For patients with chronic obstructive pulmonary disease (COPD), greater improvements in lung function have been demonstrated for triple versus dual inhaled therapies in traditional spirometry studies. This study was the first to use functional respiratory imaging (FRI), known for increased sensitivity to airway changes versus spirometry, to assess the effect of the inhaled corticosteroid (ICS) component (budesonide) on lung function in patients with moderate-to-severe COPD and a blood eosinophil count > 150 cells/mm3. Patients in this Phase IIIb (NCT03836677), randomized, double-blind, crossover study received twice-daily budesonide/glycopyrrolate/formoterol fumarate (BGF) 320/18/9.6 μg fixed-dose triple therapy and glycopyrrolate/formoterol fumarate (GFF) 18/9.6 μg fixed-dose dual therapy over 4 weeks, each delivered via a single metered dose Aerosphere inhaler. Primary endpoints were the improvements from baseline for each treatment in specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and resistance (siRaw) measured via FRI taken at total lung capacity (Day 29). Secondary outcomes included spirometry and body plethysmography. Adverse events were monitored throughout the study. A total of 23 patients were randomized and included in the intent-to-treat analysis (mean age 64.9 years, 78.3% males, 43.5% current smokers, mean predicted post-bronchodilator forced expiratory volume in 1 s [FEV1] 63.6%). BGF and GFF both statistically significantly increased siVaw from baseline at Day 29 (geometric mean ratio [GM], 95% confidence interval [CI]: 1.72 [1.38, 2.13] and 1.53 [1.28, 1.83], respectively, both p < 0.0001), with a greater increase observed for BGF versus GFF (GM, 95% CI 1.09 [1.03, 1.16], p = 0.0061). Statistically significant reductions in siRaw were also observed with both BGF and GFF (GM, 95% CI 0.50 [0.39, 0.63] and 0.52 [0.40, 0.67], respectively, both p < 0.0001). Additionally, significant improvements from baseline in post-dose FEV1 were observed with BGF and GFF (mean 346 mL, p = 0.0003 and 273 mL, p = 0.0004, respectively). Safety findings were consistent with the known profiles of BGF and GFF. As observed using FRI, triple therapy with BGF resulted in greater increases in airway volume, and reductions in airway resistance versus long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual therapy with GFF, reflecting the ICS component’s contribution in patients with moderate-to-severe COPD. Trial registration: ClinicalTrials.gov, NCT03836677. Registered 11 February 2019, https://clinicaltrials.gov/ct2/show/NCT03836677

中文翻译：

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COPD患者布地奈德/格隆溴铵/富马酸福莫特罗和格隆溴铵/富马酸福莫特罗计量吸入器的功能性呼吸成像评估：吸入皮质类固醇的价值

对于慢性阻塞性肺疾病 (COPD) 患者，传统肺活量测定研究表明，三联吸入疗法与双重吸入疗法相比，肺功能有更大的改善。本研究首次使用功能性呼吸成像 (FRI) 来评估吸入皮质类固醇 (ICS) 成分（布地奈德）对中重度患者肺功能的影响，功能性呼吸成像 (FRI) 以对气道变化的敏感性高于肺活量测定法而闻名。 COPD 和血嗜酸性粒细胞计数 > 150 个细胞/mm3。此 IIIb 期 (NCT03836677) 随机、双盲、交叉研究中的患者每天接受两次布地奈德/格隆溴铵/富马酸福莫特罗 (BGF) 320/18/9.6 μg 固定剂量三联疗法和格隆溴铵/富马酸福莫特罗 (GFF) 18 /9.6 μg 固定剂量双重治疗，持续 4 周，每个通过一个单一的计量剂量 Aerosphere 吸入器输送。主要终点是每次治疗在特定（即校正肺叶容积）基于图像的气道容积 (siVaw) 和通过 FRI 在总肺活量（第 29 天）测量的阻力（siRaw）方面的改善。次要结果包括肺活量测定法和身体体积描记法。在整个研究过程中监测不良事件。共有 23 名患者被随机分组​​并纳入意向治疗分析（平均年龄 64.9 岁，男性占 78.3%，目前吸烟者占 43.5%，平均预测的支气管扩张剂后 1 秒用力呼气量 [FEV1] 63.6%）。在第 29 天，BGF 和 GFF 均显着增加了 siVaw（几何平均比 [GM]，95% 置信区间 [CI]：分别为 1.72 [1.38, 2.13] 和 1.53 [1.28, 1.83]，均 p < 0.0001） , 观察到 BGF 与 GFF 的增加更大（GM，95% CI 1.09 [1.03, 1.16]，p = 0.0061）。在 BGF 和 GFF 中也观察到 siRaw 的统计学显着降低（GM，95% CI 分别为 0.50 [0.39, 0.63] 和 0.52 [0.40, 0.67]，均 p < 0.0001）。此外，使用 BGF 和 GFF 观察到给药后 FEV1 较基线显着改善（分别为 346 mL，p = 0.0003 和 273 mL，p = 0.0004）。安全性结果与 BGF 和 GFF 的已知特征一致。正如使用 FRI 观察到的那样，与 GFF 的长效毒蕈碱拮抗剂/长效 β2-激动剂 (LAMA/LABA) 双联疗法相比，BGF 三联疗法导致气道容积更大增加，气道阻力降低，反映了 ICS 成分的贡献在中度至重度 COPD 患者中。试用注册：ClinicalTrials.gov，NCT03836677。2019 年 2 月 11 日注册，https://clinicaltrials.gov/ct2/show/NCT03836677