A Cochrane review [Abstract] 1 included 18 trials with a total of 7 208 subjects with asthma and significant reversibility to bronchodilator at baseline. 16 studies recruited adults and adolescents (n=6 872) and two recruited children aged 6 to 17 years (n=336). During the intervention period, all participants remained on a stable dose of inhaled corticosteroids (ICS). The leukotriene receptor antagonists (LTRAs) used were zafirlukast 20 mg twice daily or montelukast 5 mg or 10 mg once daily, depending on the age of participants. The long-acting beta-2 agonists (LABAs) used were salmeterol 50 µg twice daily, salmeterol 50 µg once daily in one paediatric trial, or formoterol 12 µg twice daily.
Risk of exacerbations requiring systemic corticosteroids was significantly lower with LABA + ICS when compared to LTRA + ICS (11% vs 13%; RR 0.87, 95% CI 0.76 to 0.99; 8 studies, 5 923 adults and 334 children). The number needed to treat (NNT) with LABA compared to LTRA, to prevent one exacerbation over 4 to 102 weeks, was 62 (95% CI 34 to 794). The choice of LTRA, the dose of ICS, and the participants' age group did not significantly influence the magnitude of effect. Although results were inconclusive, the effect appeared stronger in the trials using a single device to administer ICS and LABA compared to those using two devices, and in trials of less than 12 weeks' duration. The addition of LABA to ICS was associated with a statistically greater improvement from baseline in lung function, as well as in symptoms, rescue medication use and quality of life, although the latter effects were modest. LTRA was superior in the prevention of exercise-induced bronchospasm. More participants were satisfied with the combination of LABA + ICS than LTRA + ICS (RR 1.12, 95% CI 1.04 to 1.20; 3 studies, 1 625 adults).
The overall risk of withdrawal was significantly lower with LABA + ICS than with LTRA + ICS (RR 0.84, 95% CI 0.74 to 0.96; 13 studies, 6 652 adults and 308 children). Although the risk of overall adverse events was equivalent between the two groups, the risk of serious adverse events (SAE) approached statistical significance in disfavour of LABA compared with LTRA (RR 1.33, 95% CI 0.99 to 1.79; 9 studies, 5 658 adults and 630 children), with no apparent impact of participants' age group.The following adverse events were reported, but no significant differences were demonstrated between groups: headache (11 studies, n = 6 538); cardiovascular events (5 studies, n= 5 163), osteopenia and osteoporosis (2 studies, n = 2 963), adverse events (10 studies, n= 5 977 adults and 300 children). A significant difference in the risk of oral moniliasis was noted, but this represents a low occurrence rate.
Comment:The findings modestly support the use of a single inhaler for the delivery of both LABA and low- or medium-dose ICS. Because of the paucity of paediatric trials, it is not possible to draw firm conclusions about the best adjunct therapy in children.
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