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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Budesonide | Research

A comparison of tiotropium, long-acting β2-agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma

Authors: Christian Vogelberg, Stanley Goldstein, LeRoy Graham, Alan Kaplan, Alberto de la Hoz, Eckard Hamelmann

Published in: Respiratory Research | Issue 1/2020

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Abstract

Diagnosing and treating asthma in paediatric patients remains challenging, with many children and adolescents remaining uncontrolled despite treatment. Selecting the most appropriate pharmacological treatment to add onto inhaled corticosteroids (ICS) in children and adolescents with asthma who remain symptomatic despite ICS can be difficult. This literature review compares the efficacy and safety of long-acting β2-agonists (LABAs), leukotriene receptor antagonists (LTRAs) and long-acting muscarinic antagonists (LAMAs) as add-on treatment to ICS in children and adolescents aged 4–17 years.
A literature search identified a total of 29 studies that met the inclusion criteria, including 21 randomised controlled trials (RCTs) of LABAs versus placebo, two RCTs of LAMAs (tiotropium) versus placebo, and four RCTs of LTRA (montelukast), all as add-on to ICS. In these studies, tiotropium and LABAs provided greater improvements in lung function than LTRAs, when compared with placebo as add-on to ICS. Although exacerbation data were difficult to interpret, tiotropium reduced the risk of exacerbations requiring oral corticosteroids when added to ICS, with or without additional controllers. LABAs and LTRAs had a comparable risk of asthma exacerbations with placebo when added to ICS. When adverse events (AEs) or serious AEs were analysed, LABAs, montelukast and tiotropium had a comparable safety profile with placebo.
In conclusion, this literature review provides an up-to-date overview of the efficacy and safety of LABAs, LTRAs and LAMAs as add-on to ICS in children and adolescents with asthma. Overall, tiotropium and LABAs have similar efficacy, and provide greater improvements in lung function than montelukast as add-on to ICS. All three controller options have comparable safety profiles.
Literature
1.
2.
3.
Ferrante G, Grutta S. Reasons for inadequate asthma control in children: an important contribution from the “French 6 Cities Study”. Multidiscip Respir Med. 2012;7:23.PubMedPubMedCentralCrossRef
4.
5.
Rodrigo GJ, Castro-Rodriguez JA. Safety of long-acting beta agonists for the treatment of asthma: clearing the air. Thorax. 2012;67(4):342–9.PubMedCrossRef
6.
Ducharme F, NiChroinin M, Greenstone I, Lasserson T. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst Rev. 2010;5:CD005535.
7.
8.
9.
10.
11.
Hamelmann E, Bateman ED, Vogelberg C, Szefler SJ, Vandewalker M, Moroni-Zentgraf P, et al. Tiotropium add-on therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138(2):441–450.e8.PubMedCrossRef
12.
Vogelberg C, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Hamelmann E, Engel M, et al. A randomised dose-ranging study of tiotropium Respimat® in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015;16:20.PubMedPubMedCentralCrossRef
13.
Szefler SJ, Murphy K, Harper T, Boner A, Laki I, Engel M, et al. A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma. J Allergy Clin Immunol. 2017;140:1277–87.PubMedCrossRef
14.
Hamelmann E, Bernstein JA, Vandewalker M, Moroni-Zentgraf P, Verri D, Unseld A, et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49:1601100.PubMedPubMedCentralCrossRef
15.
16.
17.
18.
19.
20.
Anderson DE, Kew KM, Boyter AC. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus the same dose of ICS alone for adults with asthma. Cochrane Database Syst Rev. 2015;24(8):CD011397.
21.
Kew KM, Evans DJ, Allison DE, Boyter AC. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus addition of long-acting beta2-agonists (LABA) for adults with asthma. Cochrane Database Syst Rev. 2015;2(6):CD011438.
22.
Sobieraj DM, Baker WL, Nguyen E, Weeda ER, Coleman CI, White CM, et al. Association of inhaled corticosteroids and long-acting muscarinic antagonists with asthma control in patients with uncontrolled, persistent asthma: a systematic review and meta-analysis. JAMA. 2018;319(14):1473–84.PubMedPubMedCentralCrossRef
23.
The Cochrane Collaboration’s tool for assessing risk of bias. In: Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. 5.1.0 edition. London: The Cochrane Collaboration; 2011.
24.
Chauhan BF, Chartrand C, Ni Chroinin M, Milan SJ, Ducharme FM. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015;24(11, CD007949).
25.
Castro-Rodriguez JA, Rodrigo GJ. The role of inhaled corticosteroids and montelukast in children with mild-moderate asthma: results of a systematic review with meta-analysis. Arch Dis Child. 2010;95(5):365–70.PubMedCrossRef
26.
Zhao Y, Han S, Shang J, Zhao X, Pu R, Shi L. Effectiveness of drug treatment strategies to prevent asthma exacerbations and increase symptom-free days in asthmatic children: a network meta-analysis. J Asthma. 2015;52(8):846–57.PubMedCrossRef
27.
Chauhan BF, Ben Salah R, Ducharme FM. Addition of anti-leukotriene agents to inhaled corticosteroids in children with persistent asthma. Cochrane Database Syst Rev. 2013;2(10):CD009585.
28.
Oliver AJ, Covar RA, Goldfrad CH, Klein RM, Pedersen SE, Sorkness CA, et al. Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy. Respir Res. 2016;17:37.PubMedPubMedCentralCrossRef
29.
Pearlman DS, Eckerwall G, McLaren J, Lamarca R, Puu M, Gilbert I, et al. Efficacy and safety of budesonide/formoterol pMDI vs budesonide pMDI in asthmatic children (6–<12 years). Ann Allergy Asthma Immunol. 2017;118:489–499.e1.PubMedCrossRef
30.
Stelmach I, Ozarek-Hanc A, Zaczeniuk M, Stelmach W, Smejda K, Majak P, et al. Do children with stable asthma benefit from addition of montelukast to inhaled corticosteroids: randomized, placebo controlled trial. Pulm Pharmacol Ther. 2015;31:42–8.PubMedCrossRef
31.
Vogelberg C, Engel M, Laki I, Bernstein JA, Schmidt O, El Azzi G, et al. Tiotropium add-on therapy improves lung function in children with symptomatic moderate asthma. J Allergy Clin Immunol Pract. 2018;6(6):2160–2162.e9.PubMedCrossRef
32.
Berger WE, Leflein JG, Geller DE, Parasuraman B, Miller CJ, O’Brien CD, et al. The safety and clinical benefit of budesonide/formoterol pressurized metered-dose inhaler versus budesonide alone in children. Allergy Asthma Proc. 2010;31(1):26–39.PubMed
33.
Eid NS, Noonan MJ, Chipps B, Parasuraman B, Miller CJ, O’Brien CD. Once- vs twice-daily budesonide/formoterol in 6- to 15-year-old patients with stable asthma. Pediatrics. 2010;126(3):e565–75.PubMedCrossRef
34.
Pohunek P, Kuna P, Jorup C, De Boeck K. Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma. Pediatr Allergy Immunol. 2006;17(6):458–65.PubMedCrossRef
35.
AstraZeneca plc. Efficacy and safety of budesonide/formoterol Turbuhaler® (160/4.5 mg b.i.d. delivered dose) compared to budesonide Turbuhaler® (200 mg b.i.d. metered dose) in steroid-using asthmatic adolescent patients. A double-blind, double-dummy, randomised, parallel group, phase III, multicentre study. (ATTAIN STUDY): CR-SD-039-0714. 2003.
36.
Akpinarli A, Tuncer A, Saraclar Y, Sekerel BE, Kalayci O. Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial. Arch Dis Child. 1999;81(1):45–8.PubMedPubMedCentralCrossRef
37.
Morice AH, Peterson S, Beckman O, Kukova Z. Efficacy and safety of a new pressurised metered-dose inhaler formulation of budesonide/formoterol in children with asthma: a superiority and therapeutic equivalence study. Pulm Pharmacol Ther. 2008;21(1):152–9.PubMedCrossRef
38.
Malone R, LaForce C, Nimmagadda S, Schoaf L, House K, Ellsworth A, et al. The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma. Ann Allergy Asthma Immunol. 2005;95(1):66–71.PubMedCrossRef
39.
Carroll WD, Jones PW, Boit P, Clayton S, Cliff I, Lenney W. Childhood evaluation of salmeterol tolerance--a double-blind randomized controlled trial. Pediatr Allergy Immunol. 2010;21(2 Pt 1):336–44.PubMedCrossRef
40.
Lenney W, McKay AJ, Tudur Smith C, Williamson PR, James M, Price DB. Management of Asthma in school age children on therapy (MASCOT): a randomised, double-blind, placebo-controlled, parallel study of efficacy and safety. Health Technol Assess. 2013;17:1–218.PubMedPubMedCentralCrossRef
41.
Teper AM, Zaragoza SM, Lubovich S, Rodriguez VA, Venalago C, Kofman CD. Effect of fluticasone propionate (FP) with or without salmeterol (S) on bronchial reactivity (BR) in children with mild to moderate persistent asthma [abstract]. Am Thor Soc Int Conf. 2005;C47.
42.
Murray JJ, Waitkus-Edwards KR, Yancey SW. Evaluation of fluticasone propionate and fluticasone propionate/salmeterol combination on exercise in pediatric and adolescent patients with asthma. Open Respir Med J. 2011;5:11–8.PubMedPubMedCentralCrossRef
43.
Pearlman D, Qaqundah P, Matz J, Yancey SW, Stempel DA, Ortega HG. Fluticasone propionate/salmeterol and exercise-induced asthma in children with persistent asthma. Pediatr Pulmonol. 2009;44(5):429–35.PubMedCrossRef
44.
Simons FE, Gerstner TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics. 1997;99(5):655–9.PubMedCrossRef
45.
Russell G, Williams DA, Weller P, Price JF. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol. 1995;75(5):423–8.PubMed
46.
Langton Hewer S, Hobbs J, French D, Lenney W. Pilgrim’s progress: the effect of salmeterol in older children with chronic severe asthma. Respir Med. 1995;89(6):435–40.PubMedCrossRef
47.
Verberne AA, Frost C, Duiverman EJ, Grol MH, Kerrebijn KF. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch asthma study group. Am J Respir Crit Care Med. 1998;158(1):213–9.PubMedCrossRef
48.
Meijer GG, Postma DS, Mulder PG, van Aalderen WM. Long-term circadian effects of salmeterol in asthmatic children treated with inhaled corticosteroids. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1887–92.PubMedCrossRef
49.
Simons FE, Villa JR, Lee BW, Teper AM, Lyttle B, Aristizabal G, et al. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study. J Pediatr. 2001;138(5):694–8.PubMedCrossRef
50.
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. Respir Med. 2007;101(8):1809–13.PubMedCrossRef
51.
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. Pulm Pharmacol Ther. 2007;20(6):691–700.PubMedCrossRef
52.
Cabana MD, Kunselman SJ, Nyenhuis SM, Wechsler ME. Researching asthma across the ages: insights from the National Heart, Lung, and Blood Institute’s asthma network. J Allergy Clin Immunol. 2014;133(1):27–33.PubMedPubMedCentralCrossRef
53.
Benard B, Bastien V, Vinet B, Yang R, Krajinovic M, Ducharme FM. Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice. Eur Respir J. 2017;50(2):1700148.PubMedCrossRef
54.
Ernst P, Ernst G. Neuropsychiatric adverse events of montelukast in children. Eur Respir J. 2017;50:1701020.PubMedCrossRef
Metadata
Title
A comparison of tiotropium, long-acting β2-agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma
Authors
Christian Vogelberg
Stanley Goldstein
LeRoy Graham
Alan Kaplan
Alberto de la Hoz
Eckard Hamelmann
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-1282-9

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