Pauwels R A, Yernault J C, Demedts M G, Geusens P
University Hospital, University of Ghent, Belgium.
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):827-32. doi: 10.1164/ajrccm.157.3.9610009.
There are still some concerns about the safety of high doses of inhaled glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with moderate to severe asthma in a double-blind, multicenter, cross-over study of 12 mo duration. During the 1-mo run-in period, bronchodilators were replaced by salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD). No significant differences between the two treatments regarding morning plasma cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were observed at any time point during the study. Osteocalcin and bone mineral density (BMD) were improved over baseline in the FP group, resulting in higher serum osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%; p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at half the dose of BDP, results in a similar antiasthma effect but a more favorable safety profile with respect to bone metabolism and mineral density.
高剂量吸入糖皮质激素（ICS）的安全性仍存在一些担忧。我们在一项为期12个月的双盲、多中心、交叉研究中，比较了306例中度至重度哮喘患者使用丙酸氟替卡松（FP）和二丙酸倍氯米松（BDP）的安全性和有效性。在1个月的导入期，支气管扩张剂被每日两次的50微克沙美特罗替代，早晨呼气峰值流速（PEFR）增加28升/分钟（p<0.001），第一秒用力呼气容积（FEV1）增加预测值的6.2%（p<0.001）。随机分组时，根据之前使用的500微克BDP或400微克布地奈德（BUD），将当前的ICS替换为500微克BDP或250微克FP。在研究的任何时间点，两种治疗在早晨血浆皮质醇、尿钙和羟脯氨酸排泄、FEV1和PEFR方面均未观察到显著差异。与BDP相比，FP组的骨钙素和骨密度（BMD）较基线有所改善，导致血清骨钙素水平更高（平均差异0.28纳克/毫升；p<0.001），脊柱BMD更高（1.0%；p=0.05），股骨颈BMD更高（1.6%；p<0.01），沃德三角区BMD更高（3.6%；p=0.01）。我们得出结论，以BDP一半的剂量长期使用FP，可产生相似的抗哮喘效果，但在骨代谢和骨密度方面具有更有利的安全性。
