Halpin David M G, Hamelmann Eckard H, Frith Peter A, Moroni-Zentgraf Petra M, van Hecke Benjamin, Unseld Anna, Kerstjens Huib A M, Szefler Stanley J
University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK.
Evangelisches Klinikum Bethel, Bielefeld, Germany.
Pulm Ther. 2020 Jun;6(1):131-140. doi: 10.1007/s41030-020-00113-w. Epub 2020 Mar 16.
Airway obstruction is usually assessed by measuring forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and peak expiratory flow (PEF). This post hoc study investigated comparative responses of lung function measurements in adults and adolescents (full analysis set, N = 3873) following treatment with tiotropium Respimat.
Lung function outcomes were analysed from five phase III trials in adults (≥ 18 years) with symptomatic severe, moderate and mild asthma (PrimoTinA-asthma, MezzoTinA-asthma and GraziaTinA-asthma, respectively), and one phase III trial in adolescents (12-17 years) with symptomatic moderate asthma (RubaTinA-asthma). Changes from baseline versus placebo in FEV, FVC, PEF and FEV/FVC ratio with tiotropium 5 µg or 2.5 µg added to at least stable inhaled corticosteroids at week 24 (week 12 in GraziaTinA-asthma) were analysed.
All lung function measures improved in all studies with tiotropium 5 µg (mean change from baseline versus placebo), including peak FEV (110-185 mL), peak FVC (57-95 mL) and morning PEF (15.8-25.6 L/min). Changes in adolescents were smaller than those in adults, and were statistically significant primarily for FEV and PEF, but not for FVC.
Consistent improvements were seen across all lung function measures with the addition of tiotropium to other asthma treatments in adults across all severities, whereas the improvements with tiotropium in adolescents primarily impacted measures of flow rather than lung volume. This may reflect less pronounced airway remodelling and air trapping in adolescents with asthma versus adults.
气道阻塞通常通过测量1秒用力呼气容积（FEV）、用力肺活量（FVC）和呼气峰值流速（PEF）来评估。这项事后分析研究调查了噻托溴铵Respimat治疗后成人和青少年（全分析集，N = 3873）肺功能测量的比较反应。
对五项针对有症状的重度、中度和轻度哮喘成人（分别为PrimoTinA - 哮喘、MezzoTinA - 哮喘和GraziaTinA - 哮喘，年龄≥18岁）的III期试验以及一项针对有症状的中度哮喘青少年（12 - 17岁，RubaTinA - 哮喘）的III期试验的肺功能结果进行了分析。分析了在第24周（GraziaTinA - 哮喘为第12周）至少在稳定吸入性糖皮质激素基础上加用5μg或2.5μg噻托溴铵时，FEV、FVC、PEF和FEV/FVC比值相对于安慰剂的基线变化。
在所有使用5μg噻托溴铵的研究中，所有肺功能指标均有改善（相对于安慰剂的基线平均变化），包括FEV峰值（110 - 185mL）、FVC峰值（57 - 95mL）和早晨PEF（15.8 - 25.6L/min）。青少年中的变化小于成人，且主要在FEV和PEF方面具有统计学意义，而FVC无统计学意义。
在所有严重程度的成人哮喘患者中，在其他哮喘治疗基础上加用噻托溴铵后，所有肺功能指标均持续改善，而噻托溴铵在青少年中的改善主要影响流速指标而非肺容积指标。这可能反映出与成人相比，青少年哮喘患者的气道重塑和气体潴留不太明显。
