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Agentes antileucotrienos comparados con corticosteroides inhalados para el tratamiento del asma recurrente y crónica en pacientes adultos y niños

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Referencias

References to studies included in this review

Ir a:

Abadoglu 2005 {published data only}

Abadoglu O, Mungan D, Aksu O, Erekul S, Misirligil Z. The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma. Allergol Immunopathol 2005;33(2):105‐11.

Basyigit 2004 {published data only}

Basyigit I, Yildiz F, Kacar Ozkara S, Boyaci H, Ilgazli A, Ozkarakas O. Effects of different anti‐asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics. Respirology 2004;9(4):514‐20.

Baumgartner 2003 {published data only}

Baumgartner RA, Martinez G, Edelma JM, Rodriguez Gomez GG, Berstein M, Bird S, et al. Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone. European Respiratory Journal2003; Vol. 21:123‐8.

Bleecker 2000 {unpublished data only}

Bleecker ER, Welch MJ, Weinstein SF, Kalberg C, Johnson M, Edwards L, et al. Low‐dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma. Journal of Allergy & Clinical Immunology 2000;105(6):1123‐9.

Boushey 2005 {published data only}

Boushey HA, Sorkness CA, King TS, Sullivan SD, Fahy JV, Lazarus SC, et al. Daily versus as‐needed corticosteroids for mild persistent asthma. New England Jounal of medicine 2005;352(15):1519‐1528.

Bousquet 2005 {published data only}

Bousquet J, Menten J, Tozzi CA, Polos PG. Oral montelukast sodium versus inhaled fluticasone propionate in adults with mild persistent asthma. Journal of Applied Research 2005;5(3):402‐14.

Brabson 2002 {published data only}

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;113:15‐21.

Busse 2001a {published data only}

Busse W, Wolfe J, Storms W, Srebro S, Edwards L, Johnson M, et al. Fluticasone propionate compared to Zafirlukast in controlling persistent asthma: A randomised double‐blind, placebo‐controlled trial. Journal of Family Practice 2001;50:595‐602.

Busse 2001b {published data only}

Busse W, Raphael GD, Galant S, Kalberg C, Goode‐Sellers S, Srebro S, et al. Low‐dose fluticasone propionate compared to montelukast for first‐line treatment of persistent asthma: a randomised controlled trial. Journal of Allergy & Clinical Immunology 2001;107(3):461‐8.

Caffey 2005 {published data only}

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.

Dempsey 2002a {published data only}

Dempsey OJ, Wilson AM, Lipworth BJ. Comparative efficacy and anti‐inflammatory profile of once daily low dose hfa‐triamcinolone acetonide (taa) and montelukast (ml) in patients with mild persistent atopic asthma. Journal of Allergy and Clinical Immunology 2002;109(1):68‐74.

FLTA4030 {unpublished data only}

A randomized, double‐blind, double dummy, placebo‐controlled, parallel‐group, comparative study of inhaled fluticasone propionate (88 mcg bid) versus zafirlukast (20 mg bid) in subjects who are currently receiving beta agonists alone. www.gsk‐clinicalstudyregister.com.

FLTA4031 {unpublished data only}

A randomized, double‐blind, double‐dummy, placebo‐controlled, parallel‐group, comparative study of inhaled fluticasone propionate (88 mcg bid) versus zafirlukast (20 mg bid) in subjects who are currently receiving beta agonists alone. www.gsk‐clinicalstudyregister.com.

FMS40012 {unpublished data only}

Evaluation of the potential anti‐inflammatory action of leukotriene D4 receptor antagonists: comparison of zafirlukast, an LTD4 receptor antagonist with low‐dose fluticasone propionate, an inhaled steroid on sputum eosinophils in mild asthma. GlaxoSmithKline Clinical Trial Register2005.

FPD40013 {unpublished data only}

FPD40013. A randomized, double‐blind, double dummy, parallel group comparison of fluticasone propionate inhalation powder (50 mcg BID) via discus with oral montelukast (5 mg QD) chewable tablets in children 6‐12 years of age with persistent asthma. GlaxoSmithKline Clinical Trial Register2005.

Garcia Garcia 2005 {published data only}

Garcia Garcia ML, Wahn U, Gilles L, Swern A, Tozzi CA, Polos P. Montelukast, compared with fluticasone, for control of asthma among 6‐ to 14‐year‐old patients with mild asthma: the MOSAIC study. Pediatrics 2005;116(2):360‐9.

Hughes 1999 (BDP) {unpublished data only}

Hughes GL, Edelman JM, Turpin JA, Liss C, Weeks K. Randomized, open‐label pilot study comparing the effects of montelukast sodium tablets, fluticasone aerosol inhaler, and budesonide dry powder inhaler on asthma control in mild asthmatics. American Journal of Respiratory & Critical Care Medicine 1999;159:A641.

Hughes 1999 (FP) {unpublished data only}

Hughes GL, Edelman JM, Turpin JA, Liss C, Weeks K. Randomized, open‐label pilot study comparing the effects of montelukast sodium tablets, fluticasone aerosol inhaler, and budesonide dry powder inhaler on asthma control in mild asthmatics. American Journal of Respiratory & Critical Care Medicine 1999;159:A641.

Israel 2002 {published data only}

Israel E, Chervinsky PS, Friedman B, Van Bavel J, Skalky CS, Ghannam AF, et al for the Montelukast Beclomethasone Comparison Study Group. Effects of montelukast and beclomethasone on airway function and asthma control. Journal of Allergy and Clinical Immunology 2002;110(6):847‐54.

Jayaram 2002 {published data only}

Jayaram L, Pizzichini MMM, Hussack P, Efthimiadis A, Lemiere C, Cartier A, et al. First line anti‐inflammatory treatment for asthma; inhaled steroid or leukotriene antagonist?. Respirology 2002;7(A19):21.

Jayaram 2005 {published data only}

Jayaram L, Pizzichini E, Lemiere C, Man SF, Cartier A, Hargreave FE, et al. Steroid naive eosinophilic asthma: anti‐inflammatory effects of fluticasone and montelukast. Thorax 2005;60(2):100‐5.

Jenkins 2005 {published data only}

Jenkins CR, Thien FCK, Wheatley JR, Reddel HK. Traditional and patient‐centred outcomes with three classes of asthma medication. European Respiratory Journal 2005;26(1):36‐44.

Kanazawa 2007 {published data only}

Kanazawa H, Nomura S, Asai K. Roles of angiopoietin‐1 and angiopoietin‐2 on airway microvascular permeability in asthmatic patients. Chest 2007;131(4):1035‐41.

Kanniess 2002 {published data only}

Kanniess F, Richter K, Bohme S, Jorres RA, Magnussen H. Montelukast versus fluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma. European Respiratory Journal 2002;20:853‐8.

Khan 2008 {published data only}

Khan SA, Hashmi ZY. Comparison of therapeutic values between leukotriene receptor antagonist (Montelukast) and inhaled glucocorticoid (Beclomethasone propionate) in bronchial asthma of adults. Pakistan Journal of Medical Sciences 2008;24(3):399‐405.

Kim 2000 {published and unpublished data}

Kim KT, Ginchansky EJ, Friedman BF, Srebro S, Pepsin PJ, Edwards L, et al. Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy. Annals of Allergy, Asthma, & Immunology 2000;85:398‐406.

Koenig 2008 {published data only}

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". Journal of Asthma 2008;45:681‐7.

Kooi 2008 {published data only}

Kooi EMW, Schokker S, Marike Boezen H, de Vries TW, Vaessen‐Verberne AAPH, van der Molen T, et al. Fluticasone or montelukast for preschool children with asthma‐like symptoms: Randomized controlled trial. Pulmonary Pharmacology and Therapeutics 2008;21(5):798‐804.

Kumar 2007 {published data only}

Kumar V, Ramesh P, Lodha R, Pandey RM, Kabra SK. Montelukast vs. inhaled low‐dose budesonide as monotherapy in the treatment of mild persistent asthma: A randomized double blind controlled trial. Journal of Tropical Pediatrics 2007;53(5):325‐30.

Laitinen 1997 {unpublished data only}

Laitinen LA, Naya IP, Binks S, Harris A. Comparative efficacy of zafirlukast & low dose steroids in asthmatics on prn beta2‐agonists. European Respiratory Journal. 1997; Vol. 10, issue Suppl 25:419‐20, Abs. 2716.

Laviolette 1999 {published and unpublished data}

Laviolette M, Malmstrom K, Lu S, Chervinsky P, Pujet J‐C, Peszek I, et al. Montelukast added to inhaled beclomethasone in treatment of asthma. American Journal of Respiratory & Critical Care Medicine 1999;160(6):1862‐8.

Lazarus 2007 {published data only}

Lazarus SC, Chinchilli VM, Rollings NJ, Boushey HA, Cherniack R, Craig TJ, et al. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. American Journal of Respiratory and Critical Care Medicine 2007;175(8):783‐90.

Lu 2009 {published data only}

Lu S, Liu N, Dass SB, Reiss TF. A randomized study comparing the effect of loratadine added to montelukast with montelukast, loratadine, and beclomethasone monotherapies in patients with chronic asthma. Journal of Asthma 2009;46(5):465‐9.

Malmstrom 1999 {published and unpublished data}

Malmstrom K, Rodriguez‐Gomez G, Guerra J, Villaran C, Pineiro A, Lynn X, et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma: a randomized, controlled trial. Annals of Internal Medicine 1999;130(6):487‐95.

Maspero 2001 {published data only}

Maspero JF, Duenas‐Meza E, Volovitz B, Daza CP, Kosa L, Vrijens F, et al. Oral montelukast versus inhaled beclomethasone in 6 to 11‐year old children with asthma: results of an open‐label extension study evaluating long‐term safety, satisfaction, and adherence to therapy. Current Medical Research and Opinion2001; Vol. 17, issue 2:96‐104.

Meltzer 2002 {published data only}

Meltzer EO, Lockey RF, Friedman BF, Kalberg C, Goode‐Sellers S, Srebro S, et al for the Fluticasone Propionale Clinical Research Study Group. Efficacy and safety of low‐dose fluticasone propionate compared with montelukast for maintenance treatment of persistent asthma. Mayo Clinc Proceedings 2002;77:437‐5.

MK0479‐332 {unpublished data only}

Merck. Montelukast asthmatic smoker study. Clinicaltrials.Gov2006.

Nathan 2001 {published data only}

Nathan RA, Bleecker ER, Kalberg C and the Fluticasone Propionate Study Group. A comparison of short‐term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma. American Journal of Medicine 2001;111:195‐202.

NCT00442559 {unpublished data only}

Montelukast in mild asthmatic children with allergic rhinitis. Clinicaltrials.gov2008.

Ng 2007 {published data only}

Ng DKK, Chan CH, Wu S, Chow PY,  Wong LSW, Fu YM, et al. Oral montelukast versus inhaled budesonide in children with mild persistent asthma: A pilot study. The Hong Kong Journal of Paediatrics 2007;12(1):3‐10.

Ostrom 2005 {published data only}

Ostrom NK, Decotiis BA, Lincourt WR, Edwards LD, Hanson KM, Carranza Rosenzweig JR, et al. Comparative efficacy and safety of low‐dose fluticasone propionate and montelukast in children with persistent asthma. Journal of Pediatrics 2005;147((2):213‐20.

Overbeek 2004 {published data only}

Overbeek SE, O'Sullivan S, Leman K, Mulder PGH, Hoogsteden HC, Prins J‐B. Effect of montelukast compared with inhaled fluticasone on airway inflammation. Clinical & Experimental Allergy 2004;34(9):1388‐94.

Peroni 2005 {published data only}

Peroni D, Bodini A, Miraglia Del Giudice M, Loiacono A, Baraldi E, Boner AL, et al. Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens. Allergy 2005;60(2):206‐10.

Peters 2007 {published data only}

Peters SP, Anthonisen N, Castro M, Holbrook JT, Irvin CG, Smith LJ, et al. Randomized comparison of strategies for reducing treatment in mild persistent asthma. New England Journal of Medicine 2007;356(20):2027‐39.

Riccioni 2001 {published data only}

Riccioni G, Castronuove M, De Benedictis M, Pace‐Palitti V, Di Gioacchino M, Della Vecchia R, et al. Zafirlukast versus budesonide on bronchial reactivity in subjects with mild‐persistent asthma. International Journal of Immunopathology and Pharmacology 2001;14(2):87‐92.

Riccioni 2002a {published data only}

Riccioni G, D'Orazio N, Di Ilio C, Della Vecchia R, De Lorenzo A. Effectiveness and safety of montelukast versus budesonide at various 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]. La Clinica terapeutica 2002;153(5):317‐21.

Riccioni 2002b {published data only}

Riccioni G, Ballone E, D'Orazio N, Sensi S, Di Nicola M, Di Mascio R, et al. Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild‐persistent asthma. International Journal of Immunopathology & Pharmacology 2002;15(2):149‐55.

Riccioni 2003 {published data only}

Riccioni G, Vecchia RD, D'Orazio N, Sensi S, Guagnano MT. Comparison of montelukast and budesonide on bronchial reactivity in subjects with mild‐moderate persistent asthma. Pulmonary Pharmacology & Therapeutics 2003;16(2):111‐4.

Sheth 2001 {published data only}

Sheth K, Edwards L, Srebro S, Rickard K. Effects of baseline pulmonary function on treatment response: low‐dose fluticasone versus zafirlukast. Annals of Allergy, Asthma and IImmunology 2001;86:2001.

Sorkness 2007 {published data only}

Sorkness CA, Lemanske Jr RF, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD. Long‐term comparison of 3 controller regimens for mild‐moderate persistent childhood asthma: The Pediatric Asthma Controller Trial. Journal of Allergy & Clinical Immunology 2007;119(1):64‐72.

Stelmach 2002a {published data only}

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 & Experimental Allergy 2002;32(2):264‐9.

Stelmach 2002b {published and unpublished data}

Stelmach I, Grzelewski T, Stelmach W, Majak P, Jerzynska J, Gorski P, et al. Effect of triamcinolone acetonide, montelukast, nedocromil sodium and formoterol on eosinophil blood counts, ECP serum levels and clinical progression of asthma in children [Polish]. Polski Merkuriusz Lekarski 2002;12(69):208‐13.

Stelmach 2004 {published data only}

Stelmach I, Majak P, Jerzynska J, Stelmach W, Kuna P. Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study. Pediatric Allergy & Immunology 2004;15(4):359‐64.

Stelmach 2005 {published data only}

Stelmach I, Bobrowska‐Korzeniowska M, Majak P, Stelmach W, Kuna P. The effect of montelukast and different doses of budesonide on IgE serum levels and clinical parameters in children with newly diagnosed asthma. Pulmonary Pharmacology & Therapeutics 2005;18(5):374‐80.

Stelmach 2007 {published data only}

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.

Stelmach 2008 {published data only}

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. Journal of Allergy Clinical Immunology 2008;121(2):383‐9.

Szefler 2005 {published data only}

Szefler SJ, Phillips BR, Martinez FD, Chinchilli VM, Lemanske RF, Strunk RC. Characterization of within‐subject responses to fluticasone and montelukast in childhood asthma. Journal of Allergy and Clinical Immunology 2005;115(2):233‐42.

Szefler 2007 {published data only}

Szefler SJ, Baker JW, Uryniak T, Goldman M, Silkoff PE. Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. Journal of Allergy and Clinical Immunology 2007;120(5):1043‐50.

Tamaoki 2008 {published data only}

Tamaoki J, Isono K, Taira M, Tagaya E, Nakata J, Kawatani K, et al. Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma. Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies 2008;29(2):189‐96.

Yamauchi 2001 {published data only}

Yamauchi K, Tanifuji Y, Pan LH, Yoshida T, Sakurai S, Goto SI, et al. Effects of Pranlukast, a Leukotriene receptor antagonist, on airway inflammation in mild asthmatics. Journal of Asthma 2001;38(1):51‐7.

Yurdakul 2003 {published data only}

Yurdakul AS, Taci N, Eren A, Sipit T. Comparative efficacy of once‐daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained‐release theophylline in patients with mild persistent asthma. Respiratory Medicine 2003;97(12):1313‐9.

Zedan 2009 {published data only}

Zedan M, Gamil N, El‐Chennawi F, Maysara N, Hafeez HA, Nasef N, et al. Evaluation of different asthma phenotype responses to montelukast versus fluticasone Treatment. Pediatric Asthma, Allergy and Immunology 2009;22(2):63‐9.

Zeiger 2005 {published data only}

Zeiger RS, Bird SR, Kaplan MS, Schatz M, Pearlman DS, Orav EJ. Short‐term and long‐term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial. American Journal of Medicine 2005;118(6):649‐57.

Zeiger 2006 {published data only}

Zeiger RS, Szefler SJ, Phillips BR, Schatz M, Martinez FD, Chinchilli VM. Response profiles to fluticasone and montelukast in mild‐to‐moderate persistent childhood asthma. Journal of Allergy & Clinical Immunology 2006;117(1):45‐52.

Zielen 2010 {published data only}

Zielen S, Christmann M, Kloska M, Dogan‐Yildiz G, Lieb A, Rosewich M. Predicting short term response to anti‐inflammatory therapy in young children with asthma. Current Medical Research and Opinion 2010;26(2):483‐92.

References to studies excluded from this review

Ir a:

Abbott Pharma 1996 {published data only}

Abbott Pharmaceuticals. Zyflo Filmtab (zileuton) product description. Abbott Laboratories1996.

Al Frayh 2008 {published data only}

Al Frayh A, Abba A, Iskandarani A, Shaker DS, Zaitoun F, Shahrabani L, et al. Establishing therapeutic bioequivalence of a generic salbutamol (Butalin) metered dose inhaler to Ventolin. Biomedical Research 2008;19(1):61‐8.

Allayee 2007 {published data only}

Allayee H, Hartiala J, Lee W, Mehrabian M, Irvin CG, Conti DV, et al. The effect of montelukast and low‐dose theophylline on cardiovascular disease risk factors in asthmatics. Chest 2007;132(3):868‐74.

Allen 1997 {published data only}

Allen A, Georgiou P, Compton C, Walls C, Hibell M, Tomson DJ, et al. Lack of pharmacokinetic and pharmacodynamic interactions between pranlukast (Ultair) and terfenadine. American Thoracic Society. 1997:Abs C49.

Allen‐Ramey 2003 {published data only}

Allen‐Ramey FC, Duong PT, Goodman DC, Sajjan SG, Nelsen LM, Santanello NC, et al. Treatment effectiveness of inhaled corticosteroids and leukotriene modifiers for patients with asthma: an analysis from managed care data. Allergy & Asthma Proceedings 2003;24(1):43‐51.

Allen‐Ramey 2004 {published data only}

Allen‐Ramey FC, Anstatt DT, Riedel AA, Markson LE. Greater adherence in montelukast patients compared to those on fluticasone [Abstract]. Journal of Allergy and Clinical Immunology 2004;113(2 Suppl):S158.

Allen‐Ramey 2006 {published data only}

Allen‐Ramey FC, Markson LE, Riedel AA, Sajjan S, Weiss KB. Patterns of asthma‐related health care resource use in children treated with montelukast or fluticasone. Current Medical Research & Opinion 2006;22(8):1453‐61.

Altman 1998k {published data only}

Altman LC, Munk Z, Seltzer J, Noonan N, Shingo S, Zhang J, et al. A placebo‐controlled, dose‐ranging study of montelukast, a cysteinyl leukotriene‐receptor antagonist. Journal of Allergy & Clinical Immunology 1998;102:50‐6.

Anonymous 1997 {published data only}

Anonymous. Zileuton for asthma. Medical Letter on Drugs & Therapeutics 1997;39(995):18‐9.

Armour 2007 {published data only}

Armour C, Bosnic‐Anticevich S, Brillant M, Burton D, Emmerton L, Krass I, et al. Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community. Thorax 2007;62(6):496‐502.

Bacharier 2008 {published data only}

Bacharier LB, Phillips BR, Zeiger RS, Szefler SJ, Martinez FD, Lemanske RF, et al. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate‐to‐severe intermittent wheezing. The Journal of Allergy and Clinical Immunology 2008;122(6):1127‐35.

Bai 2010 {published data only}

Bai J, Xu PR. Montelukast in the treatment of bronchiolitis, a multi‐center, randomized, three‐blind, placebo‐controlled trial. Chinese Journal of Evidence‐Based Medicine 2010;10(9):1011‐5.

Balatsouras 2005 {published data only}

Balatsouras DG, Eliopoulos P, Rallis E, Sterpi P, Korres S, Ferekidis E. Improvement of otitis media with effusion after treatment of asthma with leukotriene antagonists in children with co‐existing disease. Drugs Under Experimental & Clinical Research 2005;31(SUPPL):7‐10.

Baren 2006 {published data only}

Baren JM, Boudreaux ED, Brenner BE, Cydulka RK, Rowe BH, Clark S, et al. Randomized controlled trial of emergency department interventions to improve primary care follow‐up for patients with acute asthma. Chest 2006;129(2):257‐65.

Barnes 1996 {published data only}

Barnes NC, Black B, Syrett N, Cohn J. Reduction of exacerbations of asthma in multi‐national clinical trials with zafirlukast (Accolate). Allergy 1996;51(Suppl 30):84.

Barnes 1997 {published data only}

Barnes NC, de Jong B, Miyamoto T. Worldwide clinical experience with the first marketed leukotriene receptor antagonist. Chest 1997;111 Suppl(2):52‐60.

Barnes 1997b {published data only}

Barnes NC, Pujet J‐C. Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo controlled, multicentre clinical study in asthma. Thorax 1997;52:523‐7.

Barnes 2001 {unpublished data only}

Barnes N, Wei LX, Reiss TF, Leff JA, Shingo S, Yu C, et al. Analysis of montelukast in mild persistent asthmatic patients with near‐normal lung function. Respiratory Medicine 2001;95(5):379‐86.

Barnes 2007 {published data only}

Barnes ML, Menzies D, Fardon TC, Burns P, Wilson AM, Lipworth BJ. Combined mediator blockade or topical steroid for treating the unified allergic airway. Allergy 2007;62(1):73‐80.

Barnes 2007a {published data only}

Barnes N, Laviolette M, Allen D, Flood‐Page P, Hargreave F, Corris P, et al. Effects of montelukast compared to double dose budesonide on airway inflammation and asthma control. Respiratory Medicine 2007;101(8):1652‐8.

Bartoli 2010 {published data only}

Bartoli ML, Dente FL, Bancalari L, Bacci E, Cianchetti S, Di Franco A, et al. Beclomethasone dipropionate blunts allergen‐induced early increase in urinary LTE4. European Journal of Clinical Investigation 2010;40(6):566‐9.

Bateman 1995 {published data only}

Bateman ED, Holgate ST, Binks SM, Tarns IP. A multicentre study to assess the steroid‐sparing potential of accolate (zafirlukast; 20 mg bd). Allergy 1995;50 Suppl(26):320, Abs P‐0709.

Bateman 2003 {published data only}

Bateman ED, Akveld M, Ho M. Greater responder rate to fluticasone propionate/salmeterol combination over montelukast plus fluticasone in asthma [abstract]. American Thoracic Society 99th International Conference 2003;B036:H90.

Baumgartner 1999 {published data only}

Baumgartner RA, Polis A, Angner R, Bird S, Reiss TF. Comparison between montelukast and inhaled beclomethasone therapy in chronic asthma: a double blind, placebo controlled, parallel study in asthmatic patients. Merck Research Laboratories1999.

Benitez 2005 {published data only}

Benitez HH, Arvizu VM, Gutierrez DJ, Fogelbach GA, Castellanos Olivares A, Vazquez Nava F, et al. Nasal budesonide plus zafirlukast vs nasal budesonide plus loratadine‐pseudoephedrine for controlling the symptoms of rhinitis and asthma. Revista Alergia Mexico 2005;52(2):90‐5.

Berger 2006 {published data only}

Berger WE, Milgrom H, Skoner DP, Tripp K, Parsey MV, Baumgartner RA. Evaluation of levalbuterol metered dose inhaler in pediatric patients with asthma: A double‐blind, randomized, placebo‐ and active‐controlled trial. Current Medical Research & Opinion 2006;22(6):1217‐26.

Bilancia 2000 {published data only}

Bilancia R, Margiotta D, Balacco D. Low doses of budesonide (B) plus montelukast (M) versus high doses of budesonide in asthmatic patients. American Journal of Respiratory and Critical Care Medicine 2000;161(supp 3):A197.

Bilderback 2004 {published data only}

Bilderback A, Krishnan JA, Riekert KA, Schiller K, Rand CS. Patterns of use for oral montelukast and inhaled fluticasone in a clinical trial [Abstract]. American Thoracic Society 100th International Conference 2004;B39:C18.

Bilderback 2005 {published data only}

Bilderback A, Rand C, Krishnan J, Riekert K, Schiller K, Zieger RS, et al. Adherence with montelukast or fluticasone and outcomes in a 1‐year clinical trial in patients with mild persistent asthma [Abstract]. American Thoracic Society International Conference 2005;D97:Poster 521.

Bisgaard 1999 {published data only}

Bisgaard H, Loland L, Anhoj J. NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast. American Journal of Respiratory & Critical Care Medicine 1999;160:1227‐31.

Bisgaard 2000 {published data only}

Bisgaard H, Nielsen KG. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children. American Journal of Respiratory & Critical Care Medicine 2000;162(1):187‐90.

Bisgaard 2005 {published data only}

Bisgaard H, Zielen S, Garcia‐Garcia ML, Johnston SL, Gilles L, Menten J, et al. Montelukast reduces asthma exacerbations in 2‐ to 5‐year‐old children with intermittent asthma. American Journal of Respiratory & Critical Care Medicine 2005;171(1):315‐22.

Bjermer 2002 {published data only}

Bjermer L, Greening A, Haahtela T, Bousquet J, Holgate ST, Picado C, et al. IMPACT study group. Addition of montelukast or salmeterol to fluticasone in patients with uncontrolled asthma: results of the IMPACT trial.. Chest. 2002:434.

Bjermer 2003 {published data only}

Bjermer L, Bisgaard H, Bousquet J, Fabbri LM, Greening AP, Haahtela T, et al. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial. BMJ 2003;327(7420):891.

Bjermer 2004 {published data only}

Bjermer L, Kocevar VS, Zhang Q, Yin DD, Polos PG. Health care resource utilization following addition of montelukast or salmeterol in fluticasone in patients with inadequately controlled asthma (IMPACT trial) [Abstract]. European Respiratory Journal 2004;24(Suppl 48):127s.

Bleecker 2006 {published data only}

Bleecker ER, Yancey SW, Baitinger LA, Edwards LD, Klotsman M, Anderson WH, et al. Salmeterol response is not affected by beta2‐adrenergic receptor genotype in subjects with persistent asthma. Journal of Allergy & Clinical Immunology 2006;118(4):809‐16.

Borker 2005 {published data only}

Borker R, Emmett A, Jhingran P, Rickard K, Dorinsky P. Determining economic feasibility of fluticasone propionate‐salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost‐effectiveness acceptability curves. Annals of Allergy Asthma & Immunology 2005;95(2):181‐9.

Bousquet 2005a {published data only}

Bousquet J, Gaugris S, Kocevar VS, Zhang Q, Yin DD, Polos PG, et al. Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: A subgroup analysis of the improving asthma control trial. Clinical & Experimental Allergy 2005;35(6):723‐7.

Bousquet 2007 {published data only}

Bousquet J, Rabe K, Humbert M, Chung KF, Berger W, Fox H, et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respiratory Medicine 2007;101(7):1483‐92.

Brannan 2001 {published data only}

Brannan JD, Anderson SD, Gomes K, King GG, Chan HK, Seale JP. Fenofenadine decreases sensitivity to and montelukast improves recovery from inhaled manitol. American Journal of Respiratory & Critical Care Medicine 2001;163(6):1420‐5.

Brocks 1996 {published data only}

Brocks DR, Upward JW, Georgiou P, Stelman G, Doyle E, Allen E, et al. The single and multiple dose pharmacokinetics of pranlukast in healthy volunteers. European Journal of Clinical Pharmacology 1996;51:303‐8.

Bronsky 1997 {published data only}

Bronsky E, Grossman J, Nathan RA, de Jong B. Pranlukast (Ultair) reduces symptoms of seasonal allergic rhinitis: results of the first US double‐blind, placebo controlled trial in 484 patients. SmithKline Beecham Pharmaceuticals1997.

Brown 2005 {published data only}

Brown ES, Stuard G, Liggin JDM, Hukovic N, Frol A, Dhanani N, et al. Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy. Biological Psychiatry 2005;57(5):543‐8.

Brown 2007 {published data only}

Brown ES, Frol AB, Khan DA, Larkin GL, Bret ME. Impact of levetiracetam on mood and cognition during prednisone therapy. European Psychiatry 2007;22(7):448‐52.

Brown 2010 {published data only}

Brown ES, Denniston D, Gabrielson B, Khan DA, Khanani S, Desai S. Randomized, double‐blind, placebo‐controlled trial of acetaminophen for preventing mood and memory effects of prednisone bursts. Allergy and Asthma Proceedings 2010;31(4):331‐6.

Bruce 2002 {published data only}

Bruce C, Palmqvist M, Sjöstrand M, Aronsson B, Arvidsson P, Lotvall J. Greater attenuation of the late asthmatic reaction by fluticasone propionate compared to montelukast. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A215.

Buchvald 2002 {published data only}

Buchvald FF, Bisgaard H. Comparison of add‐on of leukotriene receptor antagonist vs. long‐acting beta 2‐agonist of FeNO in asthmatic children on regular inhaled budesonide. European Respiratory Journal 2002;20(Suppl 38):431s.

Buchvald 2002a {published data only}

Buchvald FF, Bisgaard H. Comparison of add‐on of leukotriene receptor antagonist vs. long‐acting beta2‐agonist on FeNO in asthmatic children on regular inhaled budesonide [abstract]. European Respiratory Society Annual Congress. 2002:P2736.

Buchvald 2003 {published data only}

Buchvald F, Bisgaard H. Comparisons of the complementary effect on exhaled nitric oxide of salmeterol vs montelukast in asthmatic children taking regular inhaled budesonide. Annals of Allergy Asthma & Immunology 2003;91(3):309‐13.

Buckstein 2003 {published data only}

Bukstein DA, Luskin AT, Bernstein A. "Real‐world" effectiveness of daily controller medicine in children with mild persistent asthma. Annals of Allergy Asthma & Immunology 2003;90(5):543‐9.

Burgess 2007 {published data only}

Burgess SW, Sly PD, Cooper DM, Devadason SG. Novel spacer device does not improve adherence in childhood asthma. Pediatric Pulmonology 2007;42(8):736‐9.

Busse 1999 {published data only}

Busse W, Nelson H, Wolfe J, Kalberg C, Yancey SW, Rickard KA. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. Journal of Allergy & Clinical Immunology 1999;103:1075‐80.

Buxton 2004 {published data only}

Buxton MJ, Sullivan SD, Andersson LF, Lamm CJ, Liljas B, Busse WW, et al. Country‐specific cost‐effectiveness of early intervention with budesonide in mild asthma. European Respiratory Journal 2004;24(4):568‐74.

Cakmak 2000 {published data only}

Cakmak G, Demir T, Aydemir A, Serdaroglu E, Erginoz E, Donma O, et al. The effect of adding zafirlukast to budesonide treatment on total antoxydant capacity. European Respiratory Journal 2000;16(Supplement 31):457s.

Cakmak 2004 {published data only}

Cakmak G, Demir T, Gemicioglu B, Aydemir A, Serdaroglu E, Donma O. The effects of add‐on zafirlukast treatment to budesonide on bronchial hyperresponsiveness and serum levels of eosinophilic cationic protein and total antioxidant capacity in asthmatic patients. Tohoku Journal of Experimental Medicine 2004;204(4):249‐56.

Calhoun 1997 {published data only}

Calhoun WJ, Weisberg SC, Faiferman I, Stober PW. Pranlukast (Ultair) is effective in improving asthma: results of a 12‐week, multicenter, dose‐range study. Journal of Allergy & Clinical Immunology 1997;99:S318, Abs 1305.

Calhoun 2001 {published data only}

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 & Critical Care Medicine 2001;164(5):759‐63.

Calhoun 2004 {published data only}

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 [Abstract]. Journal of Allergy and Clinical Immunology 2004;113(Suppl 2):S117.

Camargo 2002 {published data only}

Camargo CA, Smithline HA, Marie‐Pierre M, Green SA, Reiss TF. A randomized controlled trial of intravenous montelukast in acute asthma. American Journal of Respiratory and Critical Care Medicine. 2002.

Camargo 2003 {published data only}

Camargo CA, Smithline HA, Malice MP, Green SA, Reiss TF. A randomized controlled trial of intravenous montelukast in acute asthma. American Journal of Respiratory & Critical Care Medicine 2003;167(4):528‐33.

Canino 2008 {published data only}

Canino G, Vila D, Normand SLT, Acosta‐Perez E, Ramirez R, Garcia P, et al. Reducing asthma health disparities in poor Puerto Rican children: The effectiveness of a culturally tailored family intervention. Journal of Allergy and Clinical Immunology 2008;121(3):665‐70.

Capella 2001 {published data only}

Capella GL, Frigerio E, Altomare G. A randomized trial of leukotriene receptor antagonist montelukast in moderate‐to‐severe atopic dermatitis of adults. European Journal of Dermatology 2001;11(3):209‐13.

Ceylan 2004 {published data only}

Ceylan E, Mehmet G, Sahin A. Addition of formoterol or montelukast to low‐dose budesonide: An efficacy comparison in short‐ and long‐term asthma control. Respiration 2004;71(6):594‐601.

Chan 2003 {published data only}

Chan T, Klassen TP. In children with asthma who are currently using inhaled corticosteroids, are anti‐leukotrienes more effective than placebo in improving clinical outcomes? Part A. Paediatrics & Child Health 2003;8(9):570.

Chand 2005 {published data only}

Chand JG, Singh M, Mathew JL. Randomized controlled trial comparing montelukast plus low dose inhaled budesonide with conventional dose inhaled budesonide with conventional dose inhaled budesonide in childhood moderate persistent asthma [Abstract]. Indian Journal of Allergy Asthma and Immunology 2005;19(2):108.

Chanez 2010 {published data only}

Chanez P, Contin‐Bordes C, Garcia G, Verkindre C, Didier A, De Blay F, et al. Omalizumab‐induced decrease of FcRI expression in patients with severe allergic asthma. Respiratory Medicine 2010;104(11):1608‐17.

Chen 2006 {published data only}

Chen Y‐Z, Busse WW, Pedersen S, Tan W, Lamm C‐J, O'Byrne PM. Early intervention of recent onset mild persistent asthma in children aged under 11 yrs: The Steroid Treatment As Regular Therapy in early asthma (START) trial. Pediatric Allergy & Immunology 2006;17(Suppl 17):7‐13.

Chiba 1997 {published data only}

Chiba M, Xu X, Nishime JA, Balani SK, Lin JH. Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metabolism and Disposition 1997;25(9):1022‐31.

Choi 2003 {published data only}

Choi IS, Koh YI. Effects of BCG revaccination on asthma. Allergy 2003;58(11):1114‐6.

Chopra 2005 {published data only}

Chopra N, Williams M, Rimmer M, Kahl L, Jenkins M. Salmeterol HFA is as effective as salmeterol CFC in children and adults with persistent asthma. Respiratory Medicine 2005;99(Suppl 1):S1‐S10.

Chuchalin 2002 {published data only}

Chuchalin AG, Ovcharenko SI, Goriachkina LA, Sidorenko IV, Tsoi AN, Alekseev VG, et al. The safety and efficacy of formoterol OxisRTurbuhalerR plus budesonide PulmicortRTurbuhaler 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.

Chuchalin 2007 {published data only}

Chuchalin AG, Tsoi AN, Richter K, Krug N, Dahl R, Luursema PB, et al. Safety and tolerability of indacaterol in asthma: A randomized, placebo‐controlled 28‐day study. Respiratory Medicine 2007;101(10):2065‐75.

Chung 2000 {published data only}

Chung HL, Lee JJ, Kim SG. Effect of theophylline on urinary leukotriene B4 and C4 excretion in children with asthma. Korean Journal of Asthma, Allergy and Clinical Immunology 2000;20(5):710‐6.

Ciebiada 2009 {published data only}

Ciebiada M, Gorska‐Ciebiada M, Gorski P. Fexofenadine with either montelukast or a low‐dose inhaled corticosteroid (fluticasone) in the treatment of patients with persistent allergic rhinitis and newly diagnosed asthma. Archives of Medical Science 2009;5(4):564‐9.

Claesson 1998 {published data only}

Claesson HE, Dahlen SE. Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs. Journal of Internal Medicine 1999;245(3):205‐27.

Cloud 1989 {published data only}

Cloud ML, Enas GC, Kemp J, Platts‐Mills T, Altman LC, Townley R, et al. A specific LTD4‐LTE4‐receptor antagonist improves pulmonary function in patients with mild, chronic asthma. American Review of Respiratory Disease 1989;140:1336‐9.

Covar 2008 {published data only}

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. Journal of Allergy and Clinical Immunology 2008;122(4):741‐7.

Cowan 2010 {published data only}

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;15(4):683‐90.

Currie 2003 {published data only}

Currie GP, Lee DK, Dempsey OJ, Fowler SJ, Cowan LM, Lipworth BJ. A proof of concept study to evaluate putative benefits of montelukast in moderate persistent asthmatics. British Journal of Clinical Pharmacology 2003;55(6):609‐15.

Currie 2003a {published data only}

Currie GP, Lee DK, Haggart K, Bates CE, Lipworth BJ. Effects of montelukast on surrogate inflammatory markers in corticosteroid‐treated patients with asthma. American Journal of Respiratory & Critical Care Medicine 2003;167(9):1232‐8.

Currie 2003b {published data only}

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):S146.

Cylly 2003 {published data only}

Cylly A, Kara A, Ozdemir T, Ogus C, Gulkesen KH. Effects of oral montelukast on airway function in acute asthma. Respiratory Medicine 2003;97(5):533‐6.

Dahlén 2002 {published data only}

Dahlén SE, Malmstrom K, Nizankowska E, Dahlén B, Kuna P, Kowalski M, et al. Improvement of aspirin‐intolerant asthma by montelukast, a leukotriene antagonist. A randomised, double‐blind, placebo controlled trial. American Journal of Respiratory and Critical Care Medicine 2002;165(1):9‐14.

Daikh 2003 {published data only}

Daikh BE, Ryan CK, Schwartz RH. Montelukast reduces peripheral blood eosinophilia but not tissue eosinophilia or symptoms in a patient with eosinophilic gastroenteritis and esophageal stricture. Annals of Allergy, Asthma, & Immunology 2003;90(1):2327.

Davies 2004 {published data only}

Davies GM, Dasbach EJ, Santanello NC, Knorr BA, Bratton DL. The effect of montelukast versus usual care on health care resource utilization in children aged 2 to 5 years with asthma. Clinical Therapeutics 2004;26(11):1895‐1904.

Daviskas 2007 {published data only}

Daviskas E, Anderson SD, Young IH. Inhaled mannitol changes the sputum properties in asthmatics with mucus hypersecretion. Respirology 2007;12(5):683‐91.

Dekhuijzen 2006 {published data only}

Dekhuijzen PNR. Caution recommended in prescribing long‐acting beta2‐ adrenergic agonists to patients with asthma. Nederlands Tijdschrift voor Geneeskunde 2006;150(16):889‐91.

Delaronde 2005 {published data only}

Delaronde S, Peruccio DL, Bauer BJ. Improving asthma treatment in a managed care population. American Journal of Managed Care 2005;11(6):361‐8.

Dempsey 1999 {published data only}

Dempsey OJ, Wilson AM, Sims EJ, Lipworth BJ. A comparison of once daily topical budesonide (BUD) and oral montelukast (MON) in seasonal allergic rhinitis (SAR) and asthma. European Respiratory Society. 1999.

Dempsey 2000 {published data only}

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.

Dempsey 2000a {published data only}

Dempsey OJ, Wilson AM, Sims EJ, Lipworth BJ. Additive anti‐inflammatory effects of montelukast but not salmeterol in asthmatics suboptimally controlled on inhaled steroids [abstract]. American Journal of Respiratory and Critical Care Medicine 2000;161(3 Suppl):A198.

Dempsey 2002b {published data only}

Dempsey OJ, Fowler SJ, Wilson A, Kennedy G, Lipworth BJ. Effects of adding either a leukotriene receptor antagonist or low‐dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma. Chest 2002;122(1):151‐9.

Demuro‐Mercon 2001 {published data only}

Demuro‐Mercon C, . Turpin J, Santanello N, Firriolo K, Edelman J. Montelukast improves asthma quality of life when added to fluticasone. Journal of Allergy and Clinical Immunology 2001;107(2):S248.

Dessanges 1999 {published data only}

Dessanges JF, Prefaut C, Taytard A, Matran R, Naya I, Compagnon A, et al. The effect of zafirlukast on repetitive exercise‐induced bronchoconstriction: The possible role of leukotrienes in exercise‐induced refractoriness. Journal of Allergy & Clinical Immunology 1999;104(6):1155‐61.

Deykin 2007 {published data only}

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 & Critical Care Medicine 2007;175(3):228‐34.

Diamant 1997 {published data only}

Diamant Z, et al. Effect of oral montelukast on allergen‐induced airway responses in asthmatic subjects. American Journal of Respiratory & Critical Care Medicine1997.

Diamant 2009 {published data only}

Diamant Z, Ulrik CS. Effect of add‐on montelukast to inhaled corticosteroids on excessive airway narrowing in adult asthmatics [Abstract]. American Thoracic Society International Conference. 2009:A2416.

Dicpinigaitis 2002 {published data only}

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.

Djukanovic 2010 {published data only}

Djukanovic R, Wilson SJ, Moore WC, Koenig SM, Laviolette M, Bleecker ER, et al. Montelukast added to fluticasone propionate does not alter inflammation or outcomes. Respiratory Medicine 2010;104(10):1425‐35.

Dockhorn 2000 {published data only}

Dockhorn RJ, Baumgartner RA, Leff JA, Noonan M, Vandormael K, Stricker W, et al. Comparison of the effects of intravenous and oral montelukast on airway function: A double blind, placebo controlled, three period, crossover study in asthmatic patients. Thorax 2000;55(4):260‐5.

Dorinsky 2001 {published data only}

Dorinsky P, Kalberg C, Pepsin P, Emmett A, Bowers B, Rickard K. The fluticasone/salmeterol combination product is superior to montelukast as first‐line asthma control. European Respiratory Journal 2001;18(Suppl 33):263s.

Dorinsky 2002 {published data only}

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 [Abstract]. Journal of Allergy Asthma and Immunolgy 2002;109(Suppl 1):Abstract No: 767.

Dorinsky 2004 {published data only}

Dorinsky PM, Stauffer J, Waitkus‐Edwards K, Yancey S, Prillaman BA, Sutton L. "Stepping Down" from Fluticasone Propionate/Salmeerol 100/50mcg Diskus(R) Results in Loss of Asthma Control: Lack of Effect of Ethnic Origin [Abstract]. Chest 2004;126(Suppl 4):758S.

Edelman 2000 {published data only}

Edelman JM, Ghannam A, Bird S, Dobbins T. Onset of action of montelukast and inhaled beclomethasone in achieving asthma control [abstract]. American Journal of Respiratory and Critical Care Medicine 2000;161(Suppl 3):A202.

Eliraz 2001 {published data only}

Eliraz A, Raminez‐Rivera A, Ferranti P, et al. Similar efficacy following four weeks treatment of asthmatics with formoterol 12 mcg bid delivered by two different dry powder inhalers: differences in inhaler handling. International Journal of Clinical Practice 2001;55(3):164‐70.

El Miedany 2006 {published data only}

El Miedany Y, Youssef S, Ahmed I, El Gaafary M. Safety of etoricoxib, a specific cyclooxygenase‐2 inhibitor, in asthmatic patients with aspirin‐exacerbated respiratory disease. Annals of Allergy Asthma & Immunology 2006;97(1):105‐9.

Ensom 2003 {published data only}

Ensom MHH, Chong G, Beaudin B, Bai TR. Estradiol in severe asthma with premenstrual worsening. Annals of Pharmacotherapy 2003;37(11):1610‐3.

Fabbri 1996 {published data only}

Fabbri LM, Piattella M, Caramori G, Ciaccia A. Oral vs inhaled asthma therapy. Drugs 1996;52 Suppl(6):20‐8.

Fagerson 2003 {published data only}

Fagerspm GMH. Growth and adrenocortical function in children on high‐dose inhaled steroids versus low‐dose inhaled steroids plus montelukast. Tayside Research Consortium2003.

Failla 2006 {published data only}

Failla M, Biondi G, Provvidenza Pistorio M, Gili E, Mastruzzo C, Vancheri C, et al. Intranasal steroid reduces exhaled bronchial cysteinyl leukotrienes in allergic patients. Clinical & Experimental Allergy 2006;36(3):325‐30.

Fardon 2004 {published data only}

Fardon TC. Does Fluticasone/Salmeterol combination exhibit a putative in vivo anti‐inflammatory action during step‐down?. Tayside Research Consortium2004.

Fardon 2007 {published data only}

Fardon T, Haggart K, Lee DKC, Lipworth BJ. A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma. Respiratory Medicine 2007;101(6):1218‐28.

Faul 2002 {published data only}

Faul JL, Canfield JC, Gould MK, Wilson SR, Kischner WG. A randomized, double‐blind, placebo‐controlled, crossover study comparing the effects of inhaled fluticasone propionate (880 Micrograms per day) and montelukast (10 MG per day) on glucose control patients with diabetes and asthma. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A217.

Findlay 1992 {published data only}

Findlay SR, Barden JM, Easley CB, Glass M. Effect of the oral leukotriene antagonist, ICI 204,219, on antigen‐induced bronchoconstriction in subjects with asthma. Journal of Allergy & Clinical Immunology 1992;89:1040‐5.

Finkelstein 2005 {published data only}

Finkelstein JA, Lozano P, Fuhlbrigge AL, Carey VJ, Inui TS, Soumerai SB, et al. Practice‐level effects of interventions to improve asthma care in primary care settings: The Pediatric Asthma Care Patient Outcomes Research Team. Health Services Research 2005;40(61):1737‐57.

Finn 2000 {published data only}

Finn AF, Bonuccelli CM, Traxler BM, Beatty SE. Zafirlukast improves asthma control in children treated with and without inhaled corticosteroids. European Respiratory Journal 2000;16(Supp 31):307.

Fischer 1995 {published data only}

Fischer AR, McFadden CA, Frantz R, Awni WM, Cohn J, Drazen JM, et al. Effect of chronic 5‐lipoxygenase inhibition on airway hyperresponsiveness in asthmatic subjects. American Journal of Respiratory & Critical Care Medicine 1995;152(4 part 1):1203‐07.

Fischer 1997 {published data only}

Fischer AR, Rosenberg MA, Roth M, Loper M, Jungerwirth S, Israel E. Effect of a novel 5‐lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold air. Thorax 1997;52:1074‐7.

Fish 1997 {published data only}

Fish JE, Kemp JP, Lockey RF, Glass M, Hanby L, Bonuccelli CM. Zafirlukast for symptomatic mild‐to‐moderate asthma: a 13‐week multicenter study. Clinical Therapeutics 1997;19(4):675‐90.

Fish 2000 {published data only}

Fish J, Boone R, Emmett A, Yancey S, Knobil K, Rickard K. Salmeterol added to inhaled corticosteroids (ICS) provides greater asthma control compared to montelukast [abstract]. American Journal of Respiratory and Critical Care Medicine 2000;161(Suppl 2):A203.

Fish 2001 {published data only}

Fish JE, Israel E, Murray JJ, Emmett A, Boone R, Yancey SW, et al. Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy. Chest 2001;120(2):423‐30.

FitzGerald 2009 {published data only}

FitzGerald JM, Foucart S, Coyle S, Sampalis J, Haine D, Psaradellis E, et al. Montelukast as add‐on therapy to inhaled corticosteroids in the management of asthma (the SAS trial). Canadian Respiratory Journal 2009;16(Suppl A):5A‐14A.

Fogel 2010 {published data only}

Fogel RB, Rosario N, Aristizabal G, Loeys T, Noonan G, Gaile S, et al. Effect of montelukast or salmeterol added to inhaled fluticasone on exercise‐induced bronchoconstriction in children. Annals of Allergy, Asthma and Immunology 2010;104(6):511‐7.

Franzen 1994 {published data only}

Franzen L, Kumlin M, Dahlen SE. Pharmacologic modulation of leukotriene and histamine release in the human lung. Abbott Laboratories1994.

Fritsch 2006 {published data only}

Fritsch M, Uxa S, Horak Jr F, Putschoegl B, Dehlink E, Szepfalusi Z, et al. Exhaled nitric oxide in the management of childhood asthma: A prospective 6‐months study. Pediatric Pulmonology 2006;41(9):855‐62.

Fujimura 1993 {published data only}

Fujimura M, Sakamoto S, Kamio Y, Matsuda T. Effect of a leukotriene antagonist, ONO‐1078, on bronchial hyperresponsiveness in patients with asthma. Respiratory Medicine 1993;87:133‐8.

Gabrijelcic 2004 {published data only}

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.

Gaddy 1990 {published data only}

Gaddy J, Bush RK, Margolskee D, Williams VC, Busse W. The effects of a leukotriene D4 (LTD4) antagonist (MK‐571) in mild to moderate asthma. Journal of Allergy & Clinical Immunology 1990;85:197, Abs. 216.

Galbreath 2008 {published data only}

Galbreath AD, Smith B, Wood PR, Inscore S, Forkner E, Vazquez M, et al. Assessing the value of disease management: Impact of 2 disease management strategies in an underserved asthma population. Annals of Allergy Asthma and Immunology 2008;101(6):599‐607.

Geha 2001 {published data only}

Geha RS. Desloratadine: a new, nonsedating, oral antihistamine. Journal of Allergy & Clinical Immunology 2001;107(4):751‐62.

Gelb 2008 {published data only}

Gelb AF, Karpel J, Wise RA, Cassino C, Johnson P, Conoscenti CS. Bronchodilator efficacy of the fixed combination of ipratropium and albuterol compared to albuterol alone in moderate‐to‐severe persistent asthma. Pulmonary Pharmacology and Therapeutics 2008;21(4):630‐6.

Georgiou 1997 {published data only}

Georgiou P, Compton C, Allen A, Hust R, Collie H. Pranlukast (Ultair) has no effect on cardiovascular parameters in healthy male subjects. American Thoracic Society. 1997:Abs C49.

Ghiro 2001 {published data only}

Ghiro L, Zanconato S, Rampon O, Piovan V, Scollo M, Baraldi E. Effect of Montelukast added to inhaled steroids on exhaled NO in asthmatic children. European Respiratory Journal 2001;18(Suppl 33):40s.

Ghiro 2002 {published data only}

Ghiro L, Zanconato S, Rampon O, Piovan V, Pasquale MF, Baraldi E. Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children. European Respiratory Journal 2002;20(3):630‐4.

Gold 2001 {published data only}

Gold M, Jõgi R, Mulder PGH, Akveld MLM. Salmeterol/fluticasone propionate combination 50/100µg bid is more effective than fluticasone propionate 100µg bid plus montelukast 10 mg once daily in reducing exacerbations. European Respiratory Journal 2001;18(Supp 33):262s.

Gold 2001a {published data only}

Gold M, Jõgi R, Mulder PGH, Akveld MLM. Salmeterol/fluticasone propionate combination 50/100µg bid is more effective than fluticasone propionate 100µg bid plus montelukast 10 mg once daily in reducing exacerbations. European Respiratory Journal 2001;18(Supp 33):262s.

Green 2002 {published data only}

Green RH, Brightling S, Mckenna B, Hargadon B, Parker D, Wardlaw AJ, et al. A placebo controlled comparison of formoterol, montelukast or higher dose of inhaled corticosteroids in subjects with symptomatic asthma despite treatment with low dose inhaled corticosteroids. Thorax 2002;57(3):11.

Green 2002a {published data only}

Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P, et al. Asthma exacerbations and sputum eosinophil counts: A randomised controlled trial. Lancet 2002;360(9347):1715‐21.

Green 2006 {published data only}

Green RH, Brightling CE, McKenna S, Hargadon B, Neale N, Parker D, et al. Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness. European Respiratory Journal 2006;27(6):1144‐51.

Greenberger 2003 {published data only}

Greenberger PA. Therapy in the management of the rhinitis/asthma complex. Allergy & Asthma Proceedings 2003;24(6):403‐7.

Grosclaude 2003 {published data only}

Grosclaude M, Cerruti JL, Delannay B, Hérent M, Spilthooren F, Desfougčres JL. A fixed combination of fluticasone and salmeterol permits better control of asthma than a beclomethasone dipropionate and montelukast combination. Allergie et immunologie 2003;35(9):356‐62.

Grossman 1995 {published data only}

Grossman J, Bronsky E, Busse W, Montanaro A, Southern L, Tinkelman D, et al. A multicenter, double‐blind, placebo‐controlled study to evaluate the safety, tolerability and clinical activity of oral, twice‐daily LTA, Pranlukast (SB 205312) in patients with mild to moderate asthma. Journal of Allergy & Clinical Immunology 1995;95(1):352, Abs 846.

Grossman 1997 {published data only}

Grossman J, Faiferman I, Dubb JW, Tompson DJ, Busse W, Bronsky E, et al. Results of the first U.S. double‐blind, placebo‐controlled, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist. Journal of Asthma 1997;34(4):321‐8.

Grzelewska‐Rzymowska 2003 {published data only}

Grzelewska‐Rzymowska I, Malolepszy J, de 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):S10‐S19.

Grzelewski 2006 {published data only}

Grzelewski T, Jerzynska J, Stelmach I. Budesonide and montelukast once daily inhibits exercise induced bronchoconstriction in 6 to 18 year old children with asthma. Journal of Allergy and Clinical Immunology 2006;117((2 Suppl 1)):S93.

Guilbert 2004 {published data only}

Guilbert TW, Morgan WJ, Krawiec M, Lemanske Jr RF, Sorkness C, Szefler SJ, et al. The Prevention of Early Asthma in Kids study: Design, rationale and methods for the Childhood Asthma Research and Education network. Controlled Clinical Trials 2004;25(3):286‐310.

Gupta 1999 {published data only}

Gupta RC, Dixit R, Khilnani G, Gupta N, Joshi N, Saluja M. Comparative efficacy of budesonide and azelastine nasal spray in nasobronchial allergy. Indian Journal of Allergy and Applied Immunology 1999;13(1):11‐6.

Gupta 2007 {published data only}

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.

Gylfors 2005 {published data only}

Gylfors P, Dahlen SE, Larsson K, Kumlin M. Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate [Abstract]. European Respiratory Journal 2005;26(Suppl 49):3687.

Gyllfors 2003 {published data only}

Gyllfors P, Bochenek G, Overholt J, Drupka D, Kumlin M, Sheller J, et al. Biochemical and clinical evidence that aspirin‐intolerant asthmatic subjects tolerate the cyclooxygenase 2‐selective analgetic drug celecoxib. Journal of Allergy & Clinical Immunology 2003;111(5):1116‐21.

Gyllfors 2006 {published data only}

Gyllfors P, Dahlen SE, Kumlin M, Larsson K, Dahlen B. Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate. Journal of Allergy & Clinical Immunology 2006;118(1):78‐83.

Haahtela 1994 {published data only}

Haahtela T, Jarvinen M, Kava T, Kiviranta K, Koskinen S, Lehtonen K, et al. Effects of discontinuing inhaled budesonide in patients with mild asthma. New England Journal of Medicine 1994;331:700‐5.

Hakim 2007 {published data only}

Hakim F, Vilozni D, Adler A, Livnat G, Tal A, Bentur L. The effect of montelukast on bronchial hyperreactivity in preschool children. Chest 2007;131(1):180‐6.

Hamilton 1998 {published data only}

Hamilton AL, Faiferman I, Stober P, Watson RM, O'Byrne PM. Pranlukast, a cysteinyl leukotriene receptor antagonist, attenuates allergen‐induced early and late phase bronchoconstriction and airway hyperresponsiveness in asthmatic subjects. SmithKline Beecham Pharmaceuticals1998.

Harmanci 2006 {published data only}

Harmanci K, Bakirtas A, Turktas I, Degim T. Oral montelukast treatment of preschool‐aged children with acute asthma. Annals of Allergy Asthma & Immunology 2006;96(5):731‐5.

Hartwig 2004 {published data only}

Hartwig KC, DiNella JV, Chiappetta K, Clark MP, Ameredes BT, Calhoun WJ. Progressive improvement in airway hyperresponsiveness (AHR) over one year with fluticasone but not montelukast therapy in asthma: the OFTIRA trial [Abstract]. American Thoracic Society 100th International Conference 2004;A58:Poster K44.

Hassall 1998 {published data only}

Hassell SM, Miller C, Harris A. Zafirlukast (Accolate) reduces the need for oral steroid bursts. American Journal of Respiratory & Critical Care Medicine 1998;157(3):A411.

Havlucu 2005 {published data only}

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.

Hay 1997 {published data only}

Hay DWP. Pharmacology of leukotriene receptor antagonists: more than inhibitors of bronchoconstriction. Chest 1997;111(2):35S‐45S.

Hendeles 2004 {published data only}

Hendeles L, Erb TA, Bird S, Hustard CM, Edelman JM. Post‐exercise response to albuterol after addition of montelukast or salmeterol to inhaled fluticasone [Abstract]. Journal of Allergy and Clinical Immunology 2004;113(Suppl 2):S34.

Henderson 1994 {published data only}

Henderson WR. The role of leukotrienes in inflammation. Annals of Internal Medicine 1994;121(9):684‐97.

Hernandez 2002 {published data only}

Hernandez D, Namenyi M, Fiterman J, Price DB, Beeh KM, Fletcher CP, et al. Adding montelukast versus doubling the budesonide dose in persistent asthma: a subgroup analysis of the COMPACT study [abstract]. European Respiratory Society Annual Congress. 2002:P2406.

Hood 1999 {published data only}

Hood PP, Cotter TP, Costello JF, Sampson AP. Effect of intravenous corticosteroid on ex vivo leukotriene generation by blood leucocytes of normal and asthmatic patients. Thorax 1999;54(12):1075‐82.

Hothersall 2008 {published data only}

Hothersall EJ, Chaudhuri R, McSharry C, Donnelly I, Lafferty J, McMahon AD, et al. Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma. Thorax 2008;63(12):1070‐5.

Houghton 2004 {published data only}

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.

Howland 1994 {published data only}

Howland III W, Segal A, Glass M, Minkwitz MC. 6‐week therapy with the oral leukotriene‐receptor antagonist, ICI 204,219, in the treatment of asthma. Journal of Allergy & Clinical Immunology 1994;93(1 Part 2):259, Abs. 581.

Hozawa 2009 {published data only}

Hozawa S, Haruta Y, Terada M, Yamakido M. Effects of the addition of beta2‐agonist tulobuterol patches to inhaled corticosteroid in patients with asthma. Allergology International 2009;58(4):509‐18.

Hsieh 1996 {published data only}

Hsieh, K‐H. Evaluation of efficacy of traditional chinese medicines in the treatment of childhood bronchial asthma: clinical trial, immunological tests and animal study. Pediatric Allergy & Immunology 1996;7:130‐40.

Huang 2003 {published data only}

Huang CJ, Wang CH, Liu WT, Yang MC, Lin HC, Yu CT, et al. Zafirlukast Improves Pulmonary Function in Patients with Moderate Persistent Asthma Receiving Regular Inhaled Steroids: A Prospective Randomized Control Study. Chang Gung Medical Journal 2003;26(8):554‐60.

Huang 2003a {published data only}

Huang CJ, Wang CH, Lin HC, Yu CT, Shiao JR, Tan CG, et al. Zafirlukast improves pulmonary function in patients with moderate persistent asthma receiving regular inhaled steroids: a randomized control study [abstract]. American Thoracic Society 99th International Conference 2003;B036:Poster H80.

Hui K 1991 {published data only}

Hui K, Barnes NC. Lung function improvement in asthma with a cysteinyl‐leukotriene receptor antagonist. Lancet 1991;337:1062‐3.

Igde 2009 {published data only}

Igde M, Anlar FY. The efficacy of montelukast monotherapy in moderate persistent asthmatic children. Iranian Journal of Allergy Asthma & Immunology 2009;8(3):169‐70.

Ikeda 1997 {published data only}

Ikeda K, Hyashi M, Obata H, Fujita H, Nakanishi T, Izumi T. Two weeks' observation of pranlukast (ONO‐1078), leukotriene receptor antagonist) by peak expiratory flow rate (PEFR) was enough to evaluate clinical efficacies in severe chronic adult asthmatics. American Thoracic Society. 1997:Abs C49.

Ilowite 2004 {published data only}

Ilowite J, Webb R, Friedman B, Kerwin E, Bird SR, Hustad CM, et al. Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double‐blind, multicenter study. Annals of Allergy Asthma & Immunology 2004;92(6):641‐8.

Inoue 2007 {published data only}

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.

Irvin 2003 {published data only}

Irvin C, Anthonisen N, Castro M, Holbrook J, Kaminsky DA, Lima J, et al. Effectiveness of Low‐Dose Theophylline as Add‐on Therapy in the Treatment of Asthma: The LODO Trial [Abstract]. Chest 2003;124(4):3355.

Irvin 2007 {published data only}

Irvin CG, Kaminsky DA, Anthonisen NR, Castro M, Hanania NA, Holbrook JT, et al. Clinical trial of low‐dose theophylline and montelukast in patients with poorly controlled asthma. American Journal of Respiratory & Critical Care Medicine 2007;175(3):235‐42.

Israel 1990 {published data only}

Israel E, Dermarkarkian R, Rosenberg M, Sperling R, Taylor G, Rubin P, et al. The effects of a 5‐lipoxygenase inhibitor on asthma induced by cold, dry air. New England Journal of Medicine 1990;323:1740‐4.

Israel 1992 {published data only}

Israel E, Drazen J, Pearlman H, Cohn J, Rubin P. A double‐blind multicenter study of zileuton, a potent 5‐lipoxygenase (5‐LO) inhibitor versus placebo in the treatment of spontaneous asthma in adults. Journal of Allergy & Clinical Immunology 1992;89:236, Abs. 368.

Israel 1993 {published data only}

Israel E, Rubin P, Kemp JP, Grossman J, Pierson W, Siegel SC, et al. The effect of inhibition of 5‐lipoxygenase by zileuton in mild‐to‐moderate asthma. Annals of Internal Medicine 1993;119(11):1059‐66.

Israel 1996 {published data only}

Israel E, Cohn J, Dube L, Drazen JM. Effect of treatment with zileuton, a 5‐lipoxygenase inhibitor, in patients with asthma. JAMA 1996;275(12):931‐6.

Jat 2006 {published data only}

Jat GC, Mathew JL, Singh M. Treatment with 400 mug of inhaled budesonide vs 200 mug of inhaled budesonide and oral montelukast in children with moderate persistent asthma: Randomized controlled trial. Annals of Allergy Asthma & Immunology 2006;97(3):397‐401.

Jayaram 2002a {published data only}

Jayaram L, Pizzichini M, Hussack P, Efthmiadis A, Goodwin S, Chaboillez S, et al. First line anti inflammatory treatment for asthma: inhaled steroid or leukotriene antagonist  [Abstract]. Journal of Allergy Asthma and Immunolgy  2002;109(Suppl 1):Abstract No: 746.

Jayaram 2005a {published data only}

Jayaram L, Duong M, Pizzichini MM, Pizzichini E, Kamada D, Efthimiadis A, et al. Failure of montelukast to reduce sputum eosinophilia in high‐dose corticosteroid‐dependent asthma. European Respiratory Journal 2005;25(1):41‐6.

Jayaram 2006 {published data only}

Jayaram L, Pizzichini MM, Cook RJ, Boulet LP, Lemiere C, Pizzichini E, et al. Determining asthma treatment by monitoring sputum cell counts: Effect on exacerbations. European Respiratory Journal 2006;27(3):483‐94.

Johnson 1999 {unpublished data only}

Johnson MC, Srebro S, Edwards L, Bowers B, Rickard K. Physician‐ and patient‐rated assessments correlate well with clinical efficacy measurements in a study comparing fluticasone and zafirlukast. Journal of Allergy & Clinical Immunology. 1999; Vol. 103, issue 1 Part 2:Abs. 882.

Johnston 2007 {published data only}

Johnston NW, Mandhane PJ, Dai J, Duncan JM, Greene JM, Lambert K, et al. Attenuation of the September epidemic of asthma exacerbations in children: A randomized, controlled trial of montelukast added to usual therapy. Pediatrics 2007;120(3):e702‐e712.

Jones 2002 {published data only}

Jones C, Allen FC, Duong PT, Sajjan S, Nelsen L, Itzler R, et al. Similar health care outcomes for patients treated with fluticasone propionate (FP) and montelukast sodium (MON) monotherapy   [Abstract]. Journal of Allergy Asthma and Immunolgy 2002;109(Suppl 1):Abstract No: 890.

Jonsson 2004 {published data only}

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.

Juniper 1995 {published data only}

Juniper EF, Dube L, Swanson LJ, Zileuton Study Group. The effect of zileuton, a 5‐lipoxygenase inhibitor, on asthma quality of life. Asthma. 1995.

Kalberg 1999 {published data only}

Kalberg CJ, Yancey S, Emmett AH, Rickard K. A comparison of salmeterol versus zafirlukast in patients using inhaled corticosteroids. Journal of Allergy & Clinical Immunology1999; Vol. 103, issue 1 part 2:abs 881.

Kanazawa 2004 {published data only}

Kanazawa H, Yoshikawa T, Hirata K, Yoshikawa J. Effects of pranlukast administration on vascular endothelial growth factor levels in asthmatic patients. Chest 2004;125(5):1700‐05.

Kane 1994 {published data only}

Kane G, Pollice M, Tolino M, Cohn J, Dworski R, Murray J, et al. Effect of zileuton on eosinophil influx and leukotrienes in humans undergoing segmental antigen challenge. Abbott Laboratories1994.

Kanniess 2002a {published and unpublished data}

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.

Karaman 2007 {published data only}

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 & Asthma Proceedings 2007;28(2):204‐9.

Karpel 2007 {published data only}

Karpel JP, Nayak A, Lumry W, Craig TJ, Kerwin E, Fish JE, et al. Inhaled mometasone furoate reduces oral prednisone usage and improves lung function in severe persistent asthma. Respiratory Medicine 2007;101(3):628‐37.

Katial 2010 {published data only}

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;31(1):68‐75.

Keith 2009 {published data only}

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):17A‐31A.

Kemp 1995 {published data only}

Kemp JP, Glass M, Minkwitz MC. Onset of action of the leukotriene‐receptor antagonist, zafirlukast (Accolate), in patients with asthma. Journal of Allergy & Clinical Immunology 1995;95(1 Part 2):351, Abs. 844.

Kemp 1996 {published data only}

Kemp JP. Zafirlukast, a selective leukotriene D4‐receptor antagonist: a new class of therapy for patients with asthma. Today's Therapeutic Trends 1996;14(2):89‐102.

Kemp 1998 {published data only}

Kemp JP, Tinkelman D, Sublett J, Compton C, Georgiou P. Pranlukast (Ultair) pharmacokinetics in children consistent with that of adults. American Journal of Respiratory & Critical Care Medicine 1998;157(3):A411.

Kemp 1998a {published data only}

Kemp JP, Dockhorn RJ, Shapiro GG, Nguyen HH, Reiss TF, Seidenberg BC, et al. Montelukast once daily inhibits exercise induced bronchoconstriction in 6‐14 year old children with asthma. The Journal of Pediatrics 1998;133(3):424‐28.

Kemp 1999 {published data only}

Kemp JP, Minkwitz MC, Bonuccelli CM, Warren MS. Therapeutic effect of zafirlukast as monotherapy in steroid‐naive patients with severe persistent asthma. Chest 1999;115(2):336‐42.

Ketchell 2002 {published data only}

Ketchell RI, D'Amato M, Jensen MW, O'Connor BJ. Contrasting effects of allergen challenge on airway responsiveness to cysteinyl leukotriene D(4) and methocholine in mild asthma. Thorax 2002;57(7):575‐80.

Khayyal 2003 {published data only}

Khayyal MT, el‐Ghazaly MA, el‐Khatib AS, Hatem AM, de Vries PJ, el‐Shafei S, et al. A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patients. Fundamental & Clinical Pharmacology 2003;17(1):93‐102.

Kippelen 2010 {published data only}

Kippelen P, Larsson J, Anderson SD, Brannan JD, Delin I, Dahlen B, et al. Acute effects of beclomethasone on hyperpnea‐induced bronchoconstriction. Medicine & Science in Sports & Exercise 2010;42(2):273‐80.

Kips 1991 {published data only}

Kips JC, Joos GF, de Lepeleire I, Margolskee DJ, Buntinx A, Pauwels RA, et al. MK‐571, a potent antagonist of leukotriene D4‐induced bronchoconstriction in the human. American Review of Respiratory Disease 1991;144:617‐21.

Knorr 1998 {published data only}

Knorr B, Matz J, Bernstein JA, Nguyen H, Seidenberg BC, Reiss TF, et al. Montelukast for chronic asthma in 6‐ to 14‐year‐old children. JAMA 1998;279(15):1181‐6.

Knorr 1999 {published data only}

Knorr B, Nguycn HH, Seidenberg BC, Reiss TF, Montelukast Pediatric Study Group. Montelukast, a leukotriene receptor antagonist, provides additional clinical benefit in asthmatic children aged 6 to 14 years using inhaled corticosteroids. European Respiratory Society. 1999:P363.

Koenig 2004 {published data only}

Koenig 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]. Journal of Allergy and Clinical Immunology 2004;113(Suppl 2):S94.

Kohrogi 1997 {published data only}

Kohrogi H, Iwagoe H, Fujii K, Fukuda K, Kawano O, Hamamoto J, et al. The effect of leukotriene antagonist pranlukast on moderate and severe persistent asthma continues more than one year. American Journal of Respiratory & Critical Care Medicine 1997;155:A662.

Kondo 2006 {published data only}

Kondo N, Katsunuma T, Odajima Y, Morikawa A. A randomized open‐label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children. Allergology International 2006;55(3):287‐93.

Kooi 2006 {published data only}

Kooi EMW, Schokker S, Boezen HM, de Vries TW, Vanssen‐Verberne AAP, van der Molen T, et al. Effect of fluticasone and montelukast in preschool children with asthma like symptoms [Abstract]. European Respiratory Journal 2006;28(Suppl 50):709s [P4079].

Korenblat 1998 {published data only}

Korenblat P, Chervinsky P, Wenzel S, Faiferman I, Bakst A. Pranlukast (Ultair) reduces health care utilization and improves quality of life in adult patients with mild‐to‐moderate asthma. American Journal of Respiratory & Critical Care Medicine. 1998; Vol. 157, issue 3:A411.

Kuna 1997 {published data only}

Kuna P, Malmstrom K, Dahlen SE, Nizankowska E, Kowalski M, Stevenson D, et al. Montelukast (MK‐0476), a cys‐LT1 receptor antagonist, improves asthma control in aspirin‐intolerant asthmatic patients. American Journal of Respiratory & Critical Care Medicine 1997;155(4):A975.

Kylstra 1998 {published data only}

Kylstra JW, Sweitzer DE, Miller CJ, Bonuccelli CM. Zafirlukast (Accolate) in moderate asthma: patient‐reported outcomes and peripheral eosinophil data from a 13‐week trial. American Journal of Respiratory & Critical Care Medicine 1998;157(3):A410.

Laitinen 1995 {published data only}

Laitinen LA, Zetterstrom O, Holgate ST, Binks SM, Whitney JG. Effects of Accolate (Zafirlukast; 20 mg bd) in permitting reduced therapy with inhaled steroids: a multicenter trial in patients with doses of inhaled steroid optimised between 800 and 2000 mcg per day. Allergy 1995;50 Suppl(26):320, Abs. P‐0710.

Leaker 2010 {published data only}

Leaker BR, Singh D, Barnes PJ, Imrie M, Hughes R, O'Connor B. The Effect Of The Novel Phosphodiesterase‐4 Inhibitor MEM 1414 On The Allergen‐induced Responses In mild Asthma [Abstract]. American Journal of Respiratory and Critical Care Medicine 2010;181:A5613.

Lee 2004 {published data only}

Lee DKC, Jackson CM, Haggart K, Lipworth BJ. Repeated dosing effects of mediator antagonists in inhaled corticosteroid‐treated atopic asthmatic patients. Chest 2004;125(4):1372‐7.

Lee 2004a {published data only}

Lee DK, Haggart K, Currie GP, Bates CE, Lipworth BJ. Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs 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.

Lee 2004b {published data only}

Lee DKC, Haggart K, Robb FM, Lipworth BJ. Montelukast protects against nasal lysine‐aspirin challenge in patients with aspirin‐induced asthma. European Respiratory Journal 2004;24(2):226‐30.

Lee 2004c {published data only}

Lee DKC, Lipworth BJ. Anti‐inflammatory effects of histamine H1‐receptor antagonist and leukotriene CysLT1‐receptor antagonist in patients with atopic asthma maintained on inhaled corticosteroids [Abstract]. European Respiratory Journal 2004;24(Suppl 48):221s.

Lee 2005 {published data only}

Lee DK, Fardon TC, Bates CE, Haggart K, McFarlane LC, Lipworth BJ. Airway and systemic effects of hydrofluoroalkane formulations of high‐dose ciclesonide and fluticasone in moderate persistent asthma. Chest 2005;127(3):851‐60.

Lee 2010 {published data only}

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;105(2):130‐5.

Leff 1998 {unpublished data only}

Leff JA, Busse WW, Pearlman D, Bronsky EA, Kemp J, Hendeles L, et al. Montelukast, a leukotriene‐receptor antagonist, for the treatment of mild asthma and exercise‐induced bronchoconstriction. New England Journal of Medicine 1998;339:147‐52.

Leibman 2002 {published data only}

Leibman C, Pathak D, Bowers B, Dorinsky PM, Pepsin P, Kalberg C, et al. Cost effectiveness analysis of fluticasone propionate/salmeterol combination versus montelukast in the treatment of adults with asthma [Abstract]. Journal of Allergy Asthma and Immunoly 2002;109(Suppl 1):Abstract No: 549.

Leibman 2002a {published data only}

Leibman CW, Stanford R, Emmett A, Dorinsky PM, Rickard KA. Cost‐effectiveness of fluticasone propionate‐salmeterol combination versus fluticasone + montelukast in the treatment of persistent asthma. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):B4.

Leigh 2002 {published data only}

Leigh R, Vethanayagam D, Yoshida M, Watson RM, Rerecich T, Inman MD, et al. Effects of montelukast and budesonide on airway responses and airway inflammation in asthma. American Journal of Respiratory and Critical Care Medicine 2002;166(9):1212‐7.

Leigh 2002a {published data only}

Leigh R, Vethanayagam D, Yoshida M, Watson RM, Rererich T, Killian K, et al. Effects of montelukast and budesonide alone or in combination on allergen induced early and late asthmatic responses, and post‐allergen airway hyperresponsiveness [abstract]. American Journal of Respiratory and Critical Care Medicine 2002;165(8 Suppl):A216.

Lemanske 2010 {published data only}

Lemanske RF, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, et al. Step‐up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. New England Journal of Medicine 2010;362(11):975‐85.

Li 2001 {published data only}

Li J, Zhang DH, Yang JY. Evaluation of the therapeutic effects of zafirlukast in asthma patients during reduction of high‐doses inhaled corticosteroid. Journal of Clinical Lung Section 2001;6(4):9‐11.

Liebke 2001 {published data only}

Liebke C, Sommerfeld C, Wahn U, Niggemann B. [Preventive monotherapy with montelukast versus DNCG in children with mild asthma ‐ Results of an explorative pilot study]. Article in German. Pneumologie 2001;55(5):231‐7.

Lindemann 2009 {published data only}

Lindemann J, Pampe ED, Peterkin JJ, Orozco‐Cronin P, Belofsky G, Stull D. Clinical study of the effects on asthma‐related QOL and asthma management of a medical food in adult asthma patients. Current Medical Research and Opinion 2009;25(12):2865‐75.

Lipworth 1999 {published data only}

Lipworth BJ. Comparative potency and anti‐inflammatory profile of monotherapy with either montelukast or zafirlukast, patients with mild‐moderate asthma. Academic Publications (Ongoing trial)1999.

Lis 2001 {published data only}

Lis G, Cichocka Jarosz E, Glodzik I, Szczerbinski T, Bialoruska B. Montelukast in treatment mild chronic asthma. Pol Pneumonologia i Alergologia Polska 2001;69(5‐6):257‐64.

Liu 1996 {published data only}

Liu MC, Dube LM, Lancaster J, Zileuton Study Group. Acute and chronic effects of a 5‐lipoxygenase inhibitor in asthma: a 6‐month randomized multicenter trial. Journal of Allergy & Clinical Immunology 1996;98:859‐71.

Lizaso 2003 {published data only}

Lizaso Bacaicoa M, Garcia B, Gomez B, Zabalegui A, Rodriguez M, Tabar A. Treatment of allergy to mushrooms. Anales Del Sistema Sanitario De Navarra 2003;26(Suppl 2):129‐37.

Lockey 1995 {published data only}

Lockey RF, Lavins BJ, Snader L. Effects of 13 weeks of treatment with ICI 204,219 (Accolate) in patients with mild to moderate asthma. Journal of Allergy & Clinical Immunology 1995;95(Part 2):350, Abs. 839.

Lofdahl 1999 {published data only}

Lofdahl CG, Reiss TF, Leff JA, Israel E, Noonan MJ, Finn AF, et al. Randomized, placebo controlled trial of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ 1999;318(7202):87‐90.

Luppo 2005 {published data only}

Luppo A, Haag J, Maschio L, Alzua E, Nine LF, Lazaroni A. Evaluation of the variation of the PC 20 in patients treated with zafirlukast. Prensa Medica Argentina 2005;92(8):548‐9.

Lyseng‐Williamson 2003 {published data only}

Lyseng‐Williamson KA. Plosker GL. Inhaled salmeterol/fluticasone propionate combination: A pharmacoeconomic review of its use in the management of asthma. Pharmacoeconomics 2003;21(13):951‐89.

Macfarlane 2000 {published data only}

Macfarlane AJ, Ying S, Smith SJ, Mannings P, Ryan M, Pavord I, et al. Inhibition of allergen‐induced late phase reactions by zafirlukast and beclomethasone may be mediated by attenuation of eotaxin‐ and rantes‐ mediated eosinophil recruitment. American Journal of Respiratory and Critical Care Medicine 2000;161(Suppl 3):A834.

Magnussen 2008 {published data only}

Magnussen H, Bugnas B, van Noord J, Schmidt P, Gerken F, Kesten S. Improvements with tiotropium in COPD patients with concomitant asthma. Respiratory Medicine 2008;102(1):50‐6.

Majak 2010 {published data only}

Majak P, Rychlik B, Pulaski L, Blauz A, Agnieszka B, Bobrowska‐Korzeniowska M, et al. Montelukast treatment may alter the early efficacy of immunotherapy in children with asthma. Journal of Allergy and Clinical Immunology 2010;125(6):1220‐7.

Malerba 2002 {published data only}

Malerba M, Radaeli A, Ceriani L, Amato M, Tomenzoli D, Nicolai P, et al. Comparison of oral montelukast and inhaled fluticasone in the treatment of asthma associated with chronic rhinopolyposis: A single‐blind, randomized, pilot study. Current Therapeutic Research, Clinical & Experimental 2002;63(6):355‐65.

Marchese 1998 {published data only}

Marchese A, McHugh C, Kehler J, Bi H. Determination of pranlukast and its metabolites in human plasma by LC/MS/MS with PROSPEKT on‐line solid‐phase extraction. SmithKline Beecham Pharmaceuticals1998.

Margolskee 1991 {published data only}

Margolskee D, Bodman S, Dockhorn R, Irael E, Kemp J, Mansmann H, et al. The therapeutic effects of MK‐571, a potent and selective leukotriene (LT) D4 receptor antagonist, in patients with chronic asthma. Journal of Allergy & Clinical Immunology 1991;87(1 Part 2):309, Abs. 677.

Marogna 2010 {published data only}

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 & Clinical Immunology 2010;20(2):146‐52.

Maspero 2008 {published data only}

Maspero J, Guerra F, Orozco S, Soto M, Gutierrez‐Schwanhauser J, Mechali DG, et al. The efficacy of inhaled salmeterol/fluticasone propionate diskus/accuhaler compared with oral montelukast in children with persistent asthma PEACE (PEdiatric Asthma Control Evaluation ) [Abstract]. American Thoracic Society International Conference. 2008:A709.

Maspero 2008a {published data only}

Maspero J, Soto‐Ramos M, Guerra F, Chan R, Sharma R, Pedersen S. Improved asthma control and fewer exacerbations with inhaled salmeterol/fluticasone propionate compared with oral montelukast in children with persistent asthma: PEACE (Pediatric Asthma Control Evaluation) [Abstract]. Chest 2008;134(4):51001s.

Maspero 2008b {published data only}

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.

Mastruzzo 2010 {published data only}

Mastruzzo C, Contrafatto MR, Crimi C, Palermo F, Vancheri C, Crimi N. Acute additive effect of montelukast and beclomethasone on AMP induced bronchoconstriction. Respiratory Medicine 2010;104(10):1417‐24.

Matsunaga 2004 {published data only}

Matsunaga K, Nishimoto T, Hirano T, Nakanishi M, Yamagata T, Minakata Y, et al. Effect of a leukotriene receptor antagonist on the prevention of recurrent asthma attacks after an emergency room visit. Allergology International 2004;53(4):341‐7.

McCarthy 2003 {published data only}

McCarthy TP, Woodcock AA, Pavord ID, Allen DJ, Parker D, Rice L. A comparison of the anti‐inflammatory and clinical effects of salmeterol 25mcg/fluticasone propionate 50mcg combination (SFC 50) with fluticasone propionate (FP) plus montelukast (M) in patients with mild to moderate asthma [abstract]. American Thoracic Society 99th International Conference 2003;B036:H89.

McGill 1996 {published data only}

McGill K, Busse WW. Zileuton. Lancet 1996;348:519‐24.

Mclvor 2009 {published data only}

McIvor RA, Kaplan A, Koch C, Sampalis JS. Montelukast as an alternative to low‐dose inhaled corticosteroids in the management of mild asthma (the SIMPLE trial): an open‐label effectiveness trial. Canadian Respiratory Journal 2009;16(Suppl A):11A‐21A.

Mehuys 2008 {published data only}

Mehuys E, Van Bortel L, De Bolle L, Van Tongelen I, Remon JP, Annemans L, et al. Does pharmacist intervention lead to appropriate use of asthma medication and improved asthma control?. Farmaceutisch Tijdschrift Voor Belgie 2008;85(1):1‐9.

Mendes 2004 {published data only}

Mendes ES, Campos MA, Hurtado A, Wanner A. Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma. American Journal of Respiratory & Critical Care Medicine 2004;169(10):1131‐4.

Mendes 2004a {published data only}

Mendes ES, Campos MA, Hurtado A, Wanner A. Anti‐inflammatory actions of montelukast and fluticasone propionate as assessed by airway blood flow [Abstract]. American Thoracic Society 100th International Conference 2004;D31:Poster C6.

Menendez 2001 {published data only}

Menendez R, Standford RH, Edwards L, Kalberg C, Rickard K. Cost‐efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma. Pharmacoeconomics 2001;19(8):865‐74.

Meyer 2003 {published data only}

Meyer KA, Arduino JM, Santanello NC, Knorr BA, Bisgaard H. Response to montelukast among subgroups of children aged 2 to 14 years with asthma. Journal of Allergy & Clinical Immunology 2003;111(4):757‐62.

Micheletto 1997 {published data only}

Micheletto C, Turco P, Dal Negro R. Accolate 20 mg works as steroid sparing in moderate asthma. American Journal of Respiratory & Critical Care Medicine 1997;155(4):A664.

Miraglia 2007 {published data only}

Miraglia del Giudice M, Piacentini GL, Capasso M, Capristo C, Maiello N, Boner AL, et al. Formoterol, montelukast, and budesonide in asthmatic children: Effect on lung function and exhaled nitric oxide. Respiratory Medicine 2007;101(8):1809‐13.

Mitchell 2005 {published data only}

Mitchell EA, Didsbury PB, Kruithof N, Robinson E, Milmine M, Barry M, et al. A randomized controlled trial of an asthma clinical pathway for children in general practice. Acta Paediatrica 2005;94(2):226‐33.

Miyamoto 1999 {published data only}

Miyamoto T, Accolate™ clinical trial committee. Effects of zafirlukast on symptoms and pulmonary function of asthmatic patients with and without corticosteroids. European Respiratory Society. 1999:P835.

Molitor 2005 {published data only}

Molitor S, Liefring E, Traytmann M. Asthma control with the salmeterol‐fluticasone‐combination disc compared to standard treatment. Pneumologie 2005;59(3):167‐73.

Montani 2007 {published data only}

Montani D. Randomized comparison of strategies for reducing treatment in mild persistent asthma. Revue De Pneumologie Clinique 2007;63(6):390.

Moreira 2008 {published data only}

Moreira A, Delgado L, Haahtela T, Fonseca J, Moreira P, Lopes C, et al. Physical training does not increase allergic inflammation in asthmatic children. European Respiratory Journal 2008;32(6):1570‐5.

Morris 2010 {published data only}

Morris CR, Becker AB, Pineiro A, Massaad R, Green SA, Smugar SS, et al. A randomized, placebo‐controlled study of intravenous montelukast in children with acute asthma. Annals of Allergy, Asthma and Immunology 2010;104(2):161‐71.

Mosnaim 2002 {published data only}

Mosnaim GS. The role of montelukast in the prevention of acute episodes of asthma in children ages 2 to 14 years [Dissertation]. Rush University2002:75.

Mosnaim 2008 {published data only}

Mosnaim GS, Cohen MS, Rhoads CH, Rittner SS, Powell LH. Use of MP3 players to increase asthma knowledge in inner‐city African‐American adolescents. International Journal of Behavioral Medicine 2008;15(4):341‐6.

Murphy 2006 {published data only}

Murphy K, Ververeli K, Harvey BM, Duke AL, Chapas‐Crilly J, Uryniak T, et al. Antibody response after varicella vaccination in children treated with budesonide inhalation suspension or non‐steroidal conventional asthma therapy. International Journal of Clinical Practice 2006;60(12):1548‐57.

Najberg 2008 {published data only}

Najberg E, Smorczewska‐Kiljan A, Ksiayk J, Kaczmarewicz E, Pludowski P, Jaworski M, et al. Effect of one year treatment with inhaled budesonide on bone density and mineralization in children with bronchial asthma. Alergia Astma Immunologia 2008;13(4):217‐26.

Nakagawa 1992 {published data only}

Nakagawa N, Obata T, Kobayashi T, Okada Y, Nambu F, Terawaki T, et al. In vivo pharmacologic profile of ONO‐1078: a potent, selective and orally active peptide leukotriene (LT) antagonist. Japanese Journal of Pharmacology 1992;60(3):217‐25.

Nakajima 2001 {published data only}

Nakajima S, Tohda Y, Fujimura M, Taniguchi H, Takagi K, Igarashi T, et al. Effects of montelukast on tapering inhaled corticosteroids in patients with asthma. European Respiratory Journal 2001;18(Suppl 33):260s.

Nakazono 2004 {published data only}

Nakazono H, Mukoyama T, Shinomiya N. The effects of the leukotriene receptor antagonist, pranlukast, on long‐term treatment in children with persistent asthma. Journal of the Medical Society of Toho University 2004;51(6):339‐46.

Nathan 1998 {published data only}

Nathan RA, Bernstein JA, Bielory L, Bonuccelli CM, Calhoun WJ, Galant SP, et al. Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction. Journal of Allergy & Clinical Immunology 1998;102:935‐42.

Nathan 2000 {published data only}

Nathan BA, Boone RI, Emmett AH, Knobil K, Yancey SW, Rickard KA. Salmeterol and inhaled corticosteroids provide greater asthma control than montelukast and inhaled corticosteroids [Abstract]. Chest 2000;118(Suppl 4):85S.

Nathan 2004 {published data only}

Nathan RA, Philpot E, Faris M, Prillaman B, Yancey S, Dorinsky P. In patients taking fluticasone propionate/salmeterol 100/50µg Diskus(r) for asthma, the addition of fluticasone propionate nasal spray 200µg QD to treat concomitant allergic rhinitis has a safety profile comparable to the addition of montelukast 10mg QD or placebo [Abstract]. Journal of Allergy and Clinical Immunology 2004;113(Suppl 2):S202.

Nathan 2005 {published data only}

Nathan RA, Yancey SW, Waitkus‐Edwards K, Prillaman BA, Stauffer JL, Philpot E, et al. Fluticasone propionate nasal spray is superior to montelukast for allergic rhinitis while neither affects overall asthma control. Chest 2005;128(4):1910‐20.

Nayak 1998 {published data only}

Nayak AS, Anderson P, Charous BL, Williams K, Simonson S. Equivalence of adding Zafirlukast versus double‐dose inhaled corticosteroids in asthmatic patients symptomatic on low‐dose inhaled corticosteroids. Journal of Allergy & Clinical Immunology 1998;101(1 pt 2):S233, Abs. 965.

NCT00096954 {unpublished data only}

A Study to Evaluate the Efficacy of Xolair in Atopic Asthmatics (EXACT). ClinicalTrials.Gov2004.

NCT00140881 {unpublished data only}

A Study to Determine the Effect of Montelukast Sodium as an Episode Modifier in the Treatment of Infrequent Episodic Asthma in Children. ClinicalTrials.Gov.

NCT00196547 {unpublished data only}

Montelukast in Modulating Exacerbations of Asthma in Children. ClinicalTrials.Gov2005.

NCT00213252 {unpublished data only}

Use of Montelukast to Treat Children With Mild to Moderate Acute Asthma. ClinicalTrials.Gov2005.

NCT00299065 {unpublished data only}

Safety Study of Zileuton Injection in Patients With Asthma. ClinicalTrials.Gov2006.

NCT00319488 {unpublished data only}

Childhood Asthma Research and Education (CARE) Network Trial ‐ Acute Intervention Management Strategies (AIMS). ClinicalTrial.Gov2006.

NCT00395408 {unpublished data only}

Linear Growth Study. ClinicalTrials.Gov2006.

NCT00421018 {unpublished data only}

Optimization of Asthma Treatment Through Exhaled NO for Increased Asthma‐Related Quality of Life (NOAK). ClinicalTrials.gov2007.

NCT00462592 {unpublished data only}

Comparison of Combination Therapy: Montelukast and Inhaled Steroid on Exercise Induced Bronchoconstriction. ClinicalTrials.Gov2007.

NCT00471809 {unpublished data only}

Childhood Asthma Research and Education (CARE) Network Trial ‐ Montelukast or Azithromycin for Reduction of Inhaled Corticosteroids in Childhood Asthma (MARS). ClinicalTrials.Gov2007.

NCT00486343 {unpublished data only}

Zileuton CR vs Placebo in Poorly Controlled Asthma Patients on Moderate Dose ICS. ClinicalTrials.Gov2007.

NCT00504946 {unpublished data only}

Pharmacological Modulations of Allergen‐Specific Immunotherapy. ClinicalTrials.Gov2007.

NCT00545324 {unpublished data only}

First Step With Singulair® Therapy (FIRST). ClinicalTrials.Gov2007.

NCT00545844 {unpublished data only}

Singulair(R) In Asthma And Allergic Rhinitis. ClinicalTrials.Gov2007.

NCT00575861 {unpublished data only}

Zileuton and Exhaled Nitric Oxide in Asthmatics. ClinicalTrials.Gov2007.

NCT00666679 {unpublished data only}

Study of Inhaled Corticosteroid Plus Montelukast Compared With Inhaled Corticosteroid Therapy Alone in Patients With Chronic Asthma. ClinicalTrials.Gov2008.

NCT00699062 {unpublished data only}

Effect of Montelukast on the Airway Remodeling. ClinicalTrials.Gov2008.

NCT00755794 {unpublished data only}

The Singulair® Add‐on Study Effectiveness of Adding Montelukast to Inhaled Corticosteroids in Adult Subjects With Uncontrolled Asthma (SAS). ClincalTrials.Gov2008.

NCT00756418 {unpublished data only}

Montelukast Post‐Marketing Comparative Study With Theophyline Added to Inhaled Corticosteroid. ClinicalTrials.Gov2008.

NCT00913328 {unpublished data only}

Effect of Add‐on Montelukast to Inhaled Corticosteroids on Airway Responsiveness (SINGDEN). ClinicalTrials.Gov2009.

NCT00943397 {unpublished data only}

Effect of Add‐on Montelukast to Inhaled Corticosteroids on Airway Responsiveness (SINGDEN). ClinicalTrials.Gov2009.

NCT01055041 {unpublished data only}

Controller Medications in the Management of Bronchial Asthma. ClinicalTrials.Gov2010.

NCT01241084 {unpublished data only}

Beneficial Effects of Lactobacillus Reuteri DSM 17938 Supplementation on Asthmatic Children. ClinicalTrials.Gov2010.

Negro 1997 {published data only}

Negro JM, Miralles JC, Ortiz JL, Funes E, Garcia A. Leukotrienes and its antagonists in allergic disorders. Allergologia et Immunopathologia 1997;25(2):104‐12.

Neki 2006 {published data only}

Neki NS, Kazal HL. Comparative efficacy and safety profile of montelukast v/s beclomethasone in mild persistent asthma [Abstract]. Indian Journal of Allergy Asthma and Immunology 2006;20(2):124.

Nelson 2001 {published data only}

Nelson HS, Nathan RA, Kalberg C, Yancey SW, Rickard KA. Comparison of inhaled salmeterol and oral zafirlukast in asthmatic patients using concomitant inhaled corticosteroids. Medgenmed Computer File: Medscape General Medicine 2001;3(4):3.

Nelson 2004 {published data only}

Nelson H, Stauffer J, Yancey S, Prillaman B, Sutton L, Dorinsky. 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;D36:A49.

Nelson 2004a {published data only}

Nelson HS, Yancey S, Waitkus‐Edwards K, Prillaman B, Philpot E, Dorinsky P. In patients taking fluticasone propionate/salmeterol 100/50µg Diskus(r) for asthma, fluticasone propionate nasal spray 200µg QD is superior to montelukast 10mg QD in the treatment of allergic rhinitis in patients with coexistent allergic rhinitis: implication for the one airway hypothesis [Abstract]. Journal of Allergy and Clinical Immunology 2004;113(Suppl 2):S200.

Nelson 2006 {published data only}

Nelson HS, Weiss ST, Bleecker EK, Yancey SW, Dorinsky PM. The salmeterol multicenter asthma research trial: A comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. chest 2006;129(1):15‐26.

Nishima 2005 {published data only}

Nishima S, Furusho K, Morikawa A, Mochizuki H, Akasaka T, Sugimoto H, et al. Pranlukast inhibits exercise‐induced bronchospasm in asthmatic children: A randomized, multicenter, double‐blind, placebo‐controlled two‐period crossover trial. Pediatric Asthma Allergy & Immunology 2005;18(1):5‐11.

Nishimura 1999 {published data only}

Nishimura K, Hajiro T, Ishihara K, Hasegawa T, Taniguchi H, Katayama S, et al. Additive effect of pranlukast in combination with inhaled corticosteroid in the treatment of patients with chronic asthma. European Respiratory Journal. 1999:P837.

Nishiyama 2006 {published data only}

Nishiyama O, Taniguchi H, Kondoh Y, Kimura T, Kato K, Kume H, et al. Comparison of the effects of tulobuterol patch and salmeterol in moderate to severe asthma. Clinical & Experimental Pharmacology & Physiology 2006;33(11):1016‐21.

Nishizawa 2002 {published data only}

Nishizawa Y, Greicy‐Goto H, Tanigaki Y, Fushiki S. Sparing effect of Saibokuto inhalation on inhaled beclomethasone dipropionate to halved of reduction of inhaled beclomethasone dipropionate‐dose: Well‐controlled comparative study of Saiboku‐to‐inhalation and sodium cromoglycate‐inhalation. Japanese. Oto‐Rhino‐Laryngology Tokyo 2002;45(Suppl 1):8‐15.

Noonan 1998 {published data only}

Noonan MJ, Chervinsky P, Brandon M, Zhang J, Kundu S, McBurney J, et al. Montelukast, a potent leukotriene receptor antagonist, causes dose‐related improvements in chronic asthma. European Respiratory Journal 1998;11:1232‐9.

Noonan 1999 {unpublished data only}

Noonan G, Reiss TF, Shingo S, Nguyen HH, Knorr B. Montelukast (MK‐0476) maintains long‐term asthma control in adult and pediatric patients (aged >6 years). Merck Research Laboratories1999.

Nsouli 2000 {published data only}

Nsouli SM, McNutt WJ. The addition of montelukast to a low dose inhaled corticosteroid compared with a double‐dose of an inhaled corticosteroid in patients with persistent asthma. Annals of Allergy, Asthma & Immunology 2000;84:159.

Nsouli 2001 {published data only}

Nsouli SM, McNutt WJ. The additive effects of montelukast and salmeterol in moderate asthmatics who are uncontrolled on a low dose on inhaled corticosteroids. Annals of Allergy, Asthma & Immunology 2001; 86:81.;86:81.

O'Byrne 1997 {published data only}

O'Byrne PM. Leukotrienes in the pathogenesis of asthma. Chest 1997;111:27S‐34S.

O'Byrne 1997a {published data only}

O'Byrne PM, Barnes NC. Summary: the future promise of mediator inhibitors in 'New oral preventive therapy in asthma and oral leukotriene receptor antagonism'. European Respiratory Review1997; Vol. 7, issue Review 46:274‐7.

O'Byrne 1997b {published data only}

O'Byrne PM, Israel E, Drazen JM. Antileukotrienes in the treatment of asthma. Annals of Internal Medicine 1997;127:472‐80.

O'Connor 1994 {published data only}

O'Connor GT, Weiss ST. Clinical and symptom measures. American Journal of Respiratory & Critical Care Medicine 1994;149:S21‐8.

O'Connor 2004 {published data only}

O'Connor RD, Nelson H, Borker R, Emmett A, Jhingran P, Rickard K, et al. Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma. Pharmacoeconomics 2004;22(12):815‐25.

O'Connor 2006 {published data only}

O'Connor RD, Gilmore AS, Manjunath R, Stanford RH, Legorreta AP, Jhingran PM. Comparing outcomes in patients with persistent asthma: a registry of two therapeutic alternatives. Current Medical Research & Opinion 2006;22(3):453‐61.

O'Shaughnessy 1996 {published data only}

O'Shaughnessy TC, Georgiou P, Howland K, Dennis M, Compton CH, Barnes NC. Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers. Thorax 1996;52:519‐22.

O'Sullivan 2002 {published data only}

O'Sullivan S, McWeeney M, Akveld M, Berelowitz KS, Burke CM, Poulter LW. Effect of the addition of montelukast to inhaled fluticasone propionate on immunopathology in bronchial biopsies from mild to moderate asthmatics [abstract]. European Respiratory Society Annual Congress. 2002:P2405.

O'Sullivan 2002a {published data only}

O'Sullivan S, McWeeny M, Akveld M, Berelowitz KS, Burke CM, Poulter LW. Effect of the addition of montelukast to inhaled fluticasone propionate on immunopathology in bronchial biopsies from mild to moderate asthmatics. European Respiratory Journal 2002;20(Suppl 38):388s.

O'Sullivan 2003 {published data only}

O'Sullivan S, Akveld M, Burke CM, Poulter LW. Effect of the addition of montelukast to inhaled fluticasone propionate on airway inflammation. American Journal of Respiratory and Critical Care Medicine 2003;167(5):745‐50.

Obase 2001 {published data only}

Obase Y, Shimoda T, Tomari S, Mitsuta K, Fukushima C, Kawano K, et al. Efficacy and safety of long‐term treatment of asthma in patients with pranlukast, a cysteinyl‐leukotriene‐receptor antagonist: a four‐year follow‐up study. Annals of Allergy, Asthma, & Immunology 2001;87(1):43‐7.

Obata 1992 {published data only}

Obata T, Okada Y, Motoishi M, Nakagawa N, Terawaki T, Aishita H. In vitro antagonism of ONO‐1078, a newly developed anti‐asthma agent, against peptide leukotrienes in isolated guinea pig tissues. Japanese Journal of Pharmacology 1992;60:227‐37.

Odjakova 2000 {published data only}

Odjakova TT, Peneva MA, Kissiova KP, Balev SS, Radkov JD. Changes in some lymphocyte markers after therapy with fluticasone propionate and montelukast in patients with bronchial asthma. European Respiratory Journal 2000;16(Suppl 31):163s.

Ohbayashi 2007 {published data only}

Ohbayashi H, Adachi M, Ichinose M, Ohta K, Kokubu F, Sano Y, et al. A multicenter, open‐label, randomized comparison of suppressive effects on asthmatic inflammation of lower airways and improved effects on health‐related QOL between HFA‐BDP and fluticasone propionate. Japanese Journal of Allergology 2007;56(6):577‐86.

Ohbayashi 2009 {published data only}

Ohbayashi H, Shibata N, Adachi M. The evaluation of the additional effect of pranlukast to salmeterol/fluticasone combination therapy using impulse oscillometry system in a randomized crossover study [Abstract]. American Thoracic Society International Conference 2009;A2764:Poster J32.

Ohbayashi 2009a {published data only}

Ohbayashi H, Shibata N, Hirose T, Adachi M. Additional effects of pranlukast in salmeterol/fluticasone combination therapy for the asthmatic distal airway in a randomized crossover study. Pulmonary Pharmacology & Therapeutics 2009;22(6):574‐9.

Ohkura 2009 {published data only}

Ohkura N, Fujimura M, Tokuda A, Takato H, Tamori S, Waseda Y, et al. Additional effects of pranlukast on exhaled nitric oxide levels in patients with persistent asthma. Therapeutic Research 2009;30(8):1361‐6.

Ohta 2009 {published data only}

Ohta K, Miyamoto T, Amagasaki T, Yamamoto M. Efficacy and safety of omalizumab in an Asian population with moderate‐to‐severe persistent asthma. Respirology 2009;14(8):1156‐65.

Okudaira 1997 {published data only}

Okudaira H. Challenge studies of a leukotriene receptor antagonist. Chest 1997;111:46S‐51S.

Oosaki 1997 {published data only}

Oosaki R, Mizushima Y, Kashii T, Kawasaki A, Kobayashi M. Therapeutic effect of pranlukast, a selective cysteinyl leukotriene receptor antagonist, on bronchial asthma. International Archives of Allergy & Immunology 1997;114(1):97‐100.

Oosaki 1997a {published data only}

Oosaki R, Mizushima Y, Kawasaki A, Kashii T, Mita H, Shida T, et al. Urinary excretion of leukotriene E4 and 11‐dehydrothromboxane B2 in patients with spontaneous asthma attacks. International Archives of Allergy & Immunology 1997;114:373‐8.

Oppenheimer 2008 {published data only}

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.

Ostrom 2003 {published data only}

Ostrom NK, DeCotiis BA, Lincourt WR, Edwards LD, Crim CC. A comparison of low does fluticasone propionate and montelukast in children 6‐12 years of age with persistent asthma [abstract]. American Thoracic Society 99th International Conference 2003;A117:D70.

Overbeek 2002 {published data only}

Overbeek SE, O'Sullivan S, Leman K, Mulder PGM, Hoogsteden, Prins JB. Treatment with montelukast is less effective in reducing eosinophilic airway inflammation than fluticasone propionate in atopic asthmatics. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A215.

Palmqvist 2003 {published data only}

Palmqvist M, Bruce C, Sjostrand M, Arvidsson P, Lotvall J. Inhibiton of allergen‐induced late asthmatics reaction by montelukast vs fluticasone propionate [Abstract]. European Respiratory Journal 2003;22(Suppl 45):2220.

Palmqvist 2005 {published data only}

Palmqvist M, Bruce C, Sjostrand M, Arvidsson P, Lotvall J. Differential effects of fluticasone and montelukast on allergen‐induced asthma. Allergy 2005;60(1):65‐70.

Panettieri 1997 {published data only}

Panettieri RA, Tan EML, Ciocca V, Luttman MA, Leonard TB, Hay DWP. Effects of LTD4 on human airways smooth muscle cell proliferation, matrix expression and contraction in vitro: differential sensitivity to cysteinyl leukotriene receptor antagonists. SmithKline Beecham Pharmaceuticals1997.

Papadopoulos 2009 {published data only}

Papadopoulos NG, Philip G, Giezek H, Watkins M, Smugar SS, Polos PG. The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity. Journal of Asthma 2009;46(4):413‐420.

Pasaoglu 2008 {published data only}

Pasaoglu G, Mungan D, Abadoglu O, Misirligil Z. Leukotriene receptor antagonists: a good choice in the treatment of premenstrual asthma?. Journal of Asthma 2008;45(2):95‐99.

Patel 2010 {published data only}

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;56(4):270‐274.

Paterson 1999 {published data only}

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. 1999:P3490.

Pavord 2007 {published data only}

Pavord I, Woodcock A, Parker D, Rice L, SOLTA study group. Salmeterol plus fluticasone propionate versus fluticasone propionate plus montelukast: a randomised controlled trial investigating the effects on airway inflammation in asthma. Respiratory Research 2007;8:67.

Pearlman 1999 {published data only}

Pearlman DS, Ostrom NK, Bronsky EA, Bonuccelli CM, Hanby LA. The leukotriene D4‐receptor antagonist zafirlukast attenuates exercise‐induced bronchoconstriction in children. Journal of Pediatrics 1999;134:273‐9.

Pearlman 2002 {published data only}

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.

Pedersen 2007 {published data only}

Pedersen S, Agertoft L, Williams‐Herman D, Kuznetsova O, Reiss TF, Knorr B, et al. Placebo‐controlled study of montelukast and budesonide on short‐term growth in prepubertal asthmatic children. Pediatric Pulmonology 2007;42(9):838‐43.

Pereira 1989 {published data only}

Pereira CAdC, Brito VC, Olieveira VMC, Paitl CE, Nery LE, Romaldini H, et al. Effects of corticosteroids administered early by inhalation in stable chronic obstructive pulmonary diseases. American Review of Respiratory Disease 1989;15(52):1348‐53.

Perng 2004 {published data only}

Perng DW, Huang HY, Lee YC, Perng RP. Leukotriene modifier vs inhaled corticosteroid in mild‐to‐moderate asthma: Clinical and anti‐inflammatory effects. Chest 2004;125(5):1693‐9.

Peroni 2005a {published data only}

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 & Asthma Proceedings 2005;26(4):283‐6.

Philip 2005 {published data only}

Philip G, Nayak AS, Berger WE, Leynadier F, Vrijens F, Dass SB, et al. The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis. Allergologie 2005;28(9):343‐54.

Phipatanakul 2003 {published data only}

Phipatanakul W, Greene C, Downes SJ, Cronin B, Eller TJ, Schneider LC, et al. Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Annals of Allergy Asthma & Immunology 2003;91(1):49‐54.

Phipatanakul 2003a {published data only}

Phipatanakul W, Greene C, Downes S, Cronin B, Schneider L, Irani A. The efficacy of montelukast as an addictive and steroid sparing agent in children with asthma previously maintained on inhaled corticosteroid therapy [Abstract]. Journal of Allergy and Clinical Immunology 2003;111(Suppl 2):S146.

Pieters 2005 {published data only}

Pieters WR, Wilson KK, Smith HC, Tamminga JJ, Sondhi S. Salmeterol/fluticasone propionate versus fluticasone propionate plus montelukast: a cost‐effective comparison for asthma. Treatments in Respiratory Medicine 2005;4(2):129‐38.

Pizzichini 1999 {unpublished data only}

Pizzichini E, Leff JA, Reiss TF, Hendeles L, Boulet L‐P, Wei LX, et al. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. European Respiratory Journal 1999;14(1):12‐8.

Plaza 2005 {published data only}

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 physicians randomized trial. Spa Medicina Clinica 2005;124(6):201‐6.

Pogson 2008 {published data only}

Pogson ZEK, Antoniak MD, Pacey SJ, Lewis SA, Britton JR, Fogarty AW. Does a low sodium diet improve asthma control?: A randomized controlled trial. American Journal of Respiratory and Critical Care Medicine 2008;178(2):132‐8.

Pohl 2006 {published data only}

Pohl WR, Vetter N, Zwick H, Hrubos W. Adjustable maintenance dosing with budesonide/formoterol or budesonide: Double‐blind study. Respiratory Medicine 2006;100(3):551‐60.

Polos 2003 {published data only}

Polos PG. Montelukast or salmeterol added to fluticasone in uncontrolled asthma: a subgroup analysis of the IMPACT study [Abstract]. Journal of Allergy and Clinical Immunology 2003;111(Suppl 2):S126.

Polos 2004 {published data only}

Polos P, Garcia Garcia ML, Gilles L, Tozzi CA, Knorr B, Reiss TF. Montelukast vs fluticasone in patients aged 6 to 14 with mild persistent asthma the MOSAIC study [Abstract]. European Respiratory Journal 2004;24(Suppl 48):377s.

Ponce 2009 {published data only}

Ponce Castro H, Rodríguez Espino S, Rodríguez Orozco AR. Administration of budesonide (inhaled steroid) to children to control intermittent asthma. Revista Alergia Mexico 2009;26(1):9‐12.

Price 1999 {unpublished data only}

Price DB, Wolfe S. Montelukast: real life effectiveness and cost‐effectiveness in primary care. Thorpe Medical Research1999.

Price 2002 {published data only}

Price DB, Hernandez D, Magyar P, Fiterman J, Beeh KM, James IG, et al. Adding montelukast is at least as efficacious as doubling the budesonide dose in persistent asthma: Results of the compact study. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl8):A216.

Price 2003 {published data only}

Price DB, Hernandez D, Magyar P, Fiterman J, Beeh KM, James IG, et al. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax 2003;58(3):211‐6.

Price 2004 {published data only}

Price DB, Zhang Q, Kocevar VS, Polos PG, Yin DD. Healthcare resource use the following addition of montelukast to budesonide compared to doubling the dose of budesonide in patients with inadequately controlled asthma (COMPACT trial) [Abstract]. European Respiratory Journal 2004;24(Suppl 48):126s.

Price 2006 {published data only}

Price DB, Swern A, Tozzi CA, Philip G, Polos P. Effect of montelukast on lung function in asthma patients with allergic rhinitis: analysis from the COMPACT trial. Allergy 2006;61(6):737‐42.

Pullerits 1999 {published data only}

Pullerits T, Praks L, Skoogh BE, Ani R, Lotvall J. Randomized placebo‐controlled study comparing a leukotriene receptor antagonist and a nasal glucocorticoid in seasonal allergic rhinitis. American Journal of Respiratory & Critical Care Medicine 1999;159(6):1814‐8.

Pullerits 2001 {published data only}

Pullerits T, Praks L, Baker R, Ani R, Lotvall J. Comparison of nasal fluticasone propionate, montelukast, and combined montelukast+loratadine in allergic rhinitis [abstract]. American Journal of Respiratory and Critical Care Medicine 2001;163(5 Suppl):A193.

Pullerits 2002 {published data only}

Pullerits T, Praks L, Ristioja V, Lotvall J. Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis. Journal of Allergy & Clinical Immunology 2002;109(6):949‐55.

Qaqundah 2006 {published data only}

Qaqundah PY, Sugerman RW, Ceruti E, Maspero JF, Kleha JF, Scott CA, et al. Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre‐school‐age children with asthma: A randomized, double‐blind, placebo‐controlled study. Journal of Pediatrics 2006;149(5):663‐70.

Rachelefsky 1997 {published data only}

Rachelefsky G. Childhood asthma and allergic rhinitis: the role of leukotrienes. Journal of Pediatrics 1997;131:348‐55.

Ragab 2001 {published data only}

Ragab S, Parikh A, Darby YC, Scadding GK. An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma. Clinical & Experimental Allergy 2001;31(9):1385‐91.

Ramsay 1997 {published data only}

Ramsay CF, van Kan CI, Nieman RB, Wang J, van Krieken JHJM, Willems LNA, et al. The effects of oral pranlukast on airway immunopathology and clinical parameters in patients with asthma. American Thoracic Society. 1997:Abs C21.

Ramsay 1998 {published data only}

Ramsay CF, van Kan CI, Sterk PJ, Barnes NC. Pranlukast improves spirometry and bronchial hyperresponsiveness (BHR) in patients with mild asthma. American Journal of Respiratory & Critical Care Medicine 1998;157(3):A411.

Rand 2004 {published data only}

Rand CS, Bilderbank A, Krishnan J, Riekert K, Schiller K, MIAMI Study Research Group. Adherence with oral montelukast sodium or fluticasone propionate in a clinical trial [Abstract]. Journal of Allergy and Clinical Immunology 2004;113(Suppl 2):s157.

Ratner 2003 {published data only}

Ratner PH, Howland WC, Arastu R, Philpot EE, Klein KC, Baidoo CA, et al. Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast.[comment]. Annals of Allergy Asthma & Immunology 2003;90(5):536‐42.

Reiss 1996 {published data only}

Reiss TF, Altman LC, Chervinsky P, Bewtra A, Stricker WE, Noonan GP, et al. Effects of montelukast (MK‐0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma. Journal of Allergy & Clinical Immunology 1996;98:528‐34.

Reiss 1997 {unpublished data only}

Reiss TF, White R, Noonan G, Korenblat P, Hess J, Shingo S. Montelukast (MK‐0476) a cys LT1 receptor antagonist improves the signs and symptoms of asthma over one year of treatment. European Respiratory Journal 1997;10 Suppl(25):437.

Reiss 1997b {published data only}

Reiss TF, et al. Montelukast improves asthma outcomes over a 3‐month treatment period. American Thoracic Society. 1997.

Reiss 1997c {published data only}

Reiss TF, Sorkness CA, Stricker W, Botto A, Busse WW, Kundu S, et al. Effects of montelukast (MK‐0476), a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax 1997;52(1):45‐8.

Reiss 1998 {published data only}

Reiss TF, Chervinsky P, Dockhorn RJ, Shingo S, Seidenberg B, Edwards TB. Montelukast, a once‐daily leukotriene receptor antagonist, in the treatment of chronic asthma. Archives of Internal Medicine 1998;158:1213‐20.

Reiss 2008 {published data only}

Reiss TF, Lu S, Liu N. A randomized study comparing concomitant montelukast and loratadine with montelukast, loratadine and beclomethasone in patients with chronic asthma [Abstract]. Chest 2008;134(4):93001s.

Riccioni 2001a {published data only}

Riccioni G, Guagnano MT, Castronuovo M, De Benedicts M, Della R. Zafirlukast versus budesonide on bronchial reactivity in subjects with mild‐persistent asthma. European Respiratory Journal 2001;18(Suppl 33):263s.

Riccioni 2002 {published data only}

Riccioni G, Santilli F, Guagnano MT, Vecchia RD. Montelukast versus budesonide on quality of life in asthmatic subjects [abstract]. European Respiratory Society Annual Congress. 2002:P757.

Riccioni 2003a {published data only}

Riccioni G, D'Orazio N, Castronuovo M, Menna V, Lambo MS, Di Stefano F, et al. Dosage tapering of inhalatory budesonide in subjects with mild to moderate persistent asthma treated with montelukast [Abstract]. European Respiratory Journal 2003;22(Suppl 45):Abstract No: P713.

Riccioni 2005 {published data only}

Riccioni G, Della Vecchia R, Castronuovo M, Di Ilio C, D'Orazio N. Tapering dose of inhaled budesonide in subjects with mild‐to‐moderate persistent asthma treated with montelukast: A 16‐week single‐blind randomized study. Annals of Clinical & Laboratory Science 2005;35(3):285‐9.

Rickard 1999 {published data only}

Rickard KA, Yancey S, Emmet AH, Kalberg CJ. Salmeterol compared to zafirlukast when added to inhaled corticosteroid therapy in patients with persistent asthma. European Respiratory Society. 1999:P839.

Rickard 2001 {published data only}

Rickard K, Dorinsky PM, Knobil K, Pepsin P, Akveld ML. The salmeterol/fluticasone propionate combination 50/100µg bid is more effective than oral montelukast 10mg od as a first line therapy in mild and moderate asthmatics. European Respiratory Journal 2001;18(Suppl 33):262s.

Ringdal 1997 {published data only}

Ringdal N, Whitney JG, Summerton L. Problems with inhaler technique and patient preference for oral therapy tablet zafirlukast vs. inhaled beclomethasone. European Respiratory Journal 1997;10 Suppl(25):437, abs P2806.

Ringdal 2003 {published data only}

Ringdal N, Eliraz A, Pruzinec R, Weber HH, Mulder PG, Akveld M, et al. The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Respiratory Medicine 2003;97(3):234‐41.

Robinson 2001 {published data only}

Robinson DS, Campbell D, Barnes PJ. Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double‐blind placebo‐controlled trial. Lancet 2001;357(9273):2007‐11.

Rosenhall 2003 {published data only}

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.

Rowe 2007 {published data only}

Rowe BH, Wong E, Blitz S, Diner B, Mackey D, Ross S, et al. Adding Long‐acting beta‐agonists to Inhaled Corticosteroids after Discharge from the Emergency Department for Acute Asthma: A Randomized Controlled Trial. Academic Emergency Medicine 2007;14(10):833‐40.

Ruggins 2003 {published data only}

Ruggins N. Pragmatic trial of add‐on therapy in Paediatric Asthma. National Research Register2003.

Sahn 1997 {published data only}

Sahn SA, Galant S, Murray J, Bronsky E, Spector S, Faiferman I, et al. Pranlukast (Ultair) improves FEV in patients with asthma: results of a 12‐week multicenter study vs. nedocromil. American Thoracic Society. 1997:Abs C49.

Sano 2006 {published data only}

Sano Y, Adachi M, Kiuchi T, Miyamoto T. Effects of nebulized sodium cromoglycate on adult patients with severe refractory asthma. Respiratory Medicine 2006;100(3):420‐33.

Schneider 2008 {published data only}

Schneider A, Wensing M, Biessecker K, Quinzler R, Kaufmann‐Kolle P, Szecsenyi J. Impact of quality circles for improvement of asthma care: Results of a randomized controlled trial. Journal of Evaluation in Clinical Practice 2008;14(2):185‐90.

Schuh 2009 {published data only}

Schuh S, Willan AR, Stephens D, Dick PT, Coates A. Can montelukast shorten prednisolone therapy in children with mild to moderate acute asthma? A randomized controlled trial. Journal of Pediatrics 2009;155(6):795‐800.

Schwartz 1995 {published data only}

Schwartz HJ, Petty T, Reed R, Dube LM, Swanson LJ, Zileuton Study Group. The comparative effects of zileuton, a 5‐lipoxygenase inhibitor, vs. theophylline in patients with moderate asthma: results from a 13‐week multicenter trial. ALA/ATS. 1995.

SD‐004‐0216 {published data only}

Oxis Turbuhaler® (formoterol), Accolate® (zafirlukast) or placebo as add on treatment to Pulmicort Turbuhaler® (budesonide) in asthmatic patients on inhaled steroids. AstraZeneca Clinical Trials2000.

Shah 2003 {published data only}

Shah AR. Which Is More Steroid Sparing in Persistent Bronchial Asthma: Montelukast Or Theophylline? [Abstract]. Chest 2003;124(4):107.

Shah 2004 {published data only}

Shah A, Solanki R, Shah K. Effect of add on therapy compared with doubling steroid inhalation in bronchial asthma [Abstract]. Thorax 2004;59(Suppl 2):ii70.

Shah 2006 {published data only}

Shah AR, Sharples LD, Solanki RN, Shah KV. Double‐blind, randomised, controlled trial assessing controller medications in asthma. Respiration 2006;73(4):449‐56.

Sheth 2002 {published data only}

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.

Shimoda 2005 {published data only}

Shimoda T, Kishikawa R, Shoji S, Nishima S. The efficacy of anti‐inflammatory treatment in mild intermittent bronchial asthma [Abstract]. Journal of Allergy & Clinical Immunology 2005;115(Suppl 2):S1.

Shingo 2001 {unpublished data only}

Shingo S, Zhang J, Noonan N, Reiss TF, Leff JA. A standardized composite clinical score allows safe tapering of inhaled corticosteroids in an asthma clinical trial.. Unpublished data (Personal Communication:Theodore Reiss June 2001)2001.

Shoji 1999 {published data only}

Shoji T, Yoshida S, Sakamoto H, Hasegawa H, Nakagawa H, Amayasu H. Anti‐inflammatory effect of roxithromycin in patients with aspirin‐intolerant asthma. Clinical & Experimental Allergy 1999;9(7):950‐6.

Simons 2001 {published data only}

Simons FER, Villa JR, Lee BW, Teper AM, Lyttle B, Aristizabal G, et al. Montelukast added to budesonide in children with persistent asthma: a randomised, double‐blind, crossover study. Journal of Pediatrics 2001;138(5):694‐8.

Simpson 2004 {published data only}

Simpson MD, Burton DL, Burton MA, Gissing PM, Bowman SL. Pharmaceutical Care: Impact on Asthma Medication Use. Journal of Pharmacy Practice & Research 2004;34(1):26‐9.

Sims 2003 {published data only}

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):104‐111.

Sims 2008 {published data only}

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:E233.

Smith 1993 {published data only}

Smith LJ, Glass M, Minkwitz MC. Inhibition of leukotriene D4‐induced bronchoconstriction in subjects with asthma: a concentration‐effect study of ICI 204,219. Clinical Pharmacology & Therapeutics 1993;54(4):430‐6.

Smith 1997 {published data only}

Smith LJ, Hanby LA, Simonson MS, Simonson SG. Effect of zafirlukast on leukotriene D4 (LTD4) ‐ induced bronchoconstriction in asthmatic patients receiving inhaled corticosteroids [abstract]. European Respiratory Journal 1997;10(Suppl 25):437S.

Smith 1998 {published data only}

Smith LJ, Hanby LA, Lavins BJ, Simonson SG. A single dose of zafirlukast reduces LTD4‐induced bronchoconstriction in patients on maintenance inhaled corticosteroid therapy. Annals of Allergy, Asthma, & Immunology 1998;81:43‐9.

Smugar 2009 {published data only}

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]. European Respiratory Society Annual Congress. 2009:P1221.

Smugar 2009a {published data only}

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]. European Respiratory Society Annual Congress. 2009:P1217.

Spahn 1996a {published data only}

Spahn JD, Szefler SJ. The etiology and control of bronchial hyperresponsiveness in children. Current Opinion in Pediatrics 1996;8:591‐6.

Spector 1992 {published data only}

Spector SL, Glass M, Minkwitz MC, ICI Asthma Trial Group. The effect of six weeks of therapy with oral doses of ICI 204,219 in asthmatics. American Review of Respiratory Disease 1992;145(4):A16.

Spector 1994 {published data only}

Spector SL, Smith LJ, Glass M. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 antagonist, in subjects with bronchial asthma. American Journal of Respiratory & Critical Care Medicine 1994;150:618‐23.

Spector 1995 {published data only}

Spector S, Miller CJ, Glass M. 13‐week dose‐response study with Accolate (zafirlukast) in patients with mild to moderate asthma. American Journal of Respiratory & Critical Care Medicine 1995;151(4):A379.

Spector 1996 {published data only}

Spector SL. Management of asthma with zafirlukast. Drugs 1996;52 Suppl(6):36‐46.

Stanford 2002 {published data only}

Stanford RH, Borker R, Dorinsky P, Pepsin P, Kalberg C, Emmett A, et al. The cost and efficacy of fluticasone propionate/salmeterol combination versus montelukast in the treatment of adults with persistent asthma. Chest. 2002:P422.

Stensrud 2006 {published data only}

Stensrud T, Berntsen S, Carlsen KH. Humidity influences exercise capacity in subjects with exercise‐induced bronchoconstriction (EIB). Respiratory Medicine 2006;100(9):1633‐41.

Stevenson 2005 {published data only}

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. Journal of Allergy & Clinical Immunology 2005;116(4):755‐60.

Sthoeger 2007 {published data only}

Sthoeger ZM, Eliraz A, Asher I, Berkman N, Elbirt D. The beneficial effects of Xolair (Omalizumab) as add‐on therapy in patients with severe persistent asthma who are inadequately controlled despite best available treatment (GINA 2002 step IV ‐ The Israeli arm of the INNOVATE study). Israel Medical Association Journal 2007;9(6):472‐5.

Storms 2001 {published data only}

Storms W, Michele TM, Knorr B, Noonan G, Shapiro G, Zhang J, et al. Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years. Clinical & Experimental Allergy 2001;31(1):77‐87.

Storms 2004 {published data only}

Storms W, Chervinsky P, Ghannam AF, Bird S, Hustad CM, Edelman JM, et al. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. Respiratory Medicine 2004;98(11):1051‐62.

Strauch 2003 {published data only}

Strauch E, Moske O, Thoma S, Van'S Gravesande KS, Ihorst G, Brandis M, et al. A randomized controlled trial on the effect of montelukast on sputum eosinophil cationic protein in children with corticosteroid‐dependent asthma. Pediatric Research 2003;54(2):198‐203.

Strunk 2003 {published data only}

Strunk RC, Szefler SJ, Phillips BR, Zeiger RS, Chinchilli VM, Larsen G, et al. Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. Journal of Allergy & Clinical Immunology 2003;112(5):883‐92.

Strunk 2008 {published data only}

Strunk RC, Bacharier LB, Phillips BR, Szefler SJ, Zeiger RS, Chinchilli VM, et al. Azithromycin or montelukast as inhaled corticosteroid‐sparing agents in moderate‐to‐severe childhood asthma study. The Journal of Allergy and Clinical Immunology 2008;122(6):1138‐44.

Sugihara 2010 {published data only}

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;104(11):1629‐37.

Suguro 1997 {published data only}

Suguro H, Majima T, Ichimura K, Hashimoto N, Koyama S, Horie T. Effect of a leukotriene antagonist, pranlukast hydrate, on exercise‐induced bronchoconstriction. American Thoracic Society. 1997:Abs C49.

Suissa 1997 {published data only}

Suissa S, Dennis R, Ernst P, Sheehy O, Wood‐Dauphinee S. Effectiveness of the leukotriene receptor antagonist zafirlukast for mild‐to‐moderate asthma: a randomized, double‐blind, placebo‐controlled trial. Annals of Internal Medicine 1997;126(3):177‐83.

Sutherland 2010 {published data only}

Sutherland ER, Camargo CA, Busse WW, Meltzer EO, Orgega HG, Yancey SW, et al. Comparative effect of body mass index on response to asthma controller therapy. Allergy and Asthma Proceedings 2010;31:20‐5.

Suzuki 1997 {published data only}

Suzuki N, Kudo K, Sano Y, Adachi M, Kanazawa M, Kudo S, et al. Efficacy of oral pranlukast, a leukotriene‐receptor antagonist, in the treatment of asthma: an open study in Tokyo. American Thoracic Society. 1997:Abs C49.

Svensson 1994 {published data only}

Svensson C, Greiff L, Andersson M, Alkner U, Persson CGA. Bradykinin‐, leukotriene D4‐, and histamine‐induced mucosal exudation of plasma in human airways in vivo. Abbott Laboratories1994.

Swern 2008 {published data only}

Swern AS, Tozzi CA, Knorr B, Bisgaard H. Predicting an asthma exacerbation in children 2 to 5 years of age. Annals of Allergy Asthma and Immunology 2008;101(6):626‐30.

Swernson 2003 {published data only}

Swenson C, Fell S, Liu LY, Busse W. Effect of montelukast (mont) or placebo (PL) on asthma exacerbations and markers of airway inflammation with inhaled corticosteroid (ICS) reduction [abstract]. American Thoracic Society 99th International Conference 2003;B034:Poster H47.

Tamaoki 1997 {published data only}

Tamaoki J, Kondo M, Sakai N, Nakata J, Takemura H, Nagai A, et al. Leukotriene antagonist prevents exacerbation of asthma during reduction of high‐dose inhaled corticosteroid. American Journal of Respiratory & Critical Care Medicine 1997;155:1235‐40.

Tan 2006 {published data only}

Tan WC, Lamm CJ, Chen YZ, O'Byrne PM, Pedersen S, Busse WW, et al. Effectiveness of early budesonide intervention in Caucasian versus Asian patients with asthma: 3‐Year results of the START study. Respirology 2006;11(6):767‐75.

Tashkin 1998 {published data only}

Tashkin DP, Minkwitz MC, Bonuccelli CM. Zafirlukast (Accolate) treatment results in better asthma control in patients with more moderate disease. American Journal of Respiratory & Critical Care Medicine 1998;157(3):A410.

Teper 2009 {published data only}

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]. European Respiratory Society Annual Congress. 2009:[P1215].

Terzano 2001 {published data only}

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 & Pharmacological Sciences 2001;5(1):17‐24.

Thoma 2002 {published data only}

Thoma S. Anti‐inflammatory effect of montelukast on corticosteroid‐dependent children with asthma [Dissertation] [[Reduktion der bronchialen Inflammation bei mildem bis mittelschwerem Asthma bronchiale im Kindesalter unter Additivtherapie mit Montelukast und inhalativem Budesonid]]. Universitat Freiburg2002.

Todi 2010 {published data only}

Todi VK, Lodha R, Kabra SK. Effect of addition of single dose of oral montelukast to standard treatment in acute moderate to severe asthma in children between 5 and 15 years of age: A randomised, double‐blind, placebo controlled trial. Archives of Disease in Childhood 2010;95(7):540‐3.

Tognella 2004 {published data only}

Tognella S, Micheletto C, Visconti MP, Dal Negro RW. Additive Effects of Montelukast on Bronchial Hyperresponsiveness to MCh and LTE4 Urine Levels in Mild‐persistent Atopic Asthmatics Assuming ICS [Abstract]. Chest 2004;126(Suppl 4):814S.

Tohda 2002 {published and unpublished data}

Tohda Y, Fujimura M, Taniguchi H, Takagi K, Igarashi T, Yasuhara H, et al. Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients. Clinical & Experimental Allergy 2002;32:1180‐6.

Tomari 2001 {published data only}

Tomari S, Shimoda T, Kawano T, Mitsuta K, Obase Y, Fukushima C, et al. Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma. Annals of Allergy, Asthma & Immunology i 2001;87:156‐61.

Tomita 1999 {published data only}

Tomita K, Hashimoto K, Matsumoto S, Nakamoto N, Tokuyasu H, Yamasaki A, et al. [Pranlukast allows reduction of inhaled steroid dose without deterioration in lung function in adult asthmatics]. Article in Japanese. Arerugi ‐ Japanese Journal of Allergology 1999;48:459‐65.

Tonelli 2003 {published data only}

Tonelli M, Zingoni M, Bacci E, Dente FL, Di Franco A, Giannini D, et al. Short‐term effect of the addition of leukotriene receptor antagonists to the current therapy in severe asthmatics. Pulmonary Pharmacology & Therapeutics 2003;16(4):237‐40.

Townley 1995 {published data only}

Townley R, Glass M, Minkwitz MC. 6‐week, dose‐escalation study with Accolate (zafirlukast) in patients with mild to moderate asthma. American Journal of Respiratory & Critical Care Medicine 1995;151(4):A379.

Trofor 2002 {published data only}

Trofor A, Rascarachi G, Popa E, Chiselita I. Clinical benefits of montelukast sodium treatment in chronic adult asthma. Revista Medico‐Chirurgicala a Societatii De Medici Si Naturalisti Din Iasi 2002;107(2):298‐302.

Tsai 2010 {published data only}

Tsai TC, Lu JH, Chen SJ, Tang RB. Clinical efficacy of house dust mite‐specific immunotherapy in asthmatic children. Pediatrics and Neonatology 2010;51(1):14‐8.

Tsuchida 2005 {published data only}

Tsuchida T, Matsuse H, Machida I, Kondo Y, Saeki S, Tomari S, et al. Evaluation of theophylline or pranlukast, a cysteinyl leukotriene receptor 1 antagonist, as add‐on therapy in uncontrolled asthmatic patients with a medium dose of inhaled corticosteroids. Allergy & Asthma Proceedings 2005;26(4):287‐91.

Tug 2007 {published data only}

Tug T, Godekmerdan A, Sari N, Karatas F, Erdem ES. Effects of supportive treatment such as antioxidant or leukotriene receptor antagonist drugs on inflammatory and respiratory parameters in asthma patients. Clinical Pharmacology & Therapeutics 2007;81(3):371‐6.

Tukiainen 2002 {published data only}

Tukiainen H, Rytila P, Hamalainen K M, Silvasti M S L, Keski‐Karhu J. Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid‐treated asthmatic patients. Respiratory Medicine 2002;96(4):221‐9.

Uh 2007 {published data only}

Uh ST, Jung KS, Lee YC, Shim JJ, Park SK, Lee YS, et al. A comparison of the clinical efficacy and safety of salmeterol/fluticasone propionate versus leukotriene antagonist in moderate to severe asthmatics ‐ a sub‐analysis of the SUCCESS Study [Abstract]. Respirology 2007;12(Suppl 4):A148.

Ulrik 2009 {published data only}

Ulrik CS, Diamant Z. Effect of add‐on montelukast to inhaled corticosteroids on excessive airway narrowing in adult asthmatics [Abstract]. European Respiratory Society Annual Congress. 2009:P1962.

Ulrik 2009a {published data only}

Ulrik CS, Diamant Z. Effect of montelukast on excessive airway narrowing response to methacholine in adult asthmatic patients not on controller therapy. Allergy and Asthma Proceedings 2009;30(1):64‐8.

Ulrik 2010 {published data only}

Ulrik CS, Diamant Z. Add‐on montelukast to inhaled corticosteroids protects against excessive airway narrowing. Clinical and Experimental Allergy 2010;40(4):576‐81.

Van Adelsberg 2005 {published data only}

Van Adelsberg J, Moy J, Wei LX, Tozzi CA, Knorr B, Reiss TF. Safety, tolerability, and exploratory efficacy of montelukast in 6‐ To 24‐month‐old patients with asthma. Current Medical Research & Opinion 2005;21(6):971‐9.

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Van Der Meer V, Bakker MJ, Van Den Hout WB, Rabe KF, Sterk PJ, Kievit J, et al. Internet‐based self‐management plus education compared with usual care in asthma: A randomized trial. Annals of Internal Medicine 2009;151(2):110‐20.

Vaquerizo 2003 {published data only}

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;58:204‐10.

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Verhoeven 2001 {published data only}

Verhoeven GT, Garrelds IM, Hoogsteden HC, Zijlstra FJ. Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive lung pulmonary disease. Mediators of Inflammation 2001;10(1):21‐6.

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Weinberg EG, Summerton L, Harris A. Assessment of preference for oral zafirlukast vs inhaled beclomethasone in adolescent asthmatics. ERS Annual Congress. 1998; Vol. 12, issue 28:abs P0333.

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Wenzel S, Cohn J, Trudeau J, Wilson W, Martin R, Westcott J. Zileuton (Leutrol) decreases urine LTE4, BALF LTB4 and improves lung function in nocturnal asthmatics. Abbott Laboratories1994.

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Wenzel SE, Trudeau JB, Kaminsky DA, Cohn J, Martin RJ, Westcott JY. Effect of 5‐lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. American Journal of Respiratory & Critical Care Medicine 1995;152(3):897‐905.

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Wenzel S, Chervinsky P, Kerwin E, Silvers W, Faiferman I, Dubb J. Oral Pranlukast (Ultair) vs. inhaled beclomethasone: results of a 12‐week trial in patients with asthma. American Journal of Respiratory & Critical Care Medicine 1997;155:A203.

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Westbroek J, Pasma HR. The effect of inhaled fluticasone propionate (FP) 100 µg bd compared with oral zafirlukast 20 mg bd on bronchial hyperresponsiveness in mild to moderate asthmatics [abstract]. European Respiratory Journal 1997;10(Suppl 25):243S.

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Westbroek J, Pasma HR, James MH, Thwaites RMA. Inhaled fluticasone propionate and oral zafirlukast in moderate asthma: a clinical and cost comparison [abstract]. American Journal of Respiratory and Critical Care Medicine 1998;157(Suppl 3):A416.

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Westbroek J, Pasma HR. Effects of 2 weeks of treatment with fluticasone propionate 100 mcg b.d. by comparison with zafirlukast 20 mg b.d. on bronchial hyper‐responsiveness in patients with mild to moderate asthma. Respiratory Medicine 2000;94(2):112‐8.

Williams 2001 {published and unpublished data}

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Wilson 1999 {published data only}

Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ. A comparison of salmeterol and montelukast as second‐line therapy in asthmatic patients receiving inhaled corticosteroids. European Respiratory Society. 1999:P3486.

Wilson 2000 {published data only}

Wilson AM, Orr LC, Sims EJ, Dempsey OJ. Antiasthmatic effects of mediator block versus topical corticosteroids in allergic rhinitis and asthma. American Journal of Respiratory & Critical Care Medicine 2000;162(4 part 1):1297‐301.

Wilson 2001 {published data only}

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.

Wilson 2001a {published data only}

Wilson AM, Orr LC, Sims EJ, Lipworth BJ. Effects of monotherapy with intra‐nasal corticosteroid or combined oral histamine and leukotriene receptor antagonists in seasonal allergic rhinitis. Clinical & Experimental Allergy 2001;31(1):61‐8.

Wilson 2001b {published data only}

Wilson AM, Dempsey OJ, Sims EJ, Lipworth BJ. A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma. Clinical & Experimental Allergy 2001;31(4):616‐24.

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Wilson AM, Sims EJ, Orr LC, Coutie WJ, White PS, Gardiner Q, et al. Effects of topical corticosteroid and combined mediator blockade on domiciliary and laboratory measurements of nasal function in seasonal allergic rhinitis. Annals of Allergy, Asthma, & Immunology 2001;87(4):344‐9.

Wilson 2004 {published data only}

Wilson A. Are antihistamines useful in managing asthma?. Advanced Studies in Medicine 2004;4(7A):S514‐S519.

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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;181(6):566‐77.

Wilson 2010a {published data only}

Wilson ECF, Price D, Musgrave SD, Sims EJ, Shepstone L, 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;28(7):597‐608.

Wise 2009 {published data only}

Wise RA, Bartlett SJ, Brown ED, Castro M, Cohen R, Holbrook JT, et al. Randomized trial of the effect of drug presentation on asthma outcomes: The American Lung Association Asthma Clinical Research Centers. Journal of Allergy and Clinical Immunology 2010;124(3):436‐44.

Xiang 2001 {published data only}

Xiang X D, Zhou R, Chen Y. Influence of zafirlukast on pulmonary functions and quality of life in patients with asthma. Bulletin of Hunan Medical University 2001;26(3):251‐3.

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Yaldiz E, Özkan G, Özdemir A, Gür A, Çamsari G. The role of montelukast in the reduction of high dose inhaled steroid in asthmatic patients. European Respiratory Journal 2000;16(Supp 31):457s.

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Yamamoto H, Nagata M, Kuramitsu K, Tabe K, Kiuchi H, Sakamoto Y, et al. Inhibition of analgesic‐induced asthma by leukotriene receptor antagonist ONO‐1078. American Journal of Respiratory & Critical Care Medicine 1994;150:254‐7.

Yildirim 2001 {published data only}

Yildirim Z, Ozlu T, Bulbul Y. Montelukast and budesonide vs double dose budesonide in moderate asthma. European Respiratory Journal 2001;18(Supp 33):261s.

Yildirim 2004 {published data only}

Yildirim Z, Ozlu T, Bulbul Y, Bayram H. Addition of montelukast versus double dose of inhaled budesonide in moderate persistent asthma. Respirology 2004;9(2):243‐8.

Yoo 2001 {published data only}

Yoo SH, Park SH, Song JS, Kang KH, Park CS, Yoo JH, et al. Representing Korea Pranlukast Study Group. Clinical effects of pranlukast, an oral leukotriene receptor antagonist, in mild‐to‐moderate asthma: a 4‐week randomized multicentre controlled trial. Respirology 2001;6(1):15‐21.

Yoshida 2000 {published data only}

Yoshida S, Sakamoto H, Ishizaki Y, Onuma K, Shoji T, Nakagawa H, et al. Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin‐intolerant asthma. Clinical & Experimental Allergy 2000;30(1):64‐70.

Yoshida 2002 {published data only}

Yoshida M, Vethanayagam D, Leigh R, Matsumoto K, Watson RM, Reerich T, et al. A comparison montelukast and budesonide effects on interleukin‐10 profiles in peripheral blood lymphocytes. American Journal of Respiratory and Critical Care Medicine 2002;165(Suppl 8):A217.

Zeiger 2004 {published data only}

Zeiger RS, Baker JW, Kaplan MS, Pearlman DS, Schatz M, Bird S, et al. Variability of symptoms in mild persistent asthma: baseline data from the MIAMI study. Respiratory Medicine 2004;98(9):898‐905.

Zeiger 2005a {published data only}

Zeiger RS, Edelman JM, Bird SR, Kaplan MS, Schatz M, Pearlman DS, et al. Short‐term and long‐term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomised controlled trial [Abstract]. Journal of Allergy & Clinical Immunology 2005;115(Suppl 2):S151.

Zeneca Accolate 1998 {published data only}

Zeneca Pharmaceuticals. Zafirlukast (Accolate) product monograph. Zeneca Pharmaceuticals1998.

Zhang 1999 {unpublished data only}

Zhang J, Chang Y, Reiss TF. Predicting future response using patient baseline variables and early responses to montelukast, a potent cysLT1 antagonist. Merck Research Laboratories1999.

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Zorc JJ, Scarfone RJ, Li Y, Hong T, Harmelin M, Grunstein L, et al. Scheduled follow‐up after a pediatric emergency department visit for asthma: A randomized trial. Pediatrics 2003;111(3):495‐502.

Australia 2006

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Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, Available from www.cochrane‐handbook.org, 2008.

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References to other published versions of this review

Ir a:

Ducharme 2004

Ducharme F, di Salvio F. Anti‐leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database of Systematic Reviews 2004, Issue 1. [DOI: 10.1002/14651858.CD002314.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Abadoglu 2005

Methods

DESIGN: Randomised clinical study

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 24

WITHDRAWALS: Not mentioned

AGE in years ± SD: 35.65 ± 10.75

GENDER (male %): 20.83%

ASTHMA SEVERITY: Mild persistent asthma

ASTHMA DURATION:

  • less than 5 years: 62.5%

  • 5‐10 years: 27.75%

  • more than 10 years: 9.75%

  • % pred. FEV1 (%, ± SD): 89.3 ± 14.85%

MEAN ( ± SD) β2‐AGONIST USE (puffs/day): Not described

DOSE OF inhaled corticosteroids AT STUDY ENTRY AND AT RUN‐IN: Not mentioned

ATOPY (% of patients): 54.16%

ELIGIBILITY CRITERIA: A history of recurrent symptoms of wheezing, shortness of breath, cough; Demonstration of objective signs of reversible airway obstruction by means of at least 12 % increase in FEV1 after 15 minutes with an inhalation of 200 μg salbutamol; A PC20 methacholine < 8 mg/mLas stated by the American Thoracic Society and International Asthma Guidelines. Asthma severity was determined by the frequency of asthma symptoms, pulmonary function tests.

EXCLUSION CRITERIA: On inhaled corticosteroids, leukotriene receptor antagonists, theophylline and long acting β2‐agonists within the preceding 12 months of the study; airway infection for at least 6 weeks before investigation.

Interventions

PROTOCOL

DURATION

  • Run‐in = Not mentioned

  • Intervention = 4 weeks

TEST GROUP: Montelukast

CONTROL GROUP: Fluticasone propionate

DEVICE: Not mentioned

CRITERIA FOR WITHDRAWAL FROM STUDY: Not mentioned

Outcomes

ANALYSIS: Not by intention‐to‐treat analysis

OUTCOMES: Reported at 4 weeks; Report outcomes are reported as pre‐ and post‐values (not change from baseline)

PULMONARY FUNCTION TESTS: Only pretreatment FEV1 was reported as not difference was observed after treatment

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MEDIATORS: Eosinophils count; Apoptotic eosinophils; Apoptotic ratio

ADVERSE EVENTS: Not mentioned

WITHDRAWALS: Not mentioned

ICS dose in HFA beclomethasone ‐ equivalent

250 μg

Notes

Full paper (2005)

Funding not available

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There is no report as to whether some patients withdrew from the study after randomisation

Selective reporting (reporting bias)

Low risk

 

All primary and secondary data are presented

Other bias

Low risk

No apparent other bias
Basyigit 2004

Methods

DESIGN: Randomised clinical study

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 24

WITHDRAWALS: Not mentioned

AGE in years (± SD): 35.65 ± 10.75

GENDER (male%): 20.83%

ASTHMA SEVERITY: Mild persistent asthma

ASTHMA DURATION:

  • less than 5 years: 62.5%

  • 5‐10 years: 27.75%

  • more than 10 years: 9.75%

  • % pred. FEV1(%, ± SD): 89.3 ± 14.85%

MEAN ( ± SD) β2‐AGONIST USE (puffs per day): Not described

DOSE OF inhaled corticosteroids AT STUDY ENTRY AND AT RUN‐IN: Not mentioned

ATOPY (% of patients): 54.16%

ELIGIBILITY CRITERIA:

  • mild persistent asthma;

  • FEV1 more than 80%;

  • Non smoker or ex‐smoker for more than 5 years;

  • No exacerbation in the last 3 months;

  • No history of cardiopulmonary disease other than asthma

EXCLUSION CRITERIA: Not mentioned

Interventions

PROTOCOL

DURATION:

  • Run‐in = 15 days;

  • Intervention = 8 weeks

TEST GROUP: Zafirlukast

TEST GROUP 2: Theophylline

CONTROL GROUP: Budesonide

DEVICE: Not mentioned

CRITERIA FOR WITHDRAWAL FROM STUDY: Not mentioned

Outcomes

ANALYSIS (ITT)

OUTCOMES:
Reported at 8 weeks; report outcomes are reported as pre‐ and post‐values (not change from baseline)

PULMONARY FUNCTION TESTS: Spirometry

FUNCTIONAL STATUS: Not mentioned

INFLAMMATORY MEDIATORS:

  • ECP levels;

  • Total cell count;

  • Eosinophils count

ADVERSE EVENTS: Not mentioned

WITHDRAWALS: Not mentioned

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full paper (2004)

Funding not available

Confirmation of methodology and data extraction

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

All data presented, withdrawal rate was not observed

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined but no bias is observed

Other bias

Low risk

No apparent other bias
Baumgartner 2003

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.

Confirmation of methodology obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 730
M: 313
BDP: 314
Placebo: 103

WITHDRAWALS:
M: 22 (7%)
BDP: 19 (6%)
Placebo: 10 (10%)

AGE in years ± SD:

M: 35.9 ± 14.9
BDP:35.5 ± 15.0
Placebo:35.5 ± 14.6

GENDER (% male):
M: 33%
BDP: 38 %

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not reported

% Pred. FEV1 % ± SD:
M: 69 ± 12
BDP: 68 ± 11
Placebo: 68±12

MEAN ± SD β2‐AGONIST USE (puffs/day):
M: 5.2 ± 3.7
BDP: 5.1 ± 3.3
Placebo: 5.5 ± 3.9

ATOPY:
M: 69%
BDP: 68%

ELIGIBILITY CRITERIA:

  • Age >= 15 years,

  • Current tx with only β2‐agonist,

  • Asthma history x 1 year,

  • >= 50 and <= 85% FEV1 Pred,

  • Reversibility >= 15% after two puffs short‐acting β2‐agonist,

  • Daily use of β2‐agonist > 2 puffs/day during run‐in,

  • Non‐smokers for more than 1 year,

EXCLUSION:

  • ED tx in past 1 month,

  • Hospital admission for asthma in past 3 months,

  • URTI in past 3 weeks,

  • Significant sinus disease,

  • Systemic corticosteroids in past month,

  • inhaled corticosteroids in past 2 weeks,

  • Astemizole within 3 months or xanthine derivatives,

  • Oral or long‐acting inhaled B‐agonists,

  • Cromolyn sodium or nedocromil, inhaled anticholinergic agents, oral leukotriene receptor antagonists or leukotriene synthesis inhibitors within 1 week before the start

Interventions

PROTOCOL

Duration

  • Run‐in Period: 2 weeks

  • Intervention Period: 6 weeks

TEST GROUP: Montelukast 10 mg per day

CONTROL GROUP 1: Beclomethasone 200 ug twice a day

CONTROL GROUP 2: Placebo

DEVICE: MDI (actuation inhaler)

CO‐INTERVENTION: Not specified

CRITERIA FOR WITHRAWAL FROM STUDY: Not described

Outcomes

ANALYSIS BY MODIFIED INTENTION‐TO‐TREAT

OUTCOMES reported at 6 weeks

PULMONARY FUNCTION TESTS: Change from baseline FEV1

SYMPTOM SCORES: Change in mean asthma score (6‐point)

FUNCTIONAL STATUS:

  • Change from baseline mean daily β2‐agonist use,

  • * %Asthma control days (<= 2 puffs of β2‐agonist use, no night‐time awakenings, no unscheduled asthma care, and no systemic corticosteroid rescue required),

  • Patients with exacerbations requiring systemic corticosteroids,

  • Physician global evaluation

INFLAMMATORY MEDIATORS: Change from baseline in serum eosinophils

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Merck Research Labratories

Confirmation of methodology and data extraction received from Dr Theodore Reiss

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented with reasons for withdrawal by group and adverse effects by group, analysis wad done with intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary endpoint was described

Other bias

Low risk

No apparent other bias
Bleecker 2000

Methods

DESIGN: Parallel‐group

Confirmation of methodology obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 451
Z: 220
FP: 231

WITHDRAWALS:
Z: 23 %
FP: 13%

AGE ( ± SD):
Z: 31 (12‐66)
FP: 31 (12‐68)

GENDER (% male):
Z: 49%
FP: 52%

ASTHMA SEVERITY:
Not described

% mean pred. FEV1:
Z: 68
FP: 67

Mean ( ± SD) β2‐agonist use (puffs per day): Not reported

ATOPY:
Z: 43 %
FP: 46%

ASTHMA DURATION (years): 10 years

ELIGIBILITY CRITERIA

  • Age: >= 12 years,

  • Persistent asthma for >= 6 months,

  • 50‐80% pred. FEV1,

  • Reversibility >= 12% after two puffs short‐acting β2‐agonist,

  • Use of β2‐agonist > 2 puffs,

  • During run‐in: use of rescue β2‐agonist >‐ 5 days or asthma symptom score >= 2 (on a 5‐point scale) on >= 3 days.

EXCLUSION:

  • AL < 2 weeks,

  • Inhaled or systemic corticosteroids < 2 months,

  • Life‐threatening asthma,

  • >= 3 bursts of systemic corticosteroids in < 1 year,

  • Tobacco < 1 year or > 10 pack‐year,

  • Respiratory infection < 2 weeks

Interventions

PROTOCOL

Duration
Run‐in Period: 8‐14 days

Intervention Period: 12 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

CONTROL GROUP: Inhaled Fluticasone 100 μg twice a day

DEVICE: Not described

CO‐INTERVENTION: None allowed

Outcomes

ANALYSIS ( ITT )

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS

  • *Change from baseline FEV1

  • Change from baseline in morning PEF

SYMPTOM SCORES: Change in mean symptom score (average/week)

FUNCTIONAL STATUS:

  • Change from baseline mean daily β2‐agonist use (puffs/day)

  • Change in night‐time awakenings

  • Change in symptom‐free days

  • Change in rescue‐free days

  • Patients with exacerbations requiring systemic corticosteroids

  • Patients with exacerbations requiring hospital admission

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Glaxo Wellcome

Confirmation of methodology and data extraction received from Gerry Hogan

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation of block of 4

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported with intention‐to‐treat analysis, adverse events were reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Boushey 2005

Methods

DESIGN: Parallel‐group, randomised, placebo controlled, clinical trial

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 149
Z: 76
BD: 73

WITHDRAWALS:
Z: 18.42 %
BD: 7.89 %

AGE (years±SD):
Z: 33.6 ± 11.1
BD: 33.2 ± 9.5

GENDER (% male):
Z: 38 %
BD: 34 %

ASTHMA SEVERITY: Not described

% Pred. FEV1 (mean ± SD)
Z: 88.2 ± 14.4
BD: 90.5 ± 12.6

Mean ( ± SD) β2‐agonist use (puffs/day): Not reported

ATOPY: Not reported

ASTHMA DURATION (years):

Z: 20.9 ± 13.1
BD: 17.1 ± 11.0

ELIGIBILITY CRITERIA

  • Age: 18‐61 years,

  • Persistent asthma for >= 6 months,

  • 70 percent of the predicted value of FEV1,

  • Reversibility >= 12% with short‐acting β2‐agonist or a fall in FEV1 of at least 20 percent after inhaling a concentration of methacholine of less than 16 mg/mL (PC20; lower concentrations indicate greater reactivity).

EXCLUSION:

  • Cigarette smoking,

  • Respiratory tract infection,

  • Corticosteroid use in the previous six weeks,

  • Hospitalisation or two or more visits to the emergency department for asthma in the previous year.

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks

Intervention Period: 52 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

CONTROL GROUP: Inhaled Budesonide 200 μg twice a day

DEVICE: Turbuhaler

CO‐INTERVENTION: None allowed

Outcomes

ANALYSIS: Not reported

OUTCOMES reported at 52 weeks

PULMONARY FUNCTION TESTS:

  • *Morning PEF%

  • Morning PEF post‐PICT (%)

  • FEV1 (%) (Pre‐bronchodilator, Post‐bronchodilator, Post‐PICT)

SYMPTOM SCORES: Change in mean symptom score

FUNCTIONAL STATUS

  • Change in asthma quality of life score

  • Change in asthma symptom‐free days

  • Change in PC20(log2)

INFLAMMATORY MEDIATORS:

  • Change in Sputum eosinophils(%)

  • Change in exhaled nitric oxide(%)

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by National Institute of Health

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: stratified adaptive randomisation to balance the effect of PC20, age, racial or ethnicity

Allocation concealment (selection bias)

Unclear risk

No details provided

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

The withdrawal rate was unbalanced between groups: 8.2% and 18.4% in budesonide and zafirlukast group, respectively; the reasons for withdrawal are reported but not by group. There was no report of intention‐to‐treat analysis; although this was appropriate for the main outcome (time to event), it may have biased the interpretation of the some secondary outcomes

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were defined

Other bias

Low risk

No apparent other bias
Bousquet 2005

Methods

DESIGN: Parallel‐group, randomised, clinical trial

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 645
M: 325
FP: 320

WITHDRAWALS:
M: 24 (7.4%)
FP: 17 (5.3)%

AGE: years ± SD:
M: 35.9 ± 14.3
FP: 36.6 ± 13.8

GENDER: n (% male):
M: 126 (38.8%)
FP: 113 (35.3%)

ASTHMA SEVERITY: Mild persistent asthma as defined by Global Initiative for Asthma (GINA) guidelines

ASTHMA DURATION: Not described

% Pred. FEV1 ± SD
M: 90.5 ± 12.2
FP: 88.2 ± 12.2

β2‐AGONIST USE (puffs per day):
M: 1.28 ± 1.1
FP: 1.38 ± 1.3

ATOPY: n (%)

M: 42 (12.9%)
FP: 45 (14.1%)

ELIGIBILITY CRITERIA

  • Nonsmoking males and females, 15 to 80 years of age, with a history of asthma for at least 4 months,

  • Baseline FEV1 value 80% of predicted,

  • b2‐agonist reversibility of at least 12% (FEV1 or PEF) or a positive exercise challenge test within the previous month.

  • Have demonstrated daytime symptoms and short‐acting b2‐agonist use on at least 2 days—but not every day—of the first week of the run‐in period.

  • Patients were to be in need of, but not on, controller medication, and at the time of enrolment could only be taking b‐agonists.

EXCLUSION:

  • Treated in an emergency department within 1 month,

  • Hospitalized for asthma within 3 months, or having unresolved symptoms,

  • Signs of upper respiratory tract infection within 3 weeks,

  • On corticosteroids within 1 month; cromolyn, nedocromil, or leukotriene‐receptor antagonists

  • within 2 weeks; theophylline, oral or long‐acting b‐agonists, or inhaled anticholinergics within 1 week; or terfenadine, fexofenadine, loratadine, or cetirizine within 48 hours of the first visit.

  • On immunotherapy within 6 months; however, a patient taking immunotherapy longer than 6 months prior to entry were allowed to be included if dosage was consistent throughout the duration of the study.

Interventions

PROTOCOL

Duration
Run‐in Period: 3 weeks
Intervention Period: 12 weeks

TEST GROUP: Montelukast 10 mg per day

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Metered dose inhaler (MDI)

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS

  • FEV1 (L, % change)

  • FEV1 (% of predicted)

  • AM PEF (L/min)

SYMPTOM SCORES: Days with symptoms (%)

FUNCTIONAL STATUS

  • *Asthma‐free days (%)

  • “As needed” b‐agonist use

  • Days with b‐agonist use (%)

  • Exacerbations requiring ED visits

  • Days with b‐agonist use (%)

  • Asthma rescue medication‐free days (%)

  • Asthma rescue medication‐free days with normal lung function (%)

  • Nocturnal awakenings (%)

  • Asthma specific Quality of life score

INFLAMMATORY MEDIATORS: Eosinophil count (103/μL)

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Merck & Co., Inc.

Confirmation of methodology and data extraction: not obtained

USER‐DEFINED ORDER:

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation 

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented; intention‐to‐treat analysis, reasons for withdrawal by group and adverse effects by group presented, 

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were defined

Other bias

Low risk

No apparent other bias
Brabson 2002

Methods

DESIGN: Parallel‐group, multi‐centre , randomised, double‐blind, double‐dummy, clinical trial

Confirmation of methodology not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 440
Z: 216
FP: 224

WITHDRAWALS:
Z: 45 (21%)
FP: 17 (8)%

AGE (± SD):
Z: 35 (± 16)
FP: 36 (± 14)

GENDER (% male):
Z: 75 (35%)
FP: 90 (40%)

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not described

% Pred. FEV1 (± SD):
Z: 73 ± 7
FP: 73 ± 7

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF inhaled corticosteroids AT STUDT ENTRY AND AT RUN‐IN:
BDP 256 ± 80ug/d
T 600 ± 213ug/d
BDP271 ± 73 μg/d
T 603 ± 169 μg/d

ATOPY: Not described

ELIGIBILITY CRITERIA

  • Age: >= 12 years,

  • Asthma,

  • Low‐dose inhaled corticosteroids (excluding Fluticasone, Flunisolide) at least 8 weeks ‐60 and 85 % pred FEV1 at screening and prior to randomisation

EXCLUSION:

  • During run‐in

  • >4 puffs of albuterol/day

  • >1 night‐time awakening during 7 days before randomisation

  • At screening:

  • Any oral or parenteral corticosteroids within 6 weeks

  • > 1 burst of oral corticosteroids within 6 months

  • Inhaled fluticasone or flunisolide within 4 weeks

  • Leukotriene modifiers within 1 week

Interventions

PROTOCOL

Duration
Run‐in Period: 8 days
Intervention Period: 6 weeks

TEST GROUP: Zafirlukast 20 mg twice daily

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Metered‐dose inhaler

CRITERIA FOR WITHDRAWAL FROM STUDY

  • > 20 % decrease in baseline FEV1

  • > 3 days with > 12 puffs of rescue albuterol

  • > 4 days where PF decreased by >= 20% of baseline

  • > 3 nights with awakenings due to asthma

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 6 weeks

PULMONARY FUNCTION TESTS:

  • *Change from baseline FEV1 (L)

  • Change from baseline in morning PEF (L/s)

  • Change from baseline in evening PEF(L/s)

SYMPTOM SCORES:

  • Change in symptom‐free days (%)

  • Change in mean symptom score (6‐point)

FUNCTIONAL STATUS:

  • Change from baseline in use of rescue β2‐agonist use (puffs/day)

  • Change in rescue free days (%)

  • Exacerbations requiring systemic corticosteroids

  • Exacerbations requiring ED visits

  • Change in nights with uninterrupted sleep

  • Physician‐rated global assessment of Rx effectiveness

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Glaxo SmithKline

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Details were not provided

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported including side effects; withdrawal rate with reasons by group 

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Busse 2001a

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial

Confirmation of methodology obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 338
Z: 111
FP: 113
Placebo (not used):114

WITHDRAWALS:
Z: 19%
FP: 14%

AGE (± SD): 12‐75 years
Z: 33.8 ± 13.1
FP: 29.6 ± 11.4

GENDER (% male): 50%
Z: 41 %
FP: 58%

ASTHMA SEVERITY: % moderate:
Z: 82%
FP: 77%

% Pred. FEV1 (mean ± SD): 66‐67%
Z: 69.1 ± 7.5
FP: 68.1 ± 8.3

Mean (± SD) β2‐agonist use (puffs/day)
Z: 4.7 (SE 0.27)
FP: 4.8 (SE:0.26)

ATOPY:
Z: 42%
FP: 23%

ASTHMA DURATION (years): at least 10 years
Z:69%
FP: 65%

ELIGIBILITY CRITERIA

  • Age: >= 12 years,

  • Regular use of short‐acting β2‐agonist for at least 6 weeks,

  • 50‐80% pred. FEV1,

  • Reversibility >= 12% after two puffs short‐acting β2‐agonist

EXCLUSION:

  • Life‐threatening asthma,

  • Use of tobacco within 1 year or smoking history of > 10 packs‐year,

  • Systemic corticosteroids within 6 months,

  • Inhaled corticosteroids < 1 month,

  • Use of leukotriene modifier < 1 week

Interventions

PROTOCOL

Duration
Run‐in Period: 8‐14 days to establish baseline respiratory function
Intervention Period: 12 weeks

TEST GROUP: Zafirlukast 20 mg twice a day po

CONTROL GROUP: Inhaled Fluticasone 100 μg twice a day (2 puffs of 50 μg twice a day)

DEVICE: Metered dose inhaler (no spacer)

CO‐INTERVENTION: None allowed other than rescue β2‐agonist and systemic corticosteroids

Outcomes

ANALYSIS ( ITT )

OUTCOMES reported at 6 and 12 weeks (also documented at 2, 4, 8 weeks)

PULMONARY FUNCTION TESTS:

  • *Change from baseline FEV1

  • Change from baseline in morning and evening PEF

SYMPTOM SCORES: Weekly average symptom score (6‐point scale)

FUNCTIONAL STATUS:

  • Change from baseline mean daily β2‐agonist use, averaged over 1 week (puffs/day)

  • Change in night‐time awakenings (waking/nights) averaged over 1 week

  • Change in symptom‐free days

  • Change in rescue‐free days

  • Change in QoL (Juniper)

  • Work or school loss days

  • Patients with exacerbations requiring systemic corticosteroids

  • Patients with exacerbations requiring hospital admission

  • Patient satisfaction

  • Physicians rated effectiveness

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Glaxo Wellcome

Confirmation of methodology and data extraction obtained from Shailesh Patel and Rob Pearson, Nov 2, 2001

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated in block of 6

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Busse 2001b

Methods

DESIGN: Parallel‐group, randomised, clinical trial

Confirmation of methodology obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 533
M: 262
FP: 271

WITHDRAWALS:
M: 29%
FP: 28%

AGE (± SD) years:

M: 34.4 (15‐67)
FP: 35.4 (15‐83)

GENDER (% male):
M: 42 %
FP: 47%

ASTHMA SEVERITY:
not described

% Pred. FEV1 (mean ± SD):
M: 65.4 ± 8.2
FP: 65.6 ± 9.2

Mean (± SD) β2‐agonist use (puffs/day): Not reported

ATOPY: Not reported

ASTHMA DURATION (years): Not reported

ELIGIBILITY CRITERIA:

  • Age: >= 15 years,

  • Persistent asthma for >= 6 months,

  • 50‐80% pred. FEV1,

  • Reversibility >= 15% after two puffs short‐acting β2‐agonist,

  • Regular use of β2‐agonist > 3 months,

  • During run‐in: use of rescue β2‐agonist >‐ 6 of 7 days and asthma symptom score >= 2 (on a 5‐point scale) on >= 4 of 7 days.

EXCLUSION:

  • Inhaled corticosteroids < 2 months,

  • Tobacco use < 1 year or >10 pack‐year,

  • Hospital admission for asthma in <3 months,

  • Respiratory infection < 4 weeks

Interventions

PROTOCOL

Duration
Run‐in Period: 8‐14 days

Intervention Period: 24 weeks

TEST GROUP: Montelukat 10 mg per day

CONTROL GROUP: Inhaled Fluticasone 100 μg twice a day

DEVICE: Metered dose inhaler

CO‐INTERVENTION: None allowed

Outcomes

ANALYSIS ( ITT )

OUTCOMES reported at 4, 8, 12, 16, 24 weeks

PULMONARY FUNCTION TESTS:

  • *Change from baseline FEV1 (L and %)

  • Change from baseline PEF (L/min)

SYMPTOM SCORES: Change in mean symptom score/week (6‐point scale)

FUNCTIONAL STATUS

  • Change from baseline mean daily β2‐agonist use (puffs/day)

  • Change in night‐time awakenings

  • Change in % symptom‐free days

  • Change in % rescue‐free days

  • Change in qol (Juniper)

  • Days off work or school

  • Exacerbations requiring systemic corticosteroids

  • Exacerbations requiring hospital admission

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Glaxo Wellcome

Confirmation of methodology and data extraction and additional unpublished data obtained from and Shailesh Patel and Rob Pearson

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated in block of 4

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented including reasons for withdrawals and adverse effects, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were defined

Other bias

Low risk

No apparent other bias
Caffey 2005

Methods

DESIGN: Three‐way cross‐over, placebo controlled, randomised, clinical trial

Participants

MILD TO MODREATE PERSISTENT ASTHMA MEETING NAEPP CRITERIAS

RANDOMISED: N = 24

WITHDRAWALS: 16.67%

AGE: years(range): 8.92 (5‐12)

GENDER (% male): Not reported

ASTHMA SEVERITY: Mild to moderate as per NAEPP criteria

% Pred. FEV1: mean(range)%: 88 (47‐111) %

ATOPY: Not reported

ASTHMA DURATION (years): Not reported

ELIGIBILITY CRITERIA:

  • Age: 5‐12 years,

  • Mild to moderate persistent asthma meeting NAEPP criteria diagnosed by physician,

  • Clinically stable on only one long‐term controller drug,

  • Who were capable of performing spirometry

EXCLUSION:

  • Any known hypersensitivity to any study medication,

  • Inability to meet study requirements,

  • Chronic respiratory disease other than asthma,

  • Current or past history of smoking,

  • Use of systemic corticosteroids within 1 month of the run‐in period,

  • Acute viral respiratory infection within 3 weeks of the run‐in period,

  • Use of two long‐term controller medications for control of asthma,

  • Severe asthma as defined by NAEPP,

  • known renal or adrenal disease

Interventions

PROTOCOL

Duration
Run‐in Period: 2 weeks

Intervention Period: 4 weeks

TEST GROUP: Montelukat 10 mg qd

CONTROL GROUP: Inhaled Fluticasone 50 μg twice a day

DEVICE: Aerochamber

CO‐INTERVENTION: None allowed

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 2, 4 weeks

PULMONARY FUNCTION TESTS:

  • *FEV1 (L/s)

  • AM and PM PEF (L/min; data not presented as there was no difference between groups)

SYMPTOM SCORES: Daily PM asthma symptom score (6‐point scale)

FUNCTIONAL STATUS:

  • Mean daily β2‐agonist use (puffs/day)

  • Exacerbations requiring systemic corticosteroids

INFLAMMATORY MEDIATORS: *Fractional exhaled nitric oxide (FeNO)

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full‐text publication

Funded by GlaxoSmithKline and by National Health Institute

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, reasons for withdrawal by group and adverse effects by group presented, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were described

Other bias

Low risk

No apparent other bias
Dempsey 2002a

Methods

DESIGN: Cross‐over, randomised, clinical trial

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 21

WITHDRAWALS: Not mentioned

AGE (years): N = 33.5

GENDER (% male): Not mentioned

ASTHMA SEVERITY: Mild persistent atopic asthma

ASTHMA DURATION: Not described

% Pred. FEV1: N = 96.3%

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF inhaled corticosteroids AT STUDY ENTRY AND AT RUN‐IN: Not mentioned

ATOPY: Not described

ELIGIBILITY CRITERIA: Mild persistent asthma

EXCLUSION: Not mentioned

Interventions

PROTOCOL

Duration
Run‐in Period: 1‐2 weeks
Intervention Period: 4 weeks

CONTROL GROUP: Hfa‐triamcinolone acetonide 450 μg od

TEST GROUP: Montelukast 10 mg od

DEVICE: Not mentioned

Criteria for withdrawal from study: Not mentioned

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS:

  • *Change from baseline FEV1

  • Change from baseline in morning PEF

  • Change from baseline in evening PEF

SYMPTOM SCORES: Change in mean symptoms

FUNCTIONAL STATUS: Change from baseline in night‐time use of rescue β2‐agonist use (puffs/day)

INFLAMMATORY MEDIATORS

  • Change from baseline in blood eosinophils

  • Change from baseline in exhaled NO

ADVERSE EVENTS: Not reported

WITHDRAWALS: Not reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

112.5 μg

Notes

Abs 2001

Funding not mentioned

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Single blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
FLTA4030

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

PARTICIPANTS WHO ARE RECEIVING β2‐AGONISTS ALONE

RANDOMISED:
N = 209
Z: 108
FP: 101

WITHDRAWALS:
Z: 9 (8%)
FP: 8 (8)%

AGE (± SD):
Z: 33.5 (± 12.8)
FP: 32.9 (± 12.7)

GENDER (% male):
Z: 40.74%
FP: 42.57%

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not described

% Pred. FEV1 (±SD): Not described

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF INHALED CORTICOSTEROIDS AT STUDT ENTRY AND AT RUN‐IN: Not described

ATOPY: Not described

ELIGIBILITY CRITERIA

  • Age: ≥12 years,

  • Asthma consistent with American Thoracic Society definition

  • FEV1: 50 and 85 % of pred

  • With at least 12% reversibility with albuterol MDI

  • Medica history of using short‐acting β2‐agonists at least for 3 months

EXCLUSION: Not described

Interventions

PROTOCOL

Duration
Run‐in Period: 1‐2 weeks
Intervention Period: 12 weeks

CONTROL GROUP: Fluticasone propionate 88 μg twice a day

TEST GROUP: Zafirlukast 20 mg twice a day

DEVICE: Metered dose inhaler

Criteria for withdrawal from study: Reported

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS:

  • *Morning pre‐medication FEV1

  • AM and PM peak expiratory volume in one second

SYMPTOM SCORES:

  • Asthma symptoms score,

  • Percent symptom free days,

FUNCTIONAL STATUS:

  • Albuterol MDI use,

  • Percent rescue‐free days,

  • Night‐time awakenings due to asthma,

  • Duration of asthma stability,

  • Physician global assessments.

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200

Notes

Funding not reported but trials conducted by pharmaceutical company

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
FLTA4031

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

PARTICIPANTS WHO ARE RECEIVING β2‐AGONISTS ALONE

RANDOMISED:
N = 224
Z: 111
FP: 113

WITHDRAWALS:
Z: 21 (19%)
FP: 16 (14%)

AGE (± SD):
Z: 33.8 (± 13.1)
FP: 29.6 (±11.4)

GENDER (% male):
Z: 40.54%
FP: 58.41%

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not described

FEV1 (± SD):
Z: 2.41 (± 0.63)
FP: 2.52 (± 0.53)

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF INHALED CORTICOSTEROIDS AT STUDT ENTRY AND AT RUN‐IN: Not described

ATOPY: Not described

ELIGIBILITY CRITERIA:

  • Age: ≥12 years,

  • Asthma consistent with American Thoracic Society definition

  • FEV1: 50 and 85 % of pred

  • With at least 12% reversibility with albuterol MDI

  • Medica history of using short‐acting β2‐agonists at least for 3 months

EXCLUSION: Not described

Interventions

PROTOCOL

Duration
Run‐in Period: 1‐2 weeks
Intervention Period: 12 weeks

CONTROL GROUP: Fluticasone propionate 88 μg twice a day

TEST GROUP: Zafirlukast 20 mg twice a day

DEVICE: Metered dose inhaler

Criteria for withdrawal from study: Reported

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 1, 2, 4, 6, 8, 12 weeks

PULMONARY FUNCTION TESTS:

  • *Morning pre‐medication FEV1

  • AM and PM peak expiratory volume in one second

SYMPTOM SCORES:

  • Asthma symptoms score,

  • Percent symptom free days,

FUNCTIONAL STATUS:

  • Albuterol MDI use,

  • Percent rescue‐free days,

  • Night‐time awakenings due to asthma,

  • Duration of asthma stability,

  • Physician global assessments.

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200

Notes

Funding not reported but trials conducted by pharmaceutical company

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
FMS40012

Methods

DESIGN: Randomised clinical study

Participants

PARTICIPANTS WITH MILD ASTHMA

RANDOMISED:
N = 16
Z: 8
FP: 8

WITHDRAWALS:
Z: 1 (13%)
FP: 0 (0%)

AGE (± SD):
Z: 26.3 (± 4.5)
FP: 31.8 (± 12.2)

GENDER (% male):
Z: 87.5%
FP: 62.5%

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not described

FEV1 (± SD):
Z: 4.06 (± 1.0)
FP: 3.54 (± 0.94)

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF INHALED CORTICOSTEROIDS AT STUDT ENTRY AND AT RUN‐IN: Not described

ATOPY: Described

ELIGIBILITY CRITERIA:

  • Atopic participants aged: 18‐50 years,

  • Willing to undergo repeated sputum induction procedure,

  • Non‐smoker,

  • With clinical history of asthma

EXCLUSION:

  • Received corticosteroid therapy,

  • With respiratory infection in the month prior to entering the study

  • Experienced exacerbation in the three months prior to enrolment,

  • History of life‐threatening asthma,

  • Undergone major surgery within six months prior to study

  • Received an investigational drug within a month of entry

  • Had a positive drug or alcohol screen,

  • Had clinically significant history of hepatic, renal, haematological, bleeding, cardiac, endocrine, gastrointestinal, metabolic, muscle or neurological diseases, tremors or seizure,

  • Had donated blood within 30 days,

  • Received warfarin, antihistamines at the time of enrolment.

Interventions

PROTOCOL

Duration
Run‐in Period: not reported
Intervention Period: 4 weeks

CONTROL GROUP: Fluticasone propionate 50 μg twice a day

TEST GROUP: Zafirlukast 20 mg twice a day

DEVICE: Metered dose inhaler

Criteria for withdrawal from study: Reported

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 1, 4 weeks

PULMONARY FUNCTION TESTS: FEV1

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported.

INFLAMMATORY MEDIATORS:

  • *Change in percentage of sputum eosinophils

  • Change in total eosinophils

  • Change in ECP in sputum

  • Change in histamine PC20

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

100

Notes

Funding not reported but trials conducted by pharmaceutical company

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
FPD40013

Methods

DESIGN: Parallel‐group, multi centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

PARTICIPANTS WITH PERSISTENT ASTHMA

RANDOMISED:
N = 341
MON: 168
FP: 173

WITHDRAWALS:
MON: 28 (17%)
FP: 27 (16%)

AGE (± SD):
MON: 9.4 (± 1.9)
FP: 9.5 (± 1.9)

GENDER (% male):
MON: 60.71%
FP: 58.96%

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not described

% Pred. FEV1 (± SD):
MON: 75.7 (± 7.0)
FP: 76.1 (± 6.6)

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF INHALED CORTICOSTEROIDS AT STUDT ENTRY AND AT RUN‐IN: Not described

ATOPY: Not described

ELIGIBILITY CRITERIA:

  • Aged 6‐12 years,

  • Clinically diagnosed asthma for at least 6 months,

  • FEV1 60‐85%,

EXCLUSION:

  • Life‐threatening asthma,

  • Hospitalized for asthma within 3 months of visit 1,

  • Any other significant disease.

Interventions

PROTOCOL

Duration
Run‐in Period: Not reported
Intervention Period: 12 weeks

CONTROL GROUP: Fluticasone propionate 50 μg twice a day

TEST GROUP: Montelukast 5 mg QD

DEVICE: Diskus

Criteria for withdrawal from study: Reported

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS:

  • *Percen change from baseline in morning pre‐dose FEV1 (L),

  • Change from baseline in morning PEFR

SYMPTOM SCORES: Change from baseline in percent of symptom‐free days

FUNCTIONAL STATUS: Change from baseline in total albuterol use

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

100

Notes

Funding not reported but trials conducted by pharmaceutical company

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Garcia Garcia 2005

Methods

DESIGN: Parellel‐group, randomised, clinical trial.
Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 994
M: 495
FP: 499

WITHDRAWALS:
M:7.3%
FP:6.6%

AGE: years (range):

M: 9 (6‐14)
FP: 9 (5‐15)

GENDER (% male):
M: 64.8%
FP: 58.5%

ASTHMA SEVERITY: Mild persistent asthma at step 2 of GINA guidelines

% Pred. FEV1 ± range:
M: 86.8 (34.2‐129.0)
FP: 87.7(51.8‐12.5‐0)

β2‐agonist use (puffs per day): median (range)
M: 5(0.0‐77.9)
FP: 4.8 (0.0‐78.3)

ATOPY: Not reported

ASTHMA DURATION: (years): Not reported

HISTORY OF ALLERGY:(%)
M: 61.4
FP: 61.9

ELIGIBILITY CRITERIA:

  • Age: 6‐14 years,

  • With a clinical history of mild asthma at step of the GINA guidelines of 12 months,

  • FEV1 of 80% of the predicted value (pre bronchodilator measurement),while ‐receptor agonist was withheld for 6 hours, at least twice in the run‐in period,

  • Diagnosis of mild asthma was defined on the basis of

  • (1) an increase in FEV1 or peak expiratory flow rate of 12% (absolute value), 20 to 30 minutes after inhaled ‐receptor agonist administration, at visits 1, 2, or 3;

(2) a positive methacholine or histamine provocative concentration causing a 20% decrease in FEV1 of 8 mg/mL; or

(3) a decrease in FEV1 of 15% after an exercise challenge.

  • Had to demonstrate symptoms requiring β2‐receptor agonist use on 2 and 6 days of the week for the 2 weeks before visit 3,

  • Had to be in good general health except for asthma, as indicated by medical history, physical examination, and routine laboratory data.

EXCLUSION: Not reported

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks
Intervention Period: 52 weeks

CONTROL GROUP: Fluticasone 100 μg twice a day

TEST GROUP: Montelukast 5‐mg oral tablet [10 mg if the patient turned 15 years of age during the study], once at bedtime

DEVICE: Metered dose inhaler

Criteria for withdrawal from study: Described

Outcomes

ANALYSIS ( ITT )

OUTCOMES reported at 52 weeks

PULMONARY FUNCTION TESTS: Change from baseline FEV1 (L and %)

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS:

  • *Percentage of rescue free days (i.e.. ‐receptor agonists, systemic corticosteroids, or other asthma rescue medications),

  • *Pecentage of asthma‐related health resource utilization (i.e.. an unscheduled visit to a physician, urgent/emergency care, or hospitalizations),

  • Percentage of patients requiring anti‐asthma medications other than ‐receptor agonist,

  • Percentage of patients with an asthma attack (defined as any period with worsening asthma that required an unscheduled visit to the doctor’s office, emergency department, or hospital for treatment of asthma or treatment with systemic corticosteroids, as recorded on the diary cards),

  • Percentage of days with ‐receptor agonist use,

  • Quality of life questionnaire (7‐point scale),

  • Exacerbations requiring hospital admission,

  • Asthma control,

  • Asthma‐related patient school loss,

  • Parental work loss

INFLAMMATORY MEDIATORS: Peripheral blood eosinophils level

ADVERSE EVENTS: Described

WITHDRAWALS: Described

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Merck and Co.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: electronically generated randomisation using blocking factor of 4

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, reasons for withdrawal by group and adverse effects by group presented, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary, secondary and tertiary outcomes were described

Other bias

Low risk

No apparent other bias
Hughes 1999 (BDP)

Methods

DESIGN: Parallel‐group, clinical trial.

Confirmation of methodology obtained (08/01)

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 71
M: 25
FP: 23
BDP: 23

WITHDRAWALS:
M: 0 (0%)
FP: 1 (4%)
BDP:0 (0%)

AGE (± SD):
M: 29.0 ± 11.7
FP: 30.7 ± 10.7
BDP: 31.6 ± 9.6

GENDER (% male):
M: 39%
FP:60%
BDP: 64%

ASTHMA SEVERITY: Mild

% Pred. FEV1 % ± SD:
M: 83.0 ± 11.7
FP:85.3 ± 10.7
BDP:84.9 ± 11.0

Mean (± SD) β2‐agonist use (puffs/day):
M: 1.2 ± 1.0
FP: 1.4 ± 1.5
BDP: 1.2 ± 1.5

ATOPY or ALLERGIC RHINITIS:
M:84%
FP:96%
BUD:78%

ELIGIBILITY CRITERIA:

  • Age>= 15 years old,

  • Recruited from managed care affiliated sites,

  • 6‐month history of asthma,

  • FEV1 % Pred >= 70,

  • Airway reversibility >= 12% twice,

  • β2‐agonist use 1‐6 days/wk,

  • FEV1/FVC < 80% if FEV1 reversibility 10‐12%,

  • Non or ex‐smoker (< 15 pack years),

  • No pregnancy or on birth control for women

EXCLUSION CRITERIA:

  • < 15 years,

  • Known intolerance to study medications,

  • Unable to perform spirometry,

  • Within 2 weeks of run‐in and prior to randomisation: any exacerbation requiring unscheduled visit to MD, emergent or urgent care visit, hospital admission or rescue oral corticosteroids,

  • Intake of oral or inhaled corticosteroids, nedocromil, cromolyn, salmeterol, theophylline within 1 week of study entry

Interventions

PROTOCOL

Duration
Run‐in Period: 2 weeks
Intervention Period: 4 weeks

TEST GROUP: Montelukast 10 mg

CONTROL GROUP 1: Fluticasone 100 μg twice a day

CONTROL GROUP 2: Budesonide 200 μg twice a day

DEVICE: Aerosol inhaler for Fluticasone and Dry powder inhaler for Budesonide

CO‐INTERVENTION: None allowed other than rescue B2‐agonist and systemic corticosteroids

Outcomes

ANALYSIS ( ITT)
(if received at least one study medication)

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS:

  • Change from baseline FEV1 (L)

  • Change from baseline in PEFR (L/min)

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS:

  • % Change from baseline median daily β2‐agonist use (puffs/day)

  • *Change from baseline in percentage of "rescue‐free" days (no unscheduled office visit, ER, or hospitalizations)

INFLAMMATORY MEDIATORS: Change from baseline in serum eosinophils

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Abstract & Poster (1999)

Funded by Merck

Letter, meth sent to Hughes December 1999
Confirmation of methodology, data extraction and additional data provided by Merck Laboratories.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation 

Allocation concealment (selection bias)

Low risk

Allocation by opaque consecutive numbered envelopes containing assignment

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, withdrawal and adverse effects, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary outcome was described

Other bias

Low risk

No apparent other bias
Hughes 1999 (FP)

Methods

as above

Participants

as above

Interventions

as above

Outcomes

as above

ICS dose in HFA beclomethasone ‐ equivalent

as above

Notes

as above

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation 

Allocation concealment (selection bias)

Low risk

Allocation by opaque consecutive numbered envelopes containing assignment

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, withdrawal and adverse effects, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary outcome was described

Other bias

Low risk

No apparent other bias
Israel 2002

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:

N = 782
M = 339
BDP = 332
Placebo = 111

WITHDRAWALS: n (%)
M: 11 (3.2%)
BDP: 14 (4.2%)
Placebo: 5(4.5%)

AGE: years (range):

M = 33.5 (15‐71)
BDP = 33.9 (15‐74)
placebo = 33.3 (15‐64)

GENDER: n (% male)

M = 162 (47.8%)
BDP = 156 (47%)
Placebo = 54 (48.7%)

ASTHMA SEVERITY: Not mentioned

ASTHMA DURATION: Not mentioned

% PRED. FEV1% ±SD:

M = 67.4 ± 11.1
BDP = 65.9 ± 11.7
P = 66.8 ± 12.3

MEAN (± SD) β2‐AGONIST USE (puffs/day):
M = 5.6 ± 2.9
BDP = 5.8 ± 2.9
Placebo=5.7 ± 2.6

DOSE OF inhaled corticosteroids AT STUDY ENTRY AND DURING RUN‐IN: Not reported

ATOPY: Not described

ELIGIBILITY CRITERIA:

  • >= 15 years,

  • >= 1 year history of clinical symptoms of asthma,

  • Use of only B‐agonist for asthma treatment,

  • FEV1 between 50%‐80%,

  • >= 15% increase in FEV1 after albuterol use,

  • > 2 puffs per day during run‐in,

  • Non‐smokers for at least 1 year with smoking history of no more than 7 packs‐year

EXCLUSION

  • Inhaled corticosteroids for 2 weeks prior to 1st visit,

  • URTI within 3 weeks,

  • ER visit for asthma within 1 month,

  • Hospitalization for asthma in past 3 months,

  • Systemic corticosteroids for 1 month before 1st visit

Interventions

PROTOCOL

DURATION
Run‐in: 2 weeks
Intervention: 6 weeks

TEST GROUP: Montelukast: 10 mg once daily

CONTROL GROUP 1: BDP: 200 μg twice a day

CONTROL GROUP 2: Placebo

DEVICE: MDI + spacer

CRITERIA FOR WITHDRAWAL FROM STUDY: Not described

CO‐INTERVENTION: Short‐acting anti‐histamines

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 6 weeks

PULMINARY FUNCTION TESTS
*Change from baseline FEV1

SYMPTOM SCORES: % of days with asthma control

FUNCTIONAL STATUS

  • Change from baseline in use of β2‐agonist(puffs/day)

  • Asthma exacerbations

  • Rescue corticosteroid use (%)

  • % Asthma controlled days defined as a day with <= 2 puffs of albuterol, no night‐time awakenings, and no asthma attacks

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

*primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Merck

Confirmation of methodology and data extraction not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: blinded allocation schedule produced by the study sponsor

Allocation concealment (selection bias)

Low risk

A block of allocation numbers that were assigned sequentially to consecutively randomised patients

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, withdrawal rate per group was mentioned

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were specified

Other bias

Low risk

No apparent other bias
Jayaram 2002

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 50
M = 19
FP = 18

WITHDRAWALS: Not mentioned

AGE (years): Not mentioned

GENDER (% female): Not mentioned

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not mentioned

% PRED. FEV1% ± SD: Not mentioned

MEAN ± SD β2‐AGONIST USE (puffs/day): Not mentioned

DOSE OF inhaled corticosteroids AT STUDY ENTRY AND DURING RUN‐IN: Not reported

ATOPY: Not described

ELIGIBILITY CRITERIA:

  • Corticosteroid‐naive asthma

  • Sputum eosinophils (Eo) count of > 3.5%

EXCLUSION± Not mentioned

Interventions

PROTOCOL

DURATION
Run‐in: Not mentioned
Intervention: 8 weeks

TEST GROUP: Montelukast (dose un‐specified: probably 10 mg per day)

CONTROL GROUP 1: Fluticasone (dose un‐specified)

DEVICE: Not described

CRITERIA FOR WITHDRAWAL FROM STUDY: Not described

Outcomes

ANALYSIS (ITT not specified)

OUTCOMES ‐reported at 8 weeks
Report outcomes are reported as pre‐ and post‐values (not change from baseline)

PULMINARY FUNCTION TESTS

  • FEV1

  • Morning PEFR (L/min)

  • Evening PEFR (L/min)

SYMPTOM SCORES: Change in symptoms

FUNCTIONAL STATUS: Change from baseline in use of β2‐agonist

INFLAMMATORY MEDULATOR: *Change in sputum Eo (%)

ADVERSE EVENTS: Not reported

WITHDRAWALS: Not reported

*primary outcomes

ICS dose in HFA beclomethasone ‐ equivalent

Not reported

Notes

Abstract 2002

Funding not mentioned

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Jayaram 2005

Methods

DESIGN: Parallel‐group, randomised, multicentric, placebo controlled, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED
N = 37
M:19
FP:18

WITHDRAWALS: N (%)
M: 1 (5.26%)
FP: 1 (5.56%)

AGE: years ± SD
M: 31.4 ± 9.9
FP: 35.4 ± 13.9

GENDER: N (% male)
M: 8 (42.11)
FP:8 (44.44)

ASTHMA SEVERITY: Persistent symptomatic asthma

% Pred. FEV1 % (± SD)
M: 76.7 (15.9)
FP: 72.0 (16.0)

β2‐agonist use (puffs per day) Mean (± SD):
M: 3.3 (3.1)
FP: 3.3 (2.6)

ATOPY:
M:84.21%
FP:88.89%

ELIGIBILITY CRITERIA:

  • Adult with persistent symptomatic asthma who had only taken a short acting bronchodilator for at least 2 months,

  • Asthma was diagnosed by NAEPP criteriaS or by AHR to methacholine with a PC20 of 8 mg/ml if the FEV1/SVC was 70%,

  • No symptoms of a cold or flu during the month before the start of the study,

  • Eosinophilia > 3.5 in induced sputum samples.

Interventions

PROTOCOL

DURATION
Run‐in: not mentioned
Intervention: 8 weeks

TEST GROUP: Montelukast (10 mg qd)

CONTROL GROUP: Fluticasone (250 μg per day)

DEVICE: Not described

CRITERIA FOR WITHDRAWAL FROM STUDY: Not described

Outcomes

ANALYSIS: (ITT not specified)

OUTCOMES

Reported at 8 weeks
Report outcomes are reported as pre‐ and post‐values and graph of change in values

PULMINARY FUNCTION TESTS

  • FEV1(L)

  • Morning and evening PEFR (L/min) measured but not presented

SYMPTOM SCORES: Change in symptoms (5‐35 score)

FUNCTIONAL STATUS: Pre and post use of β2‐agonist

INFLAMMATORY MEDULATOR: *Change in sputum Eosinophils (%)

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

*primary outcomes

ICS dose in HFA beclomethasone ‐ equivalent

250 μg

Notes

Full‐text publication

Funded by Glaxo Wellcome Inc;

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

High risk

Data on symptom severity, methacholine tests, PEF, skin prick test were mentioned in methodology but not described in results

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were defined

Other bias

Low risk

No apparent other bias
Jenkins 2005

Methods

DESIGN: Cross‐over, active controlled, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 58

WITHDRAWALS: n(%): 4 (6.90)

AGE: years (range): N = 38.5 (16–70)

GENDER (% male): 60.35

ASTHMA SEVERITY: Mild to moderate asthma

ASTHMA DURATION: Not described

% Pred. FEV1: mean±SD: N = 76.1 ± 11.9

β2‐AGONIST USE: puffs per day (range): 3.0 (1.0–5.5)

ATOPY: 93%

ELIGIBILITY CRITERIA:

  • Age: 16‐75 years,

  • Previous use of a short‐acting b2‐agonist with/without an inhaled corticosteroids equal or more than 500 beclomethasone equivalent

  • FEV1 of 50–90% of predicted and/or a ratio of FEV1/FVC equal or less than 70%,

  • Reversible airway obstruction (FEV1 increase equal or more than 15% pred or 200 mL after 200 salbutamol) within 6 months,

  • Asthma symptoms or short acting β2‐agonist use equal or more than 4 days/week,

  • Moderate airway hyper responsiveness (AHR), defined as the provocative dose of methacholine causing a 20% fall in FEV1 (PD20) equal or less than 2 mmol at the end of a run‐in period

EXCLUSION CIRTERIA:

  • Current smoking or smoking history 10 pack–yrs.

  • Coexisting lung disease, recent asthma exacerbation or respiratory infectionNot mentioned,

  • Current smoking or smoking history equal or more than 10 pack‐yrs

Interventions

PROTOCOL

DURATION
Run‐in: 2 weeks
Intervention: 6 weeks

TEST GROUP: Montelukast (over‐encapsulated montelukast 10 mg tablet q.d.)

CONTROL GROUP: Fluticasone propionate (Accuhaler/Diskus 250 mg twice a day)

DEVICE: (Accuhaler/Diskus)

CRITERIA FOR WITHDRAWAL FROM STUDY: Described

Outcomes

ANALYSIS: (ITT)

OUTCOMES

Reported at 6 weeks
Report outcomes are reported as pre‐ and post‐values

PULMINARY FUNCTION TESTS:

  • FEV1(L),

  • *PEF

  • PD20 methacholine mmol

SYMPTOM SCORES: *Change in symptoms (1‐6 score)

FUNCTIONAL STATUS:

  • Day symptom score,

  • Night symptom score,

  • Symptom‐free days,

  • Waking‐free nights,

  • Day salbutamol use, puffs/day,

  • Night salbutamol use, puffs/day,

  • Total QoL score,

  • Global assessment of asthma control,

INFLAMMATORY MEDULATOR: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

*primary outcomes

ICS dose in HFA beclomethasone ‐ equivalent

500 μg

Notes

Full‐text publication

Funding: Not reported;

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation 

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, intention‐to‐treat analysis,reasons for withdrawal by group and adverse effects by group described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were defined

Other bias

Low risk

No apparent other bias
Kanazawa 2007

Methods

DESIGN: Parallel‐group, active and placebo controlled, clinical trial.

Participants

ASTHMA PATIENTS

RANDOMISED:
N = 30
M: 15
FP: 15

WITHDRAWALS: Not reported

AGE: years ± SD
M: 34.9 ± 5.5
FP: 36.1 ± 6.4

GENDER: % male
M: 80%
FP: 80%

ASTHMA SEVERITY: Not mentioned

% Pred. FEV1 % (± SD)
M: 91.0 (± 5)
FP: 90 (± 3)

β2‐agonist use (puffs/day) Mean (± SD): Not reported

ATOPY: Not reported

Exhaled NO, parts per billion (± SD)

M: 12.5 (4.8)
FP: 13.4 (3.9)

SPUTUM EOSINOPHILS, % (± SD)
M: 11.0 (2.8)
FP: 12.1 (3.9)

SPUTUM ECP, ng/mL (± SD)
M: 470 (170)
FP: 500 (170)

ELIGIBILITY CRITERIA:

  • Asthmatic patients on short‐acting 2‐agonists on demand,

  • No patients were receiving oral or inhaled corticosteroids,

  • Clincally stable and none had a history of respiratory infection for at least the 4‐week period preceding the study.

Interventions

PROTOCOL

DURATION
Run‐in: 2 weeks
Intervention: 12 weeks

TEST GROUP: Montelukast capsule (10 mg at night)

CONTROL GROUP: Fluticasone propionate (200 μg twice a day)

DEVICE: Not mentioned

CRITERIA FOR WITHDRAWAL FROM STUDY: Not mentioned

Outcomes

ANALYSIS: (ITT not mentioned)

OUTCOMES

Reported at 12 weeks
Outcomes are reported as pre‐ and post‐values

PULMINARY FUNCTION TESTS:

  • FEV1(L),

  • FEV1/FVC, %

  • PD20 methacholine, mg/mL

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS AND INFLAMMATORY MEDULATOR:

  • Exhaled Nitric oxide,

  • Eosinophil cationic protein (ECP),

  • VEGF,

  • Angiopoietin‐1,

  • Aangiopoietin‐2,

  • Albumin,

ADVERSE EVENTS: Not reported

WITHDRAWALS: Not reported

ICS dose in HFA beclomethasone ‐ equivalent

400 μg

Notes

Full‐text publication

Funding: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined but no bias is observed

Other bias

Low risk

No apparent other bias
Kanniess 2002

Methods

DESIGN: Cross‐over, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 40

WITHDRAWALS: Not reported

AGE mean years (range): 37 (18‐60)

GENDER: 24 male (60%)

ASTHMA SEVERITY: Moderate allergic bronchial asthma

FEV1 % pred (Mean ±SD): 74.2 (10.6)

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

ATOPY: 100% of patients

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • FEV1 within 15% at screening value

  • 20% fall in FEV1(PC20)

  • Atopic patients according to skin‐prick test

  • Bronchodilator effect of > 15% after 200μg of salbutamol

EXCLUSION:

  • Smokers

  • Acute exacerbation or respiratory tract infection within 4 weeks before each visit

  • Inhaled corticosteroids within 3 months

  • Systemic corticosteroids within 6 months

  • Antihistamines or theophylline within 4 weeks

Interventions

PROTOCOL

DURATION
Run‐in: 1‐2 weeks
Treatment: 4 weeks
Wash‐out: 3‐8 weeks

TEST GROUP: Fluticasone 100 μg twice a day

CONTROL GROUP: Montelukast 10 mg at night‐time

DEVICE: Diskus

CRITERIA FOR WITHDRAWAL FROM STUDY: Not described

CO‐INTERVENTION: Not permitted

Outcomes

ANALYSIS (not by ITT)

OUTCOMES
Reported at 4 weeks

PULMINARY FUNCTION TESTS:

  • % Change from baseline FEV1

  • Bronchial responsiveness to methacholine (PC20)

  • Morning Peakflow rate

SYMPTOM SCORES: Symptom score daytime and night‐time (range 0‐4)

FUNCTIONAL STATUS:

  • Change from baseline in use of β2‐agonist

  • Occurence of asthma attacks and asthma flare‐ups

  • Rescue corticosteroid use

INFLAMMATORY MEDIATORS:

  • Sputum eosinophils (geometric means)

  • Exhaled NO

  • (sievers) (geometric means)

ADVERSE EVENTS: Reported

WITHDRAWALS: Not reported

PRIMARY OUTCOMES: Not reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by GlaxoSmithKline, d20354 Hamburg, Germany

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not mentioned

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented

Selective reporting (reporting bias)

Low risk

Not found

Other bias

Low risk

No apparent other bias
Khan 2008

Methods

DESIGN: Parallel‐group, active controlled, randomised, clinical trial.

Participants

ASTHMA PATIENTS

RANDOMISED:
N = 60
M: 30
BC: 30:

WITHDRAWALS: Not reported

AGE: years±SD: Not mentioned

GENDER: % male
M: 100%
BC:100%

ASTHMA SEVERITY: Not mentioned

% Pred. FEV1 % (± SD): Not reported

β2‐agonist use (puffs/day) Mean (± SD): Not reported

ATOPY: Not reported

ELIGIBILITY CRITERIA Not mentioned

EXCLUSION CRITERIA:

  • Smokers

  • Patients showing clinical signs of other diseases including diabetes mellitus, Ischaemic heart disease, pulmonary tuberculosis, chronic liver disease and rheumatoid arthritis

Interventions

PROTOCOL

DURATION
run‐in: Not mentioned
treatment: 8 weeks

TEST GROUP: Beclomethasone 250 μg daily

CONTROL GROUP: Montelukast 10 mg at night‐time

DEVICE: Not reported

CRITERIA FOR WITHDRAWAL FROM STUDY: Not described

CO‐INTERVENTION: Not permitted

Outcomes

ANALYSIS (ITT Not reported)

OUTCOMES
Reported at 8 weeks

PULMINARY FUNCTION TESTS: Peak expiratory flow rate

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Not reported

WITHDRAWALS: Not reported

PRIMARY OUTCOMES: Not reported

ICS dose in HFA beclomethasone ‐ equivalent

125 μg

Notes

Full‐text publication

Funded : Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label study

Incomplete outcome data (attrition bias)
All outcomes

High risk

No proper statistical analysis was performed; severity of patient was not determined using any guideline, 

Selective reporting (reporting bias)

Unclear risk

Primary and secondary outcomes were not defined but no bias is observed

Other bias

High risk

No details on ethical committee approval mentioned; no details on informed consent was mentioned

Kim 2000

Methods

DESIGN: Parallel‐group, clinical trial.

Confirmation of methodology: Obtained

Participants

ASYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 437
Z: 221
FP: 216

WITHDRAWALS:
Z: 46 (21%)
FP:19 (9%)

AGE (years, range):
Z: 32.9 (12‐71)
FP: 35.5 (12‐81)

GENDER (%male):
Z: 19 %
FP: 18 %

ASTHMA SEVERITY: Mild stable

FEV1 (Mean ± SD):
Z: 2.53 ± 0.04
FP: 2.58 ± 0.04

Mean (± SD) β2‐agonist use (puffs/day): Not reported

ATOPY:
Z: 58%
FP: 56%

ASTHMA DURATION: 10 years

ELIGIBILITY CRITERIA:

  • Age >= 12 years

  • 60‐85% Pred FEV1

  • >= 12% improvement after inhaled β2‐agonist use of low doses of inhaled corticosteroids (BDP 200‐400/day or triamcinolone 400‐800 μg/day for >= 8 weeks use of β2‐agonist use prn.

  • during run‐in: stable asthma, i.e., <= 4 rescue puffs/day of short‐acting β2‐agonist, <= 1 night awakening

  • FEV1 between 60% and 85%

EXCLUSION:

  • Life‐threatening asthma

  • >= 1 burst of systemic corticosteroids in < 6 months

  • Smoking in < 12 months

  • Respiratory infection in < 2 weeks

Interventions

PROTOCOL

Duration
Run‐in Period: 1 week

Intervention Period: 6 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: MDI

CO‐INTERVENTION: None

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT

OUTCOMES reported at 6 weeks

PULMONARY FUNCTION TESTS:

  • *Change from baseline FEV1 (L)

  • Change in morning PEFR (L/min)

SYMPTOM SCORES: Change in mean symptom score (6‐point scale)

FUNCTIONAL STATUS:

  • Change from baseline daily mean B2‐agonist use (puffs/day)

  • Change in night‐time awakenings

  • Change in symptom‐free days

  • Change from baseline quality of life scores

  • change in rescue‐free days

  • patients with exacerbations requiring systemic corticosteroids

  • Patients requiring hospital admission

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by Glaxo Wellcome

Confirmation of methodology and data extraction received from Gerry Hogan

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated in block of 4

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented including withdrawal with reasons by group and adverse effects by group, analysis was done by intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary out come was presented

Other bias

Low risk

No apparent other bias
Koenig 2008

Methods

DESIGN: Parellel‐group, randomised, clinical trial.

Participants

ASTHMA PATIENTS

RANDOMISED:
N = 323
M: 164
FP: 159

WITHDRAWALS: Not reported

AGE: years (SD):
M: 40.1 (13.9)
FP: 42.0 (14.5)

GENDER (%male):
M: 55 %
FP: 57 %

ASTHMA SEVERITY: Asthma patients with FEV1 between 40% and 85% of predicted normal

FEV1 % of predicated: Mean:
M: 72
FP: 74

ATOPY: Not reported

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA

  • Age 15 years and older,

  • Diagnosis of asthma using the American Thoracic Society definition,

  • 40‐85% Pred FEV1,

  • Reversibility in FEV1 of ≥ 12% within 30 minutes after inhalation of albuterol,

  • On inhaled corticosteroids at a fixed daily dosing regimen for at least 4 weeks prior to screening

EXCLUSION:

  • Life‐threatening asthma,

  • Asthma instability,

  • Concurrent respiratory disease,

  • Intermittent and seasonal asthma or exercise‐induced bronchospasm alone,

  • Any other concurrent condition/ disease that would put the safety of the participants at risk,

  • Concurrent use of medications that could have affected the course of asthma or interacted with study medications was prohibited,

  • Use of systemic corticosteroid within 4 weeks of screening

Interventions

PROTOCOL

Duration
Run‐in Period: 2 week

Intervention Period: 16 weeks

TEST GROUP: Montelukast 10 mg qd

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Flovent Diskus

CO‐INTERVENTION: None

Outcomes

ANALYSIS (ITT Not reported)

OUTCOMES reported AM PEF: at every week up to 16 weeks

FEV1 (L): at every 4 week up to 16 weeks

Other parameters: baseline and at the end of 16 weeks

PULMONARY FUNCTION TESTS:

  • FEV1 (L)

  • *Morning PEFR (L/min)

SYMPTOM SCORES: Change in mean symptom score (0‐5 point scale)

FUNCTIONAL STATUS:

  • Mean change from baseline at endpoint in morning pre‐dose FEV1

  • Patient‐rated satisfaction with treatment,

  • Percentages of symptom‐free days,

  • Rescue‐free days

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funding: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented; analysis by intention‐to‐treat; reasons for withdrawal and adverse effects described

Selective reporting (reporting bias)

Low risk

Primary and secondary end outcomes were described

Other bias

Low risk

No apparent other bias
Kooi 2008

Methods

DESIGN: Parellel‐group, randomised, clinical trial.

Participants

CHILDREN WITH ASTHMA LIKE SYMPTOMS

RANDOMISED:
N = 63
M: 18
FP: 25

WITHDRAWALS: Reported

AGE: mean years ± SD:
M: 3.8 ± 1.4
FP: 3.9 ± 1.1

GENDER (% male):
M: 66.67 %
FP: 52 %

ASTHMA SEVERITY: Children with asthma‐like symptoms (wheeze, cough and/or shortness of breath) of sufficient severity to justify the use of prophylactic asthma treatment

ATOPY:
M: 89 %
FP: 84 %

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • Age 2‐5 years,

  • With asthma‐like symptoms (wheeze, cough and/or shortness of breath) of sufficient severity to justify the use of prophylactic asthma treatment

EXCLUSION:

  • Use of systemic corticosteroids in the last 2 months,

  • Hospitalization for asthma‐related symptoms in the last 2 weeks,

  • Respiratory disorders other than asthma and poorly controlled systemic diseases,

  • Children with symptoms on less than 4 days of the 2‐week run‐in period or children who used anti‐inflammatory medication in the run‐in period

Interventions

PROTOCOL

Duration
Run‐in Period: 2 week

Intervention Period: 12 weeks

TEST GROUP: Montelukast 4 mg chewable tablet qd

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Metered dose inhaler via a plastic spacer device (Aerochambers)

CO‐INTERVENTION: None

Outcomes

ANALYSIS by intention‐to‐treat manner

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS:

  • Respiratory resistance (hPa/L/s/Hrz)

  • Forced oscillation technique

SYMPTOM SCORES: *Symptom score (wheeze, cough, shortness of breath) as recorded by caregivers in a symptom diary card

FUNCTIONAL STATUS: Rescue medication free days,

INFLAMMATORY MEDIATORS: Blood eosinophils

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funding: from Merck Sharp and Dohme.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented; intention‐to‐treat analysis; reasons for withdrawal and adverse effects were described by group; 

Selective reporting (reporting bias)

Low risk

Primary and secondary end outcomes were defined

Other bias

Low risk

No apparent other bias
Kumar 2007

Methods

DESIGN: Parellel‐group, randomised, clinical trial.

Participants

MILD PERSISTENT ASTHMA PATIENTS

RANDOMISED:
N = 62
M: 30
BD: 32

WITHDRAWALS:
M: 4
BD: 2

AGE: years±SD
M: 8.6 ± 2.14
BD: 9.87 ± 2.35

GENDER (%male):
M: 83.33 %
BD: 78.13 %

ASTHMA SEVERITY: Mild persistent asthma was defined as asthma symptoms occurring more than two times in a week but < 1 episode per day and exacerbation may affect activity, night‐time symptoms more than two times a month and peak expiratory flow rate (PEFR) more than or equal to 80% of the predicted FEV1 % of predicted: Mean(range)
M: 73.5 (66.55–81.44)
BD: 76 (67.99–83.50)

ATOPY: Not reported

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA

  • Age: 5‐15 years of either sex,

  • Recently diagnosed mild persistent asthma,

  • Asthma symptoms occurring more than two times in a week but < 1 episode per day and

exacerbation may affect activity, night‐time symptoms more than two times a month

  • PEFR more than or equal to 80% of the predicted,,

EXCLUSION:

  • With any other chronic illness like tuberculosis, cystic fibrosis,

  • Unable to use inhaler with spacer/to perform spirometry

Interventions

PROTOCOL

Duration
Run‐in Period: Not reported

Intervention Period: 12 weeks

TEST GROUP: Montelukast 10 mg qd

CONTROL GROUP: Budesonide 400 μg per day

DEVICE: Metered dose inhaler

CO‐INTERVENTION: None

Outcomes

ANALYSIS (ITT Not reported)

OUTCOMES reported: at every 4 weeks up to 12 weeks

PULMONARY FUNCTION TESTS:

  • FEV1 (L)

  • FEV1% of predicted

  • Morning PEFR (L/min)

SYMPTOM SCORES: Symptom score

FUNCTIONAL STATUS

  • Need for rescue drug,

  • Duration of rescue drug,

  • Symptom free days

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funding: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation 

Allocation concealment (selection bias)

Low risk

Packets of drugs for each patient were labelled
according to randomisation sequence by a person
not involved in initial or subsequent assessment of
the patients.

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy, identical MDIs or tables of drugs were used

Incomplete outcome data (attrition bias)
All outcomes

High risk

Total of 13.3% (4) and 6.25% (2) patients withdrew from montelukast and budesonide group, respectively and the reasons for withdrawals were reported by group. 

Selective reporting (reporting bias)

Low risk

Analysis was not done with intention‐to‐treat analysis; the data on secondary outcomes was insufficiently reported to be aggregated;  no data on visit to emergency or local practitioner. 

Other bias

Low risk

No apparent other bias
Laitinen 1997

Methods

DESIGN: Parallel‐group, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 481
Z80: 159
Z20: 162
BDP: 160

WITHDRAWALS:
Z80:10 (6.3%)
Z20:14 (8.6%)
BDP:13 (8.1)%

AGE:
Z80:38.7 ± 12.6
Z20:37.8 ± 14.0
BDP:38.3 ± 13.6

GENDER (% male):
Z80: 50.9%
Z20: 53.1%
BDP: 48.1%

% Pred. FEV1 (mean ± SD):
Z80: 79 ± 12.8
Z20:78.9 ±12.9
BDP:80.8 ± 12.7

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY/ALLERGIC RHINITIS:
Z80: 88 (55%)
Z20: 86 (53%)
BDP: 86 (54%)

ASTHMA DURATION (Years, SD):
Z80:13.4 ± 11
Z20:11.3 ± 10
BDP:13.3 ± 12

ELIGIBILITY CRITERIA:

  • Age: 12‐70 years

  • FEV1 >=60% of Pred

  • Improvement >15% FEV1 after B2‐agonist use

  • Prn short‐acting β2‐agonist with or without inhaled corticosteroids<=500 BUD or BDP or <=250 FP

  • Daytime asthma score >‐10 in past 7 days

EXCLUSION:

  • Abnormal LFT

  • Use of other asthma Rx other than prn β2‐agonist during run‐in

  • Respiratory infection during run‐in

Interventions

PROTOCOL

Duration
Run‐in Period: not described

Intervention Period: 6 weeks

TEST GROUP 1: Zafirlukast (Accolate) 20 mg twice a day p.o.

TEST GROUP 2: Zafirlukast (Accolate) 80 mg twice a day p.o.

CONTROL GROUP: Inhaled beclomethasone dipropionate 200‐250 μg twice a day

DEVICE: Not described

CO‐INTERVENTION: Not specified

Outcomes

ANALYSIS (ITT not specified)

OUTCOMES reported at 6 weeks

PULMONARY FUNCTION TESTS

  • Change from baseline FEV1 (L)

  • Change from baseline AM PEFR (L/min)

SYMPTOM SCORES: Change from baseline daytime symptom scores (max = 21)

FUNCTIONAL STATUS

  • Change from baseline mean daily B2‐agonist use (puffs/day)

  • Change from baseline nocturnal awakenings/night

INFLAMMATORY MARKERS: Change in eosinophil counts

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

225 μg

Notes

Abstract (1997)

Funded by Zeneca

Confirmation of methodology and data extraction

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation with block of 6

Allocation concealment (selection bias)

Unclear risk

Not reported 

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, withdrawals and adverse effects were reported by groups, 

Selective reporting (reporting bias)

Low risk

Not found

Other bias

Low risk

No apparent other bias
Laviolette 1999

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 642
M: 201
BDP: 200
Placebo: 48
M+BDP: 193

WITHDRAWALS:
M: 42 (21%)
BDP: 22 (11%)

AGE:
M:38 (15‐75)
BDP:39 (15‐78)

GENDER (% male):
M: 49%
BDP: 52%

% Pred. FEV1 (mean ±SD):
M: 72 ± 12
BDP: 72 ± 12

Mean (± SD) β2‐agonist use (puffs/day):
M: 3.5 ± 2.3
BDP: 3.5 ± 2.5

ATOPY/ALLERGIC RHINITIS:
M: 74%
BDP: 74%

ELIGIBILITY CRITERIA:

  • Age: > 15‐years old

  • Healthy, non‐smoking

  • History of >=one year of intermittent or persistent asthma symptoms

  • Inhaled corticosteroids treatment >= 6wks prior to pre‐study visit (inhaled corticosteroids dose comparable to beclomethasone 400‐500 μg)

  • 50‐85% FEV1 Pred

  • Improvement >15% FEV1 after B2‐agonist use

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks

Intervention Period: 16 weeks

TEST GROUP 1: Montelukast 10 mg per day + Placebo (after blind beclomethasone removal)

TEST GROUP 2: Montelukast 10 mg per day + inhaled beclomethasone 200 μg twice a day (not used in this review)

CONTROL GROUP 1: Placebo + inhaled beclomethasone 200 μg twice a day

CONTROL GROUP 2: Placebo + Placebo (not used in this review)

DEVICE: Aero‐Chamber spacer device

CO‐INTERVENTION: Not specified

Outcomes

ANALYSIS ( Intention‐to‐treat)

OUTCOMES reported at 6 and 16 weeks

PULMONARY FUNCTION TESTS

  • Change from baseline FEV1

  • Change from baseline Am PEFR

SYMPTOM SCORES: Change from baseline daytime asthma symptoms scores (6‐point scale)

FUNCTIONAL STATUS:

  • % Change from daily mean use of β2‐agonists

  • Change from baseline nocturnal awakenings (nights/week)

INFLAMMATORY MARKERS: Change from baseline peripheral blood eosinophil counts

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full Text publication (1999)

Funded by Merck

Confirmation of methodology and data received from Reiss 01 Sept 1999

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation with block of 6

Allocation concealment (selection bias)

Unclear risk

Not reported 

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

High risk

All data presented, 20.9% and 11.0% withdrawal in montelukast and beclomethasone respectively, no intention‐to‐treat analysis. 

Selective reporting (reporting bias)

Low risk

Not found

Other bias

Low risk

No apparent other bias
Lazarus 2007

Methods

DESIGN (ONLY DATA OF NONSMOKER PATIENTS ARE PRESENTED IN THIS REVIEW)
Cross‐over, multicentric, randomised, clinical trial.

Participants

CORTICOSTEROID‐NAIVE ASTHMATIC PATIENT

RANDOMISED: N = 44

WITHDRAWALS: 1 (4.6%)

AGE: mean years: 28.98 ± 5.92

GENDER (% male): Not reported

% Pred. FEV1 (mean ± SD): 80.16 ± 9.16

Mean (±SD) β2‐agonist use (puffs/day): Not reported

ATOPY/ALLERGIC RHINITIS: Not reported

DURATION OF ASTHMA: More than 10 years

ELIGIBILITY CRITERIA:

  • Corticosteroid‐naive male and female people aged 18 to 50 years old,

  • History of asthma,

  • Prebronchodilator FEV1 values of 70 to 90% of predicted

  • Airway reactivity as indicated by 12% or greater reversibility after albuterol inhalation,

  • PC20 (provocative concentration causing a 20% fall in FEV1) methacholine of less than 8 mg/ml,

  • Nonsmokers: a total lifetime smoking history of less than 2 pack‐years, and no smoking for at least 1 year

Interventions

PROTOCOL

Duration
Run‐in Period: 2‐4 weeks

Intervention Period: 16 weeks

TEST GROUP 1: Montelukast 10 mg qd

TEST GROUP 2: Inhaled beclomethasone 160 μg twice daily

DEVICE: Inhaled (HFA)–beclomethasone dipropionate or QVAR

CO‐INTERVENTION: Not specified

Outcomes

ANALYSIS (ITT‐ Not reported)

OUTCOMES reported at 8 weeks

PULMONARY FUNCTION TESTS

  • *Change from baseline FEV1

  • Change from baseline FEV1% predicted

  • Change from baseline spirometry PEFR

  • Change from baseline AM peak flow

  • Change from baseline PEFR variability,

  • Change from baseline log 2 (PC20),

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: AQOL average score

INFLAMMATORY MARKERS:

  • Change from baseline Sputum eosinophils

  • Change from baseline Sputum neutrophils,

  • Change from baseline eosinophil cationic protein,

  • Change from baseline tryptase,

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

400 μg

Notes

Full Text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: randomisation was performed online from the data coordinating centre

Allocation concealment (selection bias)

Low risk

Matching placebos were used; Treatment medication for each subject was packaged with unique number and distributed to the clinical centres

Blinding (performance bias and detection bias)
All outcomes

Low risk

Triple blind

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

All data presented; analysis was not done using intention‐to‐treat analysis; data for drop out patients was not addressed

Selective reporting (reporting bias)

Low risk

Not found

Other bias

Low risk

No apparent other bias
Lu 2009

Methods

DESIGN: Cross‐over, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 406 (including all other groups)
M:46
BECLO: 63

WITHDRAWALS: Not reported group wise

AGE: 34.11 ± 11.85

GENDER (% male): N: 48.0%

% PRED FEV1 (mean, SD): Not reported

Mean (± SD) β2‐agonist use (puffs/day): Not reported

ATOPY: Not reported

ASTHMA DURATION (years): Not reported

ELIGIBILITY CRITERIA:

  • Adult patients 15 to 65 years of age with a ≥ 1‐year clinical history of asthma symptoms,

  • FEV1 of 50% to 85% of predicted,

  • Airflow reversibility of ≥ 15%,

  • Minimum predetermined level of β2‐agonist use and daytime asthma symptoms.

EXCLUSION:

  • Received oral cromolyn or nedocromil or inhaled or intranasal corticosteroids within 2 weeks before the first visit

  • Received anti‐leukotriene agents, xanthine compounds, long‐acting β2‐agonists, or inhaled anticholinergics within 1 week before the first visit.

  • Patients who had used long‐acting antihistamines within 2 weeks of the first visit, short‐acting antihistamines within 48 hours, or astemizole within 3 months

  • With gastroesophageal reflux disease (GERD) and environmental triggers such as allergic rhinitis and smoking history.

Interventions

PROTOCOL

Duration
Run‐in Period: 2 weeks
Intervention Period: 6 weeks
Wash‐out Period: 2 weeks

TEST GROUP: Montelukast 10 mg per day at bedtime p.o.

CONTROL GROUP 1: Beclomethasone 200 μg twice a day

CONTROL GROUP 2: Placebo (not used in this review)

DEVICE: Not reported

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT ANALYSIS

OUTCOMES reported at 6 weeks

PULMONARY FUNCTION TESTS:

  • % change from baseline FEV1

  • Morning PEF

  • Evening PEF

SYMPTOM SCORES: Daytime asthma symptoms score

FUNCTIONAL STATUS: Total daily β2‐agonist use

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full Text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

All data presented, intention‐to‐treat analysis, clinical and laboratory adverse experiences were reported however withdrawal were not reported by group

Selective reporting (reporting bias)

Low risk

Primary, secondary and tertiary outcomes were defined

Other bias

Low risk

No apparent other bias
Malmstrom 1999

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:

N = 895
M:387
BDP:251
PLACEBO:257

WITHDRAWALS:
M: 33 (8.5%)
BDP:18 (7.2%)

AGE:
M: 35 (15‐78)
BDP: 35 (15‐74)

GENDER (% male):
M: 40%
BDP: 35%

‐%PRED FEV1 (mean, SD):
M : 65 ± 10
BDP: 65 ± 10

Mean (± SD) β2‐agonist use (puffs/day):
M: 5.4 ± 3.4
BDP: 5.5 ± 4.2

ATOPY:
M: 62 %
BDP:61 %

ASTHMA DURATION years(range):
M: 17 (1‐67)
BDP: 18 (0.5‐65)

ELIGIBILITY CRITERIA:

  • Age: >= 15 years old

  • History of chronic asthma for >= one year

  • 50‐85% FEV1 Pred

  • Improvement >15% FEV1 after B2‐agonist use

  • Average daily use of >= one puff of β2‐agonist

  • Minimal predefined daytime asthma symptom score (64 of a possible of 336)

EXCLUSION:

  • Inhaled or oral corticosteroids, cromolyn, or nedocromil in < 4 weeks

  • Use of long‐acting β2‐agonist, antimuscarinic or new tx with theophylline in < 2 weeks

Interventions

PROTOCOL

Duration
Run‐in Period: 2 weeks
Intervention Period: 12 weeks
Wash‐out Period: 3 weeks

TEST GROUP: Montelukast 10 mg per day at bedtime p.o.

CONTROL GROUP 1: Beclomethasone 200 μg twice a day

CONTROL GROUP 2: Placebo (not used in this review)

DEVICE: Spacer for Beclomethasone

CO‐INTERVENTION: Theophylline (10%)

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 6 and 12 weeks

PULMONARY FUNCTION TESTS:

  • *% Change from baseline FEV1

  • Change from baseline AM PEFR

SYMPTOM SCORES: Change from baseline daytime symptom scores

FUNCTIONAL STATUS

  • Change from baseline nocturnal awakenings (nights/week)

  • Change from baseline quality of life scores (Juniper)

  • % Change from baseline mean daily B2‐agonist use (puffs/day)

INFLAMMATORY MARKERS: Change from baseline peripheral blood eosinophil counts

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full Text publication (1999)

Funded by Merck

Confirmation of methodology and data extraction obtained.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation with block of 7

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, reasons for withdrawal and adverse effects were mentioned by group 

Selective reporting (reporting bias)

Low risk

Not found

Other bias

Low risk

No apparent other bias
Maspero 2001

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 124
M: 83
BDP: 41

WITHDRAWALS:
M: 5 (6%)
BDP: 3 (7%)

AGE: 6‐11 years
M: 9.5 ± 1.8 (6‐12) years
BDP:9.7 ± 1.4 (7‐12) years

GENDER (% male):
M: 64 %
BDP: 51%

BASELINE SEVERITY: Moderate

Mean % Predicted FEV1:
M: 82 ± 13
BDP:82 ± 17

ATOPY/ALLERGEN TRIGGERS:
M: 66%
BDP:61%

ASTHMA DURATION (years): Not reported

ELIGIBILITY CRITERIA:

  • Age: 6‐11 years

  • within 40% pf the 5 to 95% weight range

  • non smoker

  • baseline FEV1 >= 60 and <= 85% predicted

  • Improvement >= 12% after β2‐agonist

  • need for rescue β2‐agonist 7/14 days of the run‐in

EXCLUSION:

  • ED asthma visit in past month

  • Admission for asthma in past 3 months

  • Prior intubation

  • Unresolved URTI in past 3 weeks

  • Significant sinus infection

  • Cromolyn use within 1 month

  • Inhaled or systemic corticosteroids use in past 2 weeks or >= 3 short courses of systemic corticosteroids in past 6 months

  • Long‐acting β2‐agonist, anticholinergics, long‐acting anti‐histamine, theophylline in past 2 weeks

Interventions

PROTOCOL

Duration
Run‐in Period: unspecified
Primary RCT Period: 10 weeks
Extension Period: 6 months

TEST GROUP: Montelukast 5 mg per day at bedtime p.o.

CONTROL GROUP: Inhaled BPD 100 μg tid

DEVICE: MDI, spacer optional

CO‐INTERVENTION: Not specified

Outcomes

ANALYSIS by Intention‐to‐treat

OUTCOMES reported at 12, 24 weeks

PULMONARY FUNCTION TESTS: Change from baseline FEV1 (L)

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS

  • Days off work for parents

  • Days off school for children

  • Number of exacerbations requiring systemic corticosteroids

  • Number of exacerbations requiring admission

INFLAMMATORY MEDIATORS: *LTC4 in nasal wash

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

150 μg

Notes

Full‐text publication of primary and extension study (1999)

Funded by Merck Frosst

confirmation of methodology and data extraction obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not mentioned

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label, the criteria for election of participants from last study not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented

Selective reporting (reporting bias)

Unclear risk

Peak expiratory flow rate was mentioned in method but data was not presented in results, primary and secondary outcomes not specified

Other bias

Low risk

No apparent other bias
Meltzer 2002

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.
Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 522
M = 264
FP = 258

WITHDRAWALS; N (%)
M: 67(25%)
FP: 60 (23%)

AGE: mean (range)
M: 35.4 (15‐77) years
FP: 36.2 (15‐73) years

GENDER (% male):
M: 41 %
FP: 51 %

BASELINE SEVERITY: Moderate

% Predicted FEV1 (Mean ± SE):
M: 65.9 ± 9.1
FP: 65.6 ± 8.9

ATOPY/ALLERGEN TRIGGERS: Not reported

ASTHMA DURATION (years)
M: 74% for >= 10 years
FP: 78% for >= 10 years

ELIGIBILITY CRITERIA:

  • Non‐smoking male and female

  • Age: >= 15 years old

  • Diagnosis of asthma as per the ATS criteria for >= 6 months

  • Use of an inhaled or oral short‐acting β2‐agonist on a regular or as‐needed basis during the preceding 3 months

  • 50‐80% FEV1 Pred pre‐bronchodilator

  • Improvement >= 15% FEV1 after 200 μg of B2‐agonist use

  • At the end of the run‐in period:

  • FEV1 of 50‐80% that was within 15% of the FEV1 at screening

  • Use of albuterol to relieve asthma symptom on at least 6 to 7 days before randomisation

  • An asthma symptom score of 2 or more (based on a 1‐5‐point scale) on at least 4 of the 7 days

EXCLUSION:

  • History of life‐threatening or unstable asthma known hypersensitivity to study medication

  • Respiratory tract infections within 4 weeks of screening

  • Pregnancy

  • Smoking history of more than 10 pack‐years

  • Inhaled or systemic corticosteroids, inhaled cromolyn or nedocromil, leukotriene modifiers, anticholinergics, and theophylline products

Interventions

PROTOCOL

Duration
Run‐in Period: 8‐14 days

Intervention: 24 weeks

TEST GROUP: Montelukast 10 mg per day at bedtime p.o.

CONTROL GROUP: Inhaled FP 100 μg twice a day

DEVICE: MDI with spacer

CO‐INTERVENTION: Rx permitted: antihistamines, nasal decongestants, intranasal medications (including corticosteroids) for the treatment of rhinitis

Outcomes

ANALYSIS by intention‐to‐treat

OUTCOMES reported at 24 weeks or endpoint

PULMONARY FUNCTION TESTS

  • *% Change from baseline FEV1

  • Change from baseline AM PEFR

  • Change from baseline PM PEFR

  • Change in mean diurnal variation in PEF

SYMPTOM SCORES

  • Change from baseline daytime symptom scores (scale of 0 to 5)

  • Change in night‐time awakening (specify /week or /night) (scale of 0 to 5)

  • % symptom‐free days

  • % symptom‐free nights

FUNCTIONAL STATUS

  • Exacerbations requiring systemic corticosteroids

  • Exacerbations requiring admission

  • Global assessment of medication effectiveness

  • Patient satisfaction

  • Change in AQLQ

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication (2002)

Funded by GlaxoSmithKline

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated in block of 4

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented including withdrawal with reasons by group and adverse effects by group, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were defined

Other bias

Low risk

No apparent other bias
MK0479‐332

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

PARTICIPANTS WITH PERSISTENT ASTHMA

RANDOMISED:
N = 683
MON: 347
FP: 336

WITHDRAWALS:
MON: 51 (14.70%)
FP: 50 (14.88%)

AGE (± SD):
MON: 37.7 (± 10.4)
FP: 38.4 (± 10.7)

GENDER (% male):
MON: 53.03%
FP: 56.25%

ASTHMA SEVERITY: Not described

ASTHMA DURATION: Not described

% Pred. FEV1 (±SD):

MON: 75.7 (± 7.0)
FP: 76.1 (± 6.6)

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

DOSE OF INHALED CORTICOSTEROIDS AT STUDT ENTRY AND AT RUN‐IN: Not described

ATOPY: Not described

ELIGIBILITY CRITERIA:

  • Aged 18‐55 years,

  • Subjects with chronic asthma who actively smoke at least 0.5 to no more than 2 packs of cigarettes a day,

EXCLUSION:: Subjects with chronic obstructive pulmonary disease.

Interventions

PROTOCOL

Duration
Run‐in Period: not reported
Intervention Period: 12 weeks

CONTROL GROUP: Fluticasone propionate 250 twice a day

TEST GROUP: Montelukast 10 mg QD

DEVICE: Not reported

Criteria for withdrawal from study: Reported

Outcomes

ANALYSIS: Not reported

OUTCOMES reported at 24 weeks

PULMONARY FUNCTION TESTS: Change from baseline in morning PEFR

SYMPTOM SCORES: Change from baseline in mean day time symptom score

FUNCTIONAL STATUS: *Percentage of asthma‐control days over the 6‐month treatment period,

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

500

Notes

Funding not reported but trials conducted by pharmaceutical company

Confirmation of methodology and data extraction: not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation:not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Nathan 2001

Methods

DESIGN: Parallel‐groups, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 294
Z = 150
FP = 144

WITHDRAWALS; N (%):
Z: 12 (8%)
FP: 5 (3%)

AGE: Mean ( range)
Z: 32 (12‐70)
FP: 31 (12‐54)

GENDER (% male):
Z: 65 (43%)
FP: 65 (45%)

BASELINE SEVERITY: Not mentioned

% Pred. FEV1 (Mean ± SD):
Z: 68.9 ± 7.6
FP: 68 ± 8.5

MEAN (± SD) β2‐AGONIST USE (puffs/day):
Z = 4.4 ± 2.7
FP = 4.4 ± 2.6

ATOPY: Not reported

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • >= 12 years old

  • History of asthma according to ATS

  • 50‐80% FEV1 pred.

  • Reversibility >= 12% after 2 puffs of albuterol

  • Using inhaled or oral short acting β2‐agonist for longer than 6 weeks

  • Not using inhaled corticosteroids within 30 days

EXCLUSION:

  • Life‐threatening or unstable asthma

  • Significant uncontrolled disease other than asthma

  • URTI within 2 weeks

  • Used oral or parenteral corticosteroids within 60 days

  • Used an investigational medication within 30 days

Interventions

PROTOCOL

Duration
Run‐in Period: 7‐14 days

Intervention: 4 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Not reported

CO‐INTERVENTION: None permitted

Outcomes

PER PROTOCOL ANALYSIS (not ITT)

OUTCOMES reported at 4 and endpoint

PULMONARY FUNCTION TESTS

  • *Change from baseline in morning predose FEV1 (L)

  • Change from baseline AM PEFR

  • Change from baseline PM PEFR

SYMPTOM SCORES

  • Change from baseline in symptom score (scale of 0 to 4)

  • % symptom‐free days

  • asthma exacerbations defined as worsening of asthma requiring a change in patient's asthma therapy other than increased use of supplemental albuterol

FUNCTIONAL STATUS: % Change from baseline mean daily B2‐agonist use (puffs/day)

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication (2001)

Funded by: Not reported

Confirmation of methodology and data extraction obtained/not requested/not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

All data presented, adverse events by group were mentioned, 3% and 8% patients were withdrawn in fluticasone and zafirlukast, not a intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined, but no bias was observed

Other bias

Low risk

No apparent other bias
NCT00442559

Methods

DESIGN: Parallel‐groups, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N = 191
M = 100
ICS = 91

WITHDRAWALS; N (%):
M: 34 (34%)
ICS: 35 (38.5%)

AGE: Mean ( years, SD):
M: 5.4 (3.0)
ICS: 6.1 (2.6)

GENDER: n (% male): 39 (20.4%)

BASELINE SEVERITY: Not mentioned

% Pred. FEV1 (Mean ± SD): Not reported

β2‐AGONIST USE (puffs per day): MEAN (± SD): Not reported

ATOPY: Not reported

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • Between 2 and 14 years old

  • Diagnosed with asthma, classified as mild persistent asthma according to Global Initiative Asthma Guidelines (GINA)

  • Diagnosed with comorbid allergic rhinitis

EXCLUSION:

  • Patients with suspected with nasal‐sinus infection

  • Prior treatment with high dose inhaled corticosteroid requiring a dose higher than beclomethasone dipropionate 400 μg per day, or equivalent, other medications used in severe cases

Interventions

PROTOCOL

Duration
Intervention: 12 weeks

TEST GROUP: Montelukast 4 ‐ 5 mg per day

CONTROL GROUP: ICS

DEVICE: Not reported

CO‐INTERVENTION: None permitted

Outcomes

PER PROTOCOL ANALYSIS (not ITT)

OUTCOMES reported at 12 week endpoint

PULMONARY FUNCTION TESTS: Not reported

SYMPTOM SCORES:

  • *Change from baseline for daytime asthma symptom score

  • Change from baseline for daily allergic rhinitis symptom score

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

Not reported

Notes

Unpublised data (2008)

Funded by: Merck

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Open‐label

Incomplete outcome data (attrition bias)
All outcomes

Low risk

High withdrawal rate but balanced in both groups

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were reported

Other bias

Low risk

No apparent other bias
Ng 2007

Methods

DESIGN: Cross over, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED:
N =19
M = 13
BD = 15

WITHDRAWALS; N (%)
M: 5 (38%)
BD: 7 (47%)

AGE: Mean±SD
M: 8.53 ± 2.17
BD: 8.39 ± 2.57

GENDER (% male):
M: 8 (61.54%)
BD: 9 (60%)

BASELINE SEVERITY: Not mentioned

% Pred. FEV1 (Mean ± SD): Not mentioned

β2‐AGONIST USE (puffs per day): MEAN (± SD): Not mentioned

ATOPY: Not mentioned

ASTHMA DURATION: Not mentioned

ELIGIBILITY CRITERIA:

  • Male and female patients between 6‐ to 14‐year of age with a history of newly diagnosed mild persistent asthma,

  • FEV1 ≥80% of the predicted value (after withholding β2‐agonist for ≥ 6 hours) and to improve by ≥15% after inhaled β2‐agonist, or if they have symptoms ≥ 1 time a week but < 1 time a day, or if their night‐time symptoms are >2 times a month,

EXCLUSION:

  • Prior use of budesonide DPI, previous intubation for asthma,

  • A history of chronic pulmonary disease other than asthma, upper respiratory tract infection within 3 weeks before the first study visit, or a history of an acute sinus disease requiring antibiotic treatment 1 week before the start of the study,

  • History of taking following medication: astemizole within three months; oral, inhaled or parenteral corticosteroids within one month; cromolyn, nedocromil, oral or long‐acting β2‐agonist, antimuscarinics, cimetidine, metoclopramide, phenobarbital, phenytoin, terfenadine, loratadine, or anticholinergic agents within two weeks and theophylline within one week before the pre‐study visit;

  • Patients on immunotherapy.

Interventions

PROTOCOL

Duration
Intervention: 4 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Not reported

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT ANALYSIS

OUTCOMES reported at 8 week endpoint

PULMONARY FUNCTION TESTS: *FEV‐1 % predicted

SYMPTOM SCORES: Proportion of symptom‐free day

FUNCTIONAL STATUS: % Change from baseline mean daily B2‐agonist use (puffs/day)

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication (2007)

Funded by: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: randomisation table was prepared by pharmacist 

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Dobule blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented; intention‐to‐treat analysis was done; reason for drop outs by groups were mentioned  

Selective reporting (reporting bias)

High risk

Primary outcome was presented; however the day time asthma symptoms and nocturnal awakenings (secondary outcomes) were not presented in details 

Other bias

Low risk

No apparent other bias
Ostrom 2005

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

ASTHMATIC PATIENTS WITH AT LEAST 6‐MONTH HISTORY OF CHRONIC ASTHMA AS PER ATS GUIDELINES

RANDOMISED:
N = 342
M = 170
FP = 172

WITHDRAWALS; N(%)
M: 21%
FP: 13%

AGE: Mean years (range):
M: 9.6 (6‐12)
FP: 9.1 (5‐12)

GENDER (% male):
M: 68%
FP: 63%

BASELINE SEVERITY:
‐FEV1 of 60% to 85% of predicted

% Pred. FEV1 (Mean ± SD)
M: 76.4 ± 8.5
FP: 75.4 ± 9.4

MEAN ± SD) β2‐AGONIST USE (puffs/day)
M=2.42 ± 0.12
FP=2.26 ± 0.12

ATOPY: Not reported

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • Age: 6‐12 years,

  • At least a 6‐month history of chronic asthma as per ATS,

  • On short‐acting b2‐agonist bronchodilators over the 3 months immediately before the study,

  • FEV1 of 60% to 85% of predicted values,

  • Equal or more than 12% increase in FEV1 within 30 minutes after two puffs of albuterol,

EXCLUSION:

  • Life‐threatening asthma,

  • Hospitalization for asthma within 3 months before the study,

  • Acute viral respiratory infections within 2 weeks before the study,

  • Use of inhaled or systemic corticosteroids, inhaled long‐acting b2‐agonists, anticholinergics, or anti‐leukotriene agents within pre‐defined intervals before the study

  • Inability of the parent or guardian to provide informed consent or to comply with the use of the study medications in the child

Interventions

PROTOCOL

Duration
Run‐in Period: 8‐14 days
Intervention: 12 weeks

TEST GROUP: Montelukast sodium chewable tablet 5 mg once daily

CONTROL GROUP: Fluticasone propionate 50 μg twice daily

DEVICE: DISKUS multi‐dose powder inhaler

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS by intention‐to‐treat

OUTCOMES reported at 12 weeks or endpoint

PULMONARY FUNCTION TESTS

  • *% Change from baseline FEV1

  • Change from baseline AM and PM PEFR

SYMPTOM SCORES

  • Daytime symptom scores,

  • Night‐time symptom scores

FUNCTIONAL STATUS

  • Total albuterol use

  • Daytime albuterol use

  • Night‐time albuterol use

  • Percent rescue‐free days

  • Daytime symptom scores,

  • Night‐time symptom scores,

  • Percent symptom‐free days

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full‐text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Details were not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy 

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All outcomes are reported including withdrawal rate and reasons for withdrawals were well described by group, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary outcomes was defined

Other bias

Low risk

No apparent other bias
Overbeek 2004

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

ATOPIC MILD ASTHMA PATIENTS

RANDOMISED:
N = 36
M = 19
BDP = 17

WITHDRAWALS; %
Total: 0%

AGE: mean (range) years

M = 24.5 (19–49)
BDP = 31.6 (19–57)

GENDER (% male): 55.56%

% Pred. FEV1 Mean ± SE
M = 88.3 ± 13.6
BDP = 84.9 ± 9.7

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • Non‐smoker, atopic, mild asthma inhaled corticosteroids receiving 4800 μg of beclomethasone dipropionate or equivalent,

  • Subjects were required to have a FEV1 of equal or more than 60% of the predicted value,

  • Change in FEV1 equal or more than 12% to salbutamol and a provocative concentration of methacholine (MCh) to cause a 20% drop in FEV1 (PC20MCh) of equal or less than 4 mg/mL,

  • Positive skin prick tests to HDM,

EXCLUSION:

  • History of respiratory infection or exacerbation of asthma in the month preceding the run‐in period,

  • Use oral or systemic corticosteroids 1 month prior to the run‐in period

Interventions

PROTOCOL

Duration
Run‐in Period: 8 weeks
Intervention: 8 weeks

TEST GROUP: Montelukast sodium capsule (10 mg nocte)

CONTROL GROUP: Fluticasone propionate (100 μg twice a day) by Diskus inhaler

DEVICE: DISKUS multi‐dose inhaler

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS by intention‐to‐treat. Not reported

OUTCOMES reported at 8 weeks

PULMONARY FUNCTION TESTS

  • Change from baseline FEV1

  • Change from baseline FEV1 % predicated

  • Change from baseline PC20

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MARKERS:

  • Total number of blood eosinophils,

  • Blood ECP

  • Serum IL‐5

  • UIrinary 9a,11b‐PGF2 and LTE4

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded by GlaxoSmithKline R&D, UK

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not mentioned

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There was no withdrawal rate; all patients completed the study

Selective reporting (reporting bias)

Low risk

All outcomes reported in the manuscript are reported, including adverse events

Other bias

Low risk

No apparent other bias
Peroni 2005

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

MILD ASTHMATIC CHILDREN ALLERGIC TO HOUSE DUST MITE

RANDOMISED:
N = 24
M = 12
BDP = 12

WITHDRAWALS; N(%): 3 (12.5%)

AGE: range years: 6‐13 years

GENDER (% male): 41.67%

% Pred. FEV1 (Median%)
M = 99%
BDP = 108%

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA

  • Subjects with aged 6‐13 years,

  • Having mild to moderate asthma according to the American Thoracic Society definition,

  • Positive skin prick tests to HDM,

EXCLUSION:

  • History of respiratory infection or exacerbation of asthma in at least 2 months before the beginning of the study,

  • Allergic to furred pets.

Interventions

PROTOCOL

Duration
Intervention: Not clear

TEST GROUP: Montelukast (5 mg administered once a day in the evening),

CONTROL GROUP: Budesonide (100 µg twice daily)

DEVICE: Turbuhaler

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS by intention‐to‐treat: Not reported

PULMONARY FUNCTION TESTS

  • Change from baseline FEV1

  • FENO level

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MARKERS: Sputum eosinophil cell count (%)

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funding source: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: used randomisation table prepared by a person not included in the study

Allocation concealment (selection bias)

Unclear risk

Sealed envelope were used to allocate drug however the concealment method is not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind; centralized randomisation table and placebo preparation

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Analysis was not done by intention‐to‐treat; Data from 8.3% and 16.6% of patients were not evaluated due to lack of compliance to treatment. 

Selective reporting (reporting bias)

Low risk

Primary outcome was not defined but not bias was observed

Other bias

Low risk

No apparent other bias
Peters 2007

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

ASTHMATIC PATIENTS

RANDOMISED:
N = 500
M = 165
FP = 169

WITHDRAWALS; N (%)
M = 20
FP = 13

AGE: Mean ± SD
M = 32.4 ± 15.4
FP = 29.3 ± 14.6

GENDER (% male):
M = 42.8
FP = 39.1

% of predicted value: mean ± SD At randomisation
M = 91.9 ± 11.1
BDP = 92.8 ± 10.4

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • Adequate adherence (i.e., completion of at least 10 of the previous 14 days of daily diary cards and fluticasone treatment for at least 21 of the previous 28 days),

  • A pre‐bronchodilator FEV1 of at least 80% of the predicted value,

  • A score on the Asthma Control Questionnaire17 of less than 1.5 (range, 0 to 6, with lower values indicating less‐severe asthma, and 0.5 unit as the minimal clinically important difference),

  • Fewer than 16 puffs of a rescue β2‐agonist used per week during the final 2 weeks of

  • the run‐in period (except as medication before exercise),

  • No hospitalizations, urgent medical care (for asthma), oral corticosteroid use, or use of

  • additional asthma medication during the run‐in period,

  • Absence of febrile illness (temperature exceeding 38.0°C, or 100.4°F) within the previous 24 hours.

Interventions

PROTOCOL

Duration
Run‐in Period: 4‐6 weeks
Intervention: 16 weeks

TEST GROUP: Montelukast (Singulair, GlaxoSmithKline), 5 mg once daily for children ages 6 to 14 years and 10 mg once daily for persons 15 years or older

CONTROL GROUP: Inhaled fluticasone propionate (100 μg twice daily)

DEVICE: Flovent Diskus

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS by intention‐to‐treat

OUTCOMES reported at 16 weeks

PULMONARY FUNCTION TESTS:

  • Treatment failure — no. of patients (%)

  • Percentage of predicted FEV1 value

  • Percentage of predicted FVC value

  • Percentage of predicted PEF value

SYMPTOM SCORES

  • Asthma control score

  • Asthma symptom unit index

  • Mini‐AQLQ score

FUNCTIONAL STATUS

  • ≥ 1 Nocturnal awakening

  • Symptoms and use of medication

INFLAMMATORY MARKERS: Not reported

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funding source: Unrestricted grant from GlaxoSmithKline, a grant from the American Lung Association.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: randomised using permuted‐block design stratified by clinic and age of patient.

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Placebo and matching montelukast tablets used for the study.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data reported in detail, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary and secondary data were well defined

Other bias

Low risk

No apparent other bias
Riccioni 2001

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 48
Z = 12
BUD = 12
Z+BUD = 12
Control = 12

WITHDRAWALS;
Z = 2 (16%)
BUD = 1 (8%)
Z+BUD = 2 (16%)

AGE: mean (± SD) years
Z: 33.75 (± 11.24)
BUD: 32.15 (± 10.27)
Z+BUD: 33.44 (± 11.12)
Control: 29.15 (± 10.34)

GENDER: N (% male):
Z: 6 (50)
BUD: 6 (50)
Z+BUD: 6 (50)
Control: 6 (50)

BASELINE SEVERITY: Mild persistent

% Predicted FEV1 (Mean ± SD)
Z: 94.75 ± 7.68
BUD: 92.75 ± 9.87
Z+BUD: 92.16 ± 5.06
Control: 95.75 ± 5.84

ATOPY/ALLERGEN TRIGGERS: Not reported

ASTHMA DURATION (years): 1 year

ELIGIBILITY CRITERIA:

  • 1 year of mild persistent bronchial asthma

  • PEF > 80% pred. and PEF daily variability in 20‐30% range with positive salbutamol reversibility test

EXCLUSION:

  • URTI in last 3 weeks

  • Hospitalizations for asthma in the last 3 months

  • Treatment with antihistamines, anticholinergic, inhaled corticosteroids, theophylline drugs

  • Presence of autoimmune, hepatic, or renal disorders

  • Malabsorption, drug or alcohol addiction

  • Pregnancy or lactation

Interventions

PROTOCOL

Duration
Run‐in Period: 2 weeks
Intervention: 8 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

TEST GROUP 2: Zafirlukast 20 mg twice a day + Budesonide 400 μg twice a day

CONTROL GROUP: Budesonide 400 μg twice a day

CONTROL GROUP 2: Placebo

DEVICE: Not reported

CO‐INTERVENTION: Not reported

Outcomes

ANALYSIS PER PROTOCOL (not by ITT)

OUTCOMES
Reported at 8 weeks

PULMONARY FUNCTION TEST

  • Pre‐ and post FVC values

  • Pre‐ and post FEV1

  • Pre‐ and post PC20

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Not mentioned

WITHDRAWALS: Not reported

Primary outcome: Not specified.

ICS dose in HFA beclomethasone ‐ equivalent

400 μg

Notes

Full‐text publication (2001)

Funded by University

Confirmation of methodology and data extraction: obtained from Graziano Riccioni, Oct 2003

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

Data on asthma diary, number of puffs used, compliance of treatment were mentioned in methodology but not addressed in the results 

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined, but no bias was observed

Other bias

Low risk

No apparent other bias
Riccioni 2002a

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology: Obtained (Oct 2003)

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 40
M = 20
BUD = 20

WITHDRAWALS: Reported

AGE: years ± SD
M = 25.16 ± 7.68
BUD = 26.18 ± 6.15

GENDER (% male):
M = 11 (55)
BUD = 10 (50)

ASTHMA SEVERITY: Mild and persistent

ASTHMA DURATION: Not mentioned

% Pred. FEV1:
M = 93.15 ± 12.17
BUD = 94.73 ± 10.18

Mean (± SD) β2‐agonist use (puffs per day): Not described

ATOPY:
M = 12 (60%)
BUD = 10 (40%)

PARTICIPANTS WITH ALLERGIC RHINITIS:
M: 2 (10%)
BUD: 2 (10%)

ELIGIBILITY CRITERIA:

  • Mild persistent asthma

  • FEV1 >80%

  • Daily variability of 20‐30% in PEF

  • Diagnosed with asthma by a specialist

EXCLUSION CRITERIA:

  • URTI in last 3 weeks

  • Hospitalizations for asthma in last 3 months

  • Inhaled and systemic corticosteroids

Interventions

PROTOCOL

Duration
Run‐in: 2 weeks
Intervention: 16 weeks

TEST GROUP: 10 mg Montelukast per day

CONTROL GROUP: 400 μg Budesonide twice a day

DEVICE: Turbuhaler

CRITERIA FOR WITHDRAWAL: Mentioned

CO‐INTERVENTION: Not permitted

Outcomes

ANALYSIS PER PROTOCOL
(no ITT analysis mentioned)

OUTCOMES: Reported at 16 weeks

PULMONARY FUNCTION TEST:

  • Change from baseline in FVC

  • Change from baseline in FEV1

  • Change from baseline in PC20

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not mentioned

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported (overall, not in details)

WITHDRAWALS: Reported

Primary outcome: not specified

ICS dose in HFA beclomethasone ‐ equivalent

400 μg

Notes

Full‐text publication

Funded by the University "G. D'Annunzio"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation

Allocation concealment (selection bias)

Unclear risk

not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐blind (patient and assessor)

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined but no bias was observed

Other bias

Low risk

Not found
Riccioni 2002b

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

CONFIRMATION OF METHODOLOGY: obtained (Oct 2003)

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 45
M = 15
BUD = 15
M+BUD = 15

WITHDRAWALS:
M = 1 (7%)
BUD = 1 (7%)
M+BUD = 1 (7%)

AGE: years ± SD
M = 26.7 ± 8.6
BUD = 26.9 ± 12.3
M+BUD = 28.2 ± 10

GENDER: N (% male):
M = 9 (60)
BUD = 8 (53.3)
M+BUD = 5(33.7)

ASTHMA SEVERITY: Mild

ASTHMA DURATION: 1 year

% Pred. FEV1: mean (range):
M = 97 (85‐123)
BUD = 97 (76‐123)
M+BUD = 99 (84‐131)

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY: 100% (Definition not mentioned)

ELIGIBILITY CRITERIA:

  • Asthma as per ATS criteria

  • Confirmation of the presence of BHR by methacholine on the initial visit

  • Regular attendance of the outpatient clinic over 4 months from the initial visit

  • PEF >= 80% of predicted

  • PEF variability <= 20% as per NIH criteria

EXCLUSION:

  • ER visit for asthma exacerbation within 1 month

  • URTI in the past 4 weeks

  • Hospitalizations for asthma in past 6 months

  • Treatment with antihistamines, anticholinergics, theophylline and chromones, LABA, inhaled and oral corticosteroids

  • Bronchiectasis

  • Gastroesophageal reflux

  • Poor knowledge of the Italian language

Interventions

PROTOCOL

Duration
Run‐in: 4 weeks

Intervention: 16 weeks

TEST GROUP 1: 10 mg Montelukast once daily

TEST GROUP 2: 10 mg Montelukast once daily + 400 μg Budesonide twice a day

CONTROL GROUP: 400 μg Budesonide twice a day

DEVICE: Turbo haler

CRITERIA FOR WITHDRAWAL: Not described

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS PER PROTOCOL: not by ITT

OUTCOMES: Reported at 16 weeks

PULMONARY FUNCTION TEST:

  • Change from baseline in FVC

  • Change from baseline in FEV1

  • Change from baseline in PC20

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS:

  • Change in AQOL (Asthma Quality of Life Questionnaire ‐ Juniper) in each of 4 domains

  • Asthma exacerbations (defined as requiring systemic corticosteroids or hospital admission or ED treatment for worsening asthma or decrease in morning PEF >25%

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Not mentioned

WITHDRAWALS: Reported

Primary outcome: Not specified

ICS dose in HFA beclomethasone ‐ equivalent

400 μg

Notes

Full‐text publication

Funded by University

Confirmation of methodology and data extraction: obtained by Graziono Riccioni, Oct 2003

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

Data on compliance of treatment and adverse effects were mentioned in methodology but not addressed in the results 

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined, but no bias was observed

Other bias

Low risk

No apparent other bias
Riccioni 2003

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

ATOPIC NON‐SMOKING MILD‐PERSISTENT BRONCHIAL ASTHMATICS

RANDOMISED: N = 45
N = 51
M = 12
BUD = 14

WITHDRAWALS: Not mentioned

AGE: years ± SD:
M = 26.16 ± 5.07
BUD = 25.85 ± 10.46

GENDER (% male):
M = 58.33%
BUD = 57.14%

ASTHMA SEVERITY: Mild

ASTHMA DURATION: 1 year

% Pred. FEV1: mean ± SD:
M=94.75 ± 7.68
BUD = 99.85 ± 12.92

ATOPY: 100% (Dermatophagoides Pteronyssinus)

ELIGIBILITY CRITERIA:

  • Asthma based on typical symptoms improvement in pre‐bronchodilator forced expiratory volume in one second (FEV1) ± 15% after salbutamol,

  • FEV1 between 60 and 85% of predicted value as per NIH criteria

EXCLUSION:

  • Emergency treatment for an asthma exacerbation within one month,

  • URTI in the past 3 weeks,

  • Hospitalization for asthma in past 3 months previous to enrolment,

  • Treatment with antihistamines, anticholinergics, theophyline and chromones, b2‐long acting, inhaled and oral corticosteroids

  • Presence of autoimmune, hepatic or renal disorders, malabsorption, drug or alcohol‐addiction

  • Pregnancy or lactation

Interventions

PROTOCOL

Duration
Run‐in: 2 weeks
Intervention: 12 weeks

TEST GROUP 1: 10 mg Montelukast once daily

CONTROL GROUP: 400 μg Budesonide twice a day

DEVICE: Not mentioned

CRITERIA FOR WITHDRAWAL: Not described

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS : Not mentioned

OUTCOMES
Reported at 12 weeks

PULMONARY FUNCTION TEST:

  • Baseline and end values of %FEV1 of predicted

  • Baseline and end values of PEF % of predicted

  • Bronchial responsiveness baseline and end values PC20

SYMPTOM SCORES: Not reported

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Not mentioned

WITHDRAWALS: Not reported

Primary outcome: Not specified

ICS dose in HFA beclomethasone ‐ equivalent

400 μg

Notes

Full‐text publication

Funded: Not reported.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There is no report as to whether some patients withdrew from the study after randomisation

Selective reporting (reporting bias)

High risk

The primary outcome was not specified. The data on several outcomes was insufficiently reported to be aggregated namely,  number of puffs used each day; daily asthma diary; adverse events, FVC, compliance of treatment were not reported

Other bias

Low risk

No apparent other bias
Sheth 2001

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: unclear if stratified randomisation on baseline FEV1 value
FEV1 > 70%
N = 152
Z = 55
FP = 51
Placebo = 46

FEV1 < 70%
N = 177
Z = 52
FP = 60
Placebo = 65

WITHDRAWALS: Not reported

AGE: mean (± SD) years: Not reported

GENDER (% male): Not reported

BASELINE SEVERITY: Not reported

% Predicted FEV1:
(FEV1 > 70%)
Z: 75%
FP:76%
Placebo: 76%

(FEV1 < 70%)
Z: 63%
FP: 62%
Placebo: 63%

ATOPY/ALLERGEN TRIGGERS: Not reported

ASTHMA DURATION (years): Not reported

ELIGIBILITY CRITERIA:

  • ≽12 years old

  • Symptomatic on β2‐agonists

EXCLUSION: Not reported

Interventions

PROTOCOL

Duration
Intervention: 12 weeks

TEST GROUP: Zafirlukast 20 mg twice a day

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Not mentioned

CRITERIA FOR WITHDRAWAL: Not mentioned

CO‐INTERVENTION: Not mentioned

Outcomes

ANALYSIS (ITT)

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS

  • *Change from baseline FEV1 (L)

  • Change from baseline in morning PEF (L/s)

SYMPTOM SCORES: Change in symptom‐free days (%)

FUNCTIONAL STATUS: Change from baseline in rescue β2‐agonist use (puffs/day)

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Not reported

WITHDRAWALS: Not reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Abstract

Funding not mentioned, probably by GSK

Confirmation of methodology and data extraction: Not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated randomisation

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐blind ‐double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Primary outcome was defined

Other bias

Low risk

No apparent other bias
Sorkness 2007

Methods

DESIGN: Parallel‐group, clinical trial.

Participants

CHILDREN WITH MILD TO MODERATE PERSISTENT ASTHMA

RANDOMISED: N = 285

M = 95
FP = 96

WITHDRAWALS:
M: 12 (12.63%)
FP: 10 (9.6%)

AGE: mean ± SD years
M: 9.6 ± 2.2
FP: 9.8 ± 2.2

GENDER: % male
M: 60.0%
FP: 59.4%

ASTHMA SEVERITY: Mild to moderate

% Pred. FEV1 (mean ± SD):
M: 97.7 ± 13.6

FP:97.8 ± 12.2

ATOPY or ALLERGIC RHINITIS:
M: 76.8%
FP: 78.1%

ELIGIBILITY CRITERIA:

  • Age 6 to <= 14 years

  • Ability to perform reproducible spirometry, an FEV1 (measured more than 4 hours since the most recent use of a bronchodilator) 80% predicted normal at screening and 70% predicted normal at randomisation,

  • Methacholine FEV1 PC20 12.5 mg/mL,

  • Children with mild‐moderate persistent asthma, as defined by diary‐reported symptoms or β2‐agonist use (not including pre exercise) or peak flows < 80% calculated from the mean of morning and evening peak flows obtained during the final week of the run‐in period, on average at least 3 times per week

EXCLUSION:

  • Other lung diseases

  • Respiratory tract infection, asthma exacerbation, or systemic corticosteroid use within 4 weeks;

  • 2 or more asthma hospitalizations in the past year,

  • History of a life‐threatening asthma exacerbation,

  • 4 courses of systemic corticosteroids in the past year,

  • Cigarette smoking within the past year,

  • Pregnancy or lactation,

  • Failure to practice abstinence or use a medically acceptable birth

  • Control method,

  • History of adverse reactions to the PACT medications

Interventions

PROTOCOL

Duration
Run‐in Period: 2‐4 weeks

Intervention Period: 486 weeks

TEST GROUP: Montelukast 10 mg qd p.o.

CONTROL GROUP 1: Fluticasone propionate 100 μcg morning and 100 μcg evening

DEVICE: Flovent Diskus; GlaxoSmithKline

CO‐INTERVENTION: None permitted

Outcomes

ANALYSIS by Intention‐to‐treat

OUTCOMES reported at 48 weeks

PULMONARY FUNCTION TESTS:

  • FEV1, % predicted

  • FEV1/FVC (%)

  • AM PEF, % predicted

  • PM PEF, % predicted

SYMPTOM SCORES: Asthma control questionnaire

FUNCTIONAL STATUS:

  • *Asthma control days, % of treatment days

  • Episode‐free days, %

  • Growth, cm

INFLAMMATORY MEDIATORS: ENO, %

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

*Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: randomisation was stratified by centre

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind; double‐dummy with identical placebo

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Approximately 12% of withdrawal, balanced between  groups but the reasons for withdrawal were not specified by group.   

Selective reporting (reporting bias)

Low risk

All outcomes reported in the manuscript are reported, including adverse events

Other bias

Low risk

No apparent other bias
Stelmach 2002a

Methods

DESIGN: Parallel‐group, randomised, clinical trial.
Confirmation of methodology: Obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 91
M: 18
Triamcinolone: 19
Formoterol: 18
Placebo: 36

WITHDRAWALS:
M: 3 (17%)
Triamcinolone: 3 (17%)

AGE: years ± SD: (without withdrawals):
M: 11.1 ± 1.8 yr
Triamcinolone:12.2 ± 2.1 yr

GENDER (% male):
M: 60%
Triamcinolone:55%

ASTHMA SEVERITY: Moderate

% Pred. FEV1 % (± SD):
M: 78.1 ± 3.1
Triamcinolone:73.5 ± 4.3

Mean (± SD) β2‐agonist use (puffs/day): Not described

ALLERGIC RHINITIS:
M: 15%
Triamcinolone: 10%

ATOPY (to dust mites):
M: 100%
Triamcinolone: 100%

DURATION OF ASTHMA:
M: 3.8 ± 0.6
Triamcinolone:3.7 ± 0.5

ELIGIBILITY CRITERIA:

  • Age: 6‐18 years

  • Asthma definition as per the NIH 1997

  • Improvement in FEV1 >= 15% after 200 μg salbutamol

  • Current tx with only β2‐agonist

  • Use of β2‐agonist daily, attacks that limit daily activity, night‐time symptoms >1 / week, PEF 60‐80% of predicted, PEF variability >30%

EXCLUSION:

  • Co‐existent diseases (hepatic, gastrointestinal, renal, endocrine, neurologic, cardiovascular, malignancy, other pulmonary or hematologic disease, active upper respiratory tract infections.

  • Medication: B‐blockers, astemizole, oral corticosteroids, immunotherapy.

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks
Intervention Period: 8 weeks

TEST GROUP: Montelukast 5 mg per day if <=14 years (10 mg per day, otherwise)

CONTROL GROUP 1: Inhaled Triamcinolone acetonide 100ug/day qid

CONTROL GROUP 2: Placebo (not used in this review)

CONTROL GROUP 3: Formoterol 12 μg twice a day (not used in this review)

DEVICE: MDI (actuation inhaler)

CO‐INTERVENTION: No other Rx allowed other than rescue b2‐agonists or rescue oral corticosteroids

Outcomes

ANALYSIS per protocol

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS: Change from baseline FEV1 ‐Change from baseline in PC 20

SYMPTOM SCORES: Total score (3‐point for daytime symptoms + 3‐point for night‐time symptoms + 3 points for use of rescue β2‐agonists)

FUNCTIONAL STATUS: Patients with exacerbations requiring systemic corticosteroids

INFLAMMATORY MEDIATORS:

  • Change from baseline in serum eosinophils

  • Change from baseline in serum IL‐10

  • Change from baseline in serum ECP

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome not specified

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full Text publication (2002)

Self‐funded by authors

Confirmation of methodology and data obtained from I. Stelmach June 2003

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, reasons for withdrawal were mentioned

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined, but no bias was observed

Other bias

Low risk

No apparent other bias
Stelmach 2002b

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N =154
M: 27
Triamcinolone: 28
Formoterol: 28
Nedocromil: 26
Placebo: 45

WITHDRAWALS (N = 14)
M: 11% (3/27)
Triamcinolone: 11 % (3/28)
Formoterol: 11% (3/28)
Nedocromil: 0%
Placebo: 12% (40/45)

AGE: years ± SD:
M: 12.8 ± 1.7 yr
Triamcinolone:13,1 ± 2.4 yr

GENDER (% male):
M: 48.1%
Triamcinolone:53.6 %

ASTHMA SEVERITY: Moderate asthma

% Pred. FEV1 % ±SD: ‐ after withdrawals
M: 73.7 ± 5.4
Triamcinolone:73.2 ± 3.8

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY (described as chronic atopic):
M: 100%
Triamcinolone: 100%

ALLERGIC RHINITIS:
Montelukast: 7.1%
Triamcinolone:10.7%

DURATION OF ASTHMA (years):
M: 3.8 ± 0.5
Triamcinolone: 3.7 ± 0.6

ASTHMA SYMPTOMS:
M: 6.2 ± 1.0
Triamcinolone: 7.1 ± 0.9 (score of 0‐9)

ELIGIBILITY CRITERIA:

  • Age= 9‐17 years

  • Asthma definition according to NIH 1997

  • Reversibility: improvement in FEV1 >= 15% after 200 μg salbutamol

  • Use of β2‐agonist daily, attacks that limit daily activity, night‐time symptoms >1 / week, PEF 60‐80% of predicted, PEF variability >30%

EXCLUSION:

  • Co‐existent diseases (hepatic, gastrointestinal, renal, endocrine, neurologic, cardiovascular, malignancy, other pulmonary or haematologic disease, active upper respiratory tract infections.

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks
Intervention Period: 4 weeks

TEST GROUP: Montelukast 5 mg per day if <= 14 years (10 mg per day, otherwise)

CONTROL GROUP 1: Inhaled Triamcinolone acetonide 200ug twice a day

CONTROL GROUP 2: Placebo (not used in this review)

CONTROL GROUP 3: Formoterol 12 μg twice a day (not used in this review)

CONTROL GROUP 4: Nedocromil 0.002 g/inhalation 2 inhalations qid (not used in this review)

DEVICE: MDI (actuation inhaler)

CO‐INTERVENTION: No other Rx allowed other than rescue β2‐agonist or rescue systemic corticosteroids.

Outcomes

ANALYSIS per protocol

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS: Change from baseline FEV1 ‐Change from baseline in PC 20

SYMPTOM SCORES: Total score (3‐point for daytime symptoms + 3‐point for night‐time symptoms + 3 points for use of rescue β2‐agonists)

FUNCTIONAL STATUS
Patients with exacerbations requiring systemic corticosteroids

INFLAMMATORY MEDIATORS:

  • Change from baseline in serum eosinophils

  • Change from baseline in serum ECP

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported overall (not by group)

Primary outcome: Not specified

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full Text publication (2002)

Self‐Funded

Confirmation of methodology and data obtained from I. Stelmach June 2003

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, overall reasons for withdrawal were mentioned

Selective reporting (reporting bias)

Low risk

Primary outcome was not defined but no bias was observed

Other bias

Low risk

Not found
Stelmach 2004

Methods

DESIGN: Three armed, parallel‐group, randomised, clinical trial.

Participants

CHILDREN WITH HISTORY OF ASTHMA AND SENSITIVE TO HOUSE DUST MITES (DERMATOPHAGOIDES PTERONYSSINUS AND/OR DERMATOPHAGOIDES FARINE)

RANDOMISED: N =250
M: 80
Triamcinolone: 83

WITHDRAWALS: N = 4
M: 2.5%
Triamcinolone: 2.41%

AGE: years ± SD:
M: 12.6 ± 2.097 yr
Triamcinolone:11.9 ± 1.51 yr

GENDER (% male):
M: 57.69 %
Triamcinolone:54.32 %

ASTHMA SEVERITY: Mild to moderate asthma

% Pred. FEV1 % ±SD ‐ after withdrawals:
M: 76.2 ± 5.16
Triamcinolone:74.3 ± 3.88

ATOPY (described as chronic atopic):
M: 100%
Triamcinolone: 100%

DURATION OF ASTHMA (years):
M: 3.9 ± 0.58
Triamcinolone: 3.7 ± 0.54

ASTHMA SYMPTOMS:
M: 6.6 ± 1.05
Triamcinolone: 6.9 ± 0.99

ELIGIBILITY CRITERIA:

Age= 6‐18 years

  • Diagnosis of bronchial asthma with a duration of at least 6 months before the first visit

  • Had been no exacerbations or need for any other treatment for 6 months and no hospitalizations for asthma occurred within 6 months of the pre study visit

Interventions

PROTOCOL

Duration
Run‐in Period: Not mentioned
Intervention Period: 4 weeks

TEST GROUP: Montelukast 5 mg tablets in children aged 6–14 yr or 10 mg tablets in children over 14 yr of age

CONTROL GROUP 1: Inhaled Triamcinolone acetonide two puffs twice a day (400 μg/day),

DEVICE: Azmacort, Aventis, USA

CO‐INTERVENTION: No other Rx allowed other than rescue b2‐agonists or rescue oral corticosteroids

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT: Not reported

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS:

  • Baseline and end point FEV1% of predicted

  • Baseline and end point in PC20

SYMPTOM SCORES: Total asthma score

INFLAMMATORY MEDIATORS: Eosinophil blood count

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported overall (not by group)

Primary outcome not specified

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full Text publication

Funded: Not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule 

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Open labelled

Incomplete outcome data (attrition bias)
All outcomes

Low risk

The withdrawal rate was low (2%) and balanced between  groups and the reasons for withdrawal were specified by group.  

Selective reporting (reporting bias)

High risk

The primary  outcome was not specified and the results of the Paediatric asthma quality of life questionnaire and adverse effects were not presented. The data was not reported as analysed by intention‐to‐treat analysis.

Other bias

Low risk

No apparent other bias
Stelmach 2005

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

CHILDREN WITH NEWLY DIAGNOSED ASTHMA AND SENSITIVE TO HOUSE‐DUST MITES (DERMATOPHAGOIDES PTERONYSSINUS AND/OR DERMATOPHAGOIDES FARINE)

RANDOMISED: N = 51
M: 17
Medium dose BD (400 mg/day): 16

High dose BD (800 mg/day): 18

WITHDRAWALS: N = 2
M: 5.88%
Medium dose BP (400 mg/day): 6.25%

AGE: years ± SD
M: 12.1 ± 1.6

Medium dose BD (400 mg/day): 11.6 ± 1.4

High dose BD (800 mg/day): 11.6 ± 1.8

GENDER: % male:

M: 56.3

Medium dose BD (400 mg/day): 60

High dose BD (800 mg/day): 55.6

ASTHMA SEVERITY: Newly diagnosed asthma and sensitive to house‐dust mites (Dermatophagoides pteronyssinus or/and Dermatophagoides farinae)

% Pred. FEV1 % ±SD ‐ after withdrawals:

M: 83.4 ± 0.4

Medium dose BD (400 mg/day): 84.3 ± 0.5

High dose BD (800 mg/day): 83.4 ± 0.3

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY (described as chronic atopic): Not described

ALLERGIC RHINITIS: Not described

DURATION OF ASTHMA (years): Not described

ASTHMA SYMPTOMS: Not described

ELIGIBILITY CRITERIA:

  • Age: 6–18

  • Newly diagnosed asthma and sensitive to house‐dust mites (Dermatophagoides pteronyssinus or/and Dermatophagoides farinae),

  • Diagnosis of asthma based on typical symptoms and improvement in the pre bronchodilator forced

  • expiratory volume in 1 sec (FEV1) of R15% after salbutamol (200 mg).

  • Not received corticosteroids and anti‐leukotriene therapy prior to the study.

Interventions

PROTOCOL

Duration
Run‐in Period: Not mentioned
Intervention Period: 6 months

TEST GROUP: Montelukast sodium 5 mg tablets in children aged 6–14 yr or 10 mg tablets in children over 14 yr of age

CONTROL GROUP 1 (Medium dose): Inhaled Budesonide 400 mg/day

CONTROL GROUP 2 (High dose): Inhaled Budesonide 800 mg/day

DEVICE: Dry powder capsule (Miflonide, Novartis, Switzerland)

CO‐INTERVENTION:: No other Rx allowed other than rescue b2‐agonists

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT: Not reported

OUTCOMES reported at 6 months

PULMONARY FUNCTION TESTS: FEV1% of predicted

SYMPTOM SCORES: Total asthma score

INFLAMMATORY MEDIATORS:

  • *Total IgE (IU/ml)

  • *Dermatophagoides pteronyssinus (IU/ml)

  • *Dermatophagoides farinae (IU/ml)

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported by group

*Primary outcomes

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full Text publication

Funded: Not mentioned

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Doubl blind, double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

The withdrawal rate was low, balanced between groups with reasons for withdrawal reported by group. 

Selective reporting (reporting bias)

Low risk

All outcomes reported in the manuscript are reported, including adverse events

Other bias

Low risk

No apparent other bias
Stelmach 2007

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

CHILDREN WITH NEWLY DIAGNOSED ASTHMA AND SENSITIVE TO HOUSE‐DUST MITES (DERMATOPHAGOIDES PTERONYSSINUS AND/OR DERMATOPHAGOIDES FARINE)

RANDOMISED: N = 51
M: 29

BD: 29

M + BD: 29

Formoterol + BD: 29

Placebo: 29

WITHDRAWALS: N = 2

M: 0

BD: 0

M + BD: 0

Formoterol + BD: 0

Placebo: 2

AGE: years ± SD

M: 10.4 ± 2.9

BD: 12 ± 3.1

M + BD: 11 ± 3.2

Formoterol + BD: 8.79 ± 2.4

Placebo: 11.4 ± 3.3

GENDER: % male

M: 62.1

BD: 69

M + BD: 69

Formoterol + BD: 58.6

Placeboe: 70.4

ASTHMA SEVERITY: Newly diagnosed asthma and sensitive to house‐dust mites (Dermatophagoides pteronyssinus or/and Dermatophagoides farinae)

% Pred. FEV1 % ± SD:

M: 95.5 ± 2.1

BD: 94.4 ± 1.8

M + BD: 94.8 ± 2.1

Formoterol + BD: 93.1 ± 2.3

Placebo: 94.8 ± 1.8

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY (described as chronic atopic): Not described

ALLERGIC RHINITIS: Not described

DURATION OF ASTHMA (years ± SD):

M: 3.85 ± 0.61

BD: 3.97 ± 0.52

M + BD: 3.79 ± 0.58

Formoterol + BD: 3.93 ± 0.63

Placebo: 3.88 ± 0.47

ASTHMA SYMPTOMS: Not described

ELIGIBILITY CRITERIA:
INCLUSION CRITERIAS:

  • Male and female outpatients,

  • Aged 6–18,

  • With a clinical diagnosis of bronchial asthma with a duration of at least 6 months before the first visit

  • With current history of moderate persistent asthma

EXCLUSION CRITERIAS:

  • With active upper respiratory tract infection within 3 weeks before the study and acute sinus disease requiring antibiotic treatment within 1 month before the study, previous intubation, or asthma hospitalisation during the 3 months before the first visit.

  • Other clinically significant pulmonary, hematologic, hepatic, gastrointestinal, renal, endocrine, neurologic, cardiovascular, and/or psychiatric diseases or malignancy that either put the patient at risk when participating in the study or could influence the results of the study or the patient’s ability to participate in the study as judged by the investigator.

  • On beta‐blockers (eye drops included), astemizole within 3 months, or oral corticosteroids within 1 month before the first visit. Patients who were receiving immunotherapy

Interventions

PROTOCOL

Duration
Run‐in Period: Not mentioned
Intervention Period: 4 weeks

TEST GROUP: Montelukast sodium 5 mg tablets in children aged 6–14 yr or 10 mg tablets in children over 14 yr of age

CONTROL GROUP 1: Inhaled Budesonide 200 mg/day

CONTROL GROUP 2: Montelukast 5 or 10 mg tablets and Inhaled Budesonide200 mg/day

CONTROL GROUP 3: Formoterol mg/day and Inhaled Budesonide200 mg/day

CONTROL GROUP 4: Placebo

DEVICE: Turbuhaler

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT: Not reported

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS:

  • FEV1% of predicted

  • FEF25–75 (% pred.)

  • SRaw (% pred.)

  • Rint (% pred.)

SYMPTOM SCORES: Not described

INFLAMMATORY MEDIATORS: Not described

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported by group

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full Text publication

Funded: Grants from the Medical University of Lodz, Poland

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule 

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind; double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, balanced numbers in all groups, reason for withdrawal by group reported,

Selective reporting (reporting bias)

Low risk

Primary and secondary outcome was not specified but no bias was observed

Other bias

Low risk

No apparent other bias
Stelmach 2008

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

CHILDREN WITH SYMPTOMATIC ASTHMA AND SENSITIVE TO HOUSE‐DUST MITES (DERMATOPHAGOIDES PTERONYSSINUS AND/OR DERMATOPHAGOIDES FARINE)

RANDOMISED: N =100
M: 20

BD: 20

M + BD: 20

Formoterol + BD: 20

Placebo: 20

WITHDRAWALS: N = 9
M: 3

BD: 0

M + BD: 3

Formoterol + BD: 2

Placebo: 1

AGE: years (range)

M: 11.8 (7‐17)

BD: 11.9 (6‐16)

M + BD: 12.2 (7‐18)

Formoterol + BD: 11.3 (6‐18)

Placebo: 12.1 (7‐15)

GENDER (% male): Not reported

ASTHMA SEVERITY: Not reported

% Pred. FEV1 % ±SD:

M: 93.5 ± 11.4

BD:92.2 ± 13.5

M + BD: 90.2 ± 10.2

Formoterol + BD: 91.1 ± 11.2

Placebo: 92.4 12.7

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY (described as chronic atopic): Not described

ALLERGIC RHINITIS: Not described

DURATION OF ASTHMA (years): Not reported

ASTHMA SYMPTOMS: Not reported

INCLUSION CRITERIAS:

  • Male and female outpatients,

  • Age 6 to 18,

  • With a clinical diagnosis of bronchial asthma with a duration of at least 6 months before the first visit

  • FEV1 of 70% or more and a documented decrease in FEV1 of 20% or more after a standard exercise challenge test.

EXCLUSION CRITERIAS:

  • With active upper respiratory tract infection within 3 weeks before the study and acute sinus disease requiring antibiotic treatment within 1 month before the study, previous intubation, or asthma hospitalizations during the 3 months before the pre study visit.

  • Other clinically significant pulmonary, hematologic, hepatic, gastrointestinal, renal, endocrine, neurologic, cardiovascular, and/or psychiatric diseases or malignancy that either put the patient at risk when participating in the study or could influence the results of the study or the patient’s ability to participate in the study as judged by the investigator.

  • On β2‐blockers (eye drops included) or oral corticosteroids within 1 month before the first visit.

  • On immunotherapy

Interventions

PROTOCOL

Duration
Run‐in Period: Not mentioned
Intervention Period: 4 weeks

TEST GROUP: Montelukast sodium 5 mg tablets in children aged 6–14 yr or 10 mg tablets in children over 14 yr of age

CONTROL GROUP 1: Inhaled Budesonide 200 mg/day

CONTROL GROUP 2: Montelukast 5 or 10 mg tablets and Inhaled Budesonide200 mg/day

CONTROL GROUP 3: Formoterol mg/day and Inhaled Budesonide200 mg/day

CONTROL GROUP 4: Placebo

DEVICE: Turbuhaler

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT: Not reported

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS: AUC0‐20min of FEV1

Maximum % fall in FEV1

SYMPTOM SCORES: Not described

INFLAMMATORY MEDIATORS: Not described

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full Text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind; double‐dummy

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

The overall withdrawal rate was 10% (N = 9)  but it was not presented by group. This might be of importance as the only reason for withdrawal was poor efficacy. 

Selective reporting (reporting bias)

Low risk

Primary outcome was not  pre‐specified however no bias was observed

Other bias

Low risk

No apparent other bias
Szefler 2005

Methods

DESIGN: Cross‐over, randomised, clinical trial.

Participants

PATIENTS WITH MILD TO MODERATE PERSISTENT ASTHMA

RANDOMISED: N = 144

WITHDRAWALS: no (%)

N = 17, (11.81%)

M: 11 (7.64%)

FP: 6 (4.17%)

AGE: years ± SD: Not reported

GENDER (% male): Not reported

ASTHMA SEVERITY: Not reported

% Pred. FEV1 % ± SD: Not reported

Mean (± SD) β2‐agonist use (puffs/day): Not reported

ATOPY: Not reported

ALLERGIC RHINITIS: Not reported

DURATION OF ASTHMA (years): Not reported

ASTHMA SYMPTOMS:Not reported

INCLUSION CRITERIAS:

  • Children with 6 to 17 years of age with mild‐to‐moderate asthma

  • Had asthma symptoms or rescue bronchodilator use on average of 3 or more days per week during

  • the previous 4 weeks

  • Improvement in FEV1 of 12% or greater after maximal bronchodilation or methacholine PC20 of 12.5 mg/mL

  • or less.

  • Had no corticosteroid treatment within 4 weeks, no leukotriene‐modifying agents within 2 weeks,

  • No history of respiratory tract infection within 4 weeks of enrolment

EXCLUSION CRITERIAS:

  • Had severe asthma or FEV1 of less than 70% of predicted value,

Interventions

PROTOCOL

Duration
Run‐in Period: not reported
Intervention Period: 52 weeks

TEST GROUP: Montelukast sodium 5‐mg chewable tablet for those 6 to 14 years of age and 10‐mg tablet for those 15 to 18 years of age

CONTROL GROUP 1: Flovent Diskus, 100 μg per inhalation administered as one inhalation twice a day

DEVICE: Diskus

Outcomes

ANALYSIS NOT BY INTENTION‐TO‐TREAT

OUTCOMES reported at 8 weeks

PULMONARY FUNCTION TESTS:

  • *Prebronchodilator FEV1 % predicted

  • Prebronchodilator FEV1/FVC (%)

FUNCTIONAL TESTS:

  • Bronchodilator use per week

  • Maximum bronchodilator response (% change in FEV1)

  • Methacholine PC20 (mg/mL)

SYMPTOM SCORES: Not reported

INFLAMMATORY MEDIATORS:

  • eNO (ppb)

  • Blood TEC (cells/mm3)

  • Serum ECP (mg/L)

  • Serum IgE (kU/L)

  • uLTE4 (pg/mg creatinine)

ADVERSE EVENTS: Reported by groups

WITHDRAWALS: Reported

*Primary outcomes

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full Text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: by minimization method for several factors

Allocation concealment (selection bias)

Unclear risk

Nnot reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

No intention‐to‐treat analysis, 8.4% and 15.1% of withdrawal in ICS and montelukast groups respectively

Selective reporting (reporting bias)

Low risk

Primary outcome was specified

Other bias

Low risk

No apparent other bias
Szefler 2007

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

PATIENTS WITH MILD PERSISTENT ASTHMA

RANDOMISED: N = 395
M: 198

BD: 197

WITHDRAWALS: no (%)

N = 115, (29.1%)

M: 52 (26.40%)

BD: 63 (31.98%)

AGE: years ± SD

M: 4.7 ± 1.9

BD: 4.6 ± 2.0

GENDER (% male):

M: 118 ± 59.9

BD: 122 ± 61.9

ASTHMA SEVERITY: Not reported

% Pred. FEV1 % ± SD:

M: 91.67 ± 18.07

BD:89.88 ± 17.75

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY (described as chronic atopic): Not described

ALLERGIC RHINITIS: Not described

DURATION OF ASTHMA (years): Not reported

ASTHMA SYMPTOMS: Not reported

INCLUSION CRITERIAS:

  • Children 2 to 8 years of age with symptoms of mild persistent asthma as determined by 2002 NAEPP

  • guidelines1 or had, in the year before screening,

  • History of 3 wheezing episodes that lasted > 1 day and affected sleep.

  • A cumulative asthma symptom score (daytime plus night‐time) of 2 on 3 of 7 consecutive days,

EXCLUSION CRITERIAS:

  • History of severe or unstable asthma;

  • Hypersensitivity to budesonide or montelukast sodium;

  • A clinically significant disease (past or present) or other medical condition that, in the opinion of the investigator, could interfere with the study or place the subject at risk because of participation in the study;

  • Acute exacerbation of asthma or a respiratory tract infection within 30 days before screening that, in the

  • opinion of the investigator, could have affected the results of the study;

  • Used montelukast or an inhaled corticosteroids within 1 week of screening, systemic corticosteroids within 2 weeks of screening or during the run‐in period, or omalizumab within 6 months of screening

Interventions

PROTOCOL

Duration
Run‐in Period: 3‐21 days
Intervention Period: 52 weeks

TEST GROUP: Montelukast sodium 4 or 5 mg tablets

CONTROL GROUP 1: Budesonide inhalation suspension 0.5 mg/day

DEVICE: Not described

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT

OUTCOMES reported at 52 weeks

PULMONARY FUNCTION TESTS:

  • AM PEF

  • PM PEF

  • FEV1 (L)

  • % Predicted FEV1

FUNCTIONAL TESTS:

  • *Time to first additional asthma medication for mild or severe asthma exacerbation,

  • Exacerbations

  • Rescue medication–free days, %

  • Asthma‐free days, %

SYMPTOM SCORES

  • AM asthma symptom score

  • PM asthma symptom score

INFLAMMATORY MEDIATORS: Not described

ADVERSE EVENTS: Reported by groups

WITHDRAWALS: Reported

*Primary outcomes

ICS dose in HFA beclomethasone ‐ equivalent

250 μg

Notes

Full Text publication

Funded: AstraZeneca LP

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Open labelled and study subjects could be discontinued at any time at the discretion of the investigators.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

the withdrawal data is presented by group, however the large withdrawal rate (29%), similar in both group, while acceptable for the main outcome (time to event) raise doubt about the validity of the secondary outcomes

Selective reporting (reporting bias)

Low risk

All outcomes are reported

Other bias

Low risk

No apparent other bias
Tamaoki 2008

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Participants

NEWLY DIAGNOSED MILD INTERMITTENT ASTHMA PATIENTS

RANDOMISED: N = 85
PRAN: 42

BD: 43

WITHDRAWALS: no (%)

N = 11 (12.94%)

PRAN: 6 (14.29%)

BD: 5 (11.63%)

AGE: years ± SD

PRAN: 36 ± 3

BD: 38 ± 4

GENDER (% male)

PRAN: 27.7

BD: 26.32

ASTHMA SEVERITY: Not reported

% Pred. FEV1 % ± SD:

PRAN: 84.6 ± 2.0

BD: 85.0 ± 2.1

Mean (±SD) β2‐agonist use (puffs/day): Not described

ATOPY (described as chronic atopic): Not described

ALLERGIC RHINITIS: Not described

DURATION OF ASTHMA (years):

PRAN: 1.6 ± 1.1

BD: 2.0 ± 1.2

ASTHMA SYMPTOMS SCORE:
PRAN: 5.4 ± 0.4

BD: 5.7 ± 0.5

INCLUSION CRITERIAS:

  • Newly diagnosed mild intermittent asthma aged 21 years,

  • Whose daytime symptoms of less than once a week but at least once during 3 months before the study,

  • FEV1 or PEF of 80% of predicted normal and diurnal variation of PEF 20%

EXCLUSION CRITERIAS:

  • Treated with inhaled or systemic corticosteroids, inhaled long‐acting 2‐agonists, theophylline, leukotriene receptor antagonists, or other controller medications within the previous 6 months

  • On inhaled sodium cromoglycate, histamine H1‐antagonists or nonsteroidal anti‐inflammatory drugs used within 4 weeks before entry into this study.

  • History of serious diseases or other lung conditions.

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks
Intervention Period: 8 weeks

TEST GROUP: Pranlukast 225 mg twice a day

CONTROL GROUP: Inhaled BDP 100 μg twice a day

DEVICE: Metered‐dose inhaler using a spacing chamber

Outcomes

ANALYSIS BY INTENTION‐TO‐TREAT: Not reported

OUTCOMES reported at 8 weeks

PULMONARY FUNCTION TESTS:

  • AM PEF

  • PM PEF

  • Change in FEV1 (L)

FUNCTIONAL TESTS: Changes in the use of supplemental 2‐agonist

SYMPTOM SCORES: Asthma symptom score

INFLAMMATORY MEDIATORS:

  • Eosinophil (%)

  • Mast cell (%)

  • ECP (ng/mL)

  • Tryptase (ng/mL)

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

100 μg

Notes

Full Text publication

Funded: Not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: randomised using balanced block of four

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, drop‐outs are reported by group and were balanced between the two groups

Selective reporting (reporting bias)

Low risk

No apparent other bias

Other bias

Low risk

No apparent other bias
Yamauchi 2001

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

‐Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 30
P: 10
BDP: 10
Placebo: 10 (not used)

WITHDRAWALS: Not reported

AGE (± SD) years:
P: 40.6 ± 2.02
BDP: 42.2 ± 3.32

GENDER (% male):
M: 60%
BDP: 70%

ASTHMA SEVERITY: Mild persistent or mild intermittent

% Pred. FEV1 (mean ± SD)
P: 91.8 ± 3.21
BDP: 92.0 ±2.18

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY:
P: 60%
BDP: 60%

ASTHMA DURATION (years): Not reported

ELIGIBILITY CRITERIA:

  • < 15% variability in PEF over preceding 2 weeks

  • No upper respiratory tract infection in preceding 4 weeks

  • Treatment with inhaled β2‐agonist on demand or oral slow‐release theophylline or oral β2‐agonist

  • No inhaled or systemic corticosteroids

EXCLUSION CRITERIA: Not described.

Interventions

PROTOCOL

Duration
Run‐in Period: not described if any
Intervention Period: 4 weeks

TEST GROUP: Pranlukast 450 mg/day

CONTROL GROUP: Inhaled Beclomethasone 400 μg/day

DEVICE: Not reported

CO‐INTERVENTION: Theophylline
M: 11%
BCP: 10%

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS: Change in morning and evening PEFR

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MEDIATORS:

  • Sputum eosinophil (%)

  • Exhaled NO2 concentration (ppb)

ADVERSE EVENTS: Not reported

WITHDRAWALS: Not reported

Primary outcome: Not specified

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication (2001)

Funded by the Ministry of Education, Science, Sports and Culture in Japan

Confirmation of data and methodology requested

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

No details on blinding provided

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

All data presented, no intention‐to‐treat analysis and withdrawal rate is not reported

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes were not defined, but no bias was observed

Other bias

Low risk

No apparent other bias
Yurdakul 2003

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 74
M: 25

BDP: 25
THEO: 24 (not used)

WITHDRAWALS: Reported

AGE (years ± SD):
M: 34.3 ± 5
BDP: 34.9 ± 5

THEO: 33.5 ± 5

GENDER (% male):

M: 20%
BDP: 20%

THEO: 25%

ASTHMA SEVERITY: Mild persistent

% Pred. FEV1 (mean ± SD):
M: 84.8 ± 5.3
BDP: 84.5 ± 4.1

THEO: 86.6 ± 5.5

Mean (± SD) β2‐agonist use (puffs/day): Not described

ATOPY: Not reported

ASTHMA DURATION (years): Not reported

INCLUSION CRITERIAS:

  • Aged 23–45 years ,

  • Having mild persistent asthma according to the criteria of GINA,

  • Baseline FEV1 at least 80% of the predicted normal value, with an increase of at least 15% in FEV1 from the baseline value after the inhalation of 400 mg of salbutamol.

  • On inhaled budesonide at a dose of 200 mg a day or equivalent doses of beclomethasone dipropionate or fluticasone propionate and short‐acting b2‐agonist irregularly for at least 2 months prior to study.

EXCLUSION CRITERIAS:

  • With respiratory tract infection, smokers or had a respiratory disorder other than asthma disease,

  • Had asthma exacerbations within the preceding 2 months,

  • Pregnant or lactating women or with hypersensitivity to sympathomimetic amines,

  • Women of childbearing potential who did not use a reliable contraceptive method.

Interventions

PROTOCOL

Duration
Run‐in Period: Not described if any
Intervention Period: 4 weeks

TEST GROUP: Pranlukast 450 mg/day

CONTROL GROUP: Inhaled Beclomethasone 400 μg/day twice a day

DEVICE: Not reported

CO‐INTERVENTION: Theophylline
M: 11%
BCP: 10%

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS:

  • *AM PEFR

  • FEV1 % predicted

SYMPTOM SCORES:

  • Day time symptom score

  • Night‐time symptoms score

FUNCTIONAL STATUS: Mean number of rescue inhalations, puffs/day

INFLAMMATORY MEDIATORS: Not reported

ADVERSE EVENTS: Reported exacerbation by groups

WITHDRAWALS: Not reported

*Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication (2003)

Funded by: Not reported

Confirmation of data and methodology: Not done

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: simple random sampling method according to random number table 

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label

Incomplete outcome data (attrition bias)
All outcomes

High risk

No intention‐to‐treat analysis and no reported withdrawal rate 

Selective reporting (reporting bias)

Low risk

All outcomes reported in the manuscript are reported, including adverse events by group

Other bias

Low risk

No apparent other bias
Zedan 2009

Methods

DESIGN: Parallel‐group, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 56
M: 27

FP: 29

WITHDRAWALS: Reported

AGE: years ± SD:
N: 9.45 ± 2.42

GENDER (% male): 64.15%

ASTHMA SEVERITY: Moderate persistent asthma

% Pred. FEV1 (mean ± SD): Not reported

Mean (±SD) β2‐agonist use (puffs/day): Not described

ATOPY: Not reported

ASTHMA DURATION (years): N: 5.36

ELIGIBILITY CRITERIAS:

  • Presence of typical asthma symptoms,

  • Improvement in the pre bronchodilator FEV1 of ≥ 12% after administration of salbutamol (200 μg),

  • Positive skin prick test for Dermatophagoides pteronyssimus and Dermatophagoides farinae, cat and dog epithelial cells, and molds and pollen antigens (Omega, Canada)

Interventions

PROTOCOL

Duration
Run‐in Period: 4 weeks
Intervention Period: 4 weeks

TEST GROUP: Montelukast 5 mg at bed time

CONTROL GROUP: Fluticasone propionate (100 μg twice daily)

DEVICE: Pressurized metered‐dose inhaler

CO‐INTERVENTION: Short‐acting β2 agonists

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 4 weeks

PULMONARY FUNCTION TESTS: FEV1

SYMPTOM SCORES: Not reported

FUNCTIONAL STATUS: Not reported

INFLAMMATORY MEDIATORS:

  • IgE,

  • sIL‐2R,

  • sICAM‐1,

  • sVICAM‐1

  • Eosinophilic percentage

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full‐text publication (2009)

Funded by: Not reported

Confirmation of data and methodology: Not done

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not described

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Non‐blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented, withdrawal rate per group presented

Selective reporting (reporting bias)

Low risk

Not found

Other bias

Low risk

No apparent other bias
Zeiger 2005

Methods

DESIGN: Parallel‐group, multi‐centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 380
M = 189
FP = 191

WITHDRAWALS; N (%):
M: 25 (12.5%)
FP: 28 (14%)

AGE: Mean ( years ± SD):
M: 33.9 ± 14.8
FP: 36.5 ± 13.8

GENDER (% male):
M: 58 (30.2%)
FP: 59 (30.9%)

BASELINE SEVERITY: Mild and moderate

% Pred. FEV1 ± SD:
M: 93 ± 8.9
FP: 94.8 ± 10.8

MEAN (± SD) β2‐AGONIST USE (puffs/day):
M = 3.4 ± 1.2
FP = 3.6 ± 1.4

ATOPY: Not reported

ASTHMA DURATION: >=4 months

ELIGIBILITY CRITERIA

  • Asthmatic outpatients 15 to 85 years old

  • Clinical history of asthma >= 4 months

  • Average baseline FEV1 >= 80% pred. with no qualifying value below 70%

  • Daytime symptoms and B‐agonist use on an average of >= and <= 6 days per week in the last 2 weeks of the run‐in period

  • Reversibility by one of the following methods during baseline: FEV1 or PEFR, methacholine PC20 or exercise challenge

EXCLUSION: Not reported

Interventions

PROTOCOL

Duration
Run‐in Period: 3 weeks
Intervention: 12 weeks

TEST GROUP: Montelukast 10 mg od

CONTROL GROUP: Fluticasone 100 μg twice a day

DEVICE: Not reported

CO‐INTERVENTION: Not reported

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 12 weeks

PULMONARY FUNCTION TESTS:

  • Change in FEV1 % predicted

  • Change from baseline PEFR

SYMPTOM SCORES: Asthma symptoms

FUNCTIONAL STATUS:

  • *% Change from baseline asthma rescue free days

  • % change from baseline in days with B‐agonist use

  • As needed albuterol use per day

  • Asthma specific quality of life

  • Asthma control

INFLAMMATORY MARKERS: Blood eosinophil count

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

* Primary outcome

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full paper (2005)

Funded by Merck & Co. Inc

Confirmation of methodology and data extraction: Not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: computer‐generated allocation schedule

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐blind,double dummies: "appropriate matching placebo'

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Modified intention‐to‐treat with low and similar withdrawal rate (6% LTRA versus  9% FP); 

Selective reporting (reporting bias)

Unclear risk

Primary outcome (rescue‐free days) reported; poorly reported clinical and laboratory adverse health events 

Other bias

Low risk

No apparent other bias
Zeiger 2006

Methods

DESIGN: Cross over, multi‐centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 144

WITHDRAWALS; N (%):
M: 25 (12.5%)
FP: 28 (14%)

AGE: Mean years ± SD:
N: 17 ± 11.80%

GENDER (% male): Not reported

BASELINE SEVERITY: Mild and moderate persistent asthma

% Pred. FEV1 (Mean ± SD): Not reported

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

ATOPY: Not reported

ASTHMA DURATION: Not reported

ELIGIBILITY CRITERIA:

  • Absence of corticosteroid therapy within 4 weeks, leukotriene modifier agents within 2 weeks, and respiratory tract infection within 4 weeks of enrolment;

  • Asthma symptoms or rescue bronchodilator use on average of 3 or more days/week for 4 weeks before enrolment;

  • 12% or greater FEV1 reversibility after maximum bronchodilation or methacholine dose required to reduce baseline FEV1 by 20% (methacholine PC20 12.5 mg/mL);

  • FEV1 of 70% of predicted value or greater.

Interventions

PROTOCOL

Duration
Intervention: 8 weeks

TEST GROUP: Montelukast 5‐mg chewable tablet for those 6 to 14 years of age or as a 10‐mg for 15 to 18 years of age

CONTROL GROUP: Fluticasone propionate 100 mg per inhalation administered as twice a day

DEVICE: Flovent Diskus

CO‐INTERVENTION: Not reported

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 8 weeks

PULMONARY FUNCTION TESTS:

  • FEV1/FVC (%)

  • Peak flow variability (%)

  • Morning PEF

  • R5 (kPa/L/s)

  • AX (kPa/L)

SYMPTOM SCORES:

  • Average no. of ACDs (d/wk)

  • ACQ overall score (units)

FUNCTIONAL STATUS

  • Asthma control days

  • Albuterol use (no. of puffs/wk)

INFLAMMATORY MARKERS: eNO

ADVERSE EVENTS: Not reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full paper (2006)

Funded by: Not reported

Confirmation of methodology and data extraction: Not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Means of randomisation: minimization method

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐blind using double dummies: " placebo for the alternative drug"

Incomplete outcome data (attrition bias)
All outcomes

High risk

No intention‐to‐treat analysis; withdrawal rate 12.5% and most withdrew because of treatment failure (i.e. requiring treatment with systemic corticosteroids with an imbalance between treatment period (2 FP and 10 in Montelukast)

Selective reporting (reporting bias)

Low risk

All outcomes reported 

Other bias

Low risk

No apparent other bias
Zielen 2010

Methods

DESIGN: Parallel‐group, single centre, randomised, clinical trial.

Confirmation of methodology: Not obtained

Participants

SYMPTOMATIC PARTICIPANTS

RANDOMISED: N = 102

WITHDRAWALS; N
M: 2
FP: 0

AGE: N: 4.94

GENDER (% male): N: 58.82%

BASELINE SEVERITY: Episodic asthmatics

% Pred. FEV1 (Mean ± SD): N: 98.8%

MEAN (± SD) β2‐AGONIST USE (puffs/day): Not reported

ATOPY: Not reported

ASTHMA DURATION: Not reported

INCLUSION CRITERIAS:

  • Male or female patients age 4–7 years,

  • Diagnosis of mild intermittent bronchial asthma in the past 6–12 months as stated by the investigator

  • Use of inhaled β2‐agonists less than 1/week (max 3 puffs)

  • Exacerbation‐free interval more than 4 weeks prior to visit 1

EXCLUSION CRITERIAS:

  • Chronic persistent asthma,

  • Severe concomitant diseases,

  • Suspected non‐compliance,

  • Age below 4 and age above 7 years

Interventions

PROTOCOL

Duration
Intervention: 6 weeks

TEST GROUP: Montelukast 4‐mg chewable tablet for those 4 to 6 years of age or as a 5‐mg for older than 6 years

CONTROL GROUP: Inhaled fluticasone 100 mg twice daily

DEVICE: By spacer

CO‐INTERVENTION: Inhaled salbutamol

Outcomes

ANALYSIS ( ITT not specified)

OUTCOMES reported at 6 weeks

PULMONARY FUNCTION TESTS:

  • FEV1 pred. (%)

  • FEV1/FVC

  • Airway reversibility (%)

  • PD20 FEV1 (mg)

SYMPTOM SCORES: Asthma symptoms

FUNCTIONAL STATUS: Number of exacerbations

INFLAMMATORY MARKERS:

  • Eosinophils

  • Cumulative specific IgE (kU/L)

ADVERSE EVENTS: Reported

WITHDRAWALS: Reported

ICS dose in HFA beclomethasone ‐ equivalent

200 μg

Notes

Full paper (2010)

Funded by: Disclosed for all funds for authors

Confirmation of methodology and data extraction: Not obtained

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Means of randomisation: not reported

Allocation concealment (selection bias)

Unclear risk

Not reported

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All data presented,

Selective reporting (reporting bias)

Low risk

Primary outcome and secondary outcomes reported, withdrawal by group reported 

Other bias

Low risk

No apparent other bias

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Abbott Pharma 1996

Not a randomised controlled trial

Al Frayh 2008

Intervention was not anti‐leukotriene

Allayee 2007

Control intervention was not inhaled corticosteroid

Allen 1997

Not a randomised controlled trial

Allen‐Ramey 2003

Not a randomised controlled trial

Allen‐Ramey 2004

Not a randomised controlled trial

Allen‐Ramey 2006

Not a randomised controlled trial

Altman 1998k

Control intervention was not inhaled corticosteroid

Anonymous 1997

Not a randomised controlled trial

Armour 2007

Intervention was not anti‐leukotriene

Bacharier 2008

Intervention was given < 4 weeks

Bai 2010

Participants were not people with asthma

Balatsouras 2005

Participants were not people with asthma

Control intervention was not inhaled corticosteroid

Baren 2006

Intervention was not anti‐leukotriene

Barnes 1996

Control intervention was not inhaled corticosteroid

Barnes 1997

Not a randomised controlled trial

Barnes 1997b

Control intervention was not inhaled corticosteroid

Barnes 2001

Not a randomised controlled trial (meta‐analysis)

Barnes 2007

Participants received additional non‐permitted co‐interventions (cetirizine with montelukast and intranasal beclomethasone with inhaled beclomethasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Barnes 2007a

Participants received additional non‐permitted co‐interventions (montelukast with inhaled budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Bartoli 2010

Intervention was not anti‐leukotriene

Bateman 1995

Control intervention was not inhaled corticosteroids

Bateman 2003

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Baumgartner 1999

Duplicate of published paper in Eur Respir J 2003;21:123‐128.

Benitez 2005

Participants received additional non‐permitted co‐interventions (budesonide with zafirlukast and oral loratadine/pseudoephedrine with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Berger 2006

Intervention was not anti‐leukotriene

Bilancia 2000

Participants received additional non‐permitted co‐interventions (combination of budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Bilderback 2004

Duplicate of published paper in Journal of Allergy & Clinical Immunology 2007;119(4):916‐923.

Bilderback 2005

Duplicate of published paper in Journal of Allergy & Clinical Immunology 2007;119(4):916‐923.

Bisgaard 1999

Control intervention was not inhaled corticosteroids.
Participants received additional non‐permitted co‐interventions (inhaled steroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid.
Outcomes did not reflect control of asthma (airway inflammation).
Intervention < 4 weeks

Bisgaard 2000

Control intervention was not inhaled corticosteroid

Bisgaard 2005

Control intervention was not inhaled corticosteroid

Bjermer 2002

Control intervention was not placebo

Bjermer 2003

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone and salmeterole with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Bjermer 2004

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone and salmeterole with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Bleecker 2006

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Borker 2005

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone and salmeterole with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Bousquet 2005a

Not a randomised controlled trial

Bousquet 2007

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Brannan 2001

Intervention administered < 4 weeks
Control intervention was not inhaled corticosteroid

Brocks 1996

Participants were not people with asthma

Bronsky 1997

Participants were not people with asthma

Brown 2005

Intervention was not anti‐leukotriene

Brown 2007

Intervention was not anti‐leukotriene

Brown 2010

Intervention was not anti‐leukotriene

Bruce 2002

Outcome measures did not reflect asthma control

Buchvald 2002

Duplicate of published paper in Annals of Allergy Asthma & Immunology 2003;91(3):309‐313.

Buchvald 2002a

Duplicate of published paper in Annals of Allergy Asthma & Immunology 2003;91(3):309‐313.

Buchvald 2003

Control intervention was not inhaled corticosteroid

Buckstein 2003

Not a randomised controlled trial

Burgess 2007

Intervention was not anti‐leukotriene

Busse 1999

Control intervention was not inhaled corticosteroid
Participants received additional non‐permitted co‐interventions (inhaled steroids) other than short‐acting beta2‐agonists
Outcomes did not reflect control of asthma (provocation challenge)

Buxton 2004

Intervention was not anti‐leukotriene

Cakmak 2000

Control intervention was not placebo

Cakmak 2004

Participants received additional non‐permitted co‐interventions (zafirlukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Calhoun 1997

Control intervention was not inhaled corticosteroid

Calhoun 2001

Participants received additional non‐permitted co‐intervention other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Calhoun 2004

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Camargo 2002

Acute asthma setting

Camargo 2003

Control intervention was not inhaled corticosteroid

Acute asthma setting

Canino 2008

Not a randomised controlled trial

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Capella 2001

Participants were non‐asthmatics (atopic dermatitis)

Ceylan 2004

Participants received additional non‐permitted co‐interventions (formoterol with budesonide and montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Chan 2003

Not a randomised controlled trial

Chand 2005

Participants received additional non‐permitted co‐interventions (montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Chanez 2010

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroids

Chen 2006

Intervention was not anti‐leukotriene

Chiba 1997

Not a randomised controlled trial

Choi 2003

Intervention was not anti‐leukotriene

Chopra 2005

Intervention was not anti‐leukotriene

Chuchalin 2002

Intervention was not anti‐leukotriene

Chuchalin 2007

Intervention was not anti‐leukotriene

Chung 2000

Intervention was not anti‐leukotriene

Ciebiada 2009

Participants received additional non‐permitted co‐interventions (fexofenadine with montelukast and fexofenadine with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Claesson 1998

Not a randomised controlled trial

Cloud 1989

Control intervention was not inhaled corticosteroid

Covar 2008

Duplicate of published paper in Journal of Allergy & Clinical Immunology 2007;119(1):64‐72.

Cowan 2010

Participants received additional non‐permitted co‐interventions (cromoglycate, formoterol with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid;

Intervention was given < 4 weeks

Currie 2003

Intervention was given < 4 weeks

Currie 2003a

Intervention was given < 4 weeks;

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Currie 2003b

Duplicate of published paper in Journal of Respiratory & Critical Care Medicine 2003;167(9):1232‐1238.

Cylly 2003

Ongoing trial

Dahlén 2002

Control intervention was not inhaled corticosteroid;
Participants received additional non‐permitted co‐interventions (inhaled steroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Daikh 2003

Participants were not people with asthma

Davies 2004

Not a randomised controlled trial;

All patients not received inhaled corticosteroid as controlled intervention

Daviskas 2007

Control intervention was not inhaled corticosteroid

Dekhuijzen 2006

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Delaronde 2005

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Dempsey 1999

Intervention administered for < 4 weeks

Dempsey 2000

Intervention administered <4 weeks

Dempsey 2000a

Control intervention was not placebo

Dempsey 2002b

Control intervention was not placebo

Demuro‐Mercon 2001

Control intervention was not inhaled corticosteroid

Dessanges 1999

Participants received additional non‐permitted co‐interventions (inhaled steroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid
Intervention lasted <4 weeks
Outcomes did not reflect control of asthma (provocation challenge)

Deykin 2007

Participants received additional non‐permitted co‐interventions (salmeterol with montelukast and salmeterol with beclomethasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Diamant 1997

Control intervention was not inhaled corticosteroidervention administered for < 4 weeks
Outcomes were solely the result of provocation

Diamant 2009

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Dicpinigaitis 2002

Outcome measures did not reflect asthma control

Djukanovic 2010

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Dockhorn 2000

Control intervention was not inhaled corticosteroid
Intervention administered for < 4 weeks

Dorinsky 2001

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Dorinsky 2002

Not a randomised controlled trial

Dorinsky 2004

Intervention was not anti‐leukotriene

Edelman 2000

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

El Miedany 2006

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Eliraz 2001

Intervention was not anti‐leukotriene

Ensom 2003

Not a randomised controlled trial

Intervention was not anti‐leukotriene

Control intervention was not inhaled corticosteroid

Fabbri 1996

Not a randomised controlled trial

Fagerson 2003

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Failla 2006

Intervention was not anti‐leukotriene

Fardon 2004

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Fardon 2007

Not a randomised controlled trial.

Intervention was not anti‐leukotriene.

Faul 2002

Outcome measures did not reflect asthma control

Findlay 1992

Control intervention was not inhaled corticosteroid.

Intervention administered for < 4 weeks

Finkelstein 2005

Not a randomised controlled trial.

Intervention was not anti‐leukotriene

Finn 2000

Control intervention was not inhaled corticosteroid (but placebo).

A small number of placebo‐treated patients also received co‐intervention with inhaled steroids (N = 42), but co‐intervention with inhaled steroids was not randomly assigned.

Fischer 1995

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Fischer 1997

Control intervention was not inhaled corticosteroid

Fish 1997

Control intervention was not inhaled corticosteroid

Fish 2000

Participants received additional non‐permitted co‐interventions (salmeterol with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Fish 2001

Co‐intervention with inhaled corticosteroid.
Control intervention was not inhaled corticosteroid.

FitzGerald 2009

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Fogel 2010

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone and fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Franzen 1994

Not a randomised controlled trial

Fritsch 2006

Intervention was not anti‐leukotriene

Fujimura 1993

Control intervention was not inhaled corticosteroid

Gabrijelcic 2004

Not a randomised controlled trial.

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Gaddy 1990

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks, intravenously

Galbreath 2008

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Geha 2001

Intervention was not anti‐leukotriene

Gelb 2008

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Georgiou 1997

Control intervention was not inhaled corticosteroid.
Participants were not asthmatics.
Intervention administered for < 4 weeks.

Ghiro 2001

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Ghiro 2002

Outcome measures did not reflect asthma control

Gold 2001

Control intervention was not placebo

Gold 2001a

Control intervention was not placebo

Green 2002

Control intervention was not placebo.
Co‐intervention with inhaled steroids.

Green 2002a

Intervention was not anti‐leukotriene

Green 2006

Participants received additional non‐permitted co‐interventions (montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Greenberger 2003

Not a randomised controlled trial

Grosclaude 2003

Participants received additional non‐permitted co‐interventions (montelukast with beclomethasone and salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Grossman 1995

Control intervention was not inhaled corticosteroid

Grossman 1997

Control intervention was not inhaled corticosteroid

Grzelewska‐Rzymowska 2003

Intervention was not anti‐leukotriene

Grzelewski 2006

Participants received additional non‐permitted co‐interventions (montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Guilbert 2004

Intervention was not anti‐leukotriene

Gupta 1999

Intervention was not anti‐leukotriene.

Participants were not people with asthma.

Gupta 2007

Participants received additional non‐permitted co‐interventions (fluticasone+salmeterol with montelukast and salmeterol+levocetirizine with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Gylfors 2005

Duplicate of published paper in Journal of Allergy & Clinical Immunology 2006;118(1):78‐83.

Gyllfors 2003

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Gyllfors 2006

Intervention was not anti‐leukotriene

Haahtela 1994

Intervention was not anti‐leukotriene

Hakim 2007

Control intervention was not inhaled corticosteroid

Hamilton 1998

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Harmanci 2006

Control intervention was not inhaled corticosteroid

Hartwig 2004

Not a randomised controlled trial

Hassall 1998

Control intervention was not inhaled corticosteroid

Havlucu 2005

Participants received additional non‐permitted co‐interventions (formoterole with budesonide) other than short‐acting beta2‐agonists and/or short course of oral ccorticosteroid

Hay 1997

Not a randomised controlled trial

Hendeles 2004

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Henderson 1994

Not a randomised controlled trial

Hernandez 2002

Participants received additional non‐permitted co‐interventions (montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Hood 1999

Participants were not people with asthma.
Intervention was not anti‐leukotriene.
Intervention administered for < 4 weeks.

Hothersall 2008

Intervention was not anti‐leukotriene

Houghton 2004

Intervention was not anti‐leukotriene

Howland 1994

Control intervention was not inhaled corticosteroid

Hozawa 2009

Intervention was not anti‐leukotriene

Hsieh 1996

Intervention was not anti‐leukotriene

Huang 2003

Participants received additional non‐permitted co‐interventions (zafirlukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Huang 2003a

Duplicate of published paper in Chang Gung Medical Journal. 2003;26(8):554‐560

Hui K 1991

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.

Igde 2009

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Ikeda 1997

Not a randomised controlled trial

Ilowite 2004

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Inoue 2007

Intervention was not anti‐leukotriene

Irvin 2003

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Irvin 2007

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Israel 1990

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Israel 1992

Control intervention was not inhaled corticosteroid

Israel 1993

Control intervention was not inhaled corticosteroid

Israel 1996

Control intervention was not inhaled corticosteroid

Jat 2006

Participants received additional non‐permitted co‐interventions (montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Jayaram 2002a

Duplication

Jayaram 2005a

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Jayaram 2006

Intervention was not anti‐leukotriene

Johnson 1999

Duplicate of published paper in J Fam Pract 2001;50:595‐602.

Johnston 2007

Participants received additional non‐permitted co‐interventions (montelukast with other antihistaminc drugs) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Jones 2002

Not a randomised controlled trial

Jonsson 2004

Intervention was not anti‐leukotriene

Juniper 1995

Control intervention was not inhaled corticosteroid

Kalberg 1999

Control intervention was not inhaled corticosteroid

Kanazawa 2004

Control intervention was not inhaled corticosteroid

Kane 1994

Not a randomised controlled trial

Kanniess 2002a

Control intervention was not placebo

Karaman 2007

Participants received additional non‐permitted co‐interventions (montelukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Karpel 2007

Intervention was not anti‐leukotriene

Katial 2010

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Keith 2009

Participants received additional non‐permitted co‐interventions (montelukast with inhaled coticosteroid and long acting beta2 agoinit with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Kemp 1995

Control intervention was not inhaled corticosteroid

Kemp 1996

Not a randomised controlled trial

Kemp 1998

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.

Kemp 1998a

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Kemp 1999

Not a randomised controlled trial (meta‐analysis of RCTs)

Ketchell 2002

Intervention was not anti‐leukotriene

Khayyal 2003

Intervention was not anti‐leukotriene

Kippelen 2010

Intervention was not anti‐leukotriene

Kips 1991

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks, intravenously.

Knorr 1998

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Knorr 1999

Control intervention were not placebo

Koenig 2004

Duplication of paper in The Journal of Asthma 2008;45( 8):681‐687

Kohrogi 1997

Not a randomised controlled trial

Kondo 2006

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Kooi 2006

Duplication of paper in Pulmonary Pharmacology and Therapeutics 2008;21(5):798‐804

Korenblat 1998

Use of higher than licensed dose of leukotriene receptor antagonists (Pranlukast 600 mcg/day vs. 450 mcg/day)

Kuna 1997

Control intervention was not inhaled corticosteroid

Kylstra 1998

Control intervention was not inhaled corticosteroid

Laitinen 1995

Control intervention was not inhaled corticosteroid

Leaker 2010

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroids.

Lee 2004

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Intervention administered for < 4 weeks

Lee 2004a

Intervention was not anti‐leukotriene

Lee 2004b

Control intervention was not inhaled corticosteroid

Lee 2004c

Duplication of paper in Chest 2004;125(4):1372‐1377

Lee 2005

Intervention was not anti‐leukotriene

Lee 2010

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroids.

Leff 1998

Control intervention was not inhaled corticosteroid.
Outcomes were solely the result of provocation.

Leibman 2002

Duplication of paper in American Journal of Respiratory and Critical Care Medicine 2002. 165 (Suppl 8): B4

Leibman 2002a

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone and fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Leigh 2002

Intervention administered for < 4 weeks

Leigh 2002a

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Lemanske 2010

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Li 2001

Control intervention was not placebo

Liebke 2001

Control intervention was not placebo (it was sodium cromoglycate)

Lindemann 2009

Intervention was not anti‐leukotriene

Lipworth 1999

Ongoing trial

Lis 2001

Control intervention was not inhaled corticosteroid.

Intervention administered for < 4 weeks.

Liu 1996

Control intervention was not inhaled corticosteroid

Lizaso 2003

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Lockey 1995

Control intervention was not inhaled corticosteroid

Lofdahl 1999

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Luppo 2005

Control intervention was not inhaled corticosteroid

Lyseng‐Williamson 2003

Not a randomised controlled trial

Macfarlane 2000

Not a randomised controlled trial

Magnussen 2008

Intervention was not anti‐leukotriene

Majak 2010

Participants received additional non‐permitted co‐interventions (ICS with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Malerba 2002

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Marchese 1998

Not a randomised controlled trial

Margolskee 1991

Control intervention was not inhaled corticosteroid

Marogna 2010

Participants received additional non‐permitted co‐interventions (formoterol/fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Maspero 2008

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Maspero 2008a

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Maspero 2008b

Participants received additional non‐permitted co‐interventions (salmeterol with budesonide) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Mastruzzo 2010

Intervention was given < 4 weeks

Matsunaga 2004

Control intervention was not inhaled corticosteroid.

Intervention administered for < 4 weeks.

McCarthy 2003

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast and salmeterol with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

McGill 1996

Not a randomised controlled trial

Mclvor 2009

Not a randomised controlled trial;

Control intervention was not inhaled corticosteroid

Mehuys 2008

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Mendes 2004

Intervention administered for < 4 weeks

Mendes 2004a

Intervention administered for < 4 weeks

Menendez 2001

Duplicate of published paper in J Allergy Clin Immunol 2000;105:1123‐1129;

Outcomes did not reflect control of chronic asthma

Meyer 2003

Not a randomised controlled trial

Micheletto 1997

Control intervention was not inhaled corticosteroid

Miraglia 2007

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Mitchell 2005

Intervention was not anti‐leukotriene

Miyamoto 1999

Control intervention was not placebo

Molitor 2005

Intervention was not anti‐leukotriene.

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Montani 2007

Duplicate of published paper in New Engl J of Med 2007;356(20):2027‐2039

Moreira 2008

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Morris 2010

Participants received additional non‐permitted co‐interventions (montelukast with other anti‐asthma therapies) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid.

Acute asthma setting.

Mosnaim 2002

Control intervention was not inhaled corticosteroid

Mosnaim 2008

Intervention was not anti‐leukotriene

Murphy 2006

Intervention was not anti‐leukotriene

Najberg 2008

Intervention was not anti‐leukotriene

Nakagawa 1992

Not a randomised controlled trial

Nakajima 2001

Participants received additional non‐permitted co‐interventions (beclomethazone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Nakazono 2004

Control intervention was not inhaled corticosteroid

Nathan 1998

Control intervention was not inhaled corticosteroid

Nathan 2000

Participantsreceived additional non‐permitted co‐interventions (salmeterol with ICS and ICS with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Nathan 2004

Duplication of paper in Chest 2005;128(4):1910‐1920

Nathan 2005

Participants received additional non‐permitted co‐interventions (fluticasone+salmeterol with montelukast) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Nayak 1998

Control intervention was not inhaled corticosteroid

NCT00096954

Test group is not anti‐leukotrienes.

Control group is not ICS.

NCT00140881

Ongoing and results are not available

NCT00196547

Ongoing and results are not available

NCT00213252

Ongoing and results are not available

NCT00299065

Ongoing and results are not available

NCT00319488

Ongoing and results are not available

NCT00395408

Ongoing and results are not available

NCT00421018

Ongoing and results are not available

NCT00462592

Ongoing and results are not available

NCT00471809

Terminated and results are not available

NCT00486343

Terminated and results are not available

NCT00504946

Ongoing and results are not available

NCT00545324

Ongoing and results are not available

NCT00545844

Control group received non‐permitted drugs (Montelukast and long‐acting beta 2 agonist)

NCT00575861

Ongoing and results are not available

NCT00666679

Test group received non‐permitted drug (Mometasone)

NCT00699062

Ongoing and results are not available

NCT00755794

Ongoing and results are not available

NCT00756418

Ongoing and results are not available

NCT00913328

Ongoing and results are not available

NCT00943397

Control group is not ICS

NCT01055041

Ongoing and results are not available

NCT01241084

Ongoing and results are not available.

Test group is not anti‐leukotrienes.

Negro 1997

Not a randomised controlled trial

Neki 2006

Not a randomised controlled trial

Nelson 2001

Control intervention were not placebo

Nelson 2004

Participants received additional non‐permitted co‐interventions (fluticasone+salmeterol with montelukast) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Nelson 2004a

Participants received additional non‐permitted co‐interventions (fluticasone+salmeterol with montelukast) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid.

Participants were not people with asthma.

Nelson 2006

Intervention was not anti‐leukotriene

Nishima 2005

Control intervention was not inhaled corticosteroid

Nishimura 1999

Control intervention were not placebo

Nishiyama 2006

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Nishizawa 2002

Intervention was not anti‐leukotriene

Noonan 1998

Control intervention was not inhaled corticosteroid

Noonan 1999

Not a randomised controlled trial

Nsouli 2000

Control intervention was not placebo

Nsouli 2001

Control intervention was not placebo

O'Byrne 1997

Not a randomised controlled trial

O'Byrne 1997a

Not a randomised controlled trial

O'Byrne 1997b

Not a randomised controlled trial

O'Connor 1994

Not a randomised controlled trial

O'Connor 2004

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

O'Connor 2006

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

O'Shaughnessy 1996

Participants were not people with asthma
Outcomes were solely the result of provocation

O'Sullivan 2002

Duplicate of published abstract in European Respiratory Journal 2002;20(Suppl 38):388s

O'Sullivan 2002a

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

O'Sullivan 2003

Control intervention was not placebo

Obase 2001

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Obata 1992

Not a randomised controlled trial

Odjakova 2000

Not a randomised controlled trial

Ohbayashi 2007

Intervention was not anti‐leukotriene

Ohbayashi 2009

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone+salmeterold) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Ohbayashi 2009a

Participants received additional non‐permitted co‐interventions (pranlukast with fluticasone) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Ohkura 2009

Participants received additional non‐permitted co‐interventions (pranlukast with inhaled corticosteroids+long acting beta2 agonists) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Ohta 2009

Intervention was not anti‐leukotriene;

Control intervention was not inhaled corticosteroid

Okudaira 1997

Not a randomised controlled trial

Oosaki 1997

Not a randomised controlled trial

Oosaki 1997a

Not a randomised controlled trial

Oppenheimer 2008

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone+salmeterold) other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Ostrom 2003

Duplicate of published abstract in Journal of Pediatrics 2005;147(2):213‐220

Overbeek 2002

Outcomes measures did not reflect asthma control

Palmqvist 2003

Intervention administered for < 4 weeks

Palmqvist 2005

Intervention administered for < 4 weeks

Panettieri 1997

Not a randomised controlled trial

Papadopoulos 2009

Control intervention was not inhaled corticosteroid

Pasaoglu 2008

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Patel 2010

Participants received additional non‐permitted co‐interventions (budesonide+formoterol with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Paterson 1999

Intervention administered for < 4 weeks

Pavord 2007

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Pearlman 1999

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Pearlman 2002

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Pedersen 2007

Intervention administered for < 4 weeks

Pereira 1989

Participants were not people with asthma

Perng 2004

Participants received additional non‐permitted co‐interventions (zafirlukast with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Peroni 2005a

Participants received additional non‐permitted co‐interventions (budesonide with montelukast and formoterol with budesonide) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Philip 2005

Control intervention was not inhaled corticosteroid

Phipatanakul 2003

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroid) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Phipatanakul 2003a

Duplication of paper published in Annals of Allergy Asthma & Immunology 2003;91(1):49‐54

Pieters 2005

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Pizzichini 1999

Control intervention was not inhaled corticosteroid

Plaza 2005

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Pogson 2008

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Pohl 2006

Intervention was not anti‐leukotriene

Polos 2003

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast and salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Polos 2004

Duplication of paper published in Pediatrics 2005;116(2):360‐369

Ponce 2009

Participants received additional non‐permitted co‐interventions (budesonide+salmeterol with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Price 1999

Control intervention was not inhaled corticosteroid

Price 2002

Control intervention were not placebo

Price 2003

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Price 2004

Duplication;

Participants received additional non‐permitted co‐interventions (eg. montelukast with budesonide)

Price 2006

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Pullerits 1999

Participants were not people with asthma (allergic rhinitis)

Pullerits 2001

Participants were not people with asthma

Pullerits 2002

Participants were not people with asthma

Qaqundah 2006

Intervention was not anti‐leukotriene;

Rachelefsky 1997

Not a randomised controlled trial

Ragab 2001

Not a randomised controlled trial

Ramsay 1997

Control intervention was not inhaled corticosteroid

Ramsay 1998

Control intervention was not inhaled corticosteroid

Rand 2004

Duplication of full paper in Journal of Allergy & Clinical Immunology 2007;119(4):916‐923

Ratner 2003

Participants were not people with asthma

Reiss 1996

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid.

Intervention administered for < 4 weeks.

Reiss 1997

Control intervention was not inhaled corticosteroid.

Duplication of full paper in Clin Exp Allergy 2001;31:1‐10.

Reiss 1997b

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Reiss 1997c

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid.

Intervention administered for < 4 weeks.

Reiss 1998

Control intervention was not inhaled corticosteroid

Reiss 2008

Duplication of paper published in Journal of Asthma 2009;46(5):465‐469

Riccioni 2001a

Duplication of International Journal of Immunopathology and Pharmacology 2001:14(2):87‐92

Riccioni 2002

Not a randomised controlled trial

Riccioni 2003a

Not a randomised controlled trial

Riccioni 2005

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Rickard 1999

Control intervention was not placebo

Rickard 2001

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Ringdal 1997

Outcomes did not reflect control of chronic or acute asthma

Ringdal 2003

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Robinson 2001

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid.

Intervention administered for < 4 weeks.

Rosenhall 2003

Intervention was not anti‐leukotriene

Rowe 2007

Intervention was not anti‐leukotriene

Ruggins 2003

Participants received additional non‐permitted co‐interventions (inhaled corticosteroids with montelukast and salmeterol with inhaled corticosteroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Sahn 1997

Control intervention was not inhaled corticosteroid

Sano 2006

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Schneider 2008

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Schuh 2009

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Schwartz 1995

Control intervention was not inhaled corticosteroid

SD‐004‐0216

Participants received additional non‐permitted co‐interventions (budesonide with zafirlukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Shah 2003

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Shah 2004

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Shah 2006

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Sheth 2002

Participants received additional non‐permitted co‐interventions other than short‐acting ß2‐agonists and/or short course of oral corticosteroid

Shimoda 2005

Duplication

Shingo 2001

Control intervention was not inhaled corticosteroid

Shoji 1999

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Simons 2001

Control intervention was not inhaled corticosteroid

Simpson 2004

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Sims 2003

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid.

Intervention administered for < 4 weeks.

Sims 2008

Duplication

Smith 1993

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.

Smith 1997

Treatments were administered for <4 weeks

Smith 1998

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Smugar 2009

Participants received additional non‐permitted co‐interventions (montelukast with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Smugar 2009a

Duplication of full paper in Annals of Allergy Asthma & Immunology 2010;104(6):511‐517

Spahn 1996a

Not a randomised controlled trial

Spector 1992

Control intervention was not inhaled corticosteroid

Spector 1994

Control intervention was not inhaled corticosteroid

Spector 1995

Control intervention was not inhaled corticosteroid

Spector 1996

Not a randomised controlled trial

Stanford 2002

Non‐permitted drugs

Stensrud 2006

Not a randomised controlled trial

Stevenson 2005

Intervention was not anti‐leukotriene

Sthoeger 2007

Intervention was not anti‐leukotriene

Storms 2001

Not a randomised controlled trial.

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Storms 2004

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Strauch 2003

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Strunk 2003

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Strunk 2008

Participants received additional non‐permitted co‐interventions (budesonide+salmeterol with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Sugihara 2010

Intervention was given < 4 weeks

Suguro 1997

Not a randomised controlled trial

Suissa 1997

Control intervention was not inhaled corticosteroid

Sutherland 2010

Not a randomised controlled trial‐retrospective analysis

Suzuki 1997

Not a randomised controlled trial

Svensson 1994

Control intervention was not inhaled corticosteroid

Swern 2008

Not a randomised controlled trial.

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Swernson 2003

Participants received additional non‐permitted co‐interventions (ICS with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Tamaoki 1997

Control intervention was not inhaled corticosteroid

Tan 2006

Intervention was not anti‐leukotriene

Tashkin 1998

Control intervention was not inhaled corticosteroid

Teper 2009

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Terzano 2001

Intervention was not anti‐leukotriene

Thoma 2002

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Todi 2010

Participants received additional non‐permitted co‐interventions (antiasthmatic drugs with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Tognella 2004

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Tohda 2002

Control intervention was not placebo

Tomari 2001

Control intervention was not placebo

Tomita 1999

Participants received additional non‐permitted co‐interventions (inhaled and oral corticosteroids) other than short‐acting beta2‐agonists

Tonelli 2003

Not a randomised controlled trial;

Participants received additional non‐permitted co‐interventions (antihistaminic drugs) other than short‐acting beta2‐agonists

Townley 1995

Control intervention was not inhaled corticosteroid

Trofor 2002

Not a randomised controlled trial.

Control intervention was not inhaled corticosteroid.

Tsai 2010

Intervention was not anti‐leukotriene.

Control intervention was not inhaled corticosteroid.

Tsuchida 2005

Participants received additional non‐permitted co‐interventions (beclomethasone with pranlukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Tug 2007

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Tukiainen 2002

Intervention was not anti‐leukotriene

Uh 2007

Participants received additional non‐permitted co‐interventions (salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Ulrik 2009

Duplication of work presented in Am J Respir Crit Care Med 2009;179:A2416

Ulrik 2009a

Control intervention was not inhaled corticosteroid

Ulrik 2010

Control intervention was not inhaled corticosteroid.

Participants received additional non‐permitted co‐interventions (montelukast with inhaled corticosteroids) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid.

Van Adelsberg 2005

Control intervention was not inhaled corticosteroid

Van Der Meer 2009

Intervention was not anti‐leukotriene;

Control intervention was not inhaled corticosteroid

Vaquerizo 2003

Control intervention was not placebo

Vastagh 2003

Intervention was not anti‐leukotriene

Verhoeven 2001

Participants were not asthmatics (COPD)

Verini 2007

Participants received additional non‐permitted co‐interventions (fluticasone with montelukast and salmeterol with fluticasone) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid.

Intervention administered for < 4 weeks.

Vermeulen 2007

Intervention was not anti‐leukotriene

Vethanayagam 2002

Intervention administered for < 4 weeks

Vidal 2001

Intervention administered for < 4 weeks

Vidal 2001a

Intervention administered for < 4 weeks

Virchow 1997

Control intervention was not inhaled corticosteroid

Virchow 1997a

Duplication

Virchow 1997b

Control intervention was not inhaled corticosteroid

Virnig 2008

Participants received additional non‐permitted co‐interventions (other antiasthmatic drugs with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Volovitz 1999

Duplication of full paper in Curr Med Res Opin 2001;17(2):96‐104

Von Berg 2002

Intervention was not anti‐leukotriene

Wada 2000

Participants received additional non‐permitted co‐interventions (inhaled steroids) other than short‐acting beta2‐agonists

Wada 2009

Control intervention was not inhaled corticosteroid

Wahedna 1999

Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Warren 2003

Ongoing clinical trial.

Wasserman 2006

Intervention was not anti‐leukotriene

Wechsler 1998

Not a randomised controlled trial

Weinberg 1998

Outcomes did not reflect control of chronic or acute asthma

Weiss 2010

Control intervention was not inhaled corticosteroids

Welch 1994

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.

Wen 2008

Intervention was not anti‐leukotriene

Wenzel 1994

Control intervention was not inhaled corticosteroid

Wenzel 1995

Control participants were not people with asthma.
Intervention administered for < 4 weeks.

Wenzel 1997

Duplication of data published in American Journal of Respiratory & Critical Care Medicine 1998;157:A411

Westbroek 1997

Intervention was not anti‐leukotriene

Westbroek 1998

Intervention administered for < 4 weeks

Westbroek 2000

Intervention administered for < 4 weeks

Williams 2001

Duplication of three studies

Wilson 1999

Control intervention was not placebo

Wilson 2000

Control intervention was not inhaled corticosteroid;
Intervention administered for < 4 weeks

Wilson 2001

Intervention administered for < 4 weeks

Wilson 2001a

Participants were not prople with asthma

Wilson 2001b

Intervention administered for < 4 weeks

Wilson 2001c

Outcome measures did not reflect asthma control

Wilson 2004

Not a randomised controlled trial

Wilson 2010

Not a randomised controlled trial

Wilson 2010a

Participants received additional non‐permitted co‐interventions (ICS with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Wise 2009

Control intervention was not inhaled corticosteroid

Xiang 2001

Control intervention was not placebo

Yaldiz 2000

Participants received additional non‐permitted co‐intervention (ICS with montelukast)

Yamamoto 1994

Control intervention was not inhaled corticosteroid.
Intervention administered for < 4 weeks.
Outcomes were solely the result of provocation.

Yildirim 2001

Control intervention was not placebo

Yildirim 2004

Participants received additional non‐permitted co‐interventions (budesonide with montelukast) other than short‐acting beta2‐agonists and/or short course of oral corticosteroid

Yoo 2001

Participants received additional non‐permitted co‐interventions (inhaled corticosteroids) other than short‐acting beta2‐agonists

Yoshida 2000

Intervention administered for < 4 weeks

Yoshida 2002

Intervention administered for < 4 weeks

Zeiger 2004

Not a randomised controlled trial

Zeiger 2005a

Duplication of full paper published in American Journal of Medicine 2005;118(6):649‐657

Zeneca Accolate 1998

Not a randomised controlled trial (product monograph)

Zhang 1999

Control intervention was not inhaled corticosteroid

Zorc 2003

Intervention was not anti‐leukotriene

Data and analyses

Open in table viewer
Comparison 1. Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Patients with at least one exacerbation requiring systemic steroids Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]
Analysis 1.1
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 1 Patients with at least one exacerbation requiring systemic steroids.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 1 Patients with at least one exacerbation requiring systemic steroids.

1.1 Paediatrics

6

1662

Risk Ratio (M‐H, Random, 95% CI)

1.35 [0.99, 1.86]

1.2 Adults

15

4415

Risk Ratio (M‐H, Random, 95% CI)

1.61 [1.12, 2.31]

2 Patients with at least one exacerbation requiring hospital admission Show forest plot

12

2715

Risk Ratio (M‐H, Fixed, 95% CI)

3.33 [1.02, 10.94]
Analysis 1.2
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 2 Patients with at least one exacerbation requiring hospital admission.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 2 Patients with at least one exacerbation requiring hospital admission.

2.1 Paediatrics

4

558

Risk Ratio (M‐H, Fixed, 95% CI)

3.04 [0.12, 73.98]

2.2 Adults

8

2157

Risk Ratio (M‐H, Fixed, 95% CI)

3.38 [0.94, 12.17]

3 Change from baseline FEV1 (L) at 4 ‐ 8 weeks Show forest plot

12

3020

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.15, ‐0.08]
Analysis 1.3
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 3 Change from baseline FEV1 (L) at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 3 Change from baseline FEV1 (L) at 4 ‐ 8 weeks.

3.1 Paediatrics

1

56

Mean Difference (IV, Random, 95% CI)

‐0.28 [‐0.69, 0.13]

3.2 Adults

11

2964

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.15, ‐0.08]

4 Change from baseline FEV1( L) 12 ‐ 16 weeks Show forest plot

8

1778

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.20, ‐0.04]
Analysis 1.4
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 4 Change from baseline FEV1( L) 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 4 Change from baseline FEV1( L) 12 ‐ 16 weeks.

4.1 Paediatrics

2

179

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.13, 0.09]

4.2 Adults

6

1599

Mean Difference (IV, Random, 95% CI)

‐0.14 [‐0.24, ‐0.05]

5 Change from baseline FEV1 (L) at 24 ‐ 26 weeks Show forest plot

3

1178

Mean Difference (IV, Random, 95% CI)

‐0.13 [‐0.22, ‐0.04]
Analysis 1.5
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 5 Change from baseline FEV1 (L) at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 5 Change from baseline FEV1 (L) at 24 ‐ 26 weeks.

5.1 Paediatrics

1

123

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.14, 0.12]

5.2 Adults

2

1055

Mean Difference (IV, Random, 95% CI)

‐0.17 [‐0.23, ‐0.11]

6 Change from baseline FEV1 (L) at 36 ‐ 52 weeks Show forest plot

2

1040

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.07, 0.00]
Analysis 1.6
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 6 Change from baseline FEV1 (L) at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 6 Change from baseline FEV1 (L) at 36 ‐ 52 weeks.

6.1 Paediatrics

2

1040

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.07, 0.00]

7 FEV1 irrespective of time of treatment Show forest plot

23

7016

Mean Difference (IV, Random, 95% CI)

‐0.11 [‐0.14, ‐0.08]
Analysis 1.7
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 7 FEV1 irrespective of time of treatment.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 7 FEV1 irrespective of time of treatment.

7.1 Paediatrics

4

1398

Mean Difference (IV, Random, 95% CI)

‐0.03 [‐0.07, 0.00]

7.2 Adults

19

5618

Mean Difference (IV, Random, 95% CI)

‐0.13 [‐0.16, ‐0.09]

8 Responders (defined as change from baseline in FEV1 >= 7.5% Show forest plot

1

Odds Ratio (Fixed, 95% CI)

Totals not selected
Analysis 1.8
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 8 Responders (defined as change from baseline in FEV1 >= 7.5%.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 8 Responders (defined as change from baseline in FEV1 >= 7.5%.

9 Change from baseline FEV1 (%) at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.9
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 9 Change from baseline FEV1 (%) at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 9 Change from baseline FEV1 (%) at 4 ‐ 8 weeks.

9.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Change from baseline FEV1 (%) 12 ‐ 16 weeks Show forest plot

2

603

Mean Difference (IV, Fixed, 95% CI)

‐5.70 [‐9.81, ‐1.59]
Analysis 1.10
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 10 Change from baseline FEV1 (%) 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 10 Change from baseline FEV1 (%) 12 ‐ 16 weeks.

10.1 Adults

2

603

Mean Difference (IV, Fixed, 95% CI)

‐5.70 [‐9.81, ‐1.59]

11 Change from baseline FEV1 (%) at 24 ‐ 26 weeks Show forest plot

2

838

Mean Difference (IV, Fixed, 95% CI)

‐8.20 [‐10.85, ‐5.55]
Analysis 1.11
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 11 Change from baseline FEV1 (%) at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 11 Change from baseline FEV1 (%) at 24 ‐ 26 weeks.

11.1 Adults

2

838

Mean Difference (IV, Fixed, 95% CI)

‐8.20 [‐10.85, ‐5.55]

12 Change from baseline FEV1 % of predicted at 4 ‐ 8 weeks Show forest plot

2

219

Mean Difference (IV, Random, 95% CI)

‐2.58 [‐6.56, 1.40]
Analysis 1.12
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 12 Change from baseline FEV1 % of predicted at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 12 Change from baseline FEV1 % of predicted at 4 ‐ 8 weeks.

12.1 Paediatrics

1

183

Mean Difference (IV, Random, 95% CI)

‐0.54 [‐4.82, 3.74]

12.2 Adults

1

36

Mean Difference (IV, Random, 95% CI)

‐4.6 [‐8.86, ‐0.34]

13 Change from baseline FEV1 % of predicated at 12 ‐ 16 weeks Show forest plot

3

948

Mean Difference (IV, Fixed, 95% CI)

‐3.76 [‐5.01, ‐2.50]
Analysis 1.13
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 13 Change from baseline FEV1 % of predicated at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 13 Change from baseline FEV1 % of predicated at 12 ‐ 16 weeks.

13.1 Paediatrics

1

335

Mean Difference (IV, Fixed, 95% CI)

‐6.02 [‐9.45, ‐2.59]

13.2 Adults

2

613

Mean Difference (IV, Fixed, 95% CI)

‐3.41 [‐4.76, ‐2.06]

14 Change from baseline FEV1 % of predicated at 36 ‐ 52 weeks Show forest plot

3

1229

Mean Difference (IV, Random, 95% CI)

‐3.51 [‐7.14, 0.12]
Analysis 1.14
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 14 Change from baseline FEV1 % of predicated at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 14 Change from baseline FEV1 % of predicated at 36 ‐ 52 weeks.

14.1 Paediatrics

3

1229

Mean Difference (IV, Random, 95% CI)

‐3.51 [‐7.14, 0.12]

15 Change from baseline AM PEFR (L/min) at 4 ‐ 8 weeks Show forest plot

8

1926

Mean Difference (IV, Random, 95% CI)

‐15.12 [‐20.80, ‐9.44]
Analysis 1.15
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 15 Change from baseline AM PEFR (L/min) at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 15 Change from baseline AM PEFR (L/min) at 4 ‐ 8 weeks.

15.1 Paediatrics

1

332

Mean Difference (IV, Random, 95% CI)

‐7.76 [‐13.43, ‐2.09]

15.2 Adults

7

1594

Mean Difference (IV, Random, 95% CI)

‐17.63 [‐22.56, ‐12.69]

16 Change from baseline AM PEFR (L/min) at 12 ‐ 16 weeks Show forest plot

9

2601

Mean Difference (IV, Random, 95% CI)

‐19.07 [‐25.86, ‐12.27]
Analysis 1.16
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 16 Change from baseline AM PEFR (L/min) at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 16 Change from baseline AM PEFR (L/min) at 12 ‐ 16 weeks.

16.1 Paediatrics

1

335

Mean Difference (IV, Random, 95% CI)

‐16.9 [‐28.54, ‐5.26]

16.2 Adults

8

2266

Mean Difference (IV, Random, 95% CI)

‐19.57 [‐27.27, ‐11.87]

17 Change from baseline AM PEFR (L/min) at 24 ‐ 26 weeks Show forest plot

3

1718

Mean Difference (IV, Random, 95% CI)

‐21.62 [‐40.19, ‐3.05]
Analysis 1.17
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 17 Change from baseline AM PEFR (L/min) at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 17 Change from baseline AM PEFR (L/min) at 24 ‐ 26 weeks.

17.1 Adults

3

1718

Mean Difference (IV, Random, 95% CI)

‐21.62 [‐40.19, ‐3.05]

18 Change from baseline AM PEFR (L/min) at 36 ‐ 52 weeks Show forest plot

3

1028

Mean Difference (IV, Random, 95% CI)

‐5.06 [‐10.58, 0.45]
Analysis 1.18
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 18 Change from baseline AM PEFR (L/min) at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 18 Change from baseline AM PEFR (L/min) at 36 ‐ 52 weeks.

18.1 Adults

3

1028

Mean Difference (IV, Random, 95% CI)

‐5.06 [‐10.58, 0.45]

19 Change from baseline daytime symptom scores at 4 ‐ 8 weeks Show forest plot

6

1925

Std. Mean Difference (IV, Random, 95% CI)

0.20 [0.08, 0.32]
Analysis 1.19
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 19 Change from baseline daytime symptom scores at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 19 Change from baseline daytime symptom scores at 4 ‐ 8 weeks.

19.1 Paediatrics

1

393

Std. Mean Difference (IV, Random, 95% CI)

0.06 [‐0.14, 0.26]

19.2 Adults

5

1532

Std. Mean Difference (IV, Random, 95% CI)

0.23 [0.11, 0.36]

20 Change from baseline daytime symptom scores at 12 ‐ 16 weeks Show forest plot

9

2650

Std. Mean Difference (IV, Fixed, 95% CI)

0.25 [0.18, 0.33]
Analysis 1.20
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 20 Change from baseline daytime symptom scores at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 20 Change from baseline daytime symptom scores at 12 ‐ 16 weeks.

20.1 Paediatrics

2

388

Std. Mean Difference (IV, Fixed, 95% CI)

0.28 [0.08, 0.48]

20.2 Adults

7

2262

Std. Mean Difference (IV, Fixed, 95% CI)

0.25 [0.16, 0.33]

21 Change from baseline daytime symptom scores at 24 ‐ 26 weeks Show forest plot

3

1719

Std. Mean Difference (IV, Random, 95% CI)

0.22 [0.02, 0.42]
Analysis 1.21
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 21 Change from baseline daytime symptom scores at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 21 Change from baseline daytime symptom scores at 24 ‐ 26 weeks.

21.1 Adults

3

1719

Std. Mean Difference (IV, Random, 95% CI)

0.22 [0.02, 0.42]

22 Change from baseline daytime symptom scores at 36 ‐ 52 weeks Show forest plot

2

582

Std. Mean Difference (IV, Random, 95% CI)

0.16 [‐0.02, 0.34]
Analysis 1.22
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 22 Change from baseline daytime symptom scores at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 22 Change from baseline daytime symptom scores at 36 ‐ 52 weeks.

22.1 Paediatrics

2

582

Std. Mean Difference (IV, Random, 95% CI)

0.16 [‐0.02, 0.34]

23 Change from baseline night‐time awakenings at 4 ‐ 8 week Show forest plot

3

798

Std. Mean Difference (IV, Random, 95% CI)

0.22 [‐0.02, 0.46]
Analysis 1.23
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 23 Change from baseline night‐time awakenings at 4 ‐ 8 week.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 23 Change from baseline night‐time awakenings at 4 ‐ 8 week.

23.1 Adults

3

798

Std. Mean Difference (IV, Random, 95% CI)

0.22 [‐0.02, 0.46]

24 Change from baseline night‐time awakenings at 12 ‐ 16 weeks Show forest plot

9

2916

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [0.11, 0.26]
Analysis 1.24
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 24 Change from baseline night‐time awakenings at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 24 Change from baseline night‐time awakenings at 12 ‐ 16 weeks.

24.1 Adults

9

2916

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [0.11, 0.26]

25 Change from baseline night‐time awakenings at 24 ‐ 26 weeks Show forest plot

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.23 [0.11, 0.35]
Analysis 1.25
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 25 Change from baseline night‐time awakenings at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 25 Change from baseline night‐time awakenings at 24 ‐ 26 weeks.

25.1 Adults

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.23 [0.11, 0.35]

26 Change from baseline mean daily use of β2‐agonists at 4 ‐ 8 weeks Show forest plot

10

3264

Std. Mean Difference (IV, Random, 95% CI)

0.20 [0.07, 0.34]
Analysis 1.26
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 26 Change from baseline mean daily use of β2‐agonists at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 26 Change from baseline mean daily use of β2‐agonists at 4 ‐ 8 weeks.

26.1 Paediatrics

1

393

Std. Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.22, 0.17]

26.2 Adults

9

2871

Std. Mean Difference (IV, Random, 95% CI)

0.24 [0.10, 0.38]

27 Change from baseline mean daily use of β2‐agonists at 12 ‐ 16 weeks Show forest plot

11

3367

Std. Mean Difference (IV, Fixed, 95% CI)

0.23 [0.17, 0.30]
Analysis 1.27
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 27 Change from baseline mean daily use of β2‐agonists at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 27 Change from baseline mean daily use of β2‐agonists at 12 ‐ 16 weeks.

27.1 Paediatrics

1

335

Std. Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.20, 0.23]

27.2 Adults

10

3032

Std. Mean Difference (IV, Fixed, 95% CI)

0.26 [0.19, 0.33]

28 Change from baseline mean daily use of β2‐agonists at 24 ‐ 26 weeks Show forest plot

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.31 [0.19, 0.43]
Analysis 1.28
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 28 Change from baseline mean daily use of β2‐agonists at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 28 Change from baseline mean daily use of β2‐agonists at 24 ‐ 26 weeks.

28.1 Adults

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.31 [0.19, 0.43]

29 Change from baseline mean daily use of β2‐agonists at 36 ‐ 52 weeks Show forest plot

1

Std. Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.29
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 29 Change from baseline mean daily use of β2‐agonists at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 29 Change from baseline mean daily use of β2‐agonists at 36 ‐ 52 weeks.

29.1 Paediatrics

1

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

30 Change in rescue‐free days (%) at 4 ‐ 8 weeks Show forest plot

5

1315

Mean Difference (IV, Random, 95% CI)

‐6.83 [‐17.73, 4.07]
Analysis 1.30
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 30 Change in rescue‐free days (%) at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 30 Change in rescue‐free days (%) at 4 ‐ 8 weeks.

30.1 Paediatrics

1

393

Mean Difference (IV, Random, 95% CI)

2.72 [‐3.11, 8.55]

30.2 Adults

4

922

Mean Difference (IV, Random, 95% CI)

‐13.25 [‐18.11, ‐8.39]

31 Change in rescue‐free days (%) at 12 ‐ 16 weeks Show forest plot

7

2304

Mean Difference (IV, Random, 95% CI)

‐9.64 [‐13.71, ‐5.56]
Analysis 1.31
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 31 Change in rescue‐free days (%) at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 31 Change in rescue‐free days (%) at 12 ‐ 16 weeks.

31.1 Paediatrics

1

335

Mean Difference (IV, Random, 95% CI)

‐10.10 [‐18.97, ‐1.23]

31.2 Adults

6

1969

Mean Difference (IV, Random, 95% CI)

‐9.64 [‐14.39, ‐4.89]

32 Change in rescue‐free days (%) at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.32
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 32 Change in rescue‐free days (%) at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 32 Change in rescue‐free days (%) at 24 ‐ 26 weeks.

32.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

33 Change in rescue‐free days (%) at 36 ‐ 52 weeks Show forest plot

2

1350

Mean Difference (IV, Fixed, 95% CI)

‐2.59 [‐4.97, ‐0.21]
Analysis 1.33
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 33 Change in rescue‐free days (%) at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 33 Change in rescue‐free days (%) at 36 ‐ 52 weeks.

33.1 Paediatrics

2

1350

Mean Difference (IV, Fixed, 95% CI)

‐2.59 [‐4.97, ‐0.21]

33.2 Adults

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

34 Change in proportion of symptom‐free days (%) at 4 ‐ 8 weeks Show forest plot

3

1154

Mean Difference (IV, Fixed, 95% CI)

‐10.46 [‐14.56, ‐6.36]
Analysis 1.34
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 34 Change in proportion of symptom‐free days (%) at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 34 Change in proportion of symptom‐free days (%) at 4 ‐ 8 weeks.

34.1 Adults

3

1154

Mean Difference (IV, Fixed, 95% CI)

‐10.46 [‐14.56, ‐6.36]

35 Change in proportion of symptom‐free days (%) at 12 ‐ 16 weeks Show forest plot

8

2423

Mean Difference (IV, Fixed, 95% CI)

‐8.89 [‐11.92, ‐5.87]
Analysis 1.35
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 35 Change in proportion of symptom‐free days (%) at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 35 Change in proportion of symptom‐free days (%) at 12 ‐ 16 weeks.

35.1 Paediatrics

1

335

Mean Difference (IV, Fixed, 95% CI)

‐6.40 [‐15.82, 3.02]

35.2 Adults

7

2088

Mean Difference (IV, Fixed, 95% CI)

‐9.18 [‐12.38, ‐5.98]

36 Change in proportion of symptom‐free days (%) at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.36
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 36 Change in proportion of symptom‐free days (%) at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 36 Change in proportion of symptom‐free days (%) at 24 ‐ 26 weeks.

36.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

37 Change in proportion of symptom‐free days (%) at 36 ‐ 52 weeks Show forest plot

3

1190

Mean Difference (IV, Fixed, 95% CI)

‐5.49 [‐9.06, ‐1.91]
Analysis 1.37
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 37 Change in proportion of symptom‐free days (%) at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 37 Change in proportion of symptom‐free days (%) at 36 ‐ 52 weeks.

37.1 Paediatrics

2

575

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐9.73, ‐0.08]

37.2 Adults

1

615

Mean Difference (IV, Fixed, 95% CI)

‐6.20 [‐11.53, ‐0.87]

38 Change from baseline quality of life (QOL) at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.38
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 38 Change from baseline quality of life (QOL) at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 38 Change from baseline quality of life (QOL) at 4 ‐ 8 weeks.

38.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

39 Change from baseline quality of life (QOL) at 12 ‐ 16 weeks Show forest plot

2

1065

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.34, ‐0.09]
Analysis 1.39
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 39 Change from baseline quality of life (QOL) at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 39 Change from baseline quality of life (QOL) at 12 ‐ 16 weeks.

39.1 Adults

2

1065

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.34, ‐0.09]

40 Change from baseline quality of life (QOL) at 24 ‐ 26 weeks Show forest plot

2

1028

Mean Difference (IV, Fixed, 95% CI)

‐0.38 [‐0.54, ‐0.21]
Analysis 1.40
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 40 Change from baseline quality of life (QOL) at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 40 Change from baseline quality of life (QOL) at 24 ‐ 26 weeks.

40.1 Adults

2

1028

Mean Difference (IV, Fixed, 95% CI)

‐0.38 [‐0.54, ‐0.21]

41 Change from baseline quality of life (QOL) at 36 ‐ 52 weeks Show forest plot

1

541

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.33, 0.07]
Analysis 1.41
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 41 Change from baseline quality of life (QOL) at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 41 Change from baseline quality of life (QOL) at 36 ‐ 52 weeks.

41.1 Paediatrics

1

541

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.33, 0.07]

41.2 Adults

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

42 Days with use of β2‐agonists at 36 ‐ 52 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.42
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 42 Days with use of β2‐agonists at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 42 Days with use of β2‐agonists at 36 ‐ 52 weeks.

42.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

43 Change from baseline blood eosinophils at 4 ‐ 8 weeks Show forest plot

4

1294

Mean Difference (IV, Random, 95% CI)

0.06 [0.02, 0.10]
Analysis 1.43
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 43 Change from baseline blood eosinophils at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 43 Change from baseline blood eosinophils at 4 ‐ 8 weeks.

43.1 Adults

4

1294

Mean Difference (IV, Random, 95% CI)

0.06 [0.02, 0.10]

44 Change from baseline blood eosinophils at 12 ‐ 16 weeks Show forest plot

2

1013

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.03, 0.02]
Analysis 1.44
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 44 Change from baseline blood eosinophils at 12 ‐ 16 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 44 Change from baseline blood eosinophils at 12 ‐ 16 weeks.

44.1 Adults

2

1013

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.03, 0.02]

45 % Change in sputum eosinophils at 4 ‐ 8 weeks Show forest plot

2

117

Mean Difference (IV, Random, 95% CI)

0.71 [‐2.06, 3.47]
Analysis 1.45
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 45 % Change in sputum eosinophils at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 45 % Change in sputum eosinophils at 4 ‐ 8 weeks.

45.1 Adults

2

117

Mean Difference (IV, Random, 95% CI)

0.71 [‐2.06, 3.47]

46 % Change in sputum eosinophils at 36 ‐ 52 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.46
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 46 % Change in sputum eosinophils at 36 ‐ 52 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 46 % Change in sputum eosinophils at 36 ‐ 52 weeks.

46.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

47 LTC4 concentration (ng/mL) in nasal wash at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.47
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 47 LTC4 concentration (ng/mL) in nasal wash at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 47 LTC4 concentration (ng/mL) in nasal wash at 24 ‐ 26 weeks.

47.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

48 % Asthma control days during intervention period at 4 ‐ 8 weeks Show forest plot

2

1293

Mean Difference (IV, Fixed, 95% CI)

‐5.72 [‐10.86, ‐0.59]
Analysis 1.48
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 48 % Asthma control days during intervention period at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 48 % Asthma control days during intervention period at 4 ‐ 8 weeks.

48.1 Adults

2

1293

Mean Difference (IV, Fixed, 95% CI)

‐5.72 [‐10.86, ‐0.59]

49 % Asthma control days during intervention period at 24 ‐ 26 weeks Show forest plot

2

1185

Mean Difference (IV, Random, 95% CI)

‐8.19 [‐19.46, 3.07]
Analysis 1.49
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 49 % Asthma control days during intervention period at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 49 % Asthma control days during intervention period at 24 ‐ 26 weeks.

49.1 Adults

2

1185

Mean Difference (IV, Random, 95% CI)

‐8.19 [‐19.46, 3.07]

50 Change in PC20 at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.50
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 50 Change in PC20 at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 50 Change in PC20 at 4 ‐ 8 weeks.

50.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

51 % rescue ‐ free days at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.51
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 51 % rescue ‐ free days at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 51 % rescue ‐ free days at 24 ‐ 26 weeks.

51.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

52 Days off work or school at 24 ‐ 26 weeks Show forest plot

2

606

Mean Difference (IV, Fixed, 95% CI)

0.12 [‐0.01, 0.26]
Analysis 1.52
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 52 Days off work or school at 24 ‐ 26 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 52 Days off work or school at 24 ‐ 26 weeks.

52.1 Paediatrics

1

124

Mean Difference (IV, Fixed, 95% CI)

‐0.24 [‐1.31, 0.83]

52.2 Adults

1

482

Mean Difference (IV, Fixed, 95% CI)

0.13 [‐0.00, 0.26]

53 Change in height (cm) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.53
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 53 Change in height (cm).

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 53 Change in height (cm).

53.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

54 Patient's satisfaction at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.54
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 54 Patient's satisfaction at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 54 Patient's satisfaction at 4 ‐ 8 weeks.

54.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

55 Physician's satisfaction at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected
Analysis 1.55
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 55 Physician's satisfaction at 4 ‐ 8 weeks.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 55 Physician's satisfaction at 4 ‐ 8 weeks.

55.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

56 Overall Withdrawals Show forest plot

42

10939

Risk Ratio (M‐H, Random, 95% CI)

1.22 [1.08, 1.38]
Analysis 1.56
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 56 Overall Withdrawals.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 56 Overall Withdrawals.

56.1 Paediatrics

18

3397

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.88, 1.21]

56.2 Adults

24

7542

Risk Ratio (M‐H, Random, 95% CI)

1.31 [1.11, 1.54]

57 Withdrawal due to poor asthma control/exacerbations Show forest plot

26

7669

Risk Ratio (M‐H, Fixed, 95% CI)

2.56 [2.01, 3.27]
Analysis 1.57
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 57 Withdrawal due to poor asthma control/exacerbations.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 57 Withdrawal due to poor asthma control/exacerbations.

57.1 Paediatrics

7

1219

Risk Ratio (M‐H, Fixed, 95% CI)

2.17 [1.20, 3.94]

57.2 Adults

19

6450

Risk Ratio (M‐H, Fixed, 95% CI)

2.64 [2.02, 3.45]

58 Withdrawals due to adverse effects Show forest plot

25

8518

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.95, 1.63]
Analysis 1.58
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 58 Withdrawals due to adverse effects.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 58 Withdrawals due to adverse effects.

58.1 Paediatrics

8

2330

Risk Ratio (M‐H, Fixed, 95% CI)

1.27 [0.70, 2.33]

58.2 Adults

17

6188

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.91, 1.67]

59 Overall Adverse effects Show forest plot

22

7818

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.95, 1.05]
Analysis 1.59
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 59 Overall Adverse effects.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 59 Overall Adverse effects.

59.1 Paediatrics

3

1460

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.90, 1.15]

59.2 Adults

19

6358

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.94, 1.05]

60 Elevated liver enzymes Show forest plot

7

1761

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.58, 2.19]
Analysis 1.60
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 60 Elevated liver enzymes.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 60 Elevated liver enzymes.

60.1 Paediatrics

1

118

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.03, 7.68]

60.2 Adults

6

1643

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.60, 2.36]

61 Upper respiratory tract infections Show forest plot

8

2729

Odds Ratio (M‐H, Fixed, 95% CI)

1.04 [0.84, 1.29]
Analysis 1.61
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 61 Upper respiratory tract infections.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 61 Upper respiratory tract infections.

61.1 Paediatrics

5

1514

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.81, 1.36]

61.2 Adults

3

1215

Odds Ratio (M‐H, Fixed, 95% CI)

1.01 [0.69, 1.50]

62 Headache Show forest plot

24

8872

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.89, 1.11]
Analysis 1.62
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 62 Headache.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 62 Headache.

62.1 Paediatrics

6

2589

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.81, 1.37]

62.2 Adults

18

6283

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.86, 1.10]

63 Nausea Show forest plot

17

5563

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.64, 1.08]
Analysis 1.63
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 63 Nausea.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 63 Nausea.

63.1 Paediatrics

2

465

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.28, 2.31]

63.2 Adults

15

5098

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.64, 1.09]

64 Oral candidiasis Show forest plot

3

865

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.05, 1.19]
Analysis 1.64
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 64 Oral candidiasis.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 64 Oral candidiasis.

64.1 Adults

3

865

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.05, 1.19]

65 Hoarseness Show forest plot

2

734

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.03, 2.24]
Analysis 1.65
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 65 Hoarseness.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 65 Hoarseness.

65.1 Adults

2

734

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.03, 2.24]

66 Death Show forest plot

13

5489

Risk Ratio (M‐H, Fixed, 95% CI)

3.05 [0.32, 29.26]
Analysis 1.66
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 66 Death.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 66 Death.

66.1 Paediatrics

2

1114

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.12, 73.46]

66.2 Adults

11

4375

Risk Ratio (M‐H, Fixed, 95% CI)

3.10 [0.13, 75.82]

67 Primary outcome ‐ stratified by anti‐leukotrienes Show forest plot

21

6077

Odds Ratio (M‐H, Random, 95% CI)

1.61 [1.20, 2.16]
Analysis 1.67
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 67 Primary outcome ‐ stratified by anti‐leukotrienes.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 67 Primary outcome ‐ stratified by anti‐leukotrienes.

67.1 Monelukast

15

4352

Odds Ratio (M‐H, Random, 95% CI)

1.55 [1.14, 2.12]

67.2 Zafirlukast

6

1725

Odds Ratio (M‐H, Random, 95% CI)

1.92 [0.88, 4.20]

68 Primary outcome ‐ stratified by duration of intervention Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]
Analysis 1.68
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 68 Primary outcome ‐ stratified by duration of intervention.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 68 Primary outcome ‐ stratified by duration of intervention.

68.1 4‐8 weeks

9

2346

Risk Ratio (M‐H, Random, 95% CI)

1.74 [0.78, 3.87]

68.2 12‐16 weeks

7

1541

Risk Ratio (M‐H, Random, 95% CI)

2.06 [1.43, 2.96]

68.3 24‐26 weeks

2

657

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.55, 2.45]

68.4 36‐52 weeks

3

1533

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.87, 1.91]

69 Main outcome ‐stratified by severity of airway obstruction Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]
Analysis 1.69
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 69 Main outcome ‐stratified by severity of airway obstruction.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 69 Main outcome ‐stratified by severity of airway obstruction.

69.1 Mean FEV1 60‐80% of predicted

11

3922

Risk Ratio (M‐H, Random, 95% CI)

2.03 [1.41, 2.91]

69.2 Mean FEV1 ≥80% of predicted

10

2155

Risk Ratio (M‐H, Random, 95% CI)

1.25 [0.97, 1.61]

70 Primary outcome ‐ stratified by methodological quality Show forest plot

21

6061

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]
Analysis 1.70
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 70 Primary outcome ‐ stratified by methodological quality.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 70 Primary outcome ‐ stratified by methodological quality.

70.1 High quality

11

4366

Risk Ratio (M‐H, Random, 95% CI)

1.62 [1.29, 2.03]

70.2 Poor quality

10

1695

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.74, 2.43]

71 Primary outcome‐ stratified by funding source Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]
Analysis 1.71
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 71 Primary outcome‐ stratified by funding source.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 71 Primary outcome‐ stratified by funding source.

71.1 Funded by producers of ICS

9

2638

Risk Ratio (M‐H, Random, 95% CI)

1.71 [1.05, 2.80]

71.2 Funded by producers of AL

5

2797

Risk Ratio (M‐H, Random, 95% CI)

1.52 [0.99, 2.35]

71.3 No industry funding or not reported

7

642

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.90, 1.66]

72 Primary outcome ‐ stratified by HFC‐BDP equivalent Show forest plot

21

6077

Odds Ratio (M‐H, Random, 95% CI)

1.61 [1.20, 2.16]
Analysis 1.72
Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 72 Primary outcome ‐ stratified by HFC‐BDP equivalent.

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 72 Primary outcome ‐ stratified by HFC‐BDP equivalent.

72.1 100‐150 μg HFA‐BDP equivalent

3

216

Odds Ratio (M‐H, Random, 95% CI)

0.74 [0.26, 2.08]

72.2 200‐250 μg HFA‐BDP equivalent

15

5767

Odds Ratio (M‐H, Random, 95% CI)

1.75 [1.29, 2.38]

72.3 400‐500 μg HFA‐BDP equivalent

3

94

Odds Ratio (M‐H, Random, 95% CI)

0.54 [0.11, 2.78]

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Forest plot of comparison: 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), outcome: 1.1 Patients with at least one exacerbation requiring systemic steroids.
Figuras y tablas -
Figure 2

Forest plot of comparison: 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), outcome: 1.1 Patients with at least one exacerbation requiring systemic steroids.

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In the control group (on ICS) 7 people out of 100 had at least one exacerbation requiring systemic steroids over 4 to 52 weeks, compared to 10 (95% CI 8 to 13) out of 100 for the active treatment group given LRTA.
Figuras y tablas -
Figure 3

In the control group (on ICS) 7 people out of 100 had at least one exacerbation requiring systemic steroids over 4 to 52 weeks, compared to 10 (95% CI 8 to 13) out of 100 for the active treatment group given LRTA.

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Funnel plot of comparison: 1 Anti‐leukotriene (AL) versus. Inhaled glucocorticoids (in HFC‐BDP equivalent), outcome: Patients with at least 1 exacerbation requiring systemic corticosteroids.
Figuras y tablas -
Figure 4

Funnel plot of comparison: 1 Anti‐leukotriene (AL) versus. Inhaled glucocorticoids (in HFC‐BDP equivalent), outcome: Patients with at least 1 exacerbation requiring systemic corticosteroids.

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In the control group (on ICS) 2 people out of 100 had withdrawal due to poor control over 4 to 52 weeks, compared to 6 (95% CI 4 to 7) out of 100 for the active treatment group (given LRTA).
Figuras y tablas -
Figure 5

In the control group (on ICS) 2 people out of 100 had withdrawal due to poor control over 4 to 52 weeks, compared to 6 (95% CI 4 to 7) out of 100 for the active treatment group (given LRTA).

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 1 Patients with at least one exacerbation requiring systemic steroids.
Figuras y tablas -
Analysis 1.1

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 1 Patients with at least one exacerbation requiring systemic steroids.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 2 Patients with at least one exacerbation requiring hospital admission.
Figuras y tablas -
Analysis 1.2

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 2 Patients with at least one exacerbation requiring hospital admission.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 3 Change from baseline FEV1 (L) at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.3

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 3 Change from baseline FEV1 (L) at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 4 Change from baseline FEV1( L) 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.4

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 4 Change from baseline FEV1( L) 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 5 Change from baseline FEV1 (L) at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.5

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 5 Change from baseline FEV1 (L) at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 6 Change from baseline FEV1 (L) at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.6

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 6 Change from baseline FEV1 (L) at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 7 FEV1 irrespective of time of treatment.
Figuras y tablas -
Analysis 1.7

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 7 FEV1 irrespective of time of treatment.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 8 Responders (defined as change from baseline in FEV1 >= 7.5%.
Figuras y tablas -
Analysis 1.8

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 8 Responders (defined as change from baseline in FEV1 >= 7.5%.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 9 Change from baseline FEV1 (%) at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.9

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 9 Change from baseline FEV1 (%) at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 10 Change from baseline FEV1 (%) 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.10

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 10 Change from baseline FEV1 (%) 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 11 Change from baseline FEV1 (%) at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.11

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 11 Change from baseline FEV1 (%) at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 12 Change from baseline FEV1 % of predicted at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.12

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 12 Change from baseline FEV1 % of predicted at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 13 Change from baseline FEV1 % of predicated at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.13

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 13 Change from baseline FEV1 % of predicated at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 14 Change from baseline FEV1 % of predicated at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.14

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 14 Change from baseline FEV1 % of predicated at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 15 Change from baseline AM PEFR (L/min) at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.15

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 15 Change from baseline AM PEFR (L/min) at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 16 Change from baseline AM PEFR (L/min) at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.16

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 16 Change from baseline AM PEFR (L/min) at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 17 Change from baseline AM PEFR (L/min) at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.17

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 17 Change from baseline AM PEFR (L/min) at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 18 Change from baseline AM PEFR (L/min) at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.18

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 18 Change from baseline AM PEFR (L/min) at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 19 Change from baseline daytime symptom scores at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.19

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 19 Change from baseline daytime symptom scores at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 20 Change from baseline daytime symptom scores at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.20

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 20 Change from baseline daytime symptom scores at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 21 Change from baseline daytime symptom scores at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.21

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 21 Change from baseline daytime symptom scores at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 22 Change from baseline daytime symptom scores at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.22

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 22 Change from baseline daytime symptom scores at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 23 Change from baseline night‐time awakenings at 4 ‐ 8 week.
Figuras y tablas -
Analysis 1.23

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 23 Change from baseline night‐time awakenings at 4 ‐ 8 week.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 24 Change from baseline night‐time awakenings at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.24

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 24 Change from baseline night‐time awakenings at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 25 Change from baseline night‐time awakenings at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.25

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 25 Change from baseline night‐time awakenings at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 26 Change from baseline mean daily use of β2‐agonists at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.26

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 26 Change from baseline mean daily use of β2‐agonists at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 27 Change from baseline mean daily use of β2‐agonists at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.27

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 27 Change from baseline mean daily use of β2‐agonists at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 28 Change from baseline mean daily use of β2‐agonists at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.28

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 28 Change from baseline mean daily use of β2‐agonists at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 29 Change from baseline mean daily use of β2‐agonists at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.29

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 29 Change from baseline mean daily use of β2‐agonists at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 30 Change in rescue‐free days (%) at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.30

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 30 Change in rescue‐free days (%) at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 31 Change in rescue‐free days (%) at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.31

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 31 Change in rescue‐free days (%) at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 32 Change in rescue‐free days (%) at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.32

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 32 Change in rescue‐free days (%) at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 33 Change in rescue‐free days (%) at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.33

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 33 Change in rescue‐free days (%) at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 34 Change in proportion of symptom‐free days (%) at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.34

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 34 Change in proportion of symptom‐free days (%) at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 35 Change in proportion of symptom‐free days (%) at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.35

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 35 Change in proportion of symptom‐free days (%) at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 36 Change in proportion of symptom‐free days (%) at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.36

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 36 Change in proportion of symptom‐free days (%) at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 37 Change in proportion of symptom‐free days (%) at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.37

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 37 Change in proportion of symptom‐free days (%) at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 38 Change from baseline quality of life (QOL) at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.38

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 38 Change from baseline quality of life (QOL) at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 39 Change from baseline quality of life (QOL) at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.39

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 39 Change from baseline quality of life (QOL) at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 40 Change from baseline quality of life (QOL) at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.40

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 40 Change from baseline quality of life (QOL) at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 41 Change from baseline quality of life (QOL) at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.41

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 41 Change from baseline quality of life (QOL) at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 42 Days with use of β2‐agonists at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.42

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 42 Days with use of β2‐agonists at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 43 Change from baseline blood eosinophils at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.43

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 43 Change from baseline blood eosinophils at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 44 Change from baseline blood eosinophils at 12 ‐ 16 weeks.
Figuras y tablas -
Analysis 1.44

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 44 Change from baseline blood eosinophils at 12 ‐ 16 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 45 % Change in sputum eosinophils at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.45

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 45 % Change in sputum eosinophils at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 46 % Change in sputum eosinophils at 36 ‐ 52 weeks.
Figuras y tablas -
Analysis 1.46

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 46 % Change in sputum eosinophils at 36 ‐ 52 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 47 LTC4 concentration (ng/mL) in nasal wash at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.47

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 47 LTC4 concentration (ng/mL) in nasal wash at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 48 % Asthma control days during intervention period at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.48

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 48 % Asthma control days during intervention period at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 49 % Asthma control days during intervention period at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.49

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 49 % Asthma control days during intervention period at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 50 Change in PC20 at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.50

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 50 Change in PC20 at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 51 % rescue ‐ free days at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.51

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 51 % rescue ‐ free days at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 52 Days off work or school at 24 ‐ 26 weeks.
Figuras y tablas -
Analysis 1.52

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 52 Days off work or school at 24 ‐ 26 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 53 Change in height (cm).
Figuras y tablas -
Analysis 1.53

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 53 Change in height (cm).

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 54 Patient's satisfaction at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.54

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 54 Patient's satisfaction at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 55 Physician's satisfaction at 4 ‐ 8 weeks.
Figuras y tablas -
Analysis 1.55

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 55 Physician's satisfaction at 4 ‐ 8 weeks.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 56 Overall Withdrawals.
Figuras y tablas -
Analysis 1.56

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 56 Overall Withdrawals.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 57 Withdrawal due to poor asthma control/exacerbations.
Figuras y tablas -
Analysis 1.57

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 57 Withdrawal due to poor asthma control/exacerbations.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 58 Withdrawals due to adverse effects.
Figuras y tablas -
Analysis 1.58

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 58 Withdrawals due to adverse effects.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 59 Overall Adverse effects.
Figuras y tablas -
Analysis 1.59

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 59 Overall Adverse effects.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 60 Elevated liver enzymes.
Figuras y tablas -
Analysis 1.60

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 60 Elevated liver enzymes.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 61 Upper respiratory tract infections.
Figuras y tablas -
Analysis 1.61

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 61 Upper respiratory tract infections.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 62 Headache.
Figuras y tablas -
Analysis 1.62

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 62 Headache.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 63 Nausea.
Figuras y tablas -
Analysis 1.63

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 63 Nausea.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 64 Oral candidiasis.
Figuras y tablas -
Analysis 1.64

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 64 Oral candidiasis.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 65 Hoarseness.
Figuras y tablas -
Analysis 1.65

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 65 Hoarseness.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 66 Death.
Figuras y tablas -
Analysis 1.66

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 66 Death.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 67 Primary outcome ‐ stratified by anti‐leukotrienes.
Figuras y tablas -
Analysis 1.67

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 67 Primary outcome ‐ stratified by anti‐leukotrienes.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 68 Primary outcome ‐ stratified by duration of intervention.
Figuras y tablas -
Analysis 1.68

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 68 Primary outcome ‐ stratified by duration of intervention.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 69 Main outcome ‐stratified by severity of airway obstruction.
Figuras y tablas -
Analysis 1.69

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 69 Main outcome ‐stratified by severity of airway obstruction.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 70 Primary outcome ‐ stratified by methodological quality.
Figuras y tablas -
Analysis 1.70

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 70 Primary outcome ‐ stratified by methodological quality.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 71 Primary outcome‐ stratified by funding source.
Figuras y tablas -
Analysis 1.71

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 71 Primary outcome‐ stratified by funding source.

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Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 72 Primary outcome ‐ stratified by HFC‐BDP equivalent.
Figuras y tablas -
Analysis 1.72

Comparison 1 Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent), Outcome 72 Primary outcome ‐ stratified by HFC‐BDP equivalent.

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Comparison 1. Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Patients with at least one exacerbation requiring systemic steroids Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]

1.1 Paediatrics

6

1662

Risk Ratio (M‐H, Random, 95% CI)

1.35 [0.99, 1.86]

1.2 Adults

15

4415

Risk Ratio (M‐H, Random, 95% CI)

1.61 [1.12, 2.31]

2 Patients with at least one exacerbation requiring hospital admission Show forest plot

12

2715

Risk Ratio (M‐H, Fixed, 95% CI)

3.33 [1.02, 10.94]

2.1 Paediatrics

4

558

Risk Ratio (M‐H, Fixed, 95% CI)

3.04 [0.12, 73.98]

2.2 Adults

8

2157

Risk Ratio (M‐H, Fixed, 95% CI)

3.38 [0.94, 12.17]

3 Change from baseline FEV1 (L) at 4 ‐ 8 weeks Show forest plot

12

3020

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.15, ‐0.08]

3.1 Paediatrics

1

56

Mean Difference (IV, Random, 95% CI)

‐0.28 [‐0.69, 0.13]

3.2 Adults

11

2964

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.15, ‐0.08]

4 Change from baseline FEV1( L) 12 ‐ 16 weeks Show forest plot

8

1778

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.20, ‐0.04]

4.1 Paediatrics

2

179

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.13, 0.09]

4.2 Adults

6

1599

Mean Difference (IV, Random, 95% CI)

‐0.14 [‐0.24, ‐0.05]

5 Change from baseline FEV1 (L) at 24 ‐ 26 weeks Show forest plot

3

1178

Mean Difference (IV, Random, 95% CI)

‐0.13 [‐0.22, ‐0.04]

5.1 Paediatrics

1

123

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.14, 0.12]

5.2 Adults

2

1055

Mean Difference (IV, Random, 95% CI)

‐0.17 [‐0.23, ‐0.11]

6 Change from baseline FEV1 (L) at 36 ‐ 52 weeks Show forest plot

2

1040

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.07, 0.00]

6.1 Paediatrics

2

1040

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.07, 0.00]

7 FEV1 irrespective of time of treatment Show forest plot

23

7016

Mean Difference (IV, Random, 95% CI)

‐0.11 [‐0.14, ‐0.08]

7.1 Paediatrics

4

1398

Mean Difference (IV, Random, 95% CI)

‐0.03 [‐0.07, 0.00]

7.2 Adults

19

5618

Mean Difference (IV, Random, 95% CI)

‐0.13 [‐0.16, ‐0.09]

8 Responders (defined as change from baseline in FEV1 >= 7.5% Show forest plot

1

Odds Ratio (Fixed, 95% CI)

Totals not selected

9 Change from baseline FEV1 (%) at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

9.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Change from baseline FEV1 (%) 12 ‐ 16 weeks Show forest plot

2

603

Mean Difference (IV, Fixed, 95% CI)

‐5.70 [‐9.81, ‐1.59]

10.1 Adults

2

603

Mean Difference (IV, Fixed, 95% CI)

‐5.70 [‐9.81, ‐1.59]

11 Change from baseline FEV1 (%) at 24 ‐ 26 weeks Show forest plot

2

838

Mean Difference (IV, Fixed, 95% CI)

‐8.20 [‐10.85, ‐5.55]

11.1 Adults

2

838

Mean Difference (IV, Fixed, 95% CI)

‐8.20 [‐10.85, ‐5.55]

12 Change from baseline FEV1 % of predicted at 4 ‐ 8 weeks Show forest plot

2

219

Mean Difference (IV, Random, 95% CI)

‐2.58 [‐6.56, 1.40]

12.1 Paediatrics

1

183

Mean Difference (IV, Random, 95% CI)

‐0.54 [‐4.82, 3.74]

12.2 Adults

1

36

Mean Difference (IV, Random, 95% CI)

‐4.6 [‐8.86, ‐0.34]

13 Change from baseline FEV1 % of predicated at 12 ‐ 16 weeks Show forest plot

3

948

Mean Difference (IV, Fixed, 95% CI)

‐3.76 [‐5.01, ‐2.50]

13.1 Paediatrics

1

335

Mean Difference (IV, Fixed, 95% CI)

‐6.02 [‐9.45, ‐2.59]

13.2 Adults

2

613

Mean Difference (IV, Fixed, 95% CI)

‐3.41 [‐4.76, ‐2.06]

14 Change from baseline FEV1 % of predicated at 36 ‐ 52 weeks Show forest plot

3

1229

Mean Difference (IV, Random, 95% CI)

‐3.51 [‐7.14, 0.12]

14.1 Paediatrics

3

1229

Mean Difference (IV, Random, 95% CI)

‐3.51 [‐7.14, 0.12]

15 Change from baseline AM PEFR (L/min) at 4 ‐ 8 weeks Show forest plot

8

1926

Mean Difference (IV, Random, 95% CI)

‐15.12 [‐20.80, ‐9.44]

15.1 Paediatrics

1

332

Mean Difference (IV, Random, 95% CI)

‐7.76 [‐13.43, ‐2.09]

15.2 Adults

7

1594

Mean Difference (IV, Random, 95% CI)

‐17.63 [‐22.56, ‐12.69]

16 Change from baseline AM PEFR (L/min) at 12 ‐ 16 weeks Show forest plot

9

2601

Mean Difference (IV, Random, 95% CI)

‐19.07 [‐25.86, ‐12.27]

16.1 Paediatrics

1

335

Mean Difference (IV, Random, 95% CI)

‐16.9 [‐28.54, ‐5.26]

16.2 Adults

8

2266

Mean Difference (IV, Random, 95% CI)

‐19.57 [‐27.27, ‐11.87]

17 Change from baseline AM PEFR (L/min) at 24 ‐ 26 weeks Show forest plot

3

1718

Mean Difference (IV, Random, 95% CI)

‐21.62 [‐40.19, ‐3.05]

17.1 Adults

3

1718

Mean Difference (IV, Random, 95% CI)

‐21.62 [‐40.19, ‐3.05]

18 Change from baseline AM PEFR (L/min) at 36 ‐ 52 weeks Show forest plot

3

1028

Mean Difference (IV, Random, 95% CI)

‐5.06 [‐10.58, 0.45]

18.1 Adults

3

1028

Mean Difference (IV, Random, 95% CI)

‐5.06 [‐10.58, 0.45]

19 Change from baseline daytime symptom scores at 4 ‐ 8 weeks Show forest plot

6

1925

Std. Mean Difference (IV, Random, 95% CI)

0.20 [0.08, 0.32]

19.1 Paediatrics

1

393

Std. Mean Difference (IV, Random, 95% CI)

0.06 [‐0.14, 0.26]

19.2 Adults

5

1532

Std. Mean Difference (IV, Random, 95% CI)

0.23 [0.11, 0.36]

20 Change from baseline daytime symptom scores at 12 ‐ 16 weeks Show forest plot

9

2650

Std. Mean Difference (IV, Fixed, 95% CI)

0.25 [0.18, 0.33]

20.1 Paediatrics

2

388

Std. Mean Difference (IV, Fixed, 95% CI)

0.28 [0.08, 0.48]

20.2 Adults

7

2262

Std. Mean Difference (IV, Fixed, 95% CI)

0.25 [0.16, 0.33]

21 Change from baseline daytime symptom scores at 24 ‐ 26 weeks Show forest plot

3

1719

Std. Mean Difference (IV, Random, 95% CI)

0.22 [0.02, 0.42]

21.1 Adults

3

1719

Std. Mean Difference (IV, Random, 95% CI)

0.22 [0.02, 0.42]

22 Change from baseline daytime symptom scores at 36 ‐ 52 weeks Show forest plot

2

582

Std. Mean Difference (IV, Random, 95% CI)

0.16 [‐0.02, 0.34]

22.1 Paediatrics

2

582

Std. Mean Difference (IV, Random, 95% CI)

0.16 [‐0.02, 0.34]

23 Change from baseline night‐time awakenings at 4 ‐ 8 week Show forest plot

3

798

Std. Mean Difference (IV, Random, 95% CI)

0.22 [‐0.02, 0.46]

23.1 Adults

3

798

Std. Mean Difference (IV, Random, 95% CI)

0.22 [‐0.02, 0.46]

24 Change from baseline night‐time awakenings at 12 ‐ 16 weeks Show forest plot

9

2916

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [0.11, 0.26]

24.1 Adults

9

2916

Std. Mean Difference (IV, Fixed, 95% CI)

0.18 [0.11, 0.26]

25 Change from baseline night‐time awakenings at 24 ‐ 26 weeks Show forest plot

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.23 [0.11, 0.35]

25.1 Adults

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.23 [0.11, 0.35]

26 Change from baseline mean daily use of β2‐agonists at 4 ‐ 8 weeks Show forest plot

10

3264

Std. Mean Difference (IV, Random, 95% CI)

0.20 [0.07, 0.34]

26.1 Paediatrics

1

393

Std. Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.22, 0.17]

26.2 Adults

9

2871

Std. Mean Difference (IV, Random, 95% CI)

0.24 [0.10, 0.38]

27 Change from baseline mean daily use of β2‐agonists at 12 ‐ 16 weeks Show forest plot

11

3367

Std. Mean Difference (IV, Fixed, 95% CI)

0.23 [0.17, 0.30]

27.1 Paediatrics

1

335

Std. Mean Difference (IV, Fixed, 95% CI)

0.02 [‐0.20, 0.23]

27.2 Adults

10

3032

Std. Mean Difference (IV, Fixed, 95% CI)

0.26 [0.19, 0.33]

28 Change from baseline mean daily use of β2‐agonists at 24 ‐ 26 weeks Show forest plot

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.31 [0.19, 0.43]

28.1 Adults

2

1055

Std. Mean Difference (IV, Fixed, 95% CI)

0.31 [0.19, 0.43]

29 Change from baseline mean daily use of β2‐agonists at 36 ‐ 52 weeks Show forest plot

1

Std. Mean Difference (IV, Fixed, 95% CI)

Totals not selected

29.1 Paediatrics

1

Std. Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

30 Change in rescue‐free days (%) at 4 ‐ 8 weeks Show forest plot

5

1315

Mean Difference (IV, Random, 95% CI)

‐6.83 [‐17.73, 4.07]

30.1 Paediatrics

1

393

Mean Difference (IV, Random, 95% CI)

2.72 [‐3.11, 8.55]

30.2 Adults

4

922

Mean Difference (IV, Random, 95% CI)

‐13.25 [‐18.11, ‐8.39]

31 Change in rescue‐free days (%) at 12 ‐ 16 weeks Show forest plot

7

2304

Mean Difference (IV, Random, 95% CI)

‐9.64 [‐13.71, ‐5.56]

31.1 Paediatrics

1

335

Mean Difference (IV, Random, 95% CI)

‐10.10 [‐18.97, ‐1.23]

31.2 Adults

6

1969

Mean Difference (IV, Random, 95% CI)

‐9.64 [‐14.39, ‐4.89]

32 Change in rescue‐free days (%) at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

32.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

33 Change in rescue‐free days (%) at 36 ‐ 52 weeks Show forest plot

2

1350

Mean Difference (IV, Fixed, 95% CI)

‐2.59 [‐4.97, ‐0.21]

33.1 Paediatrics

2

1350

Mean Difference (IV, Fixed, 95% CI)

‐2.59 [‐4.97, ‐0.21]

33.2 Adults

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

34 Change in proportion of symptom‐free days (%) at 4 ‐ 8 weeks Show forest plot

3

1154

Mean Difference (IV, Fixed, 95% CI)

‐10.46 [‐14.56, ‐6.36]

34.1 Adults

3

1154

Mean Difference (IV, Fixed, 95% CI)

‐10.46 [‐14.56, ‐6.36]

35 Change in proportion of symptom‐free days (%) at 12 ‐ 16 weeks Show forest plot

8

2423

Mean Difference (IV, Fixed, 95% CI)

‐8.89 [‐11.92, ‐5.87]

35.1 Paediatrics

1

335

Mean Difference (IV, Fixed, 95% CI)

‐6.40 [‐15.82, 3.02]

35.2 Adults

7

2088

Mean Difference (IV, Fixed, 95% CI)

‐9.18 [‐12.38, ‐5.98]

36 Change in proportion of symptom‐free days (%) at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

36.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

37 Change in proportion of symptom‐free days (%) at 36 ‐ 52 weeks Show forest plot

3

1190

Mean Difference (IV, Fixed, 95% CI)

‐5.49 [‐9.06, ‐1.91]

37.1 Paediatrics

2

575

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐9.73, ‐0.08]

37.2 Adults

1

615

Mean Difference (IV, Fixed, 95% CI)

‐6.20 [‐11.53, ‐0.87]

38 Change from baseline quality of life (QOL) at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

38.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

39 Change from baseline quality of life (QOL) at 12 ‐ 16 weeks Show forest plot

2

1065

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.34, ‐0.09]

39.1 Adults

2

1065

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.34, ‐0.09]

40 Change from baseline quality of life (QOL) at 24 ‐ 26 weeks Show forest plot

2

1028

Mean Difference (IV, Fixed, 95% CI)

‐0.38 [‐0.54, ‐0.21]

40.1 Adults

2

1028

Mean Difference (IV, Fixed, 95% CI)

‐0.38 [‐0.54, ‐0.21]

41 Change from baseline quality of life (QOL) at 36 ‐ 52 weeks Show forest plot

1

541

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.33, 0.07]

41.1 Paediatrics

1

541

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.33, 0.07]

41.2 Adults

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

42 Days with use of β2‐agonists at 36 ‐ 52 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

42.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

43 Change from baseline blood eosinophils at 4 ‐ 8 weeks Show forest plot

4

1294

Mean Difference (IV, Random, 95% CI)

0.06 [0.02, 0.10]

43.1 Adults

4

1294

Mean Difference (IV, Random, 95% CI)

0.06 [0.02, 0.10]

44 Change from baseline blood eosinophils at 12 ‐ 16 weeks Show forest plot

2

1013

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.03, 0.02]

44.1 Adults

2

1013

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.03, 0.02]

45 % Change in sputum eosinophils at 4 ‐ 8 weeks Show forest plot

2

117

Mean Difference (IV, Random, 95% CI)

0.71 [‐2.06, 3.47]

45.1 Adults

2

117

Mean Difference (IV, Random, 95% CI)

0.71 [‐2.06, 3.47]

46 % Change in sputum eosinophils at 36 ‐ 52 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

46.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

47 LTC4 concentration (ng/mL) in nasal wash at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

47.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

48 % Asthma control days during intervention period at 4 ‐ 8 weeks Show forest plot

2

1293

Mean Difference (IV, Fixed, 95% CI)

‐5.72 [‐10.86, ‐0.59]

48.1 Adults

2

1293

Mean Difference (IV, Fixed, 95% CI)

‐5.72 [‐10.86, ‐0.59]

49 % Asthma control days during intervention period at 24 ‐ 26 weeks Show forest plot

2

1185

Mean Difference (IV, Random, 95% CI)

‐8.19 [‐19.46, 3.07]

49.1 Adults

2

1185

Mean Difference (IV, Random, 95% CI)

‐8.19 [‐19.46, 3.07]

50 Change in PC20 at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

50.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

51 % rescue ‐ free days at 24 ‐ 26 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

51.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

52 Days off work or school at 24 ‐ 26 weeks Show forest plot

2

606

Mean Difference (IV, Fixed, 95% CI)

0.12 [‐0.01, 0.26]

52.1 Paediatrics

1

124

Mean Difference (IV, Fixed, 95% CI)

‐0.24 [‐1.31, 0.83]

52.2 Adults

1

482

Mean Difference (IV, Fixed, 95% CI)

0.13 [‐0.00, 0.26]

53 Change in height (cm) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

53.1 Paediatrics

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

54 Patient's satisfaction at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

54.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

55 Physician's satisfaction at 4 ‐ 8 weeks Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

55.1 Adults

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

56 Overall Withdrawals Show forest plot

42

10939

Risk Ratio (M‐H, Random, 95% CI)

1.22 [1.08, 1.38]

56.1 Paediatrics

18

3397

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.88, 1.21]

56.2 Adults

24

7542

Risk Ratio (M‐H, Random, 95% CI)

1.31 [1.11, 1.54]

57 Withdrawal due to poor asthma control/exacerbations Show forest plot

26

7669

Risk Ratio (M‐H, Fixed, 95% CI)

2.56 [2.01, 3.27]

57.1 Paediatrics

7

1219

Risk Ratio (M‐H, Fixed, 95% CI)

2.17 [1.20, 3.94]

57.2 Adults

19

6450

Risk Ratio (M‐H, Fixed, 95% CI)

2.64 [2.02, 3.45]

58 Withdrawals due to adverse effects Show forest plot

25

8518

Risk Ratio (M‐H, Fixed, 95% CI)

1.24 [0.95, 1.63]

58.1 Paediatrics

8

2330

Risk Ratio (M‐H, Fixed, 95% CI)

1.27 [0.70, 2.33]

58.2 Adults

17

6188

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.91, 1.67]

59 Overall Adverse effects Show forest plot

22

7818

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.95, 1.05]

59.1 Paediatrics

3

1460

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.90, 1.15]

59.2 Adults

19

6358

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.94, 1.05]

60 Elevated liver enzymes Show forest plot

7

1761

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.58, 2.19]

60.1 Paediatrics

1

118

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.03, 7.68]

60.2 Adults

6

1643

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.60, 2.36]

61 Upper respiratory tract infections Show forest plot

8

2729

Odds Ratio (M‐H, Fixed, 95% CI)

1.04 [0.84, 1.29]

61.1 Paediatrics

5

1514

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.81, 1.36]

61.2 Adults

3

1215

Odds Ratio (M‐H, Fixed, 95% CI)

1.01 [0.69, 1.50]

62 Headache Show forest plot

24

8872

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.89, 1.11]

62.1 Paediatrics

6

2589

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.81, 1.37]

62.2 Adults

18

6283

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.86, 1.10]

63 Nausea Show forest plot

17

5563

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.64, 1.08]

63.1 Paediatrics

2

465

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.28, 2.31]

63.2 Adults

15

5098

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.64, 1.09]

64 Oral candidiasis Show forest plot

3

865

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.05, 1.19]

64.1 Adults

3

865

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.05, 1.19]

65 Hoarseness Show forest plot

2

734

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.03, 2.24]

65.1 Adults

2

734

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.03, 2.24]

66 Death Show forest plot

13

5489

Risk Ratio (M‐H, Fixed, 95% CI)

3.05 [0.32, 29.26]

66.1 Paediatrics

2

1114

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.12, 73.46]

66.2 Adults

11

4375

Risk Ratio (M‐H, Fixed, 95% CI)

3.10 [0.13, 75.82]

67 Primary outcome ‐ stratified by anti‐leukotrienes Show forest plot

21

6077

Odds Ratio (M‐H, Random, 95% CI)

1.61 [1.20, 2.16]

67.1 Monelukast

15

4352

Odds Ratio (M‐H, Random, 95% CI)

1.55 [1.14, 2.12]

67.2 Zafirlukast

6

1725

Odds Ratio (M‐H, Random, 95% CI)

1.92 [0.88, 4.20]

68 Primary outcome ‐ stratified by duration of intervention Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]

68.1 4‐8 weeks

9

2346

Risk Ratio (M‐H, Random, 95% CI)

1.74 [0.78, 3.87]

68.2 12‐16 weeks

7

1541

Risk Ratio (M‐H, Random, 95% CI)

2.06 [1.43, 2.96]

68.3 24‐26 weeks

2

657

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.55, 2.45]

68.4 36‐52 weeks

3

1533

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.87, 1.91]

69 Main outcome ‐stratified by severity of airway obstruction Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]

69.1 Mean FEV1 60‐80% of predicted

11

3922

Risk Ratio (M‐H, Random, 95% CI)

2.03 [1.41, 2.91]

69.2 Mean FEV1 ≥80% of predicted

10

2155

Risk Ratio (M‐H, Random, 95% CI)

1.25 [0.97, 1.61]

70 Primary outcome ‐ stratified by methodological quality Show forest plot

21

6061

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]

70.1 High quality

11

4366

Risk Ratio (M‐H, Random, 95% CI)

1.62 [1.29, 2.03]

70.2 Poor quality

10

1695

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.74, 2.43]

71 Primary outcome‐ stratified by funding source Show forest plot

21

6077

Risk Ratio (M‐H, Random, 95% CI)

1.51 [1.17, 1.96]

71.1 Funded by producers of ICS

9

2638

Risk Ratio (M‐H, Random, 95% CI)

1.71 [1.05, 2.80]

71.2 Funded by producers of AL

5

2797

Risk Ratio (M‐H, Random, 95% CI)

1.52 [0.99, 2.35]

71.3 No industry funding or not reported

7

642

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.90, 1.66]

72 Primary outcome ‐ stratified by HFC‐BDP equivalent Show forest plot

21

6077

Odds Ratio (M‐H, Random, 95% CI)

1.61 [1.20, 2.16]

72.1 100‐150 μg HFA‐BDP equivalent

3

216

Odds Ratio (M‐H, Random, 95% CI)

0.74 [0.26, 2.08]

72.2 200‐250 μg HFA‐BDP equivalent

15

5767

Odds Ratio (M‐H, Random, 95% CI)

1.75 [1.29, 2.38]

72.3 400‐500 μg HFA‐BDP equivalent

3

94

Odds Ratio (M‐H, Random, 95% CI)

0.54 [0.11, 2.78]
Figuras y tablas -
Comparison 1. Anti‐leukotriene (AL) vs. Inhaled glucocorticoids (in HFC‐BDP equivalent)
Ir a la tabla de la revisión