University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk, 2610 Antwerp, Belgium.
FLUIDDA, Inc, Los Angeles, CA, USA.
Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620916990. doi: 10.1177/1753466620916990.
Functional respiratory imaging (FRI) is a quantitative postprocessing imaging technique used to assess changes in the respiratory system. Using FRI, we characterized the effects of the long-acting muscarinic antagonist (LAMA), glycopyrrolate metered dose inhaler (GP MDI), and the long-acting β-agonist (LABA), formoterol fumarate metered dose inhaler (FF MDI), on airway volume and resistance in patients with moderate-to-severe chronic obstructive pulmonary disease.
Patients in this phase IIIb, randomized, double-blind crossover study received twice-daily GP MDI (18 μg) and FF MDI (9.6 μg). Primary endpoints were specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and specific image-based airway resistance (siRaw), measured using FRI. Secondary and other endpoints included additional FRI, spirometry, and body plethysmography parameters. Postdose efficacy assessments were performed within 60-150 min of dosing on day 15.
A total of 23 patients were randomized and 19 completed both treatment periods. GP MDI and FF MDI both achieved significant improvements from baseline to day 15 in siVaw [11% ( = 0.0187) and 23% ( < 0.0001) increases, respectively] and siRaw [25% ( = 0.0219) and 44% ( < 0.0001) reductions, respectively]. Although, on average, improvements were larger for FF MDI than GP MDI, some individuals displayed greater responses with each of the two treatments. These within-patient differences increased with airway generation number. Spirometry and body plethysmography endpoints showed significant improvements from baseline in inspiratory capacity for both treatments, and numeric improvements for other endpoints.
Both GP MDI and FF MDI significantly improved siRaw and siVaw at day 15 baseline. FRI endpoints demonstrated increased sensitivity relative to spirometry and body plethysmography in detecting differences between treatments in a small number of patients. Intra-patient differences in treatment response between the LAMA and the LABA provide further support for the benefit of dual bronchodilator therapies.
CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT02937584
功能呼吸成像（FRI）是一种定量后处理成像技术，用于评估呼吸系统的变化。使用 FRI，我们描述了长效抗毒蕈碱剂（LAMA）、格隆溴铵定量气雾剂（GP MDI）和长效β-激动剂（LABA）、富马酸福莫特罗定量气雾剂（FF MDI）对中重度慢性阻塞性肺疾病患者气道容积和阻力的影响。
这项 IIIb 期、随机、双盲交叉研究的患者每天接受两次 GP MDI（18μg）和 FF MDI（9.6μg）治疗。主要终点是使用 FRI 测量的特定（即校正叶段容积）基于图像的气道容积（siVaw）和特定基于图像的气道阻力（siRaw）。次要和其他终点包括其他 FRI、肺活量测定和体描法参数。第 15 天给药后 60-150 分钟进行药效评估。
共有 23 名患者被随机分组，19 名患者完成了两个治疗期。GP MDI 和 FF MDI 均从基线到第 15 天显著改善了 siVaw[分别增加 11%（ = 0.0187）和 23%（ < 0.0001）]和 siRaw[分别减少 25%（ = 0.0219）和 44%（ < 0.0001）]。尽管 FF MDI 的改善平均大于 GP MDI，但有些个体对两种治疗的反应更大。这些患者内的差异随着气道生成数的增加而增加。两种治疗均使肺活量测定中的吸气量从基线显著改善，其他终点也有数值改善。
GP MDI 和 FF MDI 在第 15 天均显著改善了 siRaw 和 siVaw。与肺活量测定和体描法相比，FRI 终点在少数患者中检测到治疗之间的差异时显示出更高的敏感性。LAMA 和 LABA 之间治疗反应的患者内差异进一步支持了双重支气管扩张剂治疗的益处。
NCT02937584
