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

Imran Aziz, Andrew M. Wilson, Brian J. Lipworth

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25 Citations (Scopus)


Objectives: We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers.

Methods: Fifteen patients with atopic persistent asthmawere 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 washoutperiod, comparing the following once-daily nighttime treatments: (1)formoterol (FM), 12 μg, for 2 weeks and FM, 24 μg, for 2 weeks; or(2) budesonide (BUD), 400 μg, for 2 weeks and BUD, 800 μg, for2 weeks; or (3) FM, 12 μg, plus BUD, 400 μg, for 2 weeks and FM, 24μg, plus BUD, 800 μg, for 2 weeks. Adenosine monophosphate (AMP)bronchial challenge, exhaled nitric oxide (NO), and serum eosinophiliccationic protein (ECP) were evaluated at 12 h postdosing afteradministration of each placebo and after 2 and 4 weeks of eachtreatment.

Results: The results of AMP challenge(provocative concentration causing a 20% fall in FEV1) at4 weeks showed significant (p < 0.05) improvements after patientshad received all active treatments compared to placebo (20 mg/mL), withFM plus BUD, 261 mg/mL, being superior (p < 0.05) to FM alone, 82mg/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 BUDalone but not with FM alone. Combination therapy was associatedwith optimal patient preference (rank order, FM plus BUD > FM>BUD; p < 0.0005), highest domiciliary peak expiratoryflow, and lowest rescue inhaler usage. All three treatmentsproduced equivalent improvements in spirometry.

Conclusions: Patients preferred once-daily combinationtherapy, but this had no greater effect on inflammatory markers thantherapy with BUD alone. FM alone had no anti-inflammatory activity butexhibited bronchoprotection. This emphasizes the importance of firstoptimizing anti-inflammatory control with inhaled corticosteroidsbefore considering adding a regular long-actingβ2-agonist.
Original languageEnglish
Pages (from-to)1049-1058
Number of pages10
Issue number4
Publication statusPublished - Oct 2008

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