Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children
Editorial Group: Cochrane Airways Group
Published Online: 16 DEC 2013
Assessed as up-to-date: 19 NOV 2013
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD009019. DOI: 10.1002/14651858.CD009019.pub2.
- Publication Status: Edited (no change to conclusions)
- Published Online: 16 DEC 2013
Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness and cough. Treatment with inhaled steroids and bronchodilators often results in good control of symptoms, prevention of further morbidity and mortality and improved quality of life. Several steroids and beta
To assess the efficacy and safety of budesonide/formoterol in a single inhaler (SiT) to be used for both maintenance and reliever therapy in asthma in comparison with maintenance treatment provided through combination inhalers with a higher maintenance steroid dose (either fluticasone/salmeterol or budesonide/formoterol), along with additional fast-acting beta
We searched the Cochrane Airways Group Specialised Register of trials, online trial registries and drug company websites. The most recent search was conducted in November 2013.
We included parallel-group, randomised controlled trials of at least 12 weeks' duration. Studies were included if they compared single-inhaler therapy with budesonide/formoterol (SiT) versus combination inhalers at a higher maintenance dose of steroids than was given in the SiT arm (either salmeterol/fluticasone or budesonide/formoterol).
Data collection and analysis
We used standard methods expected by The Cochrane Collaboration. Primary outcomes were exacerbations requiring hospitalisation, exacerbations requiring oral corticosteroids and serious adverse events (including mortality).
Four studies randomly assigning 9130 people with asthma were included; two were six-month double-blind studies, and two were 12-month open-label studies. No trials included children younger than age 12. Trials included more women than men, with mean age ranging from 38 to 45, and mean baseline steroid dose (inhaled beclomethasone (BDP) equivalent) from 636 to 888 μg. Mean baseline forced expiratory volume in one second (FEV
Separate data for exacerbations leading to hospitalisations, to emergency room (ER) visits or to a course of oral steroids could not be obtained. Compared with higher fixed-dose combination inhalers, fewer people using SiT had exacerbations requiring hospitalisation or a visit to the ER (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57 to 0.90; I
We could not rule out the possibility that SiT increased rates of serious adverse events (OR 0.92, 95% CI 0.74 to 1.13; I
We were unable to say whether SiT improved results for several secondary outcomes (morning and evening peak expiratory flow (PEF), rescue medication use, symptoms scales), and in cases where results were significant, the effect sizes were not considered clinically meaningful (predose FEV
SiT reduces the number of people having asthma exacerbations requiring oral steroids and the number requiring hospitalisation or an ER visit compared with fixed-dose combination inhalers. Evidence for serious adverse events was unclear. The mean daily dose of inhaled corticosteroids (ICS) in SiT, including the total dose administered with reliever use, was always lower than that of the other combination groups. This suggests that the flexibility in steroid administration that is possible with SiT might be more effective than a standard fixed-dose combination by increasing the dose only when needed and keeping it low during stable stages of the disease. Data for hospitalisations alone could not be obtained, and no studies have yet addressed this question in children younger than age 12.
Plain language summary
For people with chronic asthma, is a single combination inhaler for both regular and "as-needed" treatment better than two separate inhalers?
Background for the review
Asthma is a chronic inflammation of the airways that causes flare-ups of wheezing, chest tightness and coughing. Treatment with inhaled steroids and other inhaled drugs that relax the airways (bronchodilators) often gives good control of symptoms, prevents serious flare-ups and improves quality of life. Several steroids and bronchodilators (long- and short-acting) as well as combinations of these treatments are available in a single inhaler.
This review focusses on a particular inhaled therapy called 'single-inhaler therapy' (SiT), sometimes called SMART therapy. The idea is that the SiT is taken once or twice a day and also anytime it is needed for relief of symptoms. In theory, this improves compliance, controls asthma symptoms and prevents exacerbations while allowing lower overall exposure to inhaled steroids. The drugs contained in SiT are budesonide and formoterol.
This review aimed to find out whether SiT is as safe and effective as a combination inhaler (containing a steroid and a long-acting beta-agonist (LABA)) plus another inhaler for relief of symptoms. The review looked at the effects of these treatments for adults and children with chronic asthma.
What did we find?
Four studies including 9130 adults and adolescents were included. None of the studies included children younger than age 12. The studies lasted for six months to a year, and all were funded by one drug company. Studies included more women than men, with average age of about 40. Three studies recruited people with quite similar symptoms, but one study included people with less severe asthma. The studies were well conducted, although two did not hide which treatments were being taken (known as blinding), which might have affected the results. The amount of inhaled steroids, including puffs taken for relief from symptoms, was consistently lower for SiT than for the comparison groups using two types of inhalers. Overall, we believe that the quality of the evidence was high to moderate.
Fewer people taking SiT had flare-ups that needed a hospital stay or a visit to the ER (one fewer per 100 treated than in the control group, 95% CI 0 to 2 fewer) or a course of oral steroids (two fewer per 100 treated, 95% CI one to three fewer). If more studies are published, it is unlikely that our opinions on these main findings will change. However, we could not tell whether one treatment caused more serious adverse events than the other.
SiT had a small benefit on one measure of lung function (predose forced expiratory volume in one second (FEV
In conclusion, SiT reduces the need for a hospital stay or an ER visit and for courses of oral steroids for asthma flare-ups. SiT did not increase the quantity of inhaled steroids taken overall, and it was unclear whether it increases or decreases serious side effects. Currently no data are available for the use of SiT in children younger than age 12.