Booth H, Fishwick K, Harkawat R, Devereux G, Hendrick D J, Walters E H
Department of Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
Thorax. 1993 Nov;48(11):1121-4. doi: 10.1136/thx.48.11.1121.
Beta-2 agonists protect against non-specific bronchoconstricting agents such as methacholine, but it has been suggested that the protection afforded by long acting beta 2 agonists wanes rapidly with regular treatment.
The changes in airway responsiveness were investigated during and after eight weeks of regular treatment with salmeterol 50 micrograms twice daily in 26 adult asthmatic patients, 19 of whom were receiving maintenance inhaled corticosteroids. The study was of a randomised, placebo controlled, double blind design. Airway responsiveness to methacholine was measured as PD20 by a standardised dosimeter technique 12 hours after the first dose, at four weeks and eight weeks during treatment (12 hours after the last dose of test medication), and at 60 hours, one week and two weeks after stopping treatment.
There were no significant differences between the baseline characteristics of the two groups. A significant improvement in PD20 was seen at all points during treatment with salmeterol compared with the placebo group, with no significant fall off with time. PD20 measurements returned to baseline values after cessation of treatment with no significant difference from the placebo group.
Salmeterol gave significant protection against methacholine induced bronchoconstriction 12 hours after administration. This protection was of small magnitude, but there was no significant attenuation with eight weeks of regular use and no rebound increase in airway responsiveness on stopping treatment in a group of moderate asthmatic patients, the majority of whom were receiving inhaled corticosteroids.
β2激动剂可抵御非特异性支气管收缩剂,如乙酰甲胆碱,但有观点认为,长期使用长效β2激动剂所提供的保护作用会随着常规治疗迅速减弱。
对26例成年哮喘患者进行研究,这些患者每日两次吸入50微克沙美特罗,持续八周,研究期间及结束后观察气道反应性的变化。其中19例患者同时接受维持剂量的吸入性糖皮质激素治疗。该研究采用随机、安慰剂对照、双盲设计。通过标准化剂量计技术,在首次给药后12小时、治疗4周和8周时(最后一剂试验药物后12小时)以及停药后60小时、1周和2周时,测量对乙酰甲胆碱的气道反应性(以PD20表示)。
两组的基线特征无显著差异。与安慰剂组相比,使用沙美特罗治疗期间的所有时间点,PD20均有显著改善,且未随时间显著下降。停药后,PD20测量值恢复至基线水平,与安慰剂组无显著差异。
沙美特罗在给药12小时后对乙酰甲胆碱诱导的支气管收缩具有显著保护作用。这种保护作用程度较小,但在一组中度哮喘患者(大多数患者同时接受吸入性糖皮质激素治疗)中,经过八周常规使用后,保护作用没有显著减弱,停药后气道反应性也没有反弹增加。