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

Abstract

BackgroundIn mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting β2 agonists (SABAs) on demand.ObjectiveThe 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.MethodsSixty-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.ResultsAfter 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.ConclusionsThe 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.

On-Demand Inhaled Corticosteroid and Fast-Acting Beta-2 Agonist Combination Therapy Versus Regular Inhaled Corticosteroid Plus Rescue Bronchodilator in Adults with Mild Asthma: A Network Meta-Analysis

“…One article was identi ed from the reference lists of included studies. Finally, three RCTs were included in the network meta-analysis 4,5,10 . The characteristics of these studies are shown in Table 1.…”

“…Another RCT did not demonstrate a significant difference in efficacy for asthma control between NON-REG OD-ICS / FABA and an OD-SABA without any regular treatment NON-REG OD-SABA 5 . An RCT in patients with moderate asthma showed the inferiority of NON-REG OD-ICS / FABA for asthma control relative to regular ICS with a long-acting beta-2 agonist LABA plus OD-SABA REG-ICS / LABA OD-SABA 6 .…”

On-demand Inhaled Corticosteroid and Fast-onset Beta-2 Agonist Combination Therapy Versus Conventional Treatment for Mild to Moderate Asthma: A Non-inferiority, Network Meta-analysis

“…Several previous RCTs have assessed the efficacy of OD-ICS / FOBA compared with conventional best practice in patients with mild or moderate asthma [4][5][6] . One RCT demonstrated the non-inferiority of on-demand beclomethasone with albuterol without any regular treatment relative to regular beclomethasone plus on-demand albuterol in mild asthma 6 .…”

“…Randomized controlled trials RCTs have shown that on-demand use of an ICS and fastonset beta-2 agonist FOBA , such as a short-acting beta-2 agonist SABA or formoterol, without any regular treatment OD-ICS / FOBA is effective and might be an alternative therapy to regular ICS plus SABA REG-ICS OD-SABA or regular ICS / LABA plus on-demand SABA REG-ICS / LABA OD-SABA in patients with mild to moderate asthma 4,5 . Another RCT showed the non-inferiority of on-demand use of beclomethasone in combination with albuterol without any regular treatment, relative to regular low-dose beclomethasone plus on-demand albuterol with or without regular albuterol 6 .…”

“…On-demand use may reduce the in uence of poor adherence to daily inhaled medication and may improve control of asthma and reduce the requirement for regular use of ICS and beta-2 agonist [4][5][6] . However, the effects of OD-ICS / FOBA on symptom control in patients with mild to moderate asthma are unclear, and the ideal population of patients who may bene t from this treatment is unde ned.…”