Allergo Journal

, Volume 27, Issue 7, pp 24–31 | Cite as

Long-acting muscarinic antagonists for the treatment of asthma in children — a new kid in town

  • Eckard HamelmannEmail author



Asthma is the most prevalent chronic airway disease observed in children and adolescents, yet the variety of treatment options available for this age group is limited. With many factors influencing therapeutic efficacy including patient knowledge, adherence, and therapy choice as well as delivery device, it is important to have more options to tailor to individual patient needs.


This article is an overview of recent scientific articles using a systematic literature search in PubMed and specialist databases.


Tiotropium is the first long-acting muscarinic antagonist to be licensed for treatment of asthma and has been demonstrated to be an effective add-on therapy across all age groups. Its therapeutic success in clinical trials resulted in Food and Drug Administration and the European Medicines Agency approval for asthma treatment in people over the age of 6 years in the US and EU.


Further studies into the use of tiotropium, especially in younger children, could be of interest for future treatment decisions.


children asthma treatment tiotropium 



Dry powder inhaler


Global Initiative for Asthma


Healthcare practitioner


Inhaled corticosteroids


Long-acting beta2-adrenoreceptor agonist


Long-acting muscarinic antagonist


Leukotriene receptor antagonist


Pressurised metered-dose inhalers


Short-acting inhaled beta2-agonists


Soft mist inhaler


  1. 1.
    Asher I, Pearce N. Global burden of asthma amongchildren. Int J Tuberc Lung Dis. 2014;18:1269–78. 5588/ijtld.14.0170CrossRefPubMedGoogle Scholar
  2. 2.
    GINA Report. Global strategy for asthma management and prevention. Accessed 1Aug 2017
  3. 3.
    GBD. 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017;5:691–706CrossRefGoogle Scholar
  4. 4.
    Anderson HR, Gupta R, Kapetanakis V, Asher MI, Clayton T, Robertson CF, et al. International correlations between indicators of prevalence,hospital admissions and mortality for asthma in children. Int J Epidemiol. 2008;37:573–82. Scholar
  5. 5.
    Deutsche Gesellschaft für Arbeitsmedizin und Umweltmedizin e. V., Deutsche Gesellschaft für Rehabilitations wissenschaften e.V., Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e.V., et al. Guideline for the Diagnosis and Treatment of Asthma — Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology. Pneumologie. 2017;71:849–919. Scholar
  6. 6.
    The BTS/SIGN Guideline for the management of asthma. Availableat: Accessed June 16, 2017
  7. 7.
    Plaza Moral V, Alonso Mostaza S, Alvarez Rodriguez C, Gomez-Outes A, Gómez Ruiz F, López Vina A, et al. Spanish guideline on themanagement of asthma. J Investig Allergol Clin Immunol. 2016;26(Suppl 1):1–92. 18176/jiaci.0065PubMedGoogle Scholar
  8. 8.
    FDA expands approval of Spiriva® Respimat® (tiotropium bromide) inhalation spray for maintenance treatment of asthma in children. Available at: va-respimat-tiotropium-bromide-inhalation-spray. Accessed 03March 2017Google Scholar
  9. 9.
    Asthma: Expanded indication for SPIRIVA® Respimat® for people 6 years and older. Available at: Accessed 20 March 2018
  10. 10.
    O’Byrne PM. Pharmacologic interventions to reduce the risk of asthma exacerbations. Proc Am Thorac Soc. 2004;1:105–8CrossRefPubMedGoogle Scholar
  11. 11.
    Kelly HW, Sternberg AL, Lescher R, Fuhlbrigge AL, Williams P, Zeiger RS, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904–12. Scholar
  12. 12.
    Xia Y, Kelton CM, Xue L, Guo JJ, Bian B, Wigle PR. Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma. Ther Adv Drug Saf. 2013;4:254–63. Scholar
  13. 13.
    Montuschi P. Pharmacotherapy of patients with mild persistent asthma: strategies and unresolved issues. Front Pharmacol. 2011;2:35. Scholar
  14. 14.
    Lemanske RF Jr, Mauger DT, Sorkness CA, Jackson DJ, Boehmer SJ, Martinez FD, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. NEngl JMed. 2010;362:975–85. 10.1056/NEJMoa1001278.CrossRefGoogle Scholar
  15. 15.
    Bensch G, Berger WE, Blokhin BM, Socolovsky AL, Thomson MH, Till MD, et al. One-year efficacy and safety of inhaled formoterol dry powder in children with persistent asthma. Ann AllergyAsthma Immunol. 2002;89:180–90CrossRefGoogle Scholar
  16. 16.
    Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM, SMART Study Group. The salmeterol multicenter asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15–26CrossRefPubMedGoogle Scholar
  17. 17.
    Halpin DM. Tiotropiumin asthma: what is the evidence and how does it fit in? World Allergy Organ J. 2016;9:29. https:// Scholar
  18. 18.
    Lewis TC, Robins TG, Joseph CL, et al. Identification of gaps in the diagnosis and treatment of childhood asthma using a community-based participatory research approach. J Urban Health. 2004;81:472–88. jurban/jth131CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    van Schayck CP, van Der Heijden FM, van Den Boom G, Tirimanna PR, van Herwaarden CL, et al. Underdiagnosisof asthma: is the doctor or the patient to blame? The DIMCA project. Thorax. 2000;55:562–5CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    van Aalderen WM. Childhood asthma: diagnosis and treatment. Scientifica (Cairo). 2012;2012:674204. Scholar
  21. 21.
    Burgess S, Sly P, Devadason S. Adherence with preventive medicationin childhood asthma. PulmMed. 2011; Scholar
  22. 22.
    Lavorini F, Fontana GA, Usmani OS. New inhaler devices—the good, the bad and the ugly. Respiration. 2014;88:3–15. Scholar
  23. 23.
    McQuaid EL, Kopel SJ, Klein RB, Fritz GK. Medication adherence in pediatric asthma: reasoning, responsibility, andbehavior. J Pediatr Psychol. 2003;28:323–33CrossRefPubMedGoogle Scholar
  24. 24.
    Makela MJ, Backer V, Hedegaard M, Larsson K. Adherence to inhaled therapies, health outcomes and costs in patients with asthma and COPD. Respir Med. 2013;107:1481–90. Scholar
  25. 25.
    Bender B, Milgrom H, Apter A. Adherence intervention research: what have we learned and what do we do next? J Allergy Clin Immunol. 2003;112:489–94CrossRefPubMedGoogle Scholar
  26. 26.
    Lenney J, Innes JA, Crompton GK. Inappropriate inhaler use: assessment of use and patient preference of seven inhalationdevices. EDICI. Respir Med. 2000;94:496–500CrossRefPubMedGoogle Scholar
  27. 27.
    Ibrahim M, Verma R, Garcia-Contreras L. Inhalation drug delivery devices: technology update. Med Devices (Auckl). 2015;8:131–9. Scholar
  28. 28.
    Price D, Chrystyn H, Kaplan A, Haughney J, Román-Rodríguez M, Burden A, et al. Effectiveness of same versus mixed asthma inhaler devices: a retrospective observational study in primary care. Allergy Asthma Immunol Res. 2012;4:184–91. Scholar
  29. 29.
    Aalbers R, Park HS. Positioning of long-acting muscarinic antagonists in themanagement of asthma. Allergy Asthma Immunol Res. 2017;9:386–93. aair.2017.9.5.386CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ohta S, Oda N, Yokoe T, Tanaka A, Yamamoto Y, Watanabe Y, et al. Effect of tiotropium bromide on airwayinflammation and remodelling in a mouse model of asthma. Clin Exp Allergy. 2010;40:1266–75. 2222.2010.03478.xCrossRefPubMedGoogle Scholar
  31. 31.
    SpioltoRespimat2.5microgram/2.5microgram,inhalation solution—Summary of product characteristics. Available at: Accessed 28 February 2018
  32. 32.
    Vogelberg C, Engel M, Moroni-Zentgraf P, Leonaviciute Klimantaviciene M, Sigmund R, Downie J, et al. Tiotropium in asthmatic adolescents symptomatic despite inhaled corticosteroids: a randomised dose-ranging study. Respir Med. 2014;108:1268–76. 2014.06.011CrossRefPubMedGoogle Scholar
  33. 33.
    Vogelberg C, Moroni-Zentgraf P, Leonaviciute-Klimantaviciene M, Sigmund R, Hamelmann E, Engel M, et al. A randomised dose-ranging study of tiotropiumRespimat(R) in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015;16:20. 1186/s12931-015-0175-9CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hamelmann E, Bateman ED, Vogelberg C, Szefler SJ, Vandewalker M, Moroni-Zentgraf P, et al. Tiotropium addon therapy in adolescents with moderate asthma: a 1-year randomized controlled trial. J Allergy Clin Immunol. 2016;138:441–50. Scholar
  35. 35.
    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. 1183/13993003.01100-2016CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Szefler SJ, Murphy K, Harper T, Boner A, Laki I, Engel M, et al. A phase III randomized controlled trial of tiotropium addon therapy in children with severe symptomatic asthma. JAllergyClin Immunol. 2017;140:1277–87CrossRefGoogle Scholar
  37. 37.
    Schmidt O, Hamelmann E, Vogelberg C, et al. Once daily tiotropium Respimat® add-on therapy improves lung function in children with moderate symptomatic asthma. Eur Respir J. 2016;48(Suppl 60):PA4398Google Scholar
  38. 38.
    Vrijlandt EJLE, El Azzi G, Vandewalker M, Rupp N, Harper T, Graham L, et al. Safety and efficacy of tiotropium in K Long-acting muscarinic antagonists for the treatment of asthma in children — a new kid in town review children aged 1–5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2018;6:127–37. 10.1016/S2213-2600(18)30012-2CrossRefPubMedGoogle Scholar
  39. 39.
    Huang J, Chen Y, Long Z, Zhou X, Shu J. Clinical efficacy of tiotropium in children with asthma. Pak J Med Sci. 2016;32:462–5. Scholar
  40. 40.
    SPIRIVA prescribing information. Available at: Accessed 19 February 2018
  41. 41.
    Highlights of prescribing information. Available at: Accessed 14 December 2017
  42. 42.
    ICH Harmonised Tripartite Guideline. Guideline for good clinicalpractice. J Postgrad Med. 2001;47:199–203Google Scholar
  43. 43.
    Hamelmann E, Szefler SJ. Efficacy and safety of tiotropium in children and adolescents. Drugs. 2018;78:327–38. Scholar
  44. 44.
    Tashkin DP, Dahl R, Virchow JC, et al. Once-daily tiotropium respimat® add-on to at least Ics maintenance therapy demonstrates improved lung function in patients with symptomatic asthma, independent of serum IgE or blood Eosinophillevels. J Allergy Clin Immunol. 2016;137:AB213CrossRefGoogle Scholar
  45. 45.
    Dahl R, Casale T, Pizzichini E, et al. P229 once-daily tiotropium Respimat® as add-on to at least medium- to high-dose Ics, with or withoutlaba, improves lung function in patients with symptomatic asthma, independent of allergic status. Thorax. 2014;69:A177–A8. Scholar
  46. 46.
    Bleecker ER, Buhl R, FitzGerald M, et al. Efficacy of oncedaily tiotropium Respimat in adults with asthma based on GINASteps2–5. EurRespir J.2017; Scholar
  47. 47.
    Kamin W, Frank M, Kattenbeck S, et al. A handling study to assess use of the Respimat(®) Soft Mist Inhaler in children under 5 years old. J Aerosol Med Pulm Drug Deliv. 2015;28:372–81. Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Kinderzentrum BethelEvangelisches Klinikum BethelBielefeldGermany
  2. 2.Allergy Center of the Ruhr UniversityBochumGermany

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