Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults

被引:59
作者
Aziz, I [1 ]
Wilson, AM [1 ]
Lipworth, BJ [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Dept Clin Pharmacol & Therapeut, Asthma & Allergy Res Grp, Dundee DD1 4HN, Scotland
关键词
adenosine monophosphate; bronchial hyperresponsiveness; budesonide; exhaled nitric oxide; formoterol; inflammation;
D O I
10.1378/chest.118.4.1049
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objectives: We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers. Methods: Fifteen patients with atopic persistent asthma were evaluated (mean age, 32.4 years; FEV1, 75.2% predicted) in a randomized, double-blind, double-dummy, placebo-controlled crossover study with a 1-week placebo washout period, comparing the following once-daily nighttime treatments: (1) formoterol (FM), 12 mug, for 2 weeks and FM, 24 mug, for 2 weeks; or (2) budesonide (BUD), 400 mug, for 2 weeks and BUD, 800 mug, for 2 weeks; or (3) FM, 12 mug, plus BUD, 400 mug, for 2 weeks and FM, 24 mug, plus BUD, 800 mug,for 2 weeks. Adenosine monophosphate (AMP) bronchial challenge, exhaled nitric oxide (NO), and serum eosinophilic cationic protein (ECP) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 weeks of each treatment. Results: The results of AMP challenge (provocative concentration causing a 20% fall in FEV1) at 4 weeks showed significant (p < 0.05) improvements after patients had received all active treatments compared to placebo (20 mg/mL), with FM plus BUD, 261 mg/mL, being superior (p < 0.05) to FM alone, 82 mg/mL, but not to BUD, 201 mg/mL. NO and ECP showed significant (p < 0.05) reductions compared to placebo with FM plus BUD or BUD alone but not with FM alone. Combination therapy was associated with optimal patient preference (rank order, FM plus BUD > FM > BUD; p < 0.0005), highest domiciliary peak expiratory flow, and lowest rescue inhaler usage. All three treatments produced equivalent improvements in spirometry. Conclusions: Patients preferred once-daily combination therapy, but this had no greater effect on inflammatory markers than therapy with BUD alone. FM alone had no anti-inflammatory activity but exhibited bronchoprotection. This emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acting <beta>(2)-agonist.
引用
收藏
页码:1049 / 1058
页数:10
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