超越生物标志物：临床因素能否更好地预测重度哮喘的生物制剂疗效？
2026/02/25
摘要
背景：重度哮喘疾病负担沉重，通常需要针对2型炎症的生物制剂治疗。然而，治疗反应存在异质性，传统的生物标志物，如血嗜酸性粒细胞、呼出气一氧化氮（FENO）和血清总IgE，可能无法完全解释这种 variability（变异性）。
目的：旨在评估真实世界重度哮喘患者队列中，与生物制剂治疗反应相关的临床和炎症特征。
方法：本研究是在西班牙拉科鲁尼亚大学附属医院过敏科进行的一项单中心、双向观察性研究。共纳入67例接受奥马珠单抗、美泊利珠单抗、本瑞利珠单抗、度普利尤单抗或特泽培鲁单抗治疗的重度未控制哮喘患者。患者随访时间≥12个月。在基线、治疗4-6个月和12个月时评估临床变量和炎症生物标志物。通过生物制剂亚组间的比较和Logistic回归分析，确定与治疗反应相关的因素。
结果：女性、鼻息肉、血嗜酸性粒细胞升高以及频繁急性发作与更好的生物制剂治疗反应相关。临床因素，如鼻息肉病和阿司匹林加重性呼吸系统疾病（AERD），与标准生物标志物相比，显示出与治疗反应更强的关联性。平均诊断延迟时间为12.1年，提示这可能对治疗结果存在潜在影响。
结论：超越传统的生物标志物，临床因素，尤其是鼻息肉病和AERD，可能在理解生物制剂反应模式中发挥关键作用。将这些变量纳入临床评估，可能有助于在重度哮喘管理中支持更个体化的治疗策略。
关键词： 阿司匹林性哮喘（阿司匹林加重性呼吸系统疾病–AERD）；生物治疗；生物标志物；临床因素；嗜酸性粒细胞增多；鼻息肉；精准医学；重度哮喘。
Background: Severe asthma carries a high burden and often requires biologic therapy targeting type 2 (T2) inflammation. However, treatment response is heterogeneous, and traditional biomarkers, such as blood eosinophils, fractional exhaled nitric oxide (FeNO), and total serum IgE, may not fully explain this variability .
Objective: To evaluate clinical and inflammatory characteristics associated with response to biologic therapies in a real-world cohort of severe asthma patients.
Methods: A single-center, ambispective observational study was conducted in the Allergology Department of A Coruña, Spain. Sixty-seven patients with severe uncontrolled asthma and treated with omalizumab, mepolizumab, benralizumab, dupilumab, or tezepelumab, were included. Patients were followed for ≥12 months. Clinical variables and inflammatory biomarkers were assessed at baseline, 4-6 months, and 12 months. Comparisons between biologic subgroups and logistic regression analyses were performed to identify factors associated with response.
Results: Female sex, nasal polyposis, elevated blood eosinophils, and frequent exacerbations were associated with better response to biologics. Clinical factors such as nasal polyposis and aspirin-exacerbated respiratory disease (AERD) showed a stronger association with treatment response than standard biomarkers (FeNO, blood eosinophils). The mean diagnostic delay was 12.1 years, suggesting a potential influence on therapeutic results.
Conclusion: Beyond traditional biomarkers, clinical factors particulary nasal polyposis and AERD may play a key role in understanding response patterns to biologics. Incorporating these variables into clinical assessment may help support a more personalized management approach in severe asthma.
Keywords: Aspirin-induced asthma (aspirin-exacerbated respiratory disease – AERD); biological therapy; biomarkers; clinical factors; eosinophilia; nasal polyps; precision medicine; severe asthma.
背景：重度哮喘疾病负担沉重，通常需要针对2型炎症的生物制剂治疗。然而，治疗反应存在异质性，传统的生物标志物，如血嗜酸性粒细胞、呼出气一氧化氮（FENO）和血清总IgE，可能无法完全解释这种 variability（变异性）。
目的：旨在评估真实世界重度哮喘患者队列中，与生物制剂治疗反应相关的临床和炎症特征。
方法：本研究是在西班牙拉科鲁尼亚大学附属医院过敏科进行的一项单中心、双向观察性研究。共纳入67例接受奥马珠单抗、美泊利珠单抗、本瑞利珠单抗、度普利尤单抗或特泽培鲁单抗治疗的重度未控制哮喘患者。患者随访时间≥12个月。在基线、治疗4-6个月和12个月时评估临床变量和炎症生物标志物。通过生物制剂亚组间的比较和Logistic回归分析，确定与治疗反应相关的因素。
结果：女性、鼻息肉、血嗜酸性粒细胞升高以及频繁急性发作与更好的生物制剂治疗反应相关。临床因素，如鼻息肉病和阿司匹林加重性呼吸系统疾病（AERD），与标准生物标志物相比，显示出与治疗反应更强的关联性。平均诊断延迟时间为12.1年，提示这可能对治疗结果存在潜在影响。
结论：超越传统的生物标志物，临床因素，尤其是鼻息肉病和AERD，可能在理解生物制剂反应模式中发挥关键作用。将这些变量纳入临床评估，可能有助于在重度哮喘管理中支持更个体化的治疗策略。
关键词： 阿司匹林性哮喘（阿司匹林加重性呼吸系统疾病–AERD）；生物治疗；生物标志物；临床因素；嗜酸性粒细胞增多；鼻息肉；精准医学；重度哮喘。
（南方医科大学南方医院 杨跞予 赵文驱 赵海金）
Lopez-Rodríguez R,et al.Beyond biomarkers: the role of clinical factors associated with biologic therapy response in severe asthma
Ann Med. 2026 Dec;58(1):2627026.
AbstractAnn Med. 2026 Dec;58(1):2627026.
Background: Severe asthma carries a high burden and often requires biologic therapy targeting type 2 (T2) inflammation. However, treatment response is heterogeneous, and traditional biomarkers, such as blood eosinophils, fractional exhaled nitric oxide (FeNO), and total serum IgE, may not fully explain this variability .
Objective: To evaluate clinical and inflammatory characteristics associated with response to biologic therapies in a real-world cohort of severe asthma patients.
Methods: A single-center, ambispective observational study was conducted in the Allergology Department of A Coruña, Spain. Sixty-seven patients with severe uncontrolled asthma and treated with omalizumab, mepolizumab, benralizumab, dupilumab, or tezepelumab, were included. Patients were followed for ≥12 months. Clinical variables and inflammatory biomarkers were assessed at baseline, 4-6 months, and 12 months. Comparisons between biologic subgroups and logistic regression analyses were performed to identify factors associated with response.
Results: Female sex, nasal polyposis, elevated blood eosinophils, and frequent exacerbations were associated with better response to biologics. Clinical factors such as nasal polyposis and aspirin-exacerbated respiratory disease (AERD) showed a stronger association with treatment response than standard biomarkers (FeNO, blood eosinophils). The mean diagnostic delay was 12.1 years, suggesting a potential influence on therapeutic results.
Conclusion: Beyond traditional biomarkers, clinical factors particulary nasal polyposis and AERD may play a key role in understanding response patterns to biologics. Incorporating these variables into clinical assessment may help support a more personalized management approach in severe asthma.
Keywords: Aspirin-induced asthma (aspirin-exacerbated respiratory disease – AERD); biological therapy; biomarkers; clinical factors; eosinophilia; nasal polyps; precision medicine; severe asthma.
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年龄因素在重度未控制哮喘患者气道炎症与功能中的差异性影响
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重度哮喘治疗中“生物学缓解”作为治疗目标的临床观察研究：基于英国重度哮喘注册数据的分析
