Fitzgerald D, Van Asperen P, Mellis C, Honner M, Smith L, Ambler G
Royal Alexandra Hospital for Children, Sydney, New South Wales, Australia.
Thorax. 1998 Aug;53(8):656-61. doi: 10.1136/thx.53.8.656.
Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.
The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.
There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.
FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.
既往研究表明，在接受高剂量吸入性类固醇治疗的成人以及接受低剂量吸入性类固醇治疗的儿童中，丙酸氟替卡松（FP）的疗效比二丙酸倍氯米松（BDP）高2倍。与BDP相比，提供同等疗效所需的FP剂量更低，通过肾上腺功能测定，其全身效应似乎也更少。
在一项为期12周的随机双盲交叉研究中，对30例持续性哮喘儿童（需要每日吸入1000 - 2000微克皮质类固醇）比较了每日750微克FP和每日1500微克BDP的疗效和安全性。药物通过储雾罐装置分两次给药。主要疗效变量为呼气峰值流速（PEF）。在第8周和第12周通过24小时尿游离皮质醇水平评估肾上腺功能，并在第12周进行促肾上腺皮质激素（ACTH）和低剂量促肾上腺皮质激素刺激试验（LDST）。对结果进行了序列和周期差异调整。
在两个12周治疗期内，主要疗效变量无差异（早晨PEF调整后均值差异为1.3升/分钟（95%可信区间 - 6.1至8.8），p = 0.112）以及症状评分（咳嗽、呼吸急促、喘息、气短；夜间评分调整后均值差异：-0.06（95%可信区间 - 0.14至0.03）；p = 0.136）。在BDP和FP治疗阶段发现了相似程度的轻度肾上腺功能障碍。在相应时期显示出相同的身高增长速度。
对于持续性哮喘儿童，每日750微克FP与每日1500微克BDP疗效相当。在这些非常高的剂量下，通过肾上腺功能评估，我们无法证明FP比BDP具有安全性优势。然而，肾上腺功能的测量可能受到同时使用和既往全身使用类固醇的影响，也可能受到疾病活动的影响。
