Wempe J B, Postma D S, Breederveld N, Alting-Hebing D, van der Mark T W, Koëter G H
Department of Pulmonology, University Hospital Groningen, The Netherlands.
J Allergy Clin Immunol. 1992 Mar;89(3):679-87. doi: 10.1016/0091-6749(92)90374-b.
We have investigated separate and interactive effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness. Twelve allergic subjects with asthma were treated in a double-blind, crossover, randomized study with budesonide, 1.6 mg daily for 3 weeks, prednisone, 40 mg daily, for 8 days, and placebo. After each period, dose-response curves were measured on 4 study days with doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo until a plateau in FEV1 was reached. A histamine challenge was then performed, and the provocation concentration causing a 20% fall in FEV1 (PC20) was calculated. The budesonide and prednisone regimens were equipotent. FEV1 was 81.2% of predicted after budesonide, 81.0% predicted after prednisone, and 67.5% predicted after placebo, bronchodilatation thus being 13.7% predicted (budesonide) and 13.5% predicted (prednisone). PC20 improved with 2.17 doubling concentrations (DCs) after budesonide, and 1.86 DCs after prednisone, compared with that of placebo. Salbutamol caused stronger bronchodilatation than ipratropium (26.2% versus 14.7% predicted) and a better protection against histamine challenge (3.95 versus 1.12 DC). The effects of corticosteroids and bronchodilators on FEV1 and PC20 were, in general, additive. This study emphasizes different modes of action on both airflow obstruction and airway hyperresponsiveness by corticosteroids and bronchodilators, and it demonstrates no enhancement of bronchodilator action by corticosteroids.
我们研究了皮质类固醇和支气管扩张剂对气流阻塞和气道高反应性的单独及交互作用。在一项双盲、交叉、随机研究中，对12名过敏性哮喘患者分别给予布地奈德（每日1.6毫克，共3周）、泼尼松（每日40毫克，共8天）和安慰剂进行治疗。在每个治疗阶段后，于4个研究日测量使用双倍剂量沙丁胺醇、异丙托溴铵、沙丁胺醇与异丙托溴铵的组合以及安慰剂时的剂量反应曲线，直至FEV1达到平台期。然后进行组胺激发试验，并计算引起FEV1下降20%的激发浓度（PC20）。布地奈德和泼尼松治疗方案的效果相当。布地奈德治疗后FEV1为预测值的81.2%，泼尼松治疗后为预测值的81.0%，安慰剂治疗后为预测值的67.5%，因此支气管扩张程度分别为预测值的13.7%（布地奈德）和13.5%（泼尼松）。与安慰剂相比，布地奈德治疗后PC20改善了2.17倍浓度增加（DCs），泼尼松治疗后改善了1.86 DCs。沙丁胺醇引起的支气管扩张作用强于异丙托溴铵（分别为预测值的26.2%和14.7%），且对组胺激发试验的保护作用更好（分别为3.95和1.12 DC）。皮质类固醇和支气管扩张剂对FEV1和PC20的作用总体上是相加的。本研究强调了皮质类固醇和支气管扩张剂对气流阻塞和气道高反应性的不同作用方式，并且表明皮质类固醇不会增强支气管扩张剂的作用。
