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Meta-Analysis
. 2014 Jan 24;2014(1):CD003137.
doi: 10.1002/14651858.CD003137.pub5.

Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma

Bhupendrasinh F Chauhan  1 , Francine M Ducharme
Affiliations
Meta-Analysis

Addition to inhaled corticosteroids of long-acting beta2-agonists versus anti-leukotrienes for chronic asthma

Bhupendrasinh F Chauhan et al. Cochrane Database Syst Rev. .

Abstract

Background: Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids (ICS) represent a management challenge. Long-acting beta2-agonists (LABA) and anti-leukotrienes (LTRA) are two treatment options that could be considered as add-on therapy to ICS.

Objectives: To compare the safety and efficacy of adding LABA versus LTRA to the treatment regimen for children and adults with asthma who remain symptomatic in spite of regular treatment with ICS. We specifically wished to examine the relative impact of the two agents on asthma exacerbations, lung function, symptoms, quality of life, adverse health events and withdrawals.

Search methods: We searched the Cochrane Airways Group Specialised Register until December 2012. We consulted reference lists of all included studies and contacted pharmaceutical manufacturers to ask about other published or unpublished studies.

Selection criteria: We included randomised controlled trials (RCTs) conducted in adults or children with recurrent asthma that was treated with ICS along with a fixed dose of a LABA or an LTRA for a minimum of four weeks.

Data collection and analysis: Two review authors independently assessed the risk of bias of included studies and extracted data. We sought unpublished data and further details of study design when necessary.

Main results: We included 18 RCTs (7208 participants), of which 16 recruited adults and adolescents (6872) and two recruited children six to 17 years of age (336) with asthma and significant reversibility to bronchodilator at baseline. Fourteen (79%) trials were of high methodological quality.The risk of exacerbations requiring systemic corticosteroids (primary outcome of the review) was significantly lower with the combination of LABA + ICS compared with LTRA + ICS-from 13% to 11% (eight studies, 5923 adults and 334 children; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.76 to 0.99; high-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) with LABA compared with LTRA to prevent one additional exacerbation over four 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 trials that used a single device rather than two devices to administer ICS and LABA 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 (three studies, 1625 adults; RR 1.12, 95% CI 1.04 to 1.20; moderate-quality evidence). The overall risk of withdrawal was significantly lower with LABA + ICS than with LTRA + ICS (13 studies, 6652 adults and 308 children; RR 0.84, 95% CI 0.74 to 0.96; moderate-quality evidence). 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 (nine studies, 5658 adults and 630 children; RR 1.33, 95% CI 0.99 to 1.79; P value 0.06; moderate-quality evidence), 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 = 6538); cardiovascular events (five studies, N = 5163), osteopenia and osteoporosis (two studies, N = 2963), adverse events (10 studies, N = 5977 adults and 300 children). A significant difference in the risk of oral moniliasis was noted, but this represents a low occurrence rate.

Authors' conclusions: In adults with asthma that is inadequately controlled by predominantly low-dose ICS with significant bronchodilator reversibility, the addition of LABA to ICS is modestly superior to the addition of LTRA in reducing oral corticosteroid-treated exacerbations, with an absolute reduction of two percentage points. Differences favouring LABA over LTRA as adjunct therapy were observed in lung function and, to a lesser extend, in rescue medication use, symptoms and quality of life. The lower overall withdrawal rate and the higher proportion of participants satisfied with their therapy indirectly favour the combination of LABA + ICS over LTRA + ICS. Evidence showed a slightly increased risk of SAE with LABA compared with LTRA, with an absolute increase of one percentage point. Our 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, we are unable to draw firm conclusions about the best adjunct therapy in children.

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Conflict of interest statement

Bhupendrasinh Chauhan holds a postdoctoral scholarship from one of Dr Ducharme's grants from the Canadian Institute of Health Research and has no conflicts of interest.

Francine M Ducharme has received travel support for meeting attendance, research funds, fees for speaking and consulting fees from Merck Frosst Inc (producer of montelukast), GlaxoSmithKline (producer of fluticasone, beclomethasone, salmeterol), Novartis (producer of formoterol) and/or Nycomed (producer of combination of mometasone and formoterol).

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
Forest plot of comparison: 1 Leukotriene receptor antagonists + ICS versus Long‐acting β2‐agonists + ICS, outcome: 1.1 Participants with one or more exacerbations requiring systemic corticosteroids.
4
4
In the LRTA + ICS group, 13 out of 100 people had one or more exacerbations requiring OCS over four to 102 weeks, compared with 11 (95% CI 10 to 12) of 100 for the LABA + ICS group.
5
5
Funnel plot of comparison: 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, outcome: 1.1 Participants with one or more exacerbations requiring systemic corticosteroids.
6
6
In the LRTA + ICS group, two of 100 people had serious adverse events over 4 to 102 weeks, compared with three (95% CI 2 to 4) of 100 for the LABA + ICS group.
1.1
1.1. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 1 Participants with one or more exacerbations requiring systemic corticosteroids.
1.2
1.2. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 2 Morning PEF: L/min change from baseline.
1.3
1.3. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 3 Evening PEF: L/min change from baseline.
1.4
1.4. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 4 FEV1: L, % change from baseline.
1.5
1.5. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 5 % fall in FEV1 postexercise.
1.6
1.6. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 6 FEV1: L, % change from baseline.
1.7
1.7. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 7 FEV1: % of predicted end of treatment.
1.8
1.8. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 8 Rescue‐free days: % change from baseline.
1.9
1.9. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 9 Rescue medication use: puffs/d change from baseline.
1.10
1.10. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 10 Global asthma QoL AQLQ score (higher is better): change from baseline.
1.11
1.11. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 11 Symptom‐free days: % change from baseline.
1.12
1.12. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 12 Daytime symptom scores (high is worse): change from baseline.
1.13
1.13. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 13 Morning symptoms: change from baseline.
1.14
1.14. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 14 Night‐time symptom score (five‐point scale, higher score is worse): change from baseline.
1.15
1.15. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 15 Change in number of night awakenings per week: change from baseline.
1.16
1.16. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 16 Change in % of nights with no awakenings per week: change from baseline.
1.17
1.17. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 17 Rescue‐free nights (%): change from baseline.
1.18
1.18. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 18 Withdrawals for any reason.
1.19
1.19. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 19 Withdrawals due to adverse events.
1.20
1.20. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 20 Withdrawals due to poor asthma control/asthma exacerbation.
1.21
1.21. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 21 Participants with one or more exacerbations requiring hospital admission.
1.22
1.22. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 22 Serious adverse events.
1.23
1.23. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 23 Death.
1.24
1.24. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 24 Headache.
1.25
1.25. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 25 Cardiovascular events.
1.26
1.26. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 26 Oral moniliasis.
1.27
1.27. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 27 Osteopenia/osteoporosis.
1.28
1.28. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 28 Elevated liver enzymes.
1.29
1.29. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 29 Overall adverse events.
1.30
1.30. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 30 Participants' treatment satisfaction.
1.31
1.31. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 31 Participants switched/received additional treatment.
1.32
1.32. Analysis
Comparison 1 Long‐acting β2‐agonists + ICS versus leukotriene receptor antagonists + ICS, Outcome 32 Change from baseline in serum eosinophils (× 109/L).
2.1
2.1. Analysis
Comparison 2 Subgroup and sensitivity analyses, Outcome 1 Participants with one or more exacerbations requiring systemic corticosteroids: number of inhaler devices.
2.2
2.2. Analysis
Comparison 2 Subgroup and sensitivity analyses, Outcome 2 Participants with one or more exacerbations requiring systemic corticosteroids: dose of ICS.
2.3
2.3. Analysis
Comparison 2 Subgroup and sensitivity analyses, Outcome 3 Participants with one or more exacerbations requiring systemic corticosteroids: study duration.
2.4
2.4. Analysis
Comparison 2 Subgroup and sensitivity analyses, Outcome 4 Participants with one or more exacerbations requiring systemic corticosteroids: LTRA.
2.5
2.5. Analysis
Comparison 2 Subgroup and sensitivity analyses, Outcome 5 Serious adverse events stratified by number of inhaler devices used for LABA + ICS.
2.6
2.6. Analysis
Comparison 2 Subgroup and sensitivity analyses, Outcome 6 Serious adverse events stratified by age of participants (adults vs children).
3.1
3.1. Analysis
Comparison 3 MD archive from previous review version, Outcome 1 Morning PEF (L/min): change from baseline.
3.2
3.2. Analysis
Comparison 3 MD archive from previous review version, Outcome 2 Evening PEF (L/min): change from baseline.
3.3
3.3. Analysis
Comparison 3 MD archive from previous review version, Outcome 3 FEV1 (L): change from baseline.
3.4
3.4. Analysis
Comparison 3 MD archive from previous review version, Outcome 4 Symptom‐free days (%): change from baseline.
See this image and copyright information in PMC

Update of

Comment in

References

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Adinoff 1998 {published data only}
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Bozek 2012 {published data only}
    1. Bozek A, Warkocka‐Szoltysek B, Filipowska‐Gronska A, Jarzab J. Montelukast as an add‐on therapy to inhaled corticosteroids in the treatment of severe asthma in elderly patients. Journal of Asthma 2012; Vol. 49, issue 5:530‐4. - PubMed
Brabson 2002 {published data only}
    1. Brabson JH, Clifford D, Kerwin E, Raphael G, Pepsin PJ, Edwards LD, et al. Efficacy and safety of low‐dose fluticasone propionate compared with zafirlukast in patients with persistent asthma. American Journal of Medicine 2002;113(1):15‐21. - PubMed
Buchvald 2003 {published data only}
    1. Buchvald F, Bisgaard H. Comparisons of the complementary effect on exhaled nitric oxide of salmeterol versus montelukast in asthmatic children taking regular inhaled budesonide. Annals of Allergy, Asthma & Immunology 2003;91(3):309‐13. - PubMed
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Caffey 2005 {published data only}
    1. Caffey LF, Raissy HH, Marshik P, Kelly HW. A crossover comparison of fluticasone propionate and montelukast on inflammatory indices in children with asthma. Pediatric Asthma, Allergy & Immunology 2005;18(3):123‐30.
Calhoun 2001 {published data only}
    1. Calhoun W, Sutton L, Emmett A, Dorinsky P. Asthma control with fluticasone propionate/salmeterol 100/50µg Diskus(r) versus montelukast in patients previously receiving short‐acting beta2‐agonists. The Journal of Allergy and Clinical Immunology 2004;113 Suppl 2:117.
    1. Calhoun WJ, Nelson HS, Nathan RA, Pepsin PJ, Kalberg C, Emmett A, et al. Comparison of fluticasone propionate‐salmeterol combination therapy and montelukast in patients who are symptomatic on short‐acting beta(2)‐agonists alone. American Journal of Respiratory and Critical Care Medicine 2001;164(5):759‐63. - PubMed
Cash 2001 {published data only}
    1. Cash R, Blonski J. In patients with asthma that is not well controlled with inhaled steroids, does salmeterol (Serevent) or montelukast (Singulair) offer better symptom relief?. Journal of Family Practice 2001;50(9):802. - PubMed
Chanez 2010 {published data only}
    1. Chanez P, Contin‐Bordes C, Garcia G, Verkindre C, Didier A, Blay F, et al. Omalizumab‐induced decrease of FcvarepsilonRI expression in patients with severe allergic asthma. Respiratory Medicine 2010; Vol. 104, issue 11:1608‐17. - PubMed
Chopra 2005 {published data only}
    1. Chopra N, Williams M, Rimmer M, Kahl L, Jenkins M (SMO30006 and SMO30007 International Study Teams). Salmeterol HFA is as effective as salmeterol CFC in children and adults with persistent asthma. Respiratory Medicine 2005;99 Suppl 1:1. - PubMed
Chuchalin 2002 {published data only}
    1. Chuchalin AG, Ovcharenko SI, Goriachkina LA, Sidorenko IV, Tsoi AN. The safety and efficacy of formoterol (Oxis) turbuhaler plus budesonide (Pulmicort) turbuhaler in mild to moderate asthma: a comparison with budesonide Turbuhaler alone and current non‐corticosteroid therapy in Russia. International Journal of Clinical Practice 2002;56(1):15‐20. - PubMed
Cowan 2010 {published data only}
    1. Cowan DC, Hewitt RS, Cowan JO, Palmay R, Williamson A, Lucas SJE, et al. Exercise‐induced wheeze: fraction of exhaled nitric oxide‐directed management. Respirology 2010; Vol. 15, issue 4:683‐90. - PubMed
Currie 2002 {published data only}
    1. Currie GP. National Research Register. Are there additional anti‐inflammatory effects of leukotriene receptor antagonists in persistent asthmatics receiving inhaled steroid alone and combined inhaled steroid/long acting B2‐agonists? [N0405110243]. http://www.nihr.ac.uk/Profile/Pages/NRRResults.aspx?publication_id=N0405... (accessed 13/1/14).
Currie 2003a {published data only}
    1. Currie GP, Lee DKC, Haggart K, Bates CE, Lipworth BJ. Effects of montelukast on surrogate inflammatory markers in corticosteroid‐treated patients with asthma. American Journal of Respiratory and Critical Care Medicine 2003;167(9):1232‐8. - PubMed
Currie 2003b {published data only}
    1. Currie GP, Lee DK, Haggart K, Bates CE, Lipworth BJ. Montelukast confers complimentary non‐steroid anti‐inflammatory activity in asthmatics receiving fluticasone alone and fluticasone/salmeterol combination [Abstract]. Journal of Allergy and Clinical Immunology 2003;111 Suppl 2:146.
Currie 2003c {published data only}
    1. Currie GP, Stenback S, Lipworth BJ. Effects of fluticasone versus fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma. British Journal of Clinical Pharmacology 2003;56(1):11‐7. - PMC - PubMed
Davis 2001 {published data only}
    1. Davis EA, Bowers B, Pepsin P, Kalberg C, Dorinsky P. The impact of fluticasone propionate/salmeterol combination product compared to oral montelukast on asthma related quality of life. ATS 97th International Conference; 2001 May 18‐23; San Francisco. 2001:B92, Poster 714.
Dekhuijzen 2002 {published data only}
    1. Dekhuijzen PN, Koopmans PP. Pharmacokinetic profile of zafirlukast. Clinical Pharmacokinetics 2002;41(2):105‐14. [PMID: 11888331] - PubMed
Delaronde 2005 {published data only}
    1. Delaronde S, Peruccio DL, Bauer BJ. Improving asthma treatment in a managed care population. American Journal of Managed Care 2005;11(6):361‐8. - PubMed
Dempsey 2000 {published data only}
    1. Dempsey OJ, Wilson AM, Sims EJ, Mistry C, Lipworth BJ. Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids. Chest 2000;117:950‐3. - PubMed
Deykin 2007 {published data only}
    1. Deykin A, Wechsler ME, Boushey HA, Chinchilli VM, Kunselman SJ, Craig TJ, et al. Combination therapy with a long‐acting beta‐agonist and a leukotriene antagonist in moderate asthma. American Journal of Respiratory and Critical Care Medicine 2007;175(3):228‐34. - PMC - PubMed
Dicpinigaitis 2002 {published data only}
    1. Dicpinigaitis PV, Dobkin JB, Reichel J. Antitussive effect of the leukotriene receptor antagonist zafirlukast in subjects with cough‐variant asthma. Journal of Asthma 2002;39(4):291‐7. - PubMed
Donohue 2001 {published data only}
    1. Donohue JF, Ohar JA. New combination therapies for asthma. Current Opinion in Pulmonary Medicine 2001;7(2):62‐8. - PubMed
Dorinsky 2001 {published data only}
    1. Dorinsky PM, Kalberg C, Pepsin P, Emmett A, Rickard K. Greater onset of improvement in clinical efficacy measures with first line use of the fluticasone/salmeterol combination product compared to montelukast. ATS 97th International Conference; 2001 May 18‐23; San Francisco. 2001:D31.
Dorinsky 2002 {published data only}
    1. Dorinsky P, Jones S, Kalberg C, Emmett A, Rickard K. Sustained protection against activity‐induced bronchospasm (AIB) during chronic treatment with the fluticasone propionate/salmeterol combination (FSC). American Journal of Respiratory and Critical Care Medicine 2002;165 Suppl 8:A568.
Dorinsky 2002a {published data only}
    1. Dorinsky PM, Crim C, Yancey S, Edwards L, Rickard K. First line therapy with fluticasone propionate/salmeterol combination product provides superior asthma control versus montelukast or fluticasone propionate alone. Journal of Allergy, Asthma and Immunolgy 2002;109 Suppl 1:Abstract No: 767.
Dorinsky 2004 {published data only}
    1. Dorinsky PM, Stauffer J, Waitkus‐Edwards K, Yancey S, Prillaman BA, Sutton L. "Stepping down" from fluticasone propionate/salmeterol 100/50mcg diskus(r) results in loss of asthma control: lack of effect of ethnic origin. Chest 2004;126 Suppl 4:758.
    1. Keonig S, Waitkus‐Edwards K, Yancey S, Prillman B, Dorinsky P. Loss of asthma control when patients receiving fluticasone propionate/salmeterol 100/50µg Diskus are "stepped‐down" to fluticasone propionate, salmeterol or montelukast alone [Abstract]. The Journal of Allergy and Clinical Immunology 2004;113 Suppl 2:94.
Drummond 2011 {published data only}
    1. Drummond MB, Peters SP, Castro M, Holbrook JT, Irvin CG, Smith LJ, et al. Risk factors for montelukast treatment failure in step‐down therapy for controlled asthma. Journal of Asthma 2011; Vol. 48, issue 10:1051‐7. - PMC - PubMed
Dunn 2001 {published data only}
    1. Dunn CJ, Goa KL. Zafirlukast—an update of its pharmacology and therapeutic efficacy in asthma. Drugs 2001;61(2):285‐315. - PubMed
Edelman 2000 {published data only}
    1. Edelman JM, Turpin JA, Bronsky EA, Grossman J, Kemp JP, Ghannam AF, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise‐induced bronchoconstriction. A randomized, double‐blind trial. Exercise Study Group. Annals of Internal Medicine 2000;132(2):97‐104. - PubMed
Edin 2002 {published data only}
    1. Edin HM, Prillaman B, Baitinger LA, House KW, Shah TP. Improved ability to perform strenuous activities after treatment with fluticasone propionate‐salmeterol combination. American Journal of Respiratory and Critical Care Medicine 2002;165 Suppl 8:A112.
Eliraz 2001 {published data only}
    1. Eliraz A, Ramirez‐Rivera A, Ferranti P, Holzer R, Garcia JM, Turcotte C, et al. Similar efficacy following four weeks treatment of asthmatics with formoterol 12 micrograms b.d. delivered by two different dry powder inhalers: differences in inhaler handling. International Journal of Clinical Practice 2001;55(3):164‐70. - PubMed
Eliraz 2002 {published data only}
    1. Eliraz A, Fritscher CC, Perez CMR, Boonsawat W, Nang AN, Bardin P, et al. Symbicort® (budesonide/formoterol) achieves more rapid control of asthma than fluticasone in patients with mild asthma. American Journal of Respiratory and Critical Care Medicine 2002;165 Suppl 8:A567.
Everden 2002 {published data only}
    1. Everden P, Lloyd A, Hutchinson J, Plumb J. Cost‐effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma. Respiratory Medicine 2002;96(4):250‐8. - PubMed
Gabrijelcic 2004 {published data only}
    1. Gabrijelcic J, Casas A, Rabinovich RA, Roca J, Barbera JA, Chung KF, et al. Formoterol protects against platelet‐activating factor‐induced effects in asthma. European Respiratory Journal 2004;23(1):71‐5. - PubMed
Giannini 2002 {published data only}
    1. Giannini D, Tonelli M, Franco A, Bacci E, Conti I, Dente FL, et al. Tolerance to the protective effect of salmeterol + fluticasone combination (50/250 µg) on allergen challenge in mild untreated asthmatics. American Journal of Respiratory and Critical Care Medicine 2002;165 Suppl 8:A566.
Grzelewska 2003 {published data only}
    1. Grzelewska‐Rzymowska I, Malolepszy J, Molina M, Sladek K, Zarkovic J, Siergiejko Z. Equivalent asthma control and systemic safety of inhaled budesonide delivered via HFA‐134a or CFC propellant in a broad range of doses. Respiratory Medicine 2003;97 Suppl D:10‐9. - PubMed
Gupta 2007 {published data only}
    1. Gupta S, Kansal AP, Kishan J. Comparative efficacy of combination of fluticasone and salmeterol; fluticasone, salmeterol and montelukast; fluticasone, salmeterol, and levocetirizine in moderate persistent asthma: a study of 120 patients. Chest 2007;132(4):512a.
Hanania 2011 {published data only}
    1. Hanania NA, Alpan O, Hamilos DL, Condemi JJ, Reyes‐Rivera I, Zhu J, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Annals of Internal Medicine 2011; Vol. 154, issue 9:573‐82. - PubMed
Havlucu 2005 {published data only}
    1. Havlucu Y, Yilmaz G, Goktan C, Yorgancioglu A. Usefulness of HRCT determining the distal airway inflammation in asthma [Abstract]. European Respiratory Journal 2005;26 Suppl 49:Abstract No. 2072.
Horwitz 1998 {published data only}
    1. Horwitz RJ, McGill KA, Busse WM. The role of leukotriene modifiers in the treatment of asthma. American Journal of Respiratory and Critical Care Medicine 1998;157:1363‐71. - PubMed
Houghton 2004 {published data only}
    1. Houghton CM, Langley SJ, Singh SD, Holden J, Monici Preti AP, Acerbi D, et al. Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo‐controlled, crossover study. British Journal of Clinical Pharmacology 2004;58(4):359‐66. - PMC - PubMed
Inouhe 2007 {published data only}
    1. Inoue H, Komori M, Matsumoto T, Fukuyama S, Matsumura M, Nakano T, et al. Effects of salmeterol in patients with persistent asthma receiving inhaled corticosteroid plus theophylline. Respiration 2007;74(6):611‐6. - PubMed
Jarvis 1998 {published data only}
    1. Jarvis B, Adkins JC. Management of asthma—the potential role of zafirlukast. Disease Management Health Outcomes 1998;4(6):337‐53.
Jarvis 1999 {published data only}
    1. Jarvis B, Faulds D. Inhaled fluticasone propionate: a review of its therapeutic efficacy at dosages < or = 500 microg/day in adults and adolescents with mild to moderate asthma. Drugs 1999;57(5):769‐803. - PubMed
Jenkins 2005 {published data only}
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Jonsson 2004 {published data only}
    1. Jonsson B, Berggren F, Svensson K, O'Byrne PM. An economic evaluation of combination treatment with budesonide and formoterol in patients with mild‐to‐moderate persistent asthma. Respiratory Medicine 2004;98(11):1146‐54. - PubMed
Kalberg 1999 {published data only}
    1. Kalberg CJ, Yancey S, Emmett AH, Rickard K. A comparison of salmeterol versus zafirlukast in patients using inhaled corticosteroids. Journal of Allergy and Clinical Immunology 1999;103(1 pt 2):S229. - PubMed
Kanniess 2002 {published data only}
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Kanniess 2002b {published and unpublished data}
    1. Kanniess F, Richter K, Janicki S, Schleiss MB, Jorres RA, Magnussen H. Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma. European Respiratory Journal 2002;20:1080‐7. - PubMed
Karaman 2007 {published data only}
    1. Karaman O, Arli O, Uzuner N, Islekel H, Babayigit A, Olmez D, et al. The effectiveness of asthma therapy alternatives and evaluating the effectivity of asthma therapy by interleukin‐13 and interferon gamma levels in children. Allergy and Asthma Proceedings 2007;28(2):204‐9. - PubMed
Kardos 2001 {published data only}
    1. Kardos P, Bruggenjurgen B, Martin A, Meyer‐Sabellek W, Richter K, Vogelmeier C, et al. The treatment of asthma: a study (TACO asthma control plan) introducing a new adjustable combination‐treatment plan. Pneumologie 2001;55(5):253‐7. - PubMed
Katial 2010 {published data only}
    1. Katial RK, Oppenheimer JJ, Ostrom NK, Mosnaim GS, Yancey SW, Waitkus‐Edwards KR, et al. Adding montelukast to fluticasone propionate/salmeterol for control of asthma and seasonal allergic rhinitis. Allergy and Asthma Proceedings 2010; Vol. 31, issue 1:68‐75. - PubMed
Keith 2009 {published data only}
    1. Keith PK, Koch C, Djandji M, Bouchard J, Psaradellis E, Sampalis JS, et al. Montelukast as add‐on therapy with inhaled corticosteroids alone or inhaled corticosteroids and long‐acting beta‐2‐agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial). Canadian Respiratory Journal 2009;16 Suppl A:17‐31. - PMC - PubMed
Kemp 1998 {published data only}
    1. Kemp JP. Antileukotriene drugs as oral controller therapy for asthma. European Respiratory Review 1998;8(54):190‐3.
Kerstjens 2011 {published data only}
    1. Kerstjens HA, Disse B, Schröder‐Babo W, Bantje TA, Gahlemann M, Sigmund R, et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. Journal of Allergy and Clinical Immunology 2011; Vol. 128, issue 2:308‐14. - PubMed
Knorr 2001 {published data only}
    1. Knorr B, Franchi LM, Bisgaard H, Vermeulen JH, LeSouef P, Santanello N, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001;108(3):E48. - PubMed
Koenig 2008 {published data only}
    1. Koenig SM, Ostrom N, Pearlman D, Waitkus‐Edwards K, Yancey S, Prillaman BA, et al. Deterioration in asthma control when subjects receiving fluticasone propionate/salmeterol 100/50 mcg Diskus are "stepped‐down". The Journal of Asthma 2008;45(8):681‐7. - PubMed
Kohrogi 1999 {published data only}
    1. Kohrogi H, Iwagoe H, Fuji K, Hamamoto J, Fukuda K, Hirata N, et al. The role of cysteinyl leukotrienes in the pathogenesis of asthma: clinical study of leukotriene antagonist pranlukast for 1 year in moderate and severe asthma. Respirology 1999;4:319‐23. - PubMed
Laviolette 1999 {published data only}
    1. Laviolette M, Malmstrom K, Lu S, Chervinsky P, Pujet JC, Peszek I, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. American Journal of Respiratory and Critical Medicine 1999;160:1862‐8. - PubMed
Lazarus 2001 {published data only}
    1. Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, et al. Long‐acting beta2‐agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 2001;285(20):2583‐93. - PubMed
Lee 2004 {published data only}
    1. Lee DK, Haggart K, Currie GP, Bates CE, Lipworth BJ. Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily versus fluticasone 250 microg twice daily on methacholine hyper‐responsiveness in mild‐to‐moderate persistent asthma. British Journal of Clinical Pharmacology 2004;58(1):26‐33. - PMC - PubMed
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Lee 2010 {published data only}
    1. Lee RU, White AA, Ding D, Dursun AB, Woessner KM, Simon RA, et al. Use of intranasal ketorolac and modified oral aspirin challenge for desensitization of aspirin‐exacerbated respiratory disease. Annals of Allergy, Asthma, and Immunology 2010; Vol. 105, issue 2:130‐5. - PubMed
Leflein 2002 {published data only}
    1. Leflein JG, Szefler SJ, Murphy KR, Fitzpatrick S, Cruz‐Rivera M, Miller CJ, et al. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Pediatrics 2002;109(5):866‐72. - PubMed
Lipworth 2000 {published data only}
    1. Lipworth BJ, Dempsey OJ, Aziz I, Wilson AM. Effects of adding a leukotriene antagonist or a long‐acting beta2‐agonist in asthmatic patients with the glycine‐16 beta2‐adrenoceptor genotype. American Journal of Medicine 2000;109:114‐21. - PubMed
Liu 1996 {published data only}
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LOCCS {published data only}
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Marogna 2010 {published data only}
    1. Marogna M, Colombo F, Spadolini I, Massolo A, Berra D, Zanon P, et al. Randomized open comparison of montelukast and sublingual immunotherapy as add‐on treatment in moderate persistent asthma due to birch pollen. Journal of Investigational Allergology and Clinical Immunology 2010; Vol. 20, issue 2:146‐52. - PubMed
Maspero 2008 {published data only}
    1. Maspero J, Guerra F, Cuevas F, Gutierrez JP, Soto‐Ramos M, Anderton S, et al. Efficacy and tolerability of salmeterol/fluticasone propionate versus montelukast in childhood asthma: a prospective, randomized, double‐blind, double‐dummy, parallel‐group study. Clinical Therapeutics 2008;30(8):1492‐504. - PubMed
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Matsuse 2012 {published data only}
    1. Matsuse H, Fukahori S, Tsuchida T, Kawano T, Tomari S, Matsuo N, et al. Effects of a short course of pranlukast combined with systemic corticosteroid on acute asthma exacerbation induced by upper respiratory tract infection. Journal of Asthma 2012; Vol. 49, issue 6:637‐41. - PubMed
McCarthy 2002 {published data only}
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McKinlay 2011 {published data only}
    1. McKinlay L, Williamson PA, Short PM, Fardon TC, Lipworth BJ. Proof of concept study to evaluate step‐down therapy with inhaled corticosteroid alone or additive therapy on surrogate inflammatory markers in asthma. British Journal of Clinical Pharmacology 2011; Vol. 71, issue 1:128‐31. - PMC - PubMed
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Naedele‐Risha 2001 {published data only}
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Nathan 2000 {published data only}
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Nathan 2001b {published data only}
    1. Nathan RA, Kemp JP. Efficacy of antileukotriene agents in asthma management. Annals of Allergy Asthma & Immunology 2001;86(6 Suppl 1):9‐17. - PubMed
Nathan 2005 {published data only}
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Nelson 2004 {published data only}
    1. Nelson H, Stauffer J, Yancey S, Prillaman B, Sutton L, Dorinsky P. In patients with both uncontrolled asthma and allergic rhinitis, montelukast added to fluticasone propionate/salmeterol provides no additional clinical improvements in overall asthma control regardless of baseline asthma severity [Abstract]. American Thoracic Society 100th International Conference; 2004 May 21‐26; Orlando. 2004:D36, Poster A49.
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O'Connor 2006 {published data only}
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Ollendorf 2000 {published data only}
    1. Ollendorf DA, Pozniak AS, Bowers BW, Oster G. Economic impact of salmeterol versus leukotriene modifiers in patients with chronic asthma. Chest 2000;118 Suppl 4:185.
Oppenheimer 2008 {published data only}
    1. Oppenheimer J, Mosnaim G, Waitkus‐Edwards K, Prillaman B, Ortega H. Fluticasone propionate/salmeterol via diskus is superior to montelukast in overall asthma control in subjects with both asthma and allergic rhinitis [Abstract]. Chest 2008;134(4):94002s.
Ortega‐Cisneros 1998 {published data only}
    1. Ortega‐Cisneros M, Maldonado‐Alanis ML, Rosas‐Vargas MA, Sienra‐Monge JJL. Salmeterol and inhaled beclomethasone versus high dose inhaled beclomethasone in the control of pediatric patients with moderate asthma. Annals of Allergy, Asthma & Immunology 1998;80:131, P124.
Patel 2010 {published data only}
    1. Patel YA, Patel P, Bavadia H, Dave J, Tripathi CB. A randomized, open labelled, comparative study to assess the efficacy and safety of controller medications as add on to inhaled corticosteroid and long‐acting beta2 agonist in the treatment of moderate‐to‐severe persistent asthma. Journal of Postgraduate Medicine 2010; Vol. 56, issue 4:270‐4. - PubMed
Paterson 1999 {published data only}
    1. Paterson MC, Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ. The effect of combination therapy with salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids. European Respiratory Society Conference; 1999 Oct 9‐13; Madrid. 1999:3490.
Pearlman 2002 {published data only}
    1. Pearlman DS, White MV, Lieberman AK, Pepsin PJ, Kalberg C, Emmett A, et al. Fluticasone propionate/salmeterol combination compared with montelukast for the treatment of persistent asthma. Annals of Allergy, Asthma & Immunology 2002;88(2):227‐35. - PubMed
Pedersen 2011 {published data only}
    1. Pedersen S, Maspero J, Gul N, Sharma R. Components of asthma control and treatment response of individual control criteria in children: analysis of the PEACE study. Pediatric Pulmonology 2011; Vol. 46, issue 12:1182‐8. - PubMed
Perez 2000 {published data only}
    1. Perez O. Treatment with montelukast in children with asthma [Tratamiento con montelukast en el nino con asma]. Revista Alergia Mexico 2000;47(1):30‐2. - PubMed
Peroni 2002 {published data only}
    1. Peroni DG, Piacenthi GL, Pietrobelli A, Bodini A, Boner AL. Montelukast or formoterol as second‐line therapy in asthmatic children exposed to allergens. The Journal of Allergy and Clinical Immunology 2002;109 Suppl 1:240 (Abs 730).
Peroni 2005 {published data only}
    1. Peroni DG, Piacentini GL, Bodini A, Ress M, Costella S, Boner AL. Montelukast versus formoterol as second‐line therapy in asthmatic children exposed to relevant allergens. Allergy and Asthma Proceedings 2005;26(4):283‐6. - PubMed
Petermann 2004 {published data only}
    1. Petermann W, Mutschler E. Fixed combination of inhalant steroids and long‐acting beta2 agonists, an important option in the treatment of persisting asthma. Deutsche Medizinische Wochenschrift 2004;129(5):210‐4. - PubMed
Plaza 2005 {published data only}
    1. Plaza V, Cobos A, Ignacio‐Garcia JM, Molina J, Bergonon S, Garcia‐Alonso F, et al. Cost‐effectiveness of an intervention based on the Global INitiative for Asthma (GINA) recommendations using a computerized clinical decision support system: a physician's randomized trial. Medicina Clinica 2005;124(6):201‐6. - PubMed
Price 2003 {published data only}
    1. Price D, Haughney J, Rosen JP, Morrison K. Switching to symbicort(r) from beclomethasone dipropionate (BDP) with or without salmeterol significantly improved symptom severity in patients with moderate asthma. American Thoracic Society 99th International Conference; 2003 May 16‐21; Seattle. 2003:D034, Poster C40.
Price 2011a {published data only}
    1. Price D, Musgrave SD, Wilson E, Sims E, Shepstone L, Blyth A, et al. A pragmatic single‐blind RCT and health economic evaluation of leukotriene receptor antagonists in primary care at steps two and three of the national asthma guidelines (ELEVATE). Health Technology Assessment 2011; Vol. 364, issue 18:1695‐707. - PubMed
    1. Sims E, Freeman D, Kemp L, Musgrave S, Juniper L, Gilbert R, et al. Should guidelines be revised for add on therapy in asthma? A 2 year randomized pragmatic equivalence trail of leukotriene antagonist (LTRAs) and long acting beta agonists (LABAs) with inhaled corticosteroids (ICS) in primary care [Abstract]. European Respiratory Society Annual Congress; 2008 Oct 4‐8; Berlin. 2008:E233.
    1. Sims E, Freeman D, Musgrave D, Kemp L, Ayres J. Do asthma guidelines need rewriting for add‐on therapy in asthma—results of a 2 year randomised pragmatic equivalence trial of leukotriene antagonists (LTRAs) and long‐acting beta agonists (LABAs) with inhaled corticosteroids (ICS) in primary care [Abstract]. Primary Care Respiratory Journal 2008;17(2):128.
    1. Wilson E, Price D, Musgrave S, Sims E, Shepstone L, et al. The cost‐effectiveness of leukotriene receptor antagonists versus long acting beta‐2 agonists as add‐on therapy to inhaled corticosteroids for asthma: a pragmatic trial. Pharmacoeconomics 2010;28(7):597‐608. - PubMed
Riccioni 2002 {published data only}
    1. Riccioni G, D'Orazio N, Ilio C, Della Vecchia R, Lorenzo A. Effectiveness and safety of montelukast versus budesonide at difference doses on bronchial reactivity in subjects with mild‐persistent asthma [Efficacia e tollerabilita del montelukast verso budesonide a diverso dosaggio sulla reattivita bronchiale in soggetti con asma di grado lieve‐persistente]. Clinica Terapeutica 2002;155(317):321. - PubMed
Rickard 1998 {published data only}
    1. Rickard K, Boone R, Yancey S, Emmett A. Salmeterol provides better improvement in pulmonary function than zafirlukast in patients with persistent asthma. European Respiratory Journal 1998;Suppl 29:19.
Rosenhall 2003 {published data only}
    1. Rosenhall L, Elvstrand A, Tilling B, Vinge I, Jemsby P, Stahl E, et al. One‐year safety and efficacy of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler) for the treatment of asthma. Respiratory Medicine 2003;97(6):702‐8. - PubMed
SAS40036 {unpublished data only}
    1. GlaxoSmithKline (SAS40036). A multicenter, randomized, double‐blind, double‐dummy, parallel group, 16‐week comparison of asthma control in adolescents and adults receiving either fluticasone propionate/salmeterol DISKUS combination product 100/50mcg BID, fluticasone propionate DISKUS 100mcg BID, salmeterol xinafoate DISKUS 50mcg BID, or oral montelukast 10mg QD. www.gsk‐clinicalstudyregister.com (accessed 7 March 2008).
SAS40037 {unpublished data only}
    1. GlaxoSmithKline (SAS40037). A multicenter, randomized, double‐blind, double‐dummy, parallel group, 16‐week comparison of asthma control in adolescents and adults receiving either fluticasone propionate/salmeterol DISKUS combination product 100/50mcg BID, fluticasone propionate DISKUS 100mcg BID, salmeterol xinafoate DISKUS 50mcg BID, or oral montelukast 10mg QD. www.gsk‐clinicalstudyregister.com (accessed 7 March 2008).
SAS40066 {unpublished data only}
    1. GlaxoSmithKline (SAS40066). A randomised, open‐label, crossover pilot study, assessing patient preference for ADVAIR DISKUS 100/50 BID (fluticasone propionate/salmeterol combination product 100/50mcg) versus Singulair QD (montelukast 10mg) in subjects >=15 years of age with persistent asthma. www.gsk‐clinicalstudyregister.com (accessed 7 March 2008).
Serrier 2003 {published data only}
    1. Serrier P, Roche N, Pello JY, Larguier JS, Mezzi K. Asthma control achieved with inhaled corticosteroids and long‐acting beta2‐agonists in a free or fixed combination: results of the ALISE survey. La Presse Medicale 2003;32(11):493‐7. - PubMed
Sheth 2002 {published data only}
    1. Sheth K, Borker R, Emmett A, Rickard K, Dorinsky P. Cost‐effectiveness comparison of salmeterol/fluticasone propionate versus montelukast in the treatment of adults with persistent asthma. Pharmacoeconomics 2002;20(13):909‐18. - PubMed
Sims 2003 {published data only}
    1. Sims EJ, Jackson CM, Lipworth BJ. Add‐on therapy with montelukast or formoterol in patients with the glycine‐16 beta2‐receptor genotype. British Journal of Clinical Pharmacology 2003;56(1):104‐11. - PMC - PubMed
Smith 1998 {published data only}
    1. Smith LJ. The prospects for long‐term intervention in asthma with antileukotrienes. Clinical and Experimental Allergy 1998;28 Suppl 5:154‐63. - PubMed
Smugar 2009 {published data only}
    1. Smugar SS, Fogel R, Aristizabal G, Rosario N, Loeys T, Gaile S, et al. Effect of montelukast or salmeterol added to inhaled fluticasone on response to albuterol in children with exercise‐induced bronchoconstriction [Abstract]. http://www.ersnet.org/ (accessed 13/1/14):P1221. - PubMed
Smugar 2009a {published data only}
    1. Smugar SS, Fogel R, Rosario N, Aristizabal G, Loeys T, Gaile S, et al. Attenuation of exercise‐induced bronchoconstriction with montelukast or salmeterol added to inhaled fluticasone in children [Abstract]. http://www.ersnet.org/ (accessed 13/1/14):P1217. - PubMed
Sorkness 2007 {published data only}
    1. Covar RA, Szefler SJ, Zeiger RS, Sorkness CA, Moss M, Mauger DT, et al. Factors associated with asthma exacerbations during a long‐term clinical trial of controller medications in children. The Journal of Allergy and Clinical Immunology 2008;122(4):741‐7. - PMC - PubMed
    1. Larsen GL, Morgan W, Heldt GP, Mauger DT, Boehmer SJ, Chinchilli VM, Lemanske RF, et al. Impulse oscillometry versus spirometry in a long‐term study of controller therapy for pediatric asthma. The Journal of Allergy and Clinical Immunology 2009;123(4):861‐7. - PMC - PubMed
    1. Sorkness CA, Lemanske Jr RF, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, et al. Long‐term comparison of 3 controller regimens for mild‐moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. The Journal of Allergy and Clinical Immunology 2007;119(1):64‐72. - PubMed
Stanford 2003 {published data only}
    1. Stanford R, Dorinsky P, Crim C, Yancey S, Edwards L, Rickard K. Reduction in asthma related exacerbations and exacerbation related costs during initial maintenance therapy with fluticasone propionate/salmeterol combination product versus montelukast or fluticasone propionate alone. The Journal of Allergy and Clinical Immunology 2003;111 Suppl 2:143.
Stelmach 2001 {published data only}
    1. Stelmach I, Grzelewski T, Majak P, Majak J, Bobrowska M, Jerzynska J, et al. The effect of triamcinolone, montelukast and formoterol on serum levels of il‐4, IgE and clinical parameters in children with asthma. Polski Merkuriusz Lekarski 2001;11(63):247‐51. - PubMed
Stelmach 2002 {published data only}
    1. Stelmach I, Jerzynska J, Majak P, Grzelewski T, Gorski P, Stelmach W, et al. The effect of triamcinolone acetonide, montelukast, nedocromil sodium, formoterol on levels levels of sICAM‐1, sIL‐2R in serum and clinical course of asthma in children. Polski Merkuriusz Lekarski 2002;12(68):99‐103. - PubMed
Stelmach 2002a {published data only}
    1. Stelmach I, Jerzynska J, Kuna P. A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and [beta]‐agonist treatment on IL‐10 serum levels in children with asthma. Clinical and Experimental Allergy 2002;32(2):264‐9. - PubMed
Stelmach 2007 {published data only}
    1. Stelmach I, Grzelewski T, Bobrowska‐Korzeniowska M, Stelmach P, Kuna P. A randomized, double‐blind trial of the effect of anti‐asthma treatment on lung function in children with asthma. Pulmonary Pharmacology and Therapeutics 2007;20(6):691‐700. - PubMed
Stelmach 2008 {published data only (unpublished sought but not used)}
    1. Stelmach I, Grzelewski T, Jerzynska J, Kuna P. A randomized, double‐blind trial on the effect of treatment with montelukast, budesonide, montelukast with budesonide, formoterol with budesonide on lung function and clinical symptoms in children with asthma [Abstract]. The Journal of Allergy and Clinical Immunology 2005;115 Suppl 2:151.
    1. Stelmach I, Grzelewski T, Majak P, Jerzynska J, Stelmach W, Kuna P. Effect of different antiasthmatic treatments on exercise‐induced bronchoconstriction in children with asthma. The Journal of Allergy and Clinical Immunology 2008;121(2):383‐9. - PubMed
Stempel 1998 {published data only}
    1. Stempel DA. Leukotriene modifiers in the treatment of asthma. Respiratory Care 1998;43(6):481‐9.
Stempel 2002 {published data only}
    1. Stempel DA, O'Donnell JC, Meyer JW. Inhaled corticosteroids plus salmeterol or montelukast: effects on resource utilization and costs. The Journal of Allergy and Clinical Immunology 2002;109(3):433‐9. - PubMed
Stevenson 2005 {published data only}
    1. Stevenson DD, Mehra PK, White AA, Gupta S, Woessner KM, Simon RA. Failure of tacrolimus to prevent aspirin‐induced respiratory reactions in patients with aspirin‐exacerbated respiratory disease. The Journal of Allergy and Clinical Immunology 2005;116(4):755‐60. - PubMed
Sugihara 2010 {published data only}
    1. Sugihara N, Kanada S, Haida M, Ichinose M, Adachi M, Hosoe M, et al. 24‐h bronchodilator efficacy of single doses of indacaterol in Japanese patients with asthma: a comparison with placebo and salmeterol. Respiratory Medicine 2010; Vol. 104, issue 11:1629‐37. - PubMed
Teper 2009 {published data only}
    1. Teper A, Kofman C, Zaragoza S, Rodriguez V, Lubovich S, Eguiguren C, et al. Comparison of fluticasone propionate + salmeterol (FP+S) and montelukast (MK) on bronchial reactivity (BR), pulmonary function (PF) and clinical outcome in children with mild asthma [Abstract]. http://www.ersnet.org/ (accessed 13/1/14):P1215.
Terzano 2001 {published data only}
    1. Terzano C, Allegra L, Barkai L, Cremonesi G. Beclomethasone dipropionate versus budesonide inhalation suspension in children with mild to moderate persistent asthma. European Review for Medical and Pharmacological Sciences 2001;5(1):17‐24. - PubMed
Thien 2000 {published data only}
    1. Thien F. Leukotriene antagonists—do they offer new hope for asthmatics?. Australian Family Physician 2000;29(6):547‐51. - PubMed
Tolley 2002 {published data only}
    1. Tolley K, Martin A, Rice L, McCarthy TP. Salmeterol/fluticasone propionate combination (SFC) demonstrates improved health outcomes and good cost effectiveness compared with beclomethasone dipropionate. American Journal of Respiratory and Critical Care Medicine 2002;165 Suppl 8:A112.
Vaquerizo 2003 {published data only}
    1. Vaquerizo MJ, Casan P, Castillo J, Perpina M, Sanchis J, Sobradillo V, et al. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma. Thorax 2003;58:204‐11. - PMC - PubMed
Volovitz 1999 {published data only}
    1. Volovitz B, Tabachnik E, Nussinovitch M, Shtaif B, Blau H, Gil‐Ad I, et al. Montelukast, a leukotriene receptor agonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma. The Journal of Allergy and Clinical Immunology 1999;104:1162‐7. - PubMed
Wang 2011 {published data only}
    1. Wang L, Hollenbeak CS, Mauger DT, Zeiger RS, Paul IM, Sorkness CA, et al. Cost‐effectiveness analysis of fluticasone versus montelukast in children with mild‐to‐moderate persistent asthma in the Pediatric Asthma Controller Trial. Journal of Allergy and Clinical Immunology 2011; Vol. 127, issue 1:161‐6. - PMC - PubMed
Warner 2001 {published data only}
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Wilson 1999 {published data only}
    1. Wilson AM. A comparison of salmeterol and montelukast as second‐line therapy in asthmatic patients not controlled on inhaled corticosteroids. Thorax 1999;54 Suppl 3:A66, P189.
Wilson 2001 {published data only}
    1. Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ. Evaluation of salmeterol or montelukast as second‐line therapy for asthma not controlled with inhaled corticosteroids. Chest 2001;119(4):1021‐6. - PubMed
Wilson 2010 {published data only}
    1. Wilson EC, Sims EJ, Musgrave SD, Shepstone L, Blyth A, Murdoch J, et al. Cost effectiveness of leukotriene receptor antagonists versus long‐acting beta‐2 agonists as add‐on therapy to inhaled corticosteroids for asthma: a pragmatic trial. Pharmacoeconomics 2010; Vol. 28, issue 7:597‐608. - PubMed
Wilson 2010a {published data only}
    1. Wilson E, Price D, Musgrave S, Sims E, Shepstone L, et al. The cost‐effectiveness of leukotriene receptor antagonists versus long acting beta‐2 agonists as add‐on therapy to inhaled corticosteroids for asthma: a pragmatic trial. Pharmacoeconomics 2010; Vol. 28, issue 7:597‐608. - PubMed
Wilson 2010b {published data only}
    1. Wilson SR, Strub P, Buist AS, Knowles SB, Lavori PW, Lapidus J, et al. Shared treatment decision making improves adherence and outcomes in poorly controlled asthma. American Journal of Respiratory and Critical Care Medicine 2010; Vol. 181, issue 6:566‐77. - PMC - PubMed
Wytrychowski 2001 {published data only}
    1. Wytrychowski K, Patkowski J, Kuzniar T, Malolepszy J. Zafirlucast in corticosteroid sensitive and resistant bronchial asthma [Zafirlukast w leczeniu astmy oskrzelowej wrazliewej i opornej na kortykosteroidy ‐ ocena stanu klinicznego i jakosci zycia]. Advances in Clinical and Experimental Medicine 2001;10(4):337‐47.
Yasui 2012 {published data only}
    1. Yasui H, Fujisawa T, Inui N, Kato M, Hashimoto D, Enomoto N, et al. Impact of add‐on pranlukast in stable asthma: the additive effect on peripheral airway inflammation. Respiratory Medicine 2012; Vol. 106, issue 4:508‐14. - PubMed
Yurdakul 2002 {published data only}
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Zarkovic 1998 {published data only}
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Zimmerman 2002 {published data only}
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References to studies awaiting assessment

Baek 2013 {published data only}
    1. Baek H‐S, Cho J, Kim J‐H, Oh J‐W, Lee H‐B. Ratio of leukotriene E4 to exhaled nitric oxide and the therapeutic response in children with exercise‐induced bronchoconstriction. Allergy, Asthma & Immunology Research 2013;5(1):26‐33. [] - PMC - PubMed
Braido 2012 {published data only}
    1. Braido F, Comaschi M, Valle I, Delgado L, Coccini A, Guerrera P, et al. Knowledge and Health Care resource allocation: CME/CPD course guidelines‐based efficacy. European Annals of Allergy and Clinical Immunology 2012;44(5):193‐9. [] - PubMed
Castillo 2009 {published data only}
    1. Castillo J, Valero A, Quirce S, Navarro A, Mullol J, Molina J, et al. Comorbidity of asthma and rhinitis in patients attending outpatient clinics of Spanish allergists, primary care physicians and pulmonologists. Allergy 2009;Conference: 28th Congress of the European Academy of Allergy and Clinical Immunology Abstract Book Warszawa Poland. Conference Start: 20090606 Conference End: 20090610. Conference Publication:(var.pagings):427. []
Cheng 2013 {published data only}
    1. Cheng SL, Wang HC, Kuo SH. Early achievement and maintenance of stable asthma control using initially higher‐dose inhaled corticosteroids as part of combination therapy: an open‐label pilot study. Drug Design, Development and Therapy 2013;7:477‐84. [] - PMC - PubMed
Gao 2013 {published data only}
    1. Gao J‐M, Cai F, Peng M, Ma Y, Wang B. Montelukast improves air trapping, not airway remodeling, in patients with moderate‐to‐severe asthma: A pilot study. Chinese Medical Journal 2013;126(12):2229‐34. [] - PubMed
Lenney 2013 {published data only}
    1. Lenney W, McKay AJ, Tudur Smith C, Williamson PR, James M, Price D. Management of Asthma in School age Children On Therapy (MASCOT): a randomised, double‐blind, placebo‐controlled, parallel study of efficacy and safety. Health Technology Assessment (Winchester, England) 2013;17(4):1‐238. [] - PMC - PubMed
Lipworth 2013 {published data only}
    1. Lipworth BJ, Basu K, Donald HP, Tavendale R, Macgregor DF, Ogston SA, et al. Tailored second‐line therapy in asthmatic children with the Arg(16) genotype. Clinical Science 2013;124(8):521‐8. [] - PubMed
Lujan 2013 {published data only}
    1. Lujan M, Gallardo X, Amengual MJ, Bosque M, Mirapeix RM, Domingo C. Prevalence of bronchiectasis in asthma according to oral steroid requirement: Influence of immunoglobulin levels. BioMed Research International 2013:E Pub. [] - PMC - PubMed
Okupa 2013 {published data only}
    1. Okupa AY, Sorkness CA, Mauger DT, Jackson DJ, Lemanske RFJ. Daily diaries vs retrospective questionnaires to assess asthma control and therapeutic responses in asthma clinical trials: is participant burden worth the effort?. Chest 2013;143(4):993‐9. [; 4900100000077293] - PMC - PubMed
Pavord 2013 {published data only}
    1. Pavord ID, Thomson NC, Niven RM, Corris PA, Chung KF, Cox G, et al. Safety of bronchial thermoplasty in patients with severe refractory asthma. Annals of Allergy, Asthma & Immunology 2013;111(5):402‐7. [] - PubMed
Snowise 2013 {published data only}
    1. Snowise NG, Clements D, Ho S‐Y, Follows RMA. Addition of a 5‐lipoxygenase‐activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long‐acting beta‐2‐agonist combination in subjects with asthma. Current Medical Research and Opinion 2013;29(12):1663‐74. [] - PubMed
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    1. Soroncz‐Szabo T, Adrienne N, Tao F. Estimation of the relative effects of montelukast and zafirlukast on asthma exacerbations and safety outcomes: A meta‐analysis of adjusted indirect comparisons. Allergy 2009;Conference: 28th Congress of the European Academy of Allergy and Clinical Immunology Abstract Book Warszawa Poland. Conference Start: 20090606 Conference End: 20090610. Conference Publication:(var.pagings):183. []
Virchow 2009 {published data only}
    1. Virchow J, Mehta A, Ljungblad L, Mitfessel H. An analysis of inadequately controlled asthma patients with and without co‐morbid allergic rhinitis treated with add‐on montelukast. Allergy 2009;Conference: 28th Congress of the European Academy of Allergy and Clinical Immunology Abstract Book Warszawa Poland. Conference Start: 20090606 Conference End: 20090610. Conference Publication:(var.pagings):183. []

References to ongoing studies

Fardon 2002 {published data only}
    1. Ongoing study Starting date of trial not provided. Contact author for more information.
Fardon 2004 {published data only}
    1. Ongoing study Starting date of trial not provided. Contact author for more information.
Price 2001 {published data only}
    1. Ongoing study Starting date of trial not provided. Contact author for more information.
Ruggins 2003 {unpublished data only}
    1. Ongoing study Starting date of trial not provided. Contact author for more information.

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