Kiviranta K, Turpeinen M
Department of Allergic Diseases, University Central Hospital, Helsinki, Finland.
Thorax. 1993 Oct;48(10):974-8. doi: 10.1136/thx.48.10.974.
The safety of high dose inhaled steroids has been a subject of debate. The efficacy and safety of beclomethasone dipropionate and budesonide inhalations were evaluated by measuring their effects on pulmonary function, on the hypothalamic-pituitary-adrenocortical axis, and on carbohydrate metabolism in adults with unstable asthma.
Fifteen adults with unstable asthma and 15 healthy controls were studied. Eight patients were treated with beclomethasone dipropionate in initially high (2 mg/day for five months) and subsequently lower (1 mg/day for three months) doses. Seven patients were treated with budesonide at doses of 1.6 mg/day for five months followed by 0.8 mg/day for three months. Blood glucose and serum insulin were measured in an oral glucose tolerance test and plasma cortisol in an adrenocorticotrophic hormone test. The antiasthmatic effect of treatment was evaluated by measuring peak morning expiratory flow rates and forced expiratory volume in one second (FEV1).
The FEV1 increased significantly after one month of treatment (medians 88% v 96%, p < 0.01), and nocturnal symptoms disappeared within two weeks of treatment in both groups. At one month, the high dose significantly decreased serum insulin concentrations as calculated from the areas under the incremental two hours curves in the glucose tolerance test. The decrease was 59% for beclomethasone dipropionate (medians 76 v 31 mU/l/h, p < 0.005) and 42% for budesonide (medians 79 v 46 mU/l/h, p < 0.01). The median areas at five and eight months were intermediate for both drugs. No significant differences were found when the five and eight month values were compared either with the baseline or with one month values. The difference between the baseline values of both groups and the respective values in healthy controls was significant (medians 79 v 49 mU/l/h, p < 0.01). The one month values for the patients and control subjects were similar. Paralleling the changes for insulin, the area under the incremental two hour blood glucose curve decreased significantly (medians 1.4 v 0.4 mmol/l/h, p < 0.05) during the first month of treatment. The five and eight month values were intermediate (medians 0.8 and 0.7 mmol/l/h, respectively). These changes were not significant compared with the baseline or the one month areas. Similar changes were seen in both treatment groups. Neither treatment had any significant effect on plasma cortisol in the one hour adrenocorticotrophic hormone test.
In patients stressed by uncontrolled asthma, the antiasthmatic effect of high dose beclomethasone dipropionate and budesonide was accompanied by a significant initial decrease in insulin resistance with a parallel improvement in glucose tolerance. During prolonged treatment a small increase in insulin sensitivity was found. The overall effect of beclomethasone dipropionate and budesonide inhalations on carbohydrate metabolism may be beneficial in patients with uncontrolled asthma.
高剂量吸入性类固醇的安全性一直是一个有争议的话题。通过测量倍氯米松二丙酸酯和布地奈德吸入剂对不稳定型哮喘成人患者肺功能、下丘脑 - 垂体 - 肾上腺皮质轴以及碳水化合物代谢的影响，对其疗效和安全性进行了评估。
对15例不稳定型哮喘成人患者和15名健康对照者进行了研究。8例患者先接受高剂量（2毫克/天，持续五个月）随后低剂量（1毫克/天，持续三个月）的倍氯米松二丙酸酯治疗。7例患者接受布地奈德治疗，剂量为1.6毫克/天，持续五个月，随后为0.8毫克/天，持续三个月。在口服葡萄糖耐量试验中测量血糖和血清胰岛素，在促肾上腺皮质激素试验中测量血浆皮质醇。通过测量早晨呼气峰值流速和一秒用力呼气量（FEV1）评估治疗的抗哮喘效果。
治疗一个月后FEV1显著增加（中位数88%对96%，p < 0.01），两组患者的夜间症状在治疗两周内消失。在一个月时，根据葡萄糖耐量试验中两小时增量曲线下面积计算，高剂量显著降低了血清胰岛素浓度。倍氯米松二丙酸酯降低了59%（中位数76对31 mU/l/h，p < 0.005），布地奈德降低了42%（中位数79对46 mU/l/h，p < 0.01）。两种药物在五个月和八个月时的中位数面积处于中间水平。将五个月和八个月的值与基线值或一个月的值进行比较时，未发现显著差异。两组的基线值与健康对照者的相应值之间的差异显著（中位数79对49 mU/l/h，p < 0.01）。患者和对照者的一个月值相似。与胰岛素变化平行，在治疗的第一个月，两小时血糖增量曲线下面积显著下降（中位数1.4对0.4 mmol/l/h，p < 0.05）。五个月和八个月的值处于中间水平（分别为中位数0.8和0.7 mmol/l/h）。与基线或一个月的面积相比，这些变化不显著。两个治疗组均出现类似变化。在一小时促肾上腺皮质激素试验中，两种治疗对血浆皮质醇均无显著影响。
在受未控制哮喘困扰的患者中，高剂量倍氯米松二丙酸酯和布地奈德的抗哮喘作用伴随着胰岛素抵抗的显著初始下降以及葡萄糖耐量的平行改善。在长期治疗期间，发现胰岛素敏感性有小幅增加。倍氯米松二丙酸酯和布地奈德吸入剂对碳水化合物代谢的总体影响可能对未控制哮喘患者有益。
