度普利尤单抗可降低哮喘患者痰液的放射密度并减少新痰栓形成
2026/04/28
摘要
背景：度普利尤单抗是一种白细胞介素（IL）-4和IL-13拮抗剂，可减轻哮喘患者计算机断层扫描（CT）可见的黏液栓负担。
研究问题：度普利尤单抗是否会改变中重度哮喘患者CT可见的单个黏液栓的体积、放射密度和时空行为？
研究设计与方法：对32名中重度哮喘成人患者进行评估；其中22人每2周接受一次度普利尤单抗治疗，至少持续16周，10人作为对照组。对基线和随访时CT扫描可见的所有黏液栓进行标注，以评估黏液栓数量、体积和放射密度。对单个黏液栓进行纵向评估，并将其分类为已消除、固定位置持续存在（FLP）或新出现。
结果：使用度普利尤单抗后，黏液评分、黏液栓总数和黏液栓总体积的降低幅度均大于对照组，且与第用力1秒呼气容积（FEV₁）、FEV₁/用力肺活量（FVC）以及¹²⁹氙磁共振成像通气缺陷百分比（VDP）的改善相关（所有p < 0.05）。接受度普利尤单抗治疗的患者中，36%的患者黏液栓完全消除（对照组为10%），59%的患者黏液栓未完全消除（对照组为80%）。与对照组相比，接受度普利尤单抗治疗的患者黏液栓消除比例更高（91% vs. 58%，p < 0.0001），固定位置持续存在的黏液栓（FLP）和新出现的黏液栓更少（9% vs. 42%，p < 0.0001；1[0 - 5] vs. 6[0 - 18]，p = 0.0008）。使用度普利尤单抗后，固定位置持续存在的黏液栓放射密度降低（从 - 422HU [- 759 - (- 5)]降至 - 569HU [- 738 - (- 258)]，p = 0.009），且与对照组相比，接受度普利尤单抗治疗的患者新出现的黏液栓放射密度更低（ - 573HU [- 765 - (- 320)] vs. - 387HU [- 662 - (- 26)]，p = 0.0006）。黏液栓未完全消除的患者与完全消除的患者相比，VDP持续处于较高水平（p < 0.05）。
解释：度普利尤单抗通过消除持续存在的黏液栓和减少新黏液栓的形成，减轻哮喘患者的黏液负担。尽管部分患者的黏液栓完全消除，但残留的低放射密度持续存在和新出现的黏液栓仍具有功能相关性。
Dupilumab Reduces Mucus Radiodensity and New Plug Formation in Asthma
Ekamdeep Sandhu, Nandhitha Ragunayakam, Anusha A Mappanasingam, Yonni Friedlander, Carmen Venegas Garrido, Melanie Kjarsgaard, Ashutosh Thakar, Nisarg Radadia, Manali Mukherjee, Parameswaran Nair, Sarah Svenningsen
Abstract
Background: Dupilumab, an interleukin (IL)-4 and IL-13 antagonist, reduces the burden of mucus plugs visualized by computed tomography (CT) in asthma.
Research question: Does dupilumab modify the volume, radiodensity, and temporospatial behaviour of individual CT-visible mucus plugs in patients with moderate-to-severe asthma?
Study design and methods: Thirty-two adults with moderate-to-severe asthma were evaluated; 22 received dupilumab every 2-weeks for at-least 16-weeks, and 10 were in the control group. All mucus plugs visible on CT scans acquired at baseline and follow-up were annotated to evaluate plug count, volume, and radiodensity. Individual plugs were assessed longitudinally and classified as resolved, fixed-location persistent (FLP), or new-onset.
Results: Post-dupilumab reductions in mucus score, total mucus plug count, and total plug volume were greater than control and associated with improved FEV1, FEV1/FVC, and 129Xe magnetic resonance imaging ventilation defect percent (VDP) (all p<0.05). 36% of dupilumab-treated participants had complete resolution (control: 10%) and 59% had incomplete resolution of mucus plugs (control: 80%). Compared to control, dupilumab-treated participants had more resolved (91% vs. 58%, p<0.0001), and fewer FLPs (9% vs. 42%, p<0.0001) and new-onset plugs (1[0-5] vs. 6[0-18], p=0.0008). Radiodensity of FLPs decreased post-dupilumab (-422HU [-759-(-5)] to -569HU [-738-(-258)], p=0.009), and new-onset plugs had lower radiodensity in dupilumab-treated participants compared to control (-573HU [-765-(-320)] vs. -387HU [-662-(-26)], p=0.0006). Participants with incomplete resolution had persistently higher VDP compared to those with complete resolution (p<0.05).
Interpretation: Dupilumab reduces mucus burden in asthma by resolving persistent plugs and decreasing the formation of new plugs. Despite complete resolution in a subset of participants, residual low-radiodensity persistent and new-onset plugs are functionally relevant.
背景：度普利尤单抗是一种白细胞介素（IL）-4和IL-13拮抗剂，可减轻哮喘患者计算机断层扫描（CT）可见的黏液栓负担。
研究问题：度普利尤单抗是否会改变中重度哮喘患者CT可见的单个黏液栓的体积、放射密度和时空行为？
研究设计与方法：对32名中重度哮喘成人患者进行评估；其中22人每2周接受一次度普利尤单抗治疗，至少持续16周，10人作为对照组。对基线和随访时CT扫描可见的所有黏液栓进行标注，以评估黏液栓数量、体积和放射密度。对单个黏液栓进行纵向评估，并将其分类为已消除、固定位置持续存在（FLP）或新出现。
结果：使用度普利尤单抗后，黏液评分、黏液栓总数和黏液栓总体积的降低幅度均大于对照组，且与第用力1秒呼气容积（FEV₁）、FEV₁/用力肺活量（FVC）以及¹²⁹氙磁共振成像通气缺陷百分比（VDP）的改善相关（所有p < 0.05）。接受度普利尤单抗治疗的患者中，36%的患者黏液栓完全消除（对照组为10%），59%的患者黏液栓未完全消除（对照组为80%）。与对照组相比，接受度普利尤单抗治疗的患者黏液栓消除比例更高（91% vs. 58%，p < 0.0001），固定位置持续存在的黏液栓（FLP）和新出现的黏液栓更少（9% vs. 42%，p < 0.0001；1[0 - 5] vs. 6[0 - 18]，p = 0.0008）。使用度普利尤单抗后，固定位置持续存在的黏液栓放射密度降低（从 - 422HU [- 759 - (- 5)]降至 - 569HU [- 738 - (- 258)]，p = 0.009），且与对照组相比，接受度普利尤单抗治疗的患者新出现的黏液栓放射密度更低（ - 573HU [- 765 - (- 320)] vs. - 387HU [- 662 - (- 26)]，p = 0.0006）。黏液栓未完全消除的患者与完全消除的患者相比，VDP持续处于较高水平（p < 0.05）。
解释：度普利尤单抗通过消除持续存在的黏液栓和减少新黏液栓的形成，减轻哮喘患者的黏液负担。尽管部分患者的黏液栓完全消除，但残留的低放射密度持续存在和新出现的黏液栓仍具有功能相关性。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Chest. 2026 Apr 21:S0012-3692(26)00465-4. doi: 10.1016/j.chest.2026.03.041.）
（Chest. 2026 Apr 21:S0012-3692(26)00465-4. doi: 10.1016/j.chest.2026.03.041.）
Dupilumab Reduces Mucus Radiodensity and New Plug Formation in Asthma
Ekamdeep Sandhu, Nandhitha Ragunayakam, Anusha A Mappanasingam, Yonni Friedlander, Carmen Venegas Garrido, Melanie Kjarsgaard, Ashutosh Thakar, Nisarg Radadia, Manali Mukherjee, Parameswaran Nair, Sarah Svenningsen
Abstract
Background: Dupilumab, an interleukin (IL)-4 and IL-13 antagonist, reduces the burden of mucus plugs visualized by computed tomography (CT) in asthma.
Research question: Does dupilumab modify the volume, radiodensity, and temporospatial behaviour of individual CT-visible mucus plugs in patients with moderate-to-severe asthma?
Study design and methods: Thirty-two adults with moderate-to-severe asthma were evaluated; 22 received dupilumab every 2-weeks for at-least 16-weeks, and 10 were in the control group. All mucus plugs visible on CT scans acquired at baseline and follow-up were annotated to evaluate plug count, volume, and radiodensity. Individual plugs were assessed longitudinally and classified as resolved, fixed-location persistent (FLP), or new-onset.
Results: Post-dupilumab reductions in mucus score, total mucus plug count, and total plug volume were greater than control and associated with improved FEV1, FEV1/FVC, and 129Xe magnetic resonance imaging ventilation defect percent (VDP) (all p<0.05). 36% of dupilumab-treated participants had complete resolution (control: 10%) and 59% had incomplete resolution of mucus plugs (control: 80%). Compared to control, dupilumab-treated participants had more resolved (91% vs. 58%, p<0.0001), and fewer FLPs (9% vs. 42%, p<0.0001) and new-onset plugs (1[0-5] vs. 6[0-18], p=0.0008). Radiodensity of FLPs decreased post-dupilumab (-422HU [-759-(-5)] to -569HU [-738-(-258)], p=0.009), and new-onset plugs had lower radiodensity in dupilumab-treated participants compared to control (-573HU [-765-(-320)] vs. -387HU [-662-(-26)], p=0.0006). Participants with incomplete resolution had persistently higher VDP compared to those with complete resolution (p<0.05).
Interpretation: Dupilumab reduces mucus burden in asthma by resolving persistent plugs and decreasing the formation of new plugs. Despite complete resolution in a subset of participants, residual low-radiodensity persistent and new-onset plugs are functionally relevant.
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