Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction

Nikolaos Lazarinis, Leif Jørgensen, Tommy Ekström, Leif Bjermer, Barbro Dahlén, Teet Pullerits, Gunilla Hedlin, Kai-Håkon Carlsen, Kjell Larsson, Nikolaos Lazarinis, Leif Jørgensen, Tommy Ekström, Leif Bjermer, Barbro Dahlén, Teet Pullerits, Gunilla Hedlin, Kai-Håkon Carlsen, Kjell Larsson

Abstract

Background: In mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting β2 agonists (SABAs) on demand.

Objective: The hypothesis was that a combination of budesonide and formoterol on demand diminishes EIB equally to regular inhalation of budesonide and is more effective than terbutaline inhaled on demand.

Methods: Sixty-six patients with asthma (>12 years of age) with verified EIB were randomised to terbutaline (0.5 mg) on demand, regular budesonide (400 μg) and terbutaline (0.5 mg) on demand, or a combination of budesonide (200 μg) + formoterol (6 μg) on demand in a 6-week, double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833). The patients were instructed to perform three to four working sessions per week. The main outcome was EIB 24 h after the last dosing of study medication.

Results: After 6 weeks of treatment with regular budesonide or budesonide+formoterol on demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after the last medication, was 6.6% (mean; 95% CI -10.3 to -3.0) and 5.4% (-8.9 to -1.8) smaller, respectively. This effect was superior to inhalation of terbutaline on demand (+1.5%; -2.1 to +5.1). The total budesonide dose was approximately 2.5 times lower in the budesonide+formoterol group than in the regular budesonide group. The need for extra medication was similar in the three groups.

Conclusions: The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as regular budesonide treatment despite a substantially lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.

Keywords: Asthma; Exercise.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Forced expiratory volume in 1 s (FEV1) before and after a 6 min standardised exercise test on a treadmill, while breathing dry air, before treatment (upper panel) and after 6 weeks of treatment (lower panel) with the three different treatments.
Figure 3
Figure 3
Demonstration of non-inferiority between budesonide on a regular basis (400 μg daily) and terbutaline (0.5 mg) on demand versus the combination of budesonide (400 μg) and formoterol (6.0 μg) on demand in the per protocol population. FEV1, forced expiratory volume in 1 s.

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