Casale T B, Nelson H S, Stricker W E, Raff H, Newman K B
Department of Medicine. Creighton University, Omaha, Nebraska 68131, USA.
Ann Allergy Asthma Immunol. 2001 Nov;87(5):379-85. doi: 10.1016/S1081-1206(10)62918-3.
Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels.
Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level.
One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results.
Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.
下丘脑-垂体-肾上腺（HPA）轴的抑制是吸入性糖皮质激素治疗的一种潜在全身效应，可通过监测血清、尿液和唾液中的皮质醇水平来量化。
1）比较吸入性糖皮质激素氟尼缩松和丙酸氟替卡松与安慰剂及口服泼尼松对HPA轴的影响。2）估算HPA轴抑制的剂量-效价比。
多中心、随机、安慰剂对照、开放标签的21天试验。活性治疗方案为氟尼缩松500和1000微克，每日两次；丙酸氟替卡松110、220、330和440微克，每日两次；以及泼尼松，每日7.5毫克。入选患者为年龄18至50岁的非吸烟者，患有持续性轻至中度哮喘，且在研究前6个月未使用过口服、鼻用或吸入性糖皮质激素。主要结局指标为血清皮质醇浓度曲线下22小时面积（AUC(0-22h)）；24小时尿皮质醇水平；以及上午8点唾液皮质醇水平。
153例患者被随机分配至活性治疗组或安慰剂组；125例患者完成研究且至少80%依从其治疗方案。丙酸氟替卡松和氟尼缩松均引起HPA轴的剂量依赖性抑制，丙酸氟替卡松的抑制作用在统计学上更强（P = 0.0003）。剂量-效价比显示，丙酸氟替卡松每微克剂量增加引起的血清皮质醇抑制比氟尼缩松多4.4倍。丙酸氟替卡松导致的血清皮质醇抑制的昼夜模式持续存在，而氟尼缩松则为“缓解性”。唾液和尿皮质醇数据在质量上与血清皮质醇结果相似。
丙酸氟替卡松对HPA轴的抑制作用明显强于氟尼缩松。对于需要长期吸入性糖皮质激素治疗的哮喘患者，氟尼缩松可能是一种安全的选择。
