BACKGROUND Airway hyperresponsiveness (AHR) is a hallmark of persistent asthma. However, effects of IL-4/13 blockade with dupilumab (Dupi) on AHR are unknown. OBJECTIVES This study sought to investigate the effect of 12 weeks of Dupi on AHR, asthma control, and quality of life. METHODS After a 4-week run-in on beclomethasone/formoterol maintenance and reliever therapy (baseline), participants with uncontrolled type-2 high severe asthma received open-label Dupi 300 mg twice weekly, for 12 weeks. Mannitol challenges were done at baseline, 2, 4, and 12 weeks and following a 12-week washout. Study power was 90% to detect 1 doubling difference (dd) in mannitol PD10 FEV1 threshold at week 12. RESULTS Of 24 enrolled patients, 23 completed per protocol mannitol AHR at 12 weeks. Mean baseline values were age 52 years, FEV1 82%, Asthma Control Questionnaire 2.53, mini-Asthma Quality of Life Questionnaire 3.84, inhaled corticosteroids dose 1300 μg; fractional exhaled nitric oxide 50 parts per billion; Eosinophils 552 cells/μL. Mannitol sensitivity as PD10 was significantly attenuated by week 4, and reactivity as response dose ratio by week 2. After 12 weeks of Dupi, mean dd for PD10 was 1.78 (95% CI: 1.23-2.33; P < .001) and for response dose ratio was 3.40 (95% CI: 2.25-4.55; P < .001). At week 12, Asthma Control Questionnaire improved by 1.73 (95% CI: 1.11-2.36; P < .001); mini-Asthma Quality of Life Questionnaire by 2.31 (95% CI: 1.57-3.05; P < .001); FEV1 by 0.39 L (95% CI: 0.11-0.67; P < .01); and PEF by 61 L/min (95% CI: 24-98; P < .001). Beclomethasone/formoterol maintenance and reliever therapy requirement was reduced at 12 weeks versus baseline by 1.7 puffs/d (95% CI: 0.7-2.7; P < .01). After washout at week 24, the dd change was 0.96 (95% CI: 0.02-1.91; P < .05). CONCLUSIONS Dupilumab attenuated mannitol AHR to a clinically relevant degree despite concomitant inhaled corticosteroid reduction, combined with improvements in lung function, asthma control, and quality of life.

中文翻译：

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dupilumab 对不受控制的严重哮喘中甘露醇气道高反应性的影响。


背景 气道高反应性 （AHR） 是持续性哮喘的标志。然而，用 dupilumab （Dupi） 阻断 IL-4/13 对 AHR 的影响尚不清楚。目的 本研究旨在探讨 12 周 Dupi 对 AHR、哮喘控制和生活质量的影响。方法 在接受倍氯米松/福莫特罗维持和缓解治疗 （基线） 4 周后，患有不受控制的 2 型高度严重哮喘的参与者接受开放标签的 Dupi 300 mg，每周两次，持续 12 周。甘露醇激发试验在基线、 2 、 4 和 12 周以及 12 周清除后进行。在第 12 周时检测到甘露醇 PD10 FEV1 阈值 1 倍差异 （dd） 的研究能力为 90%。结果 在 24 名入组患者中，23 名在 12 周时按照方案完成甘露醇 AHR。平均基线值为 52 岁，FEV1 82%，哮喘控制问卷 2.53，微型哮喘生活质量问卷 3.84，吸入皮质类固醇剂量 1300 μg;呼出气一氧化氮分数 十亿分之 50;嗜酸性粒细胞 552 个细胞/μL。到第 4 周，甘露醇敏感性作为 PD10 显着减弱，到第 2 周作为反应剂量比的反应性。Dupi 12 周后，PD10 的平均 dd 为 1.78 （95% CI： 1.23-2.33;P < .001），反应剂量比为 3.40 （95% CI： 2.25-4.55;P < .001）.第 12 周时，哮喘控制问卷改善了 1.73 （95% CI： 1.11-2.36;P < .001）;迷你哮喘生活质量问卷 by 2.31 （95% CI： 1.57-3.05;P < .001）;FEV1 增加 0.39 L （95% CI： 0.11-0.67;P < .01）;和 PEF 为 61 L/min （95% CI： 24-98;P < .001）.倍氯米松/福莫特罗维持和缓解治疗需求在 12 周时与基线相比减少了 1.7 吸/天 （95% CI： 0.7-2.7;P < .01）.第 24 周清除后，dd 变化为 0.96 （95% CI： 0.02-1。91;P < .05）.结论 尽管伴随着吸入皮质类固醇减少，但 Dupilumab 将甘露醇 AHR 减弱到临床相关程度，同时改善了肺功能、哮喘控制和生活质量。