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Meta-Analysis
. 2013 Dec 16;2013(12):CD009019.
doi: 10.1002/14651858.CD009019.pub2.

Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children

Kayleigh M Kew  1 , Charlotta Karner, Stephanie M Mindus, Giovanni Ferrara
Affiliations
Meta-Analysis

Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children

Kayleigh M Kew et al. Cochrane Database Syst Rev. .

Abstract

Background: 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 beta2-agonists (long- and short-acting) as well as combinations of these treatments are available in a single inhaler to be used once or twice a day, with a separate inhaler for relief of symptoms when needed (for patients in Step three or higher, according to Global Initiative for Asthma (GINA) guidelines). Budesonide/formoterol is also licenced for use as maintenance and reliever therapy from a single inhaler (SiT; sometimes referred to as SMART therapy). SiT can be prescribed at a lower dose than other combination therapy because of the additional steroid doses being received as reliever therapy. It has been suggested that using SiT improves compliance and hence reduces symptoms and exacerbations, but it is unclear whether it increases side effects associated with the use of inhaled steroids.

Objectives: 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 beta2-agonists for relief of symptoms.

Search methods: 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.

Selection criteria: 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).

Main results: 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 (FEV1) percentage predicted was between 70% and 73% in three of the trials, and 96% in another. All studies were funded by AstraZeneca and were generally free from methodological biases, although the two open-label studies were rated as having high risk for blinding, and some evidence of selective outcome reporting was found. These possible sources of bias did not lead us to downgrade the quality of the evidence. The quantity of inhaled steroids, including puffs taken for relief from symptoms, was consistently lower for SiT than for the comparison groups.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(2) = 0%, P = 0.66), and fewer had exacerbations requiring a course of oral corticosteroids (OR 0.75, 95% CI 0.65 to 0.87; I(2) = 0%, P = 0.82). This translates to one less person admitted to hospital or visiting the ER (95% CI 0 to 2 fewer) and two fewer people needing oral steroids (95% CI 1 to 3 fewer) compared with fixed-dose combination treatment with a short-acting beta-agonist (SABA) reliever (per 100 treated over eight months). No statistical heterogeneity was observed in either outcome, and the evidence was rated of high quality. Although issues with blinding were evident in two of the studies, and one study recruited a less severe population, sensitivity analyses did not change the main results, so quality was not downgraded.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(2) = 0%, P = 0.98; moderate-quality evidence, downgraded owing to imprecision).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 FEV1, nocturnal awakenings and quality of life).

Authors' conclusions: 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.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Cates plot: In the control group, 10 of 100 people had an exacerbation requiring oral steroids over eight months compared with eight (95% CI seven to nine) of 100 in the SiT group.
4
4
Cates plot: In the control group, five of 100 people had an exacerbation requiring hospitalisation or an ER visit over eight months, compared with four (95% CI three to five) of 100 in the SiT group.
1.1
1.1. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 1 Participants with exacerbations requiring oral steroids.
1.2
1.2. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 2 Participants with serious adverse events.
1.3
1.3. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 3 Participants with severe exacerbations (hospitalisation or ER visit).
1.4
1.4. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 4 Morning PEF (L/min).
1.5
1.5. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 5 Evening PEF (L/min).
1.6
1.6. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 6 FEV1 predose (mL).
1.7
1.7. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 7 Rescue medication puffs required per day.
1.8
1.8. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 8 Symptoms (ACQ‐5).
1.9
1.9. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 9 Symptom‐free days (%).
1.10
1.10. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 10 Nocturnal awakenings (%).
1.11
1.11. Analysis
Comparison 1 SiT versus higher‐dose ICS/LABA + SABA, Outcome 11 Quality of life AQLQ(S).
2.1
2.1. Analysis
Comparison 2 (Sensitivity analysis – Baseline severity), Outcome 1 Participants with exacerbations requiring oral steroids.
2.2
2.2. Analysis
Comparison 2 (Sensitivity analysis – Baseline severity), Outcome 2 Participants with serious adverse events.
2.3
2.3. Analysis
Comparison 2 (Sensitivity analysis – Baseline severity), Outcome 3 Participants with severe exacerbations (hospitalisation or ER visit).
3.1
3.1. Analysis
Comparison 3 (Sensitivity analysis – Blinding), Outcome 1 Participants with exacerbations requiring oral steroids.
3.2
3.2. Analysis
Comparison 3 (Sensitivity analysis – Blinding), Outcome 2 Participants with serious adverse events.
3.3
3.3. Analysis
Comparison 3 (Sensitivity analysis – Blinding), Outcome 3 Participants with severe exacerbations (hospitalisation or ER visit).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bousquet 2007 [AHEAD] {published and unpublished data}
    1. Bousquet J, Boulet LP. Budesonide/formoterol as maintenance and reliever therapy in uncontrolled asthma compared with high dose salmeterol/fluticasone: the AHEAD double blind study [Abstract]. European Respiratory Journal 2007;30 Suppl 51:358s [P2156].
    1. Bousquet J, Boulet LP, Peters MJ, Magnussen H, Quiralte J, Martinez‐Aguilar NE, et al. Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high‐dose salmeterol/fluticasone. Respiratory Medicine 2007;101(12):2437‐46. - PubMed
    1. Bousquet J, Miravitlles M, Wiren A. Budesonide/formoterol provides better efficacy at a lower or similar cost as compared to high dose salmeterol fluticasone treatment [Abstract]. European Respiratory Journal 2007;30 Suppl 51:193s [P1185].
    1. Cisneros C, Quiralte J, Capel M, Casado MA, Mellstrom C. Cost‐effectiveness analysis of budesonide/formoterol in the maintenance treatment and as‐needed (Symbicort SMART) versus salmeterol/fluticasone plus terbutaline in the treatment of persistent asthma in Spain. Pharmacoeconomics 2010;7(4):163‐75.
    1. Lin Dr J, Chen P, Zhou X, Sun T, Xie C, Xiu Q, et al. Budesonide/formoterol maintenance and reliever therapy in Chinese patients with asthma. Chinese Medical Journal 2012;125(17):2994‐3001. [0366‐6999] - PubMed
Kuna 2007 [COMPASS] {published and unpublished data}
    1. AstraZeneca SD. Comparison of the efficacy and safety of one inhalation of Symbicort® Turbuhaler® 160/4.5 µg bid plus as‐needed with two inhalations of SeretideTM EvohalerTM 25/125 µg bid plus Terbutaline Turbuhaler® 0.4 mg as‐needed, and one inhalation of Symbicort® Turbuhaler® 320/9 µg bid plus Terbutaline Turbuhaler® 0.4 mg as‐needed. A 6‐month, randomised, double‐blind, double‐dummy, parallel‐group, active‐controlled, multi‐centre, phase IIIB study in adult and adolescent asthmatic patients. www.astrazenecaclinicaltrials.com/‎ (accessed 26 April 2012).
    1. Boonsawat W. Cost‐effectiveness of budesonide/formoterol maintenance and rescue therapy in Thailand. Asian Biomedicine 2010;4(4):571‐8.
    1. Buhl R, Kuna P. Does the choice of ICS/LABA regimen influence exacerbation rates in asthma patients with high as needed use? [Abstract]. European Respiratory Journal 2007;30 Suppl 51:617s [P3620].
    1. Kuna P. Treatment comparison of budesonide/formoterol with salmeterol/fluticasone propionate in adults aged >=16 years with asthma: post hoc analysis of a randomized, double‐blind study. Clinical Drug Investigation 2010;30(9):565‐79. - PubMed
    1. Kuna P, Peeters M, Buhl R. Budesonide/formoterol for maintenance and relief vs higher dose ICS/LABA therapy outcomes in patients symptomatic on high dose inhaled corticosteroids (HDICS) [Abstract]. European Respiratory Journal 2007;30 Suppl 51:357s [P2152].
Stallberg 2008 [SHARE] {published and unpublished data}
    1. NCT00259766. SHARE ‐ Symbicort and Health Economics in a Real Life Evaluation. www.clinicaltrials.gov (accessed 24 April 2012). [AstraZeneca study ID: D5890L00001; clinicaltrials.gov study ID: NCT00259766]
    1. Stallberg B, Ekstrom T, Neij F, Olsson P, Skoogh BE, Wennergren G, et al. A real‐life cost‐effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma. Respiratory Medicine 2008;102(10):1360‐70. - PubMed
    1. Stallberg B, Lofdahl CG, Skoogh BE, Wennergren G, Olsson P, Neij F, et al. Budesonide/formoterol maintenance and reliever therapy effective treatment at a lower cost [Abstract]. European Respiratory Society Annual Congress; 2008 Oct 4‐8; Berlin. 2008:[4424].
Vogelmeier 2005 [COSMOS] {published and unpublished data}
    1. D'Urzo A, Vogeimeier C, Jaspal M, Merino JM, Boulet S. Symbicort (budesonide/formoterol) for both maintenance and relief reduces the exacerbation burden compared with titration of seretide (salmeterol/fluticasone) in patients with asthma, a real life study [Abstract]. American Thoracic Society International Conference; 2005 May 20‐25; San Diego. 2005:[B35] [Poster: G24].
    1. Johansson G, Andreasson EB, Larsson PE, Vogelmeier CF. Cost effectiveness of budesonide/formoterol for maintenance and reliever therapy versus salmeterol/fluticasone plus salbutamol in the treatment of asthma. Pharmacoeconomics 2006;24(7):695‐708. - PubMed
    1. Johansson G, Larsson PER, Andreasson E. Maintenance plus as needed budesonide/formoterol is cost effective compared with dose titrated salmeterol/fluticasone [Abstract]. European Respiratory Journal 2005;26 Suppl 49:Abstract No. 432.
    1. Miller E, Sears MR, McIvor A, Liovas A. Canadian economic evaluation of budesonide‐formoterol as maintenance and reliever treatment in patients with moderate to severe asthma. Canadian Respiratory Journal 2007;14(5):269‐75. - PMC - PubMed
    1. Vogelmeier C, D'Urzo A. Maintenance plus as‐needed budesonide/formoterol vs salmeterol/fluticasone in a real‐life setting [Abstract]. European Respiratory Journal 2005;26 Suppl 49:Abstract No. 2770.

References to studies excluded from this review

AstraZeneca 2005 {published data only}
    1. AstraZeneca. Symbicort single inhaler therapy for asthma in a general practice setting. www.clinicaltrials.gov (accessed 24 April 2012).
AstraZeneca 2006 {published data only}
    1. AstraZeneca. SALTO ‐ Symbicort single inhaler therapy use in adolescent adults and adults with persistent asthma. www.clinicaltrials.gov (accessed 24 April 2012).
Atienza 2013 {published data only}
    1. Atienza T, Aquino T, Fernández M, Boonsawat W, Kawai M, Kudo T, Ekelund J, Ivanov S, Carlsson LG. Budesonide/formoterol maintenance and reliever therapy via Turbuhaler versus fixed‐dose budesonide/formoterol plus terbutaline in patients with asthma: phase III study results. Respirology 2013;18(2):354‐63. - PubMed
Balanzat 2004 {published data only}
    1. Balanzat A, Centanni S, Palmqvist M, Rabe K. Budesonide/formoterol single inhaler therapy reduces over reliance on rapid acting reliever medication [Abstract]. European Respiratory Journal 2004;24 Suppl 48:344s.
D589LC00001 2011 [SAKURA] {published data only}
    1. NCT00839800. Study to Investigate the Efficacy of Symbicort SMART. (SAKURA). www.clinicaltrials.gov (accessed 24 April 2012). [AstraZeneca study ID: D589LC00001; clinicaltrials.gov study ID: NCT00839800]
Ghosh 1998 {published data only}
    1. Ghosh CS, Ravindran P, Joshi M, Nair SM. Cost effectiveness of preventer‐reliever combination in the management of chronic asthma ‐ RCT. Journal of Clinical Epidemiology 1998;51 Suppl 1:32S.
Haughney 2009 {published data only}
    1. Haughney J, Aubier M, Buhl R, Ekstrom T, Ostinelli J, Schayck CP, et al. Patient characteristics to determine an appropriate maintenance dose of budesonide/formoterol maintenance and reliever therapy [Abstract]. European Respiratory Society Annual Congress; 2009 Sept 12‐16; Vienna. 2009:[3051].
    1. Haughney J, Schayck OCP, Aubier M, Ostinelli J, Ekström T, Jörgensen L, et al. Budesonide/formoterol maintenance and reliever therapy use in elderly asthma patients [Abstract]. European Respiratory Society Annual Congress; 2010 Sept 18‐22; Barcelona. 2010:[P1212].
Loukides 2005 {published data only}
    1. Loukides S, Papageorgiou M, Karokis A, Zervas E, Christodoulopoulou A, Papageorgiou N, et al. Single inhaler therapy (SiT) with budesonide/formoterol (BUD/FUM) is effective in asthma control [Abstract]. European Respiratory Journal 2005;26 Suppl 49:Abstract No. 848.
Lundborg 2006 {published data only}
    1. Lundborg M, Wille S, Bjermer L, Tilling B, Lundgren M, Telg G, et al. Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma: An efficacy and cost‐effectiveness study. Current Medical Research and Opinion 2006;22(5):809‐21. - PubMed
O'Byrne 2005 [STAY] {published and unpublished data}
    1. Bateman ED, Palmqvist M, Juniper EF, Zhu Y, Ekstrom T. Single inhaler therapy with budesonide/formoterol has superior efficacy to fixed‐dose budesonide/formoterol or a higher dose of budesonide alone [Abstract]. American Thoracic Society 100th International Conference; 2004 May 21‐26; Orlando. 2004:A37 Poster J75.
    1. Bisgaard H, Hultquist C. Budesonide/formoterol for maintenance and as needed ‐ a new approach to asthma management in children [Abstract]. European Respiratory Journal 2005;26 Suppl 49:Abstract No. 1060.
    1. Bisgaard H, Roux P, Bjamer D, Dymek A, Vermeulen JH, Hultquist C. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest 2006;130(6):1733‐43. - PubMed
    1. Bruce SA, Scherer YK. Maintenance and symptom relief with budesonide plus formoterol reduced severe asthma exacerbations. Evidence‐Based Nursing 2005;8(3):78. - PubMed
    1. O'Byrne PM. Acute asthma intervention: Insights from the STAY study. Journal of Allergy & Clinical Immunology 2007;119(6):1332‐6. - PubMed
Rabe 2006 [SMILE] {published and unpublished data}
    1. AstraZeneca SD. Efficacy of Symbicort® Turbuhaler® 160/4.5 ìg as needed versus Oxis® 4.5 ìg as needed and Bricanyl® 0.4 mg as needed in adults and adolescents with asthma receiving Symbicort® Turbuhaler® 160/4.5 ìg twice daily as maintenance treatment. A 12‐month, randomised, double‐blind, parallel‐group, active‐controlled, phase IIIB, multi‐centre study. www.astrazenecaclinicaltrials.com/‎ (accessed 24 April 2012).
    1. Pistolesi M, Godard P, Albers R, Ekstrom T. Budesonide/formoterol single inhaler therapy (SiT) provides superior asthma control compared with fixed dose (FD) budesonide or budesonide/formoterol in patients with severe persistent asthma [Abstract]. European Respiratory Journal 2004;24 Suppl 48:509s.
    1. Rabe KF, Atienza T, Magyar P, Larsson P, Jorup C, Lalloo UG. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double‐blind study.[see comment]. Lancet 2006;368(9537):744‐53. - PubMed
    1. Wickstrom J, Dam N, Malmberg I, Hansen BB, Lange P. Cost‐effectiveness of budesonide/formoterol for maintenance and reliever asthma therapy in Denmark ‐ Cost‐effectiveness analysis based on five randomised controlled trials. Clinical Respiratory Journal 2009;3(3):169‐80. - PubMed
Riemersma 2008 {published data only}
    1. Riemersma RA, Postma DS, Molen T. Budesonide/formoterol maintenance and reliever therapy for asthma in general practice [Abstract]. American Thoracic Society International Conference; 2008 May 16‐21; Toronto. 2008:A612[#A29].

Additional references

Adams 2008
    1. Adams NP, Bestall JC, Lasserson TJ, Jones PW, Cates CJ. Fluticasone versus placebo for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD003135.pub4] - DOI - PubMed
Agarwal 2009
    1. Agarwal R, Khan A, Aggarwal AN, Gupta D. Is the SMART approach better than other treatment approaches for prevention of asthma exacerbations? A meta‐analysis. Monaldi Archives for Chest Disease 2009;71(4):161‐9. [1122‐0643: (Print)] - PubMed
Barnes 2007
    1. Barnes PJ. Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control. British Medical Journal 2007;335(7618):513. - PMC - PubMed
Bateman 2011
    1. Bateman ED, Harrison TW, Quirce S, Reddel HK, Buhl R, Humbert M, et al. Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps. http://respiratory‐research.com/content/12/1/38 (accessed 7 December 2013). [DOI: 10.1186/1465-9921-12-38] - DOI - PMC - PubMed
Bisgaard 2003
    1. Bisgaard H. Effect of long‐acting Beta2 agonists on exacerbation rates of asthma in children. Pediatric Pulmonology 2003;36(5):391‐8. - PubMed
BTS/SIGN 2012
    1. British Thoracic Society/ Scottish Intercolleate Guideline Network. British Guidelines on the Management of Asthma [revised January 2012]. http://www.sign.ac.uk/ (accessed 5 September 2012).
Cates 2008
    1. Cates CJ, Cates MJ, Lasserson TJ. Regular treatment with formoterol for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD006923.pub2] - DOI - PubMed
Cates 2008a
    1. Cates CJ, Cates MJ. Regular treatment with salmeterol for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD006363.pub2] - DOI - PMC - PubMed
Cates 2009
    1. Cates CJ, Lasserson TJ. Combination formoterol and inhaled steroid versus beta2‐agonist as relief medication for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD007085.pub2] - DOI - PMC - PubMed
Cates 2009a
    1. Cates CJ, Lasserson TJ. Combination formoterol and budesonide as maintenance and reliever therapy versus inhaled steroid maintenance for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD007313.pub2] - DOI - PMC - PubMed
Cates 2013
    1. Cates Christopher J, Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD007313.pub3; CD007313] - DOI - PMC - PubMed
Czarnecka 2012
    1. Czarnecka K, Chapman KR. The clinical impact of single inhaler therapy in asthma. Clinical and Experimental Allergy 2012;42(7):1006‐13. [1365‐2222: (Electronic)] - PubMed
Delea 2008
    1. Delea TE, Hagiwara M, Stanford RH, Stempel DA. Effects of fluticasone propionate/salmeterol combination on asthma‐related health care resource utilization and costs and adherence in children and adults with asthma. Clinical Therapeutics 2008;30(3):560‐71. - PubMed
Edwards 2010
    1. Edwards SJ, Maltzahn R, Naya IP, Harrison T. Budesonide/formoterol for maintenance and reliever therapy of asthma: a meta analysis of randomised controlled trials. International Journal of Clinical Practice 2010;64(5):619‐27. [1742‐1241: (Electronic)] - PubMed
FitzGerald 2004
    1. FitzGerald JM, Becker A, Sears MR, Mink S, Chung K, Lee J. Doubling the dose of budesonide versus maintenance treatment in asthma exacerbations. Thorax 2004;59(7):550‐6. - PMC - PubMed
GINA 2012
    1. GINA. Global strategy for asthma management and prevention. http://www.ginasthma.org/ (accessed 10 March 2013).
Greenstone 2005
    1. Greenstone IR, Ni Chroinin MN, Masse V, Danish A, Magdalinos H, Zhang X, et al. Combination of inhaled long‐acting beta2‐agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD005533] - DOI - PubMed
Harrison 2004
    1. Harrison T, Oborne J, Newton S, Tattersfield A. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Lancet 2004;363(9405):271‐5. - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. British Medical Journal 2003;327:557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration. www.cochrane‐handbook.org, 2011.
Lasserson 2011
    1. Lasserson TJ, Ferrara G, Casali L. Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD004106.pub4] - DOI - PMC - PubMed
Lipworth 2007
    1. Lipworth BJ, Jackson C. A SMART choice for primary care asthma therapy?. http://www.bmj.com/cgi/eletters/335/7618/513#178078 (accessed 13 October 2007).
Ni Chroinin 2005
    1. Ni Chroinin M, Greenstone IR, Danish A, Magdolinos H, Masse V, Zhang X, et al. Long‐acting beta2‐agonists versus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD005535] - DOI - PubMed
Palmqvist 2001
    1. Palmqvist M, Arvidsson P, Beckman O, Peterson S, Lotvall J. Onset of bronchodilation of budesonide/formoterol vs. salmeterol/fluticasone in single inhalers. Pulmonary Pharmacology and Therapeutics 2001;14(1):29‐34. - PubMed
Review Manager 5 [Computer program]
    1. The Nordic Cochrane Centre; Cochrane Collaboration. Review Manager (RevMan) Version 5. Copenhagen: The Nordic Cochrane Centre; Cochrane Collaboration, 2008.
Song 2010
    1. Song F, Parekh S, Hooper L, Loke Y, Ryder J, Sutton A, et al. Dissemination and publication of research findings: an updated review of related biases. http://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=... (accessed 7 December 2013). [DOI: 10.3310/hta14080] - DOI - PubMed
Sovani 2008
    1. Sovani MP, Whale CI, Oborne J, Cooper S, Mortimer K, Ekström T, et al. Poor adherence with inhaled corticosteroids for asthma: can using a single inhaler containing budesonide and formoterol help?. British Journal of General Practice 2008;58(546):37‐43. - PMC - PubMed
Walters 2007
    1. Walters EH, Gibson PG, Lasserson TJ, Walters JAE. Long‐acting beta2‐agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD001385.pub2] - DOI - PMC - PubMed

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