Davies R J, Stampone P, O'Connor B J
London Chest Hospital, U.K.
Respir Med. 1998 Jun;92 Suppl A:23-31. doi: 10.1016/s0954-6111(98)90214-1.
The mandatory requirement to eliminate chlorofluorocarbons (CFCs) as propellants in pharmaceutical aerosols has provided the opportunity to enhance significantly the delivery of aerosol drugs to the respiratory tract. This randomized, parallel-group, double-blind, double-dummy, multicentre study was undertaken to assess whether beclomethasone dipropionate (BDP) in hydrofluoroalkane-134a (HFA) provided equivalent control of moderately severe asthma to BDP in CFC but at approximately half the total daily dose, as might be expected from the improved lung deposition of the HFA-BDP extrafine aerosol. The novel study design included a 10-12 day run-in period to confirm that patients met established criteria of moderately severe asthma and were symptomatic on current therapy (inhaled beta-agonist plus CFC-BDP 400-800 micrograms day-1). This run-in period was followed by a short course of oral steroid therapy (prednisolone 30 mg day-1 for 7-13 days) to demonstrate steroid responsiveness [> or = 15% improvement in morning peak expiratory flow (PEF)] and to provide a within-study baseline of improved asthma control. A total of 233 patients were randomized to treatment for 12 weeks with HFA-BDP 800 micrograms day-1 (116 patients) or CFC-BDP 1500 micrograms day-1 (117 patients). The mean change from oral steroid treatment in morning PEF with HFA-BDP was equivalent to that seen with CFC-BDP at all time intervals. Changes in other measures of pulmonary function, asthma symptom scores and beta-agonist use were equivalent in the two treatment groups throughout the 12 week treatment period. The safety profile of HFA-BDP compared favourably with that of CFC-BDP with no unexpected adverse events reported. Fewer patients on HFA-BDP than on CFC-BDP had plasma cortisol levels below the normal reference range after 12 weeks of therapy (5.1% vs. 17.3%, respectively). In conclusion, HFA-BDP extrafine aerosol was found to provide equivalent control of moderately severe asthma to CFC-BDP at approximately half the daily dose with a favourable safety profile, suggesting an improved therapeutic ratio.
在药用气雾剂中强制要求淘汰作为推进剂的氯氟烃（CFCs），这为显著增强呼吸道气雾剂药物的递送提供了契机。本随机、平行组、双盲、双模拟、多中心研究旨在评估，与CFC中的丙酸倍氯米松（BDP）相比，氢氟烷烃-134a（HFA）中的BDP是否能以大约每日总剂量一半的用量，提供同等程度的中度至重度哮喘控制，这正如从HFA-BDP超细气雾剂改善的肺部沉积情况所预期的那样。这项新颖的研究设计包括一个10 - 12天的导入期，以确认患者符合中度至重度哮喘的既定标准，且在当前治疗（吸入β-激动剂加每日400 - 800微克的CFC-BDP）下有症状。在这个导入期之后，进行一个短期的口服类固醇治疗疗程（泼尼松龙每日30毫克，持续7 - 13天），以证明类固醇反应性[早晨呼气峰值流速（PEF）改善≥15%]，并提供研究内哮喘控制改善的基线。总共233名患者被随机分配接受12周的治疗，其中116名患者使用每日800微克的HFA-BDP，117名患者使用每日1500微克的CFC-BDP。在所有时间间隔内，HFA-BDP治疗组早晨PEF相对于口服类固醇治疗的平均变化与CFC-BDP治疗组所见相当。在整个12周的治疗期间，两个治疗组在其他肺功能指标、哮喘症状评分和β-激动剂使用方面的变化相当。HFA-BDP的安全性概况优于CFC-BDP，未报告意外不良事件。治疗12周后，使用HFA-BDP的患者血浆皮质醇水平低于正常参考范围的人数少于使用CFC-BDP的患者（分别为5.1%和17.3%）。总之，发现HFA-BDP超细气雾剂能以大约每日剂量一半的用量提供与CFC-BDP同等程度的中度至重度哮喘控制，且安全性概况良好，提示治疗比率有所改善。
