Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
J Allergy Clin Immunol. 2016 Mar;137(3):727-33.e1. doi: 10.1016/j.jaci.2015.06.012. Epub 2015 Jul 26.
Effects of small-particle long-acting β-agonists on the small airways have been poorly documented.
We used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.
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.
Sixteen patients completed the study as follows: mean age, 43 years; FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF(25-75)), 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; Asthma Control 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 FEF(25-75), 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.
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.
小颗粒长效β激动剂对小气道的作用尚未得到充分记录。
我们使用脉冲振荡法（IOS）比较了小颗粒和大颗粒长效β激动剂单次和重复给药的效果。
在 1 至 2 周的导入期后，患者每天接受 12μg 小颗粒氢氟烷烃 134a 福莫特罗溶液或 50μg 大颗粒沙美特罗干粉，每天两次，并在两者之间使用 1 至 2 周的洗脱期，同时吸入皮质类固醇。在第一次和最后一次给药后 60 分钟进行测量。
16 名患者完成了研究，具体如下：平均年龄 43 岁；FEV1，80%；用力呼气中期流速在用力肺活量的 25%至 75%之间（FEF25-75），48%；5Hz 时的总气道阻力，177%；5Hz 和 20Hz 之间的外周气道阻力差，0.18kPa·L-1·s；哮喘控制问卷评分，0.76；和吸入皮质类固醇剂量，550μg/d。福莫特罗在 IOS 结果和 FEF25-75（但不是 FEV1）方面均显著优于沙美特罗，在第一次给药后 5 分钟内有所改善，但在 60 分钟内并未持续。最后一次给药后，福莫特罗在整个 60 分钟内对所有 IOS 结果均有显著改善，但对 FEV1 或 FEF25-75 没有影响：60 分钟时福莫特罗与沙美特罗在 5Hz 总气道阻力方面的平均差异为 7.50%（95%CI，1.56%至 13.43%，P=0.02）；20Hz 时中央气道阻力为 5.37%（95%CI，0.13%至 10.62%，P=0.045）；5Hz 和 20Hz 之间的外周气道阻力差异为 12.76%（95%CI，1.28%至 24.24%，P=0.03）；反应面积曲线下面积为 19.46%（95%CI，7.56%至 31.36%，P=0.003）；5Hz 时的反应为 11.19%（95%CI，4.62%至 17.76%，P=0.002）；以及共振频率为 9.34%（95%CI，3.21%至 15.47%，P=0.005）。呼气峰值流量在两种药物治疗后都有显著改善。
与沙美特罗相比，福莫特罗在慢性给药后 IOS 结果显著改善，但在肺活量方面没有改善。这可能反映了更好的药物在整个肺部（包括小气道）的沉积。
