联合吸入器与单独使用吸入性糖皮质激素治疗中度持续性哮喘的比较。
Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma.
作者信息
Lee Daniel K C, Jackson Catherine M, Currie Graeme P, Cockburn Wendy J, Lipworth Brian J
机构信息
Asthma & Allergy Research Group, Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY.
出版信息
Br J Clin Pharmacol. 2003 Nov;56(5):494-500. doi: 10.1046/j.1365-2125.2003.01887.x.
AIMS
Inhalers combining long acting beta2-adrenoceptor agonists (LABA) and corticosteroids (ICS) are indicated at Step 3 of current asthma guidelines. We evaluated the relative effects of LABA + ICS combination vs ICS alone on pulmonary function, bronchoprotection, acute salbutamol recovery following methacholine bronchial challenge, and surrogate inflammatory markers in patients with moderate persistent asthma.
METHODS
Twenty-nine patients with mean FEV1 (+/- SEM) of 78 +/- 3% predicted completed a randomized, double-blind, double-dummy, cross-over study. Patients received either 4 weeks of budesonide 400 microg + formoterol 12 microg (BUD + FM) combination twice daily followed by 1 week of BUD 400 microg alone twice daily, or 4 weeks of fluticasone propionate 250 microg + salmeterol 50 microg (FP + SM) combination twice daily followed by 1 week of FP 250 microg alone twice daily. Measurements were made at baseline and following each randomized treatment.
RESULTS
FEV1 increase from pretreatment baseline as mean (+/- SEM) % predicted was significantly higher (P < 0.05) for BUD + FM (8 +/- 1%) vs BUD (2 +/- 1%), and for FP + SM (8 +/- 1%) vs FP (2 +/- 1%). The fall in FEV1 following methacholine challenge as percentage change from prechallenge baseline FEV1 was not significantly different in all four groups; BUD + FM (22 +/- 1%), BUD (24 +/- 1%), FP + SM (23 +/- 1%) and FP (23 +/- 1%). Salbutamol recovery over 30 min following methacholine challenge as area under curve (AUC %.min) was significantly blunted (P < 0.05) with BUD + FM (486.7 +/- 35.5) vs BUD (281.1 +/- 52.8), and with FP + SM (553.1 +/- 34.1) vs FP (368.3 +/- 46.7). There were no significant differences between respective combination inhalers or between respective ICS alone. Decreases in exhaled nitric oxide (NO) and serum eosinophilic cationic protein (ECP) from baseline were not significantly different between treatments.
CONCLUSIONS
Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction.
目的
长效β2肾上腺素受体激动剂（LABA）与糖皮质激素（ICS）联合吸入剂适用于当前哮喘指南的第3步治疗。我们评估了LABA + ICS联合用药与单独使用ICS对中度持续性哮喘患者肺功能、支气管保护作用、乙酰甲胆碱支气管激发试验后沙丁胺醇急性恢复情况以及替代炎症标志物的相对影响。
方法
29例预计FEV1（±标准误）为78 ± 3%的患者完成了一项随机、双盲、双模拟、交叉研究。患者接受4周的布地奈德400微克+福莫特罗12微克（BUD + FM）联合用药，每日两次，随后1周单独使用布地奈德400微克，每日两次；或者4周的丙酸氟替卡松250微克+沙美特罗50微克（FP + SM）联合用药，每日两次，随后1周单独使用丙酸氟替卡松250微克，每日两次。在基线和每次随机治疗后进行测量。
结果
与单独使用布地奈德（BUD）相比，BUD + FM组的FEV1从治疗前基线增加的预测平均值（±标准误）%显著更高（P < 0.05）（8 ± 1% 对 2 ± 1%）；与单独使用丙酸氟替卡松（FP）相比，FP + SM组的FEV1从治疗前基线增加的预测平均值（±标准误）%显著更高（P < 0.05）（8 ± 1% 对 2 ± 1%）。在所有四组中，乙酰甲胆碱激发试验后FEV1的下降作为激发前基线FEV1的百分比变化无显著差异；BUD + FM组（22 ± 1%）、BUD组（24 ± 1%）、FP + SM组（23 ± 1%）和FP组（23 ± 1%）。乙酰甲胆碱激发试验后30分钟内沙丁胺醇的恢复情况作为曲线下面积（AUC %.min），与单独使用BUD相比，BUD + FM组显著减弱（P < 0.05）（486.7 ± 35.5对281.1 ± 52.8）；与单独使用FP相比，FP + SM组显著减弱（P < 0.05）（553.1 ± 34.1对368.3 ± 46.7）。各联合吸入剂之间或单独使用各ICS之间无显著差异。治疗后呼出一氧化氮（NO）和血清嗜酸性粒细胞阳离子蛋白（ECP）较基线的下降在各治疗组之间无显著差异。
结论
与单独使用ICS相比，联合吸入剂可改善肺功能，但对呼出NO和血清ECP无增强抗炎作用，且会延迟支气管收缩后沙丁胺醇的急性恢复。
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