精准预测生物制剂疗效：重度哮喘治疗前FeNO水平指导抗IL-4Rα用药
2025/10/27
背景：重度嗜酸性粒细胞性哮喘患者治疗前的血嗜酸性粒细胞计数（BEC）、呼出气一氧化氮分数（FENO）与痰嗜酸性粒细胞（Sp-EOS）水平与单克隆抗体（mAb）治疗反应之间的关系尚不明确。我们评估了接受抗白细胞介素（IL）-5/IL-5Rα或抗IL-4Rα抗体治疗的SEA患者，治疗前BEC、FENO、Sp-EOS及其组合对疗效反应的预测价值。
方法：本研究纳入153例成年SEA患者（其中抗IL-5/IL-5Rα 59例，抗IL-4Rα 94例）。采用逻辑回归模型评估上述预测因子与12个月疗效反应及临床缓解之间的关联，覆盖四个领域：恶化率、口服糖皮质激素维持剂量、第一秒用力呼气量（FEV₁）以及哮喘控制测试（ACT）改善。
结果：在任一mAb治疗组内，治疗前BEC与Sp-EOS均与疗效反应无明显相关性。将抗IL-5/IL-5Rα与抗IL-4Rα两组数据合并分析后，FENO经对数转换每增加1个单位，其调整后的比值比（95%置信区间）为：FEV₁反应1.80（1.21–2.74），ACT反应2.15（1.29–3.75）。在抗IL-4Rα使用者中，相应数值分别为2.34（1.39–4.17）与3.60（1.73–8.84）；而在抗IL-5/IL-5Rα使用患者中，FENO与疗效反应无明显关联。此外，在不同mAb类别中，BEC、Sp-EOS或FENO与临床缓解均无显著相关性。多标志物联合亦未显著提升预测能力。
结论：在接受抗IL-4Rα抗体治疗的SEA患者中，治疗前FENO可能是某些疗效反应的良好预测指标。
关键词：2型炎症生物标志物，重度嗜酸性粒细胞性哮喘，生物制剂/单克隆抗体，抗IL-4Rα，抗IL-5/IL-5Rα，呼出气一氧化氮分数，血嗜酸性粒细胞计数，痰嗜酸性粒细胞，治疗反应预测，临床缓解
Abstract
Background: The relationship between pre-treatment levels of blood eosinophil count (BEC), fractional exhaled nitric oxide (FENO) and sputum eosinophils (Sp-EOS) and treatment response to monoclonal antibodies (mAbs) in severe eosinophilic asthma (SEA) remains unclear. We evaluated pre-treatment levels of BEC, FENO, Sp-EOS and their combinations as predictors of treatment responses in patients with SEA undergoing anti-interleukin (IL)-5/IL-5Rα or anti-IL-4Rα antibody therapies.
Methods: The study included 153 adult patients with SEA (59 anti-IL-5/IL-5Rα and 94 anti-IL-4Rα users). Logistic regression models were used to evaluate the association between predictors and 12-month treatment responses and clinical remission across four domains: exacerbation rate, maintenance of oral corticosteroid dose, forced expiratory volume in 1 s (FEV1) and asthma control test (ACT) improvement.
Results：Pre-treatment BEC and Sp-EOS were not associated with treatment responses in either mAb group. For combined data from anti-IL-5/IL-5Rα and anti-IL-4Rα users, the adjusted odds ratios (95% confidence intervals) for a 1-unit increase in log-transformed FENO were 1.8 (1.21–2.74) for FEV1 response and 2.15 (1.29–3.75) for ACT response. For anti-IL-4Rα users, these values were 2.34 (1.39–4.17) and 3.6 (1.73–8.84), respectively. No significant association between FENO and treatment response was found among anti-IL-5/IL-5Rα users. Additionally, no associations were observed between BEC, Sp-EOS or FENO and clinical remission across mAb categories. Combining biomarkers did not significantly enhance predictive ability.
Conclusion：In patients with SEA treated with anti-IL-4Rα antibodies, pre-treatment FENO may be a good predictor for certain treatment response domains.
Key words: Type 2 inflammation biomarkers, severe eosinophilic asthma, biologics/monoclonal antibodies, anti-IL-4Rα, anti-IL-5/IL-5Rα, fractional exhaled nitric oxide, blood eosinophil count, sputum eosinophils, treatment response prediction, clinical remission
方法：本研究纳入153例成年SEA患者（其中抗IL-5/IL-5Rα 59例，抗IL-4Rα 94例）。采用逻辑回归模型评估上述预测因子与12个月疗效反应及临床缓解之间的关联，覆盖四个领域：恶化率、口服糖皮质激素维持剂量、第一秒用力呼气量（FEV₁）以及哮喘控制测试（ACT）改善。
结果：在任一mAb治疗组内，治疗前BEC与Sp-EOS均与疗效反应无明显相关性。将抗IL-5/IL-5Rα与抗IL-4Rα两组数据合并分析后，FENO经对数转换每增加1个单位，其调整后的比值比（95%置信区间）为：FEV₁反应1.80（1.21–2.74），ACT反应2.15（1.29–3.75）。在抗IL-4Rα使用者中，相应数值分别为2.34（1.39–4.17）与3.60（1.73–8.84）；而在抗IL-5/IL-5Rα使用患者中，FENO与疗效反应无明显关联。此外，在不同mAb类别中，BEC、Sp-EOS或FENO与临床缓解均无显著相关性。多标志物联合亦未显著提升预测能力。
结论：在接受抗IL-4Rα抗体治疗的SEA患者中，治疗前FENO可能是某些疗效反应的良好预测指标。
关键词：2型炎症生物标志物，重度嗜酸性粒细胞性哮喘，生物制剂/单克隆抗体，抗IL-4Rα，抗IL-5/IL-5Rα，呼出气一氧化氮分数，血嗜酸性粒细胞计数，痰嗜酸性粒细胞，治疗反应预测，临床缓解
（南方医科大学南方医院 黄海伦 龚钊乾 赵海金）
（Pham D D, Lee J H, Kwon H S, et al. Biomarkers of type 2 inflammation as predictors of response to biologics for severe eosinophilic asthma[J]. ERJ Open Research, 2025, 11(4): 969-2024. DOI: 10.1183/23120541.00969-2024.）
（Pham D D, Lee J H, Kwon H S, et al. Biomarkers of type 2 inflammation as predictors of response to biologics for severe eosinophilic asthma[J]. ERJ Open Research, 2025, 11(4): 969-2024. DOI: 10.1183/23120541.00969-2024.）
Abstract
Background: The relationship between pre-treatment levels of blood eosinophil count (BEC), fractional exhaled nitric oxide (FENO) and sputum eosinophils (Sp-EOS) and treatment response to monoclonal antibodies (mAbs) in severe eosinophilic asthma (SEA) remains unclear. We evaluated pre-treatment levels of BEC, FENO, Sp-EOS and their combinations as predictors of treatment responses in patients with SEA undergoing anti-interleukin (IL)-5/IL-5Rα or anti-IL-4Rα antibody therapies.
Methods: The study included 153 adult patients with SEA (59 anti-IL-5/IL-5Rα and 94 anti-IL-4Rα users). Logistic regression models were used to evaluate the association between predictors and 12-month treatment responses and clinical remission across four domains: exacerbation rate, maintenance of oral corticosteroid dose, forced expiratory volume in 1 s (FEV1) and asthma control test (ACT) improvement.
Results：Pre-treatment BEC and Sp-EOS were not associated with treatment responses in either mAb group. For combined data from anti-IL-5/IL-5Rα and anti-IL-4Rα users, the adjusted odds ratios (95% confidence intervals) for a 1-unit increase in log-transformed FENO were 1.8 (1.21–2.74) for FEV1 response and 2.15 (1.29–3.75) for ACT response. For anti-IL-4Rα users, these values were 2.34 (1.39–4.17) and 3.6 (1.73–8.84), respectively. No significant association between FENO and treatment response was found among anti-IL-5/IL-5Rα users. Additionally, no associations were observed between BEC, Sp-EOS or FENO and clinical remission across mAb categories. Combining biomarkers did not significantly enhance predictive ability.
Conclusion：In patients with SEA treated with anti-IL-4Rα antibodies, pre-treatment FENO may be a good predictor for certain treatment response domains.
Key words: Type 2 inflammation biomarkers, severe eosinophilic asthma, biologics/monoclonal antibodies, anti-IL-4Rα, anti-IL-5/IL-5Rα, fractional exhaled nitric oxide, blood eosinophil count, sputum eosinophils, treatment response prediction, clinical remission
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空气污染促进哮喘发展为COPD
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