Clark D J, Lipworth B J
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland.
Chest. 1997 Nov 5;112(5):1248-52. doi: 10.1378/chest.112.5.1248.
The aim of our study was to compare basal unstimulated levels of plasma cortisol and adrenocorticotropic hormone (ACTH) with stimulated levels produced by the corticotropin releasing factor (CRF) test in asthmatics taking high-dose inhaled steroid therapy. In theory, the CRF test would appear to be a suitable replacement for tetracosactrin (cosyntropin) (synthetic ACTH) as a test of hypothalamic-pituitary-adrenal (HPA) axis suppression.
Ten patients with stable asthma and a mean age of 28.8 years, FEV1 of 88.9% predicted, and forced expiratory flow between 25% and 75% of FVC of 57.0% predicted, were studied in a double-blind placebo-controlled crossover design comparing 4 days with budesonide, 1,000 microg bid, and placebo. Each dose was given at 8 AM and 10 PM for 4 days by metered-dose inhaler. Measurements were made at steady-state of basal 8 AM plasma cortisol and ACTH 10 h after the eighth dose, and CRF test (100-microg i.v. bolus) was then performed.
The results for 8 AM plasma cortisol (nmol/L, means and 95% confidence interval [CI] for difference) showed that budesonide produced significant suppression compared with placebo: budesonide (284.1) vs placebo (360.9) (95% CI, 9.3 to 144.3). Suppression also occurred for peak plasma cortisol in response to CRF: budesonide (375.9) vs placebo (470.2) (95% CI, 27.0 to 161.6). ACTH (ng/L, means and 95% CI for difference) demonstrated a similar nonsignificant trend to cortisol, with suppression in both basal and stimulated forms: 8 AM ACTH, budesonide (36.6) vs placebo (42.2) (95% CI, -2.6 to 13.8); CRF peak response, budesonide (49.9) vs placebo (62.8) (95% CI, -3.6 to 29.5).
In asthmatic patients receiving inhaled budesonide, 1,000 microg bid, the suppression of basal unstimulated 8 AM plasma cortisol was mirrored by the suppression of the CRF stimulation response. These results highlight the point that when basal 8 AM plasma cortisol levels are suppressed, a comparable degree of dynamic impairment of HPA axis response is also likely to be found with physiologic testing.
我们研究的目的是比较接受高剂量吸入性类固醇治疗的哮喘患者血浆皮质醇和促肾上腺皮质激素（ACTH）的基础非刺激水平与促肾上腺皮质激素释放因子（CRF）试验产生的刺激水平。理论上，CRF试验似乎是作为下丘脑 - 垂体 - 肾上腺（HPA）轴抑制试验的替可克肽（合成ACTH）的合适替代品。
10例稳定期哮喘患者，平均年龄28.8岁，预测FEV1为88.9%，用力呼气流量在FVC的25%至75%之间，预测值为57.0%，采用双盲安慰剂对照交叉设计进行研究，比较布地奈德1000μg bid治疗4天和安慰剂治疗4天的效果。每种剂量均通过定量吸入器于上午8点和晚上10点给药，共4天。在第八剂药物后10小时的上午8点基础血浆皮质醇和ACTH的稳态下进行测量，然后进行CRF试验（静脉推注100μg）。
上午8点血浆皮质醇的结果（nmol/L，均值和差异的95%置信区间[CI]）显示，与安慰剂相比，布地奈德产生了显著抑制：布地奈德（284.1）对比安慰剂（360.9）（95%CI，9.3至144.3）。对CRF的血浆皮质醇峰值也出现了抑制：布地奈德（375.9）对比安慰剂（470.2）（95%CI，27.0至161.6）。ACTH（ng/L，均值和差异的95%CI）显示出与皮质醇类似的非显著趋势，基础和刺激形式均有抑制：上午8点ACTH，布地奈德（36.6）对比安慰剂（42.2）（95%CI， - 2.6至13.8）；CRF峰值反应，布地奈德（49.9）对比安慰剂（62.8）（95%CI， - 3.
