Dahl R, Lundback B, Malo J L, Mazza J A, Nieminen M M, Saarelainen P, Barnacle H
Department of Respiratory Diseases, University Hospital Aarhus, Denmark.
Chest. 1993 Nov;104(5):1352-8. doi: 10.1378/chest.104.5.1352.
In this 4-week, multicenter, double-blind, randomized, parallel group study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50, 100, 200, and 400 micrograms twice daily) was investigated and compared with beclomethasone dipropionate, 200 micrograms twice daily. A total of 672 patients with moderate asthma currently receiving 1,000 micrograms/d or less of an inhaled steroid were recruited. The study demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observed in morning (increase per doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 1.8, 6.8 L/min; p = 0.001) and evening peak expiratory flow rate (PEFR) (increase per doubling dose was 3.0 L/min; 95 percent CI, 0.5, 5.5 L/min; p = 0.017), clinic lung function (at 4 weeks, increase in percent predicted PEFR per doubling dose = 1.1 percent; 95 percent CI, 0.2, 2.1 percent; p = 0.022; increase in percent predicted FEV1 per doubling dose = 1.1 percent; 95 percent CI, 0.3, 1.9 percent; p = 0.10:increase in percent predicted FVC per doubling dose = 1.3 percent, 95 percent CI, 0.5, 2.1 percent; p = 0.001), and the percentage of symptom-free days over days 1 to 14 of treatment (increase per doubling dose = 1.9, 95 percent CI, 0.0, 3.9; p = 0.048). There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0.002; days 15 to 28 p = 0.01). In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease per doubling dose = 2.0 L/min, 95 percent CI, 0.4; p = 0.024). The number of asthma exacerbations was also reduced as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse events were few, and there was a similar incidence in all groups. Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the study were consistent with other clinical studies that have shown fluticasone propionate to be more potent than beclomethasone dipropionate in terms of improvement in lung function. In conclusion, this study provided evidence of a dose-related improvement in asthma control for fluticasone propionate in the dose range 100 to 800 micrograms daily, in patients with moderate asthma.
在这项为期4周的多中心、双盲、随机、平行组研究中，研究了四剂吸入丙酸氟替卡松（每日两次，每次50、100、200和400微克）的剂量效应关系，并与每日两次、每次200微克的二丙酸倍氯米松进行了比较。共招募了672名目前接受吸入性类固醇1000微克/天或更少的中度哮喘患者。该研究表明，丙酸氟替卡松可使肺功能有显著的剂量相关改善。观察到早晨（每增加一倍剂量增加4.3升/分钟；95%置信区间[CI]，1.8，6.8升/分钟；p = 0.001）和傍晚呼气峰值流速（PEFR）（每增加一倍剂量增加3.0升/分钟；95%CI，0.5，5.5升/分钟；p = 0.017）、门诊肺功能（4周时，每增加一倍剂量预测PEFR百分比增加 = 1.1%；95%CI，0.2，2.1%；p = 0.022；每增加一倍剂量预测FEV1百分比增加 = 1.1%；95%CI，0.3，1.9%；p = 0.10：每增加一倍剂量预测FVC百分比增加 = 1.3%，95%CI，0.5，2.1%；p = 0.001）以及治疗第1至14天无症状天数百分比（每增加一倍剂量增加 = 1.9，95%CI，0.0，3.9；p = 0.048）呈剂量相关线性增加。额外支气管扩张剂使用量也有剂量相关减少（第1至14天p = 0.002；第15至28天p = 0.01）。此外，随着丙酸氟替卡松剂量增加，昼夜变化显著减小（每增加一倍剂量减少 = 2.0升/分钟，95%CI，0.4；p = 0.024）。随着丙酸氟替卡松剂量增加，哮喘加重次数也减少。丙酸氟替卡松耐受性良好，不良事件较少，且所有组发生率相似。此外，没有任何下丘脑 - 垂体 - 肾上腺轴抑制的证据。该研究数据与其他临床研究一致，这些研究表明在改善肺功能方面，丙酸氟替卡松比二丙酸倍氯米松更有效。总之，本研究提供了证据，表明对于中度哮喘患者，每日100至800微克剂量范围内的丙酸氟替卡松在哮喘控制方面有剂量相关改善。
