinophilia caused by type 2 (T2) inflammation contributes to mucus plug formation and persistence. Several biologics are available to target T2 inflammation in asthma and studies have described their effects on airway mucus plugs using mucus plug scoring derived from computed tomography scans. However, the outcomes, designs and populations of the various studies have not been comprehensively summarized. A literature search was performed to identify primary publications examining the effects of biologics on mucus plugs in patients with moderate-to-severe asthma, organizing studies by design and study population. Three placebo-controlled randomized controlled trials (RCTs) were identified; one RCT of tezepelumab in patients across baseline blood eosinophil counts (BECs) and fractional exhaled nitric oxide (FeNO) levels and two RCTs of dupilumab in those with elevated BECs or sputum eosinophils and/or elevated FeNO levels. Across these RCTs, biologic treatment decreased mucus plug scores compared with placebo. In the tezepelumab RCT, greater effects were observed in patients with T2-high asthma, highlighting the association between mucus plugging and T2 inflammation. Among T2-high populations, effects were of a similar magnitude across biologics studied. Other biologics (benralizumab, mepolizumab, omalizumab and reslizumab) were evaluated in observational studies without a placebo control, demonstrating reductions in mucus plug scores after treatment. In several studies, decreases in mucus plugs with biologic treatment were associated with improvements in functional outcomes, including pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), air trapping, ventilation defects assessed by magnetic resonance imaging, asthma control and health-related quality of life. All studies showed residual plugs after biologic intervention, demonstrating a need for further understanding of how best to quantify and characterize mucus plugs to predict their response to treatment and develop optimal, individualised treatment strategies. This review highlights the relevance of assessing and targeting mucus plugs in clinical practice to help optimise patient outcomes.
Keywords: Benralizumab; Biologics; Dupilumab; Mepolizumab; Mucus plugs; Omalizumab; Severe asthma; Tezepelumab.
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性别不影响临床风险因素和2型生物标志物对哮喘急性发作的预测价值
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生物标志物在慢性气道疾病
