Brown P H, Teelucksingh S, Matusiewicz S P, Greening A P, Crompton G K, Edwards C R
Department of Medicine, Northern and Western General Hospitals, Edinburgh, UK.
Lancet. 1991 Mar 9;337(8741):576-80. doi: 10.1016/0140-6736(91)91639-c.
The aim of the study was to find out whether asthma patients whose airways obstruction is sensitive (CS) or resistant (CR) to corticosteroid treatment also differ in their cutaneous vasoconstrictor response to a potent topical glucocorticoid. Corticosteroid resistance was defined by failure of forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate to improve by at least 15% after a 2-week trial of corticosteroids (prednisolone 20 mg daily for 1 week, then 40 mg daily for 1 week) despite more than 15% improvement with inhaled beta agonists. Beclomethasone dipropionate in concentrations of 3 micrograms/ml, 10 micrograms/ml, 30 micrograms/ml, and 100 micrograms/ml was applied to forearm skin; the site was occluded under plastic and the degree of blanching assessed after 18 h. CS asthmatic subjects (n = 31), asthma patients with mild airways obstruction (n = 26), asthma patients taking long-term prednisolone (n = 13), and healthy volunteers showed similar vasoconstrictor responses. In CR asthmatic subjects (n = 15), the response (expressed in terms of either blanching intensity or the proportion of patients showing a positive response) was significantly lower than that in the CS group at concentrations of 3 micrograms/ml (p less than 0.01), 10 micrograms/ml (p less than 0.01), and 30 micrograms/ml (p less than 0.05), but not at 100 micrograms/ml. This resistance to glucocorticoids in the skin, together with reported evidence of glucocorticoid resistance in peripheral blood leucocytes, suggests a general defect in the ability of tissues to respond to glucocorticoids in CR asthma.
该研究的目的是查明气道阻塞对皮质类固醇治疗敏感(CS)或抵抗(CR)的哮喘患者在对强效外用糖皮质激素的皮肤血管收缩反应方面是否也存在差异。皮质类固醇抵抗的定义为:在进行为期2周的皮质类固醇试验(泼尼松龙每日20 mg,持续1周,然后每日40 mg,持续1周)后,尽管吸入β受体激动剂可使1秒用力呼气量(FEV1)和呼气峰值流速提高超过15%,但FEV1和呼气峰值流速至少提高15%的情况未出现。将浓度为3微克/毫升、10微克/毫升、30微克/毫升和100微克/毫升的二丙酸倍氯米松应用于前臂皮肤;该部位用塑料覆盖进行封闭,18小时后评估皮肤变白程度。CS哮喘受试者(n = 31)、轻度气道阻塞的哮喘患者(n = 26)、长期服用泼尼松龙的哮喘患者(n = 13)和健康志愿者表现出相似的血管收缩反应。在CR哮喘受试者(n = 15)中,在3微克/毫升(p < 0.01)、10微克/毫升(p < 0.01)和30微克/毫升(p < 0.05)浓度下,其反应(以皮肤变白强度或出现阳性反应的患者比例表示)显著低于CS组,但在100微克/毫升浓度下并非如此。皮肤对糖皮质激素的这种抵抗,连同外周血白细胞中糖皮质激素抵抗的报道证据,提示CR哮喘患者组织对糖皮质激素的反应能力存在普遍缺陷。