School of Engineering, Southern Polytechnic State University, Marietta, GA, USA.
J Asthma Allergy. 2013 Aug 5;6:109-16. doi: 10.2147/JAA.S48827. eCollection 2013.
We previously showed that the long-acting beta agonist (LABA) salmeterol as inhalation powder or metered-dose inhaler improves lung-function parameters assessed by impulse oscillometry (IOS) in 2- to 5-year-old children with reversible-airway disease within 15 minutes.
We studied 12- to 45-year-olds with mild persistent asthma in order to compare the onset and extent of peripheral airway effects following the first dose and after 4 weeks dosing with two inhaled corticosteroid (ICS)/LABA combinations: fluticasone propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5.
Thirty subjects with mild persistent asthma using only an as-needed short-acting beta-agonist (albuterol) who had at least a 40% change in integrated low-frequency reactance postalbuterol were selected and randomized to receive either fluticasone propionate/salmeterol or budesonide/formoterol (15 subjects each). We collected three to six IOS replicates at baseline, at 5, 20, 40, 60, 120, and 240 minutes postdose at randomization, and after 4 weeks of twice-daily dosing. Blinded investigators calculated IOS frequency-dependent resistance and reactance (R5-R20 and AX), indicative of small-airway dysfunction, and also estimated the peripheral airway resistance (Rp ) and peripheral airway compliance (Cp ), using a respiratory-impedance model.
At randomization visits, onset of action was detected as early as 5 minutes (t-test, P < 0.05) after fluticasone propionate/salmeterol by Cp , and within 5 minutes after budesonide/formoterol by R5-R20, AX, Rp , and Cp . However, after 4 weeks of dosing, only Rp was significantly different (from 60 to 120 minutes) after fluticasone propionate/salmeterol, while R5-R20, AX, Rp , and Cp were not significantly different within 240 minutes after budesonide/formoterol.
These two ICS/LABA combinations initially improved the peripheral airway function of 12- to 45-year-old asthmatics significantly in about 5 minutes or less, as measured by R5-R20, AX, Rp , and/or Cp . After regular dosing for 4 weeks, pre- to postdose differences in these parameters had diminished significantly due to improved predose status of peripheral airways. Single dosing with ICS/LABA combinations in mild persistent asthma improves small-airway function, and the effect is maintained over a 12-hour interval by regular use for 4 weeks.
我们先前的研究表明，长效β激动剂（LABA）沙美特罗作为吸入粉或定量吸入器，可在 15 分钟内改善 2 至 5 岁可逆气道疾病儿童的脉冲振荡（IOS）评估的肺功能参数。
我们研究了 12 至 45 岁的轻度持续性哮喘患者，以比较两种吸入性皮质类固醇（ICS）/ LABA 联合制剂（丙酸氟替卡松/沙美特罗 115/21 和布地奈德/福莫特罗 160/4.5）在首次剂量后和 4 周剂量后的外周气道作用的起始和程度。
选择了 30 名仅按需使用短效β激动剂（沙丁胺醇）的轻度持续性哮喘患者，这些患者在沙丁胺醇后至少有 40%的低频电抗改变，这些患者被随机分为接受丙酸氟替卡松/沙美特罗或布地奈德/福莫特罗治疗（每组 15 名）。我们在随机分组时、5、20、40、60、120 和 240 分钟后以及 4 周每天两次给药后采集了 3 到 6 次 IOS 重复测量。盲法研究者使用呼吸阻抗模型计算了 IOS 频率依赖性阻力和电抗（R5-R20 和 AX），这表明小气道功能障碍，还估计了外周气道阻力（Rp）和外周气道顺应性（Cp）。
在随机就诊时，通过 Cp 检测到丙酸氟替卡松/沙美特罗的作用起始时间早至 5 分钟（t 检验，P <0.05），而布地奈德/福莫特罗的作用起始时间则早至 5 分钟，通过 R5-R20、AX、Rp 和 Cp 检测到。然而，在 4 周的治疗后，只有 Rp 在丙酸氟替卡松/沙美特罗后在 60 至 120 分钟之间有显著差异，而布地奈德/福莫特罗在 240 分钟内的 R5-R20、AX、Rp 和 Cp 无显著差异。
这两种 ICS/LABA 联合制剂最初在大约 5 分钟或更短的时间内显著改善了 12 至 45 岁哮喘患者的外周气道功能，通过 R5-R20、AX、Rp 和/或 Cp 来衡量。经过 4 周的常规治疗后，由于外周气道的预治疗状态得到改善，这些参数的预治疗后差异明显减少。在轻度持续性哮喘中，ICS/LABA 联合制剂的单次给药可改善小气道功能，并且在 4 周的常规使用期间，可维持 12 小时的间隔。
