度普利尤单抗对持续性哮喘患者气道炎症的影响
2026/06/30
摘要
背景：靶向2型细胞因子的生物制剂可抑制中重度哮喘患者的气道炎症并改善肺功能，但其对气道黏膜炎症细胞的影响尚不明确。
目的：本研究旨在评估度普利尤单抗对持续性哮喘患者气道黏膜炎症、全身性炎症及相关基因表达的影响。
方法： 在2a期EXPEDITION研究（NCT02573233）中，将年龄18~65岁的患者随机分配至每2周皮下注射度普利尤单抗300 mg（n=20）或安慰剂（n=22）作为附加治疗，持续12周。分别于治疗前后采集支气管活检组织、支气管刷检物、支气管肺泡灌洗液及外周血标本。评估指标包括临床结局、患者报告结局、基因表达、2型生物标志物及安全性结局。
结果：与安慰剂相比，度普利尤单抗可改善肺功能和哮喘控制水平。支气管活检组织中嗜酸性粒细胞、肥大细胞及2型辅助性T细胞数量未见显著变化。度普利尤单抗治疗后，支气管肺泡灌洗液及刷检标本中M2型巨噬细胞和嗜酸性粒细胞相关基因集表达呈下调趋势。与安慰剂相比，度普利尤单抗可降低外周血中多种循环2型生物标志物水平（未校正P<0.001，校正后P<0.01），并减少支气管活检组织中杯状细胞数量（未校正P=0.0336；校正后P=0.2554）及黏液面积（未校正P=0.0426；校正后P=0.2554）。安全性特征与度普利尤单抗已知安全性数据一致。
结论：度普利尤单抗可改善肺功能和哮喘控制，同时降低循环2型生物标志物水平。虽然气道支气管活检组织中2型相关炎症细胞数量未见可测量的显著变化，但度普利尤单抗可调节炎症相关基因集的表达。上述发现从细胞和分子层面为阐明度普利尤单抗改善2型哮喘患者肺功能的驱动机制提供了证据。
Effect of Dupilumab on Airway Inflammation in Patients With Persistent Asthma.
Michael E, Wechsler; Sally E,
Abstract
BACKGROUND: Biologics targeting type 2 cytokines can inhibit airway inflammation and improve lung function in moderate-to-severe asthma; however, their impact on airway mucosal inflammatory cells is unclear.
OBJECTIVE: This study assessed the effects of dupilumab on airway mucosal and systemic inflammation, and related gene expression in patients with persistent asthma.
METHODS: In the phase 2a EXPEDITION study (NCT02573233), patients aged 18-65 years were randomised to add-on dupilumab 300 mg (n = 20) or placebo (n = 22) every 2 weeks for 12 weeks. Pre- and post-treatment bronchial biopsies, bronchial brushings, bronchoalveolar lavage (BAL) fluid and blood samples were collected. Clinical and patient-reported outcomes, gene expression, type 2 biomarkers and safety outcomes were assessed.
RESULTS: Dupilumab versus placebo improved lung function and asthma control. No significant changes in eosinophils, mast cells or type 2 helper cells were observed in bronchial biopsies. Downregulation of M2 macrophage- and eosinophil-associated gene sets was observed in BAL and brushing samples after dupilumab. Dupilumab decreased multiple circulating type 2 biomarkers in peripheral blood (p(unadj) < 0.001, p(adj) < 0.01), goblet cell numbers (p(unadj) = 0.0336; p(adj) = 0.2554) and mucus area (p(unadj) = 0.0426; p(adj) = 0.2554) in bronchial biopsies versus placebo. The safety profile was consistent with the known safety profile of dupilumab.
CONCLUSION: Dupilumab improved lung function and asthma control while reducing circulating type 2 biomarkers. No measurable impact was observed on type 2-associated inflammatory cell numbers in airway bronchial biopsies; however, dupilumab modulated the expression of inflammation-associated gene sets. These findings provide cellular and molecular data that may explain dupilumab-driven mechanisms of improved lung function in patients with type 2 asthma.
背景：靶向2型细胞因子的生物制剂可抑制中重度哮喘患者的气道炎症并改善肺功能，但其对气道黏膜炎症细胞的影响尚不明确。
目的：本研究旨在评估度普利尤单抗对持续性哮喘患者气道黏膜炎症、全身性炎症及相关基因表达的影响。
方法： 在2a期EXPEDITION研究（NCT02573233）中，将年龄18~65岁的患者随机分配至每2周皮下注射度普利尤单抗300 mg（n=20）或安慰剂（n=22）作为附加治疗，持续12周。分别于治疗前后采集支气管活检组织、支气管刷检物、支气管肺泡灌洗液及外周血标本。评估指标包括临床结局、患者报告结局、基因表达、2型生物标志物及安全性结局。
结果：与安慰剂相比，度普利尤单抗可改善肺功能和哮喘控制水平。支气管活检组织中嗜酸性粒细胞、肥大细胞及2型辅助性T细胞数量未见显著变化。度普利尤单抗治疗后，支气管肺泡灌洗液及刷检标本中M2型巨噬细胞和嗜酸性粒细胞相关基因集表达呈下调趋势。与安慰剂相比，度普利尤单抗可降低外周血中多种循环2型生物标志物水平（未校正P<0.001，校正后P<0.01），并减少支气管活检组织中杯状细胞数量（未校正P=0.0336；校正后P=0.2554）及黏液面积（未校正P=0.0426；校正后P=0.2554）。安全性特征与度普利尤单抗已知安全性数据一致。
结论：度普利尤单抗可改善肺功能和哮喘控制，同时降低循环2型生物标志物水平。虽然气道支气管活检组织中2型相关炎症细胞数量未见可测量的显著变化，但度普利尤单抗可调节炎症相关基因集的表达。上述发现从细胞和分子层面为阐明度普利尤单抗改善2型哮喘患者肺功能的驱动机制提供了证据。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Allergy 2026 May 29;(0)DOI：10.1111/all.70391. IF: 8.706）
（Allergy 2026 May 29;(0)DOI：10.1111/all.70391. IF: 8.706）
Effect of Dupilumab on Airway Inflammation in Patients With Persistent Asthma.
Michael E, Wechsler; Sally E,
Abstract
BACKGROUND: Biologics targeting type 2 cytokines can inhibit airway inflammation and improve lung function in moderate-to-severe asthma; however, their impact on airway mucosal inflammatory cells is unclear.
OBJECTIVE: This study assessed the effects of dupilumab on airway mucosal and systemic inflammation, and related gene expression in patients with persistent asthma.
METHODS: In the phase 2a EXPEDITION study (NCT02573233), patients aged 18-65 years were randomised to add-on dupilumab 300 mg (n = 20) or placebo (n = 22) every 2 weeks for 12 weeks. Pre- and post-treatment bronchial biopsies, bronchial brushings, bronchoalveolar lavage (BAL) fluid and blood samples were collected. Clinical and patient-reported outcomes, gene expression, type 2 biomarkers and safety outcomes were assessed.
RESULTS: Dupilumab versus placebo improved lung function and asthma control. No significant changes in eosinophils, mast cells or type 2 helper cells were observed in bronchial biopsies. Downregulation of M2 macrophage- and eosinophil-associated gene sets was observed in BAL and brushing samples after dupilumab. Dupilumab decreased multiple circulating type 2 biomarkers in peripheral blood (p(unadj) < 0.001, p(adj) < 0.01), goblet cell numbers (p(unadj) = 0.0336; p(adj) = 0.2554) and mucus area (p(unadj) = 0.0426; p(adj) = 0.2554) in bronchial biopsies versus placebo. The safety profile was consistent with the known safety profile of dupilumab.
CONCLUSION: Dupilumab improved lung function and asthma control while reducing circulating type 2 biomarkers. No measurable impact was observed on type 2-associated inflammatory cell numbers in airway bronchial biopsies; however, dupilumab modulated the expression of inflammation-associated gene sets. These findings provide cellular and molecular data that may explain dupilumab-driven mechanisms of improved lung function in patients with type 2 asthma.
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