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

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Abstract

Background

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.

Methods

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

Results

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.

Conclusion

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

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Abbreviations

DPI:

Dry powder inhaler

GINA:

Global Initiative for Asthma

HCP:

Healthcare practitioner

ICS:

Inhaled corticosteroids

LABA:

Long-acting beta2-adrenoreceptor agonist

LAMA:

Long-acting muscarinic antagonist

LTRA:

Leukotriene receptor antagonist

pMDI:

Pressurised metered-dose inhalers

SABA:

Short-acting inhaled beta2-agonists

SMI:

Soft mist inhaler

References

  1. Asher I, Pearce N. Global burden of asthma amongchildren. Int J Tuberc Lung Dis. 2014;18:1269–78. https://doi.org/10. 5588/ijtld.14.0170

    Article  CAS  PubMed  Google Scholar 

  2. GINA Report. Global strategy for asthma management and prevention. http://ginasthma.org/2017-ginareport-global-strategy-for-asthma-management-and-prevention/. Accessed 1Aug 2017

  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;5:691–706

    Article  Google Scholar 

  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. https://doi.org/10.1093/ije/dyn039

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1055/s-0043-119504.

    Article  Google Scholar 

  6. The BTS/SIGN Guideline for the management of asthma. Availableat: https://www.brit-thoracic.org.uk/documentlibrary/clinical-information/asthma/btssign-asthma-guideline-2016/. Accessed June 16, 2017

  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. https://doi.org/10. 18176/jiaci.0065

    PubMed  Google Scholar 

  8. FDA expands approval of Spiriva® Respimat® (tiotropium bromide) inhalation spray for maintenance treatment of asthma in children. Available at: www.boehringeringelheim.us/press-release/fda-expands-approval-spiri va-respimat-tiotropium-bromide-inhalation-spray. Accessed 03March 2017

  9. Asthma: Expanded indication for SPIRIVA® Respimat® for people 6 years and older. Available at: www.boehringeringelheim.com/press-release/expanded-asthma-indication-spiriva-respimat-eu. Accessed 20 March 2018

  10. O’Byrne PM. Pharmacologic interventions to reduce the risk of asthma exacerbations. Proc Am Thorac Soc. 2004;1:105–8

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1056/NEJMoa1203229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1177/2042098613504124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Montuschi P. Pharmacotherapy of patients with mild persistent asthma: strategies and unresolved issues. Front Pharmacol. 2011;2:35. https://doi.org/10.3389/fphar.2011.00035.

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/ 10.1056/NEJMoa1001278.

    Article  CAS  Google Scholar 

  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;89:180–90

    Article  CAS  Google Scholar 

  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;129:15–26

    Article  CAS  PubMed  Google Scholar 

  17. Halpin DM. Tiotropiumin asthma: what is the evidence and how does it fit in? World Allergy Organ J. 2016;9:29. https:// doi.org/10.1186/s40413-016-0119-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1093/ jurban/jth131

    Article  PubMed  PubMed Central  Google Scholar 

  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;55:562–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. van Aalderen WM. Childhood asthma: diagnosis and treatment. Scientifica (Cairo). 2012;2012:674204. https://doi.org/10.6064/2012/674204

    Google Scholar 

  21. Burgess S, Sly P, Devadason S. Adherence with preventive medicationin childhood asthma. PulmMed. 2011;https://doi.org/10.1155/2011/973849

    Article  Google Scholar 

  22. Lavorini F, Fontana GA, Usmani OS. New inhaler devices—the good, the bad and the ugly. Respiration. 2014;88:3–15. https://doi.org/10.1159/000363390

    Article  PubMed  Google Scholar 

  23. McQuaid EL, Kopel SJ, Klein RB, Fritz GK. Medication adherence in pediatric asthma: reasoning, responsibility, andbehavior. J Pediatr Psychol. 2003;28:323–33

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.rmed.2013.04.005

    Article  PubMed  Google Scholar 

  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;112:489–94

    Article  PubMed  Google Scholar 

  26. Lenney J, Innes JA, Crompton GK. Inappropriate inhaler use: assessment of use and patient preference of seven inhalationdevices. EDICI. Respir Med. 2000;94:496–500

    Article  CAS  PubMed  Google Scholar 

  27. Ibrahim M, Verma R, Garcia-Contreras L. Inhalation drug delivery devices: technology update. Med Devices (Auckl). 2015;8:131–9. https://doi.org/10.2147/MDER.S48888

    CAS  Google Scholar 

  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. https://doi.org/10.4168/aair.2012.4.4.184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Aalbers R, Park HS. Positioning of long-acting muscarinic antagonists in themanagement of asthma. Allergy Asthma Immunol Res. 2017;9:386–93. https://doi.org/10.4168/ aair.2017.9.5.386

    Article  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1111/j.1365- 2222.2010.03478.x

    Article  CAS  PubMed  Google Scholar 

  31. SpioltoRespimat2.5microgram/2.5microgram,inhalation solution—Summary of product characteristics. Available at: https://www.medicines.org.uk/emc/medicine/30495. Accessed 28 February 2018

  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. https://doi.org/10.1016/j.rmed. 2014.06.011

    Article  PubMed  Google Scholar 

  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. https://doi.org/10. 1186/s12931-015-0175-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1016/j.jaci.2016.01.011

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10. 1183/13993003.01100-2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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;140:1277–87

    Article  CAS  Google Scholar 

  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):PA4398

    Google Scholar 

  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. https://doi.org/ 10.1016/S2213-2600(18)30012-2

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.12669/pjms.322.8836

    Article  PubMed  PubMed Central  Google Scholar 

  40. SPIRIVA prescribing information. Available at: https://www.spiriva.com/#isi. Accessed 19 February 2018

  41. Highlights of prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021936s007lbl.pdf. Accessed 14 December 2017

  42. ICH Harmonised Tripartite Guideline. Guideline for good clinicalpractice. J Postgrad Med. 2001;47:199–203

    Google Scholar 

  43. Hamelmann E, Szefler SJ. Efficacy and safety of tiotropium in children and adolescents. Drugs. 2018;78:327–38. https://doi.org/10.1007/s40265-018-0862-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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:AB213

    Article  Google Scholar 

  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. https://doi.org/10.1136/thoraxjnl-2014-206260.357

    Article  Google Scholar 

  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;https://doi.org/10.1183/1393003.congress-2017.PA649

  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. https://doi.org/10.1089/jamp.2014.1159.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Kinderzentrum Bethel, Evangelisches Klinikum Bethel, Grenzweg 10, 33617, Bielefeld, Germany

    Eckard Hamelmann

  2. Allergy Center of the Ruhr University, Bochum, Germany

    Eckard Hamelmann

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  1. Eckard Hamelmann
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Corresponding author

Correspondence to Eckard Hamelmann.

Additional information

Funding

The author takes full responsibility for the scope, direction, content of, and editorial decisions relating to the manuscript, was involved at all stages of development, and has approved the submitted manuscript. Medical writing assistance, in the form of the preparation and revision of the draft manuscript, was supported financially by Boehringer Ingelheim and provided by Martina Stagno d’Alcontres, PhD, of MediTech Media, under the author’s conceptual direction and based on feedback from the author. Boehringer Ingelheim was given the opportunity to review the manuscript for factual accuracy only.

Conflict of interest

Eckard Hamelmann has served on scientific advisory boards and received honorarium for lectures on scientific meetings from ALK, Allergopharma, Bencard, Boehringer Ingelheim, LETI Pharma, Novartis, Nutricia, and Stallergenes.

Cite this as

Hamelmann E. Long-acting muscarinic antagonists for the treatment of asthma in children — a new kid in town. Allergo J Int 2018;27:220–7 https://doi.org/10.1007/s40629-018-0066-y

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Cite this article

Hamelmann, E. Long-acting muscarinic antagonists for the treatment of asthma in children — a new kid in town. Allergo J 27, 24–31 (2018). https://doi.org/10.1007/s15007-018-1720-x

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