高剂量吸入丙酸氟替卡松对肺功能严重受损的哮喘患者下丘脑-垂体-肾上腺轴的影响。

Effects of high-dose inhaled fluticasone propionate on the hypothalamic-pituitary-adrenal axis in asthmatic patients with severely impaired lung function.

作者信息

Lee Daniel K C, Bates Caroline E, Currie Graeme P, Cowan Louise M, McFarlane Lesley C, Lipworth Brian J

机构信息

Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.

出版信息

Ann Allergy Asthma Immunol. 2004 Sep;93(3):253-8. doi: 10.1016/S1081-1206(10)61497-4.

DOI:10.1016/S1081-1206(10)61497-4

PMID:15478385

Abstract

BACKGROUND

The effects of high-dose fluticasone propionate therapy on dynamic cortisol stimulation in severe asthma are unknown.

OBJECTIVE

To evaluate the human corticotropin-releasing factor (hCRF)-stimulated plasma cortisol response to fluticasone propionate therapy in severe asthmatic patients with impaired airway caliber (forced expiratory volume in 1 second [FEV1] < 60% of predicted) and in control subjects.

METHODS

Ten severe asthmatic patients (mean FEV1, 47% of predicted) and 10 controls (mean FEV1, 104% of predicted) received fluticasone propionate, 2,000 microg/d, via a 750-mL primed spacer for 2 weeks. Plasma cortisol levels before and after hCRF stimulation and overnight 10-hour urinary cortisol excretion corrected for creatinine concentration (OUCC) were measured at baseline after washout and 12 hours after the last dose of fluticasone propionate.

RESULTS

Baseline values before fluticasone propionate use were not significantly different in asthmatic patients vs controls for plasma cortisol before and after hCRF stimulation and OUCC. Comparing values at baseline vs after fluticasone propionate use, there was no significant suppression of plasma cortisol levels before (378.2 vs 357.4 nmol/L) or after (510.5 vs 507.9 nmol/L) hCRF stimulation or OUCC (8.2 vs 7.5 nmoL/mmoL) in asthmatic patients. In controls, all outcomes were significantly suppressed comparing values before vs after fluticasone propionate therapy: plasma cortisol levels before (423.5 vs 200.2 nmol/L; P = .002) and after (503.5 vs 291.1 nmol/L; P = .001) hCRF stimulation and OUCC (6.5 vs 2.4 nmol/mmol; P = .002).

CONCLUSION

Patients with severe persistent asthma and impaired airway caliber seem to be protected from developing systemic adverse effects with high-dose fluticasone propionate therapy, as evaluated by basal and dynamic measures of hypothalamic-pituitary-adrenal axis activity.

摘要

背景

高剂量丙酸氟替卡松治疗对重度哮喘患者动态皮质醇刺激的影响尚不清楚。

目的

评估在气道口径受损（第1秒用力呼气量[FEV1]<预测值的60%）的重度哮喘患者及对照受试者中，人促肾上腺皮质激素释放因子（hCRF）刺激下血浆皮质醇对丙酸氟替卡松治疗的反应。

方法

10例重度哮喘患者（平均FEV1为预测值的47%）和10例对照者（平均FEV1为预测值的104%）通过一个750 mL的预充储雾罐接受2000μg/d的丙酸氟替卡松治疗，持续2周。在洗脱期后的基线、最后一剂丙酸氟替卡松后12小时，测量hCRF刺激前后的血浆皮质醇水平以及校正肌酐浓度后的过夜10小时尿皮质醇排泄量（OUCC）。

结果

在哮喘患者与对照者中，使用丙酸氟替卡松前，hCRF刺激前后的血浆皮质醇水平及OUCC的基线值无显著差异。比较哮喘患者使用丙酸氟替卡松前后的数值，hCRF刺激前（378.2对357.4 nmol/L）、刺激后（510.5对507.9 nmol/L）的血浆皮质醇水平或OUCC（8.2对7.5 nmoL/mmoL）均无显著抑制。在对照者中，比较使用丙酸氟替卡松治疗前后的数值，所有结果均有显著抑制：hCRF刺激前（423.5对200.2 nmol/L；P = .002）、刺激后（503.5对291.1 nmol/L；P = .001）的血浆皮质醇水平及OUCC（6.5对2.4 nmol/mmol；P = .002）。