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

Objectives: We wished to evaluate the effects of once-daily combination the rapy on surrogate inflammatory markers. Methods: Fifteen patients with atopic persistent asthma were evaluated (mea n age, 32.4 years; FEV1, 75.2% predicted) in a randomized, double-blind, do uble-dummy, placebo-controlled crossover study with a 1-week placebo washou t period, comparing the following once-daily nighttime treatments: (1) form oterol (FM), 12 mug, for 2 weeks and FM, 24 mug, for 2 weeks; or (2) budeso nide (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,fo r 2 weeks. Adenosine monophosphate (AMP) bronchial challenge, exhaled nitri c oxide (NO), and serum eosinophilic cationic protein (ECP) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 w eeks 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 aft er patients had received all active treatments compared to placebo (20 mg/m L), 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 F M 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 pro duced equivalent improvements in spirometry. Conclusions: Patients preferred once-daily combination therapy, but this ha d no greater effect on inflammatory markers than therapy with BUD alone. FM alone had no anti-inflammatory activity but exhibited bronchoprotection. T his emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acti ng <beta>(2)-agonist.