哮喘联盟

   摘要
   背景:小颗粒长效β受体激动剂对小气道的作用鲜有记录。
   目的:我们采用脉冲震荡(IOS)以比较小颗粒和大颗粒长效β受体激动剂的单次和重复剂量效应。
   方法:在1到2周的筛选期后，患者接受为期1-2周的每日两次的12μg的小颗粒氢氟烷134a-福莫特罗溶液或者50μg的大颗粒沙美特罗干粉联合吸入糖皮质激素治疗，在试验之间有1到2周的洗脱期。在第一次服药和最后一次服药60分钟后收集数据。
   结果:16例患者完成了如下的研究：平均年龄，43岁；FEV1，80%；最大呼气中段流量 (FEF25-75)，48%；5 Hz总气道阻力，177%；5和20 Hz之间外周气道阻力差异，0.18 kPa•L-1•s；哮喘控制问卷评分，0.76；以及吸入性糖皮质激素剂量，550 μg/d。福莫特罗较沙美特罗在全部的IOS结果和 FEF25-75具有显著的提高，但是第一次剂量后5分钟FEV1无显著提高，持续未超过60分钟。在最后一次剂量后，所有的IOS结果，除FEV1和 FEF25-75，在整个60分钟内都是福莫特罗效果更显著：福莫特罗和沙美特罗的5Hz总气道阻力的平均差异为 7.50% (95% CI, 1.56% ～ 13.43%, P = 0.02)；20 Hz中心气道阻力的平均差异为5.37% (95% CI, 0.13% ～10.62%, P = 0.045)； 5和20 Hz之间外周气道阻力差异为12.76% (95% CI, 1.28% ～ 24.24%, P = .03)；曲线下电抗区域，19.46% (95% CI, 7.56% ～31.36%, P = .003)；5 Hz电抗，11.19% (95% CI, 4.62% ～17.76%, P = .002)；以及共振频率，9.34% (95% CI, 3.21%～15.47%, P = .005)。两种药物的呼气流量峰值显著改善程度相似。
   结论:与沙美特罗相比，长期应用福莫特罗IOS结果显著改善，但是呼吸量测定法的结果并没有显著改善。这一现象可能反应出福莫特罗具有更好的包括小气道在内的全肺沉积。
 

（杨冬 审校）
JAllergyClinImmunol. 2015Jul25.pii:S0091-6749(15)00861-1.doi:10.1016/j.jaci.2015.06.012. [Epub ahead of print]

 

Effects of formoterol or salmeterol on impulse oscillometry in patients with persistent asthma.
 

Manoharan A1, von Wilamowitz-Moellendorff A1, Morrison A1, Lipworth BJ2.
 

Abstract
BACKGROUND:Effects of small-particle long-acting β-agonists on the small airways have been poorly documented.
OBJECTIVE:We used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.
METHODS:After a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a-formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between. Measurements were made over 60 minutes after the first and last doses.
RESULTS:Sixteen patients completed the study as follows: mean age, 43 years; FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF25-75), 48%; total airway resistance at 5 Hz, 177%; peripheral airway resistance as the difference between 5 and 20 Hz, 0.18 kPa•L-1•s; AsthmaControl Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 μg/d. There were significantly greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first dose, which were not sustained over 60 minutes. After the last dose, all IOS outcomes, but not FEV1 or FEF25-75, were significantly better with formoterol over the entire 60 minutes: mean difference at 60 minutes between formoterol and salmeterol in total airway resistance at 5 Hz, 7.50% (95% CI, 1.56% to 13.43%, P = .02); central airway resistance at 20 Hz, 5.37% (95% CI, 0.13% to 10.62%, P = .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76% (95% CI, 1.28% to 24.24%, P = .03); reactance area under the curve, 19.46% (95% CI, 7.56% to 31.36%, P = .003); reactance at 5 Hz, 11.19% (95% CI, 4.62% to 17.76%, P = .002); and resonant frequency, 9.34% (95% CI, 3.21% to 15.47%, P = .005). Peak expiratory flow significantly improved to a similar degree with both drugs.
CONCLUSION:Significant improvements in IOS outcomes but not spirometry results occurred after chronic dosing with formoterol compared with salmeterol. This might reflect better deposition to the entire lung, including the small airways.
 

JAllergyClinImmunol. 2015Jul25.pii:S0091-6749(15)00861-1.doi:10.1016/j.jaci.2015.06.012. [Epub ahead of print]