Advertisement

Advances in Inhaled Medications

  • Aaron B. Holley
  • Linda Rogers
Chapter
Part of the Respiratory Medicine book series (RM)

Abstract

Over the past 5–10 years the methods for administering traditional asthma therapies have evolved rapidly. Inhaler design has improved, allowing for increased deposition of medicine in the lungs, and less in the oropharynx. Large, randomized trials and systematic reviews have improved our knowledge on dosing and frequency, making therapy adjustments more precise. Lastly, long-acting muscarinic antagonists (LAMAs), which are traditionally used to treat chronic obstructive pulmonary disease (COPD), were proven effective for patients with asthma. Even without the development of new medicines, there are now more options for treatment.

Keywords

Asthma Metered dose inhaler Dry powder inhaler Inhaled corticosteroid (ICS) Long-acting muscarinic antagonist (LAMA) Long-acting beta agonist (LABA) 

References

  1. 1.
    Roche N, Dekhuijzen PN. The evolution of pressurized metered-dose inhalers from early to modern devices. J Aerosol Med Pulm Drug Deliv. 2016;29:311–27.CrossRefGoogle Scholar
  2. 2.
    Laube B, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011;37:1308–31.CrossRefGoogle Scholar
  3. 3.
    Clark A, Hollingworth AM. The relationship between powder inhaler resistance and peak inspiratory conditions in healthy volunteers - implications for in vitro testing. J Aerosol Med. 1993;6:99–110.CrossRefGoogle Scholar
  4. 4.
    Nelson H. Inhalation devices, delivery systems, and patient technique. Ann Allergy Asthma Immunol. 2016;117:606–12.CrossRefGoogle Scholar
  5. 5.
    Lavorini F, Pedersen S, Usmani OS. Dilemmas, confusion, and misconceptions related to small airways directed therapy (accessed on August 28, 2016). Chest. 2017;151:1345–55.CrossRefGoogle Scholar
  6. 6.
    Muraki M, Gose K, Hanada S, et al. Which inhaled corticosteroid and long-acting B-agonist combination is better in patients with moderate-to-severe asthma, a dry powder inhaler or a pressurized metered-dose inhaler? Drug Deliv. 2017;24:1395–400.CrossRefGoogle Scholar
  7. 7.
    Ishiura Y, Fujimura M, Shiba Y, et al. A comparison of the efficacy of once-daily fluticasone furoate/vilanterole with twice-daily fluticasone propionate/salmeterol in elderly asthmatics. Drug Res (Stuttg). 2018;68:38–44.CrossRefGoogle Scholar
  8. 8.
    Lahelma S, Vahteristo M, Metev H, et al. Equivalent bronchodilation with budesonide/formoterol combination via easyhaler and turbuhaler in patients with asthma. Respir Med. 2016;120:31–5.CrossRefGoogle Scholar
  9. 9.
    Virchow J, Rodriguez-Roisin R, Papi A, et al. A randomized, double-blinded, double-dummy efficacy and safety study of budesonide-formoterol spiromax compared to budesonide-formoterol turbuhaler in adults and adolescents with persistent asthma. BMC Pulm Med. 2016;16:42.CrossRefGoogle Scholar
  10. 10.
    Hojo M, Shirai T, Hirashima J, et al. Comparison of the clinical effects of combined salmeterol/fluticasone delivered by dry powder or pressurized metered dose inhaler. Pulm Pharmacol Ther. 2016;37:43–8.CrossRefGoogle Scholar
  11. 11.
    Bell D, Mansfield L, Lomax M. A randomized, crossover trial evaluating patient handling, preference, and ease of use of the fluticasone propionate/formoterol breath-triggered inhaler. J Aerosol Med Pulm Drug Deliv. 2017;30:425–34.CrossRefGoogle Scholar
  12. 12.
    Van der Palen J, Thomas M, Chrystyn H, et al. A randomised open-label cross-over study of inhaler errors, preference and time to achieve correct inhaler use in patients with COPD or asthma: comparison of ELLIPTA with other inhaler devices. NPJ Prim Care Respir Med. 2016;26:16079.CrossRefGoogle Scholar
  13. 13.
    Chrystyn H, Price DB, Molimard M, et al. Comparison of serious inhaler technique errors made by device-naive patients using three different dry powder inhalers: a randomised, crossover, open-label study. BMC Pulm Med. 2016;16:12.CrossRefGoogle Scholar
  14. 14.
    Usmani O, Biddiscombe MF, Barnes PJ. Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size. Am J Respir Crit Care Med. 2005;172:1497–504.CrossRefGoogle Scholar
  15. 15.
    De Backer W, Devolder A, Poli G, et al. Lung deposition of BDP/Formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J Aerosol Med Pulm Drug Deliv. 2010;23:137.CrossRefGoogle Scholar
  16. 16.
    Usmani O. Small-airway disease in asthma: pharmacological considerations. Curr Opin Pulm Med. 2015;21:55–67.CrossRefGoogle Scholar
  17. 17.
    Usmani O, Singh D, Spinola M, et al. The prevalence of small airways disease in adult asthma: a systematic literature review. Respir Med. 2016;116:19–27.CrossRefGoogle Scholar
  18. 18.
    Pedersen S. Do inhaled corticosteroids inhibit growth in children? Am J Respir Crit Care Med. 2001;164:521–35.CrossRefGoogle Scholar
  19. 19.
    Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev. 2014;7:CD009878.Google Scholar
  20. 20.
    Cumming R, Mitchell P, Leeder SR. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med. 1997;337:8–14.CrossRefGoogle Scholar
  21. 21.
    Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA. 1998;280:539–43.CrossRefGoogle Scholar
  22. 22.
    Maspero J, Cherrez I, Doherty DE, et al. Appraisal of lens opacity with mometasone furoate/formoterol fumarate combination in patients with COPD or asthma. Respir Med. 2014;108:1355–62.CrossRefGoogle Scholar
  23. 23.
    Mattishent K, Thavarajah M, Blanco P, et al. Meta-review: adverse effects of inhaled corticosteroids relevant to older patients. Drugs. 2014;74:539–47.CrossRefGoogle Scholar
  24. 24.
    Masoli M, Weatherall M, Holt S, et al. Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis. Eur Respir J. 2006;28:960–7.CrossRefGoogle Scholar
  25. 25.
    Lapi F, Kezouh A, Suissa S, et al. The use of inhaled corticosteroids and the risk of adrenal insufficiency. Eur Respir J. 2013;42:79–86.CrossRefGoogle Scholar
  26. 26.
    Watkins L, Soriano JB, Mortimer K. Getting risks right on inhaled corticosteroids and adrenal insufficiency. Eur Respir J. 2013;42:9–11.CrossRefGoogle Scholar
  27. 27.
    Calverley P, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775–89.CrossRefGoogle Scholar
  28. 28.
    Wedzicha J, Calverley PM, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177:19–26.CrossRefGoogle Scholar
  29. 29.
    McKeever T, Mortimer K, Wilson A, et al. Quadrupling inhaled glucocorticoid dose to abort asthma exacerbations. N Engl J Med. 2018;378:902–10.CrossRefGoogle Scholar
  30. 30.
    O’Byrne P, Pedersen S, Carlsson LG, et al. Risks of pneumonia in patients with asthma taking inhaled corticosteroids. Am J Respir Crit Care Med. 2011;183:589–95.CrossRefGoogle Scholar
  31. 31.
    McKeever T, Harrison TW, Hubbard R, et al. Inhaled corticosteroids and the risk of pneumonia in people with asthma a case-control study. Chest. 2013;144:1788–94.CrossRefGoogle Scholar
  32. 32.
    Speizer FE, Doll R, Heaf P, Strang LB. Investigation into use of drugs preceding death from asthma. Br Med J. 1968;1:339–43.CrossRefGoogle Scholar
  33. 33.
    Pearce N, Grainger J, Atkinson M, et al. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax. 1990;45:170–5.CrossRefGoogle Scholar
  34. 34.
    Castle W, Fuller R, Hall J, Palmer J. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ. 1993;306:1034–7.CrossRefGoogle Scholar
  35. 35.
    Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM, Group SS. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15–26.CrossRefGoogle Scholar
  36. 36.
    Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006;144:904–12.CrossRefGoogle Scholar
  37. 37.
    Weatherall M, Wijesinghe M, Perrin K, Beasley R. Long-acting beta-agonists and asthma death: how useful are different study designs to evaluate the potential association? J Asthma. 2010;47:434–8.CrossRefGoogle Scholar
  38. 38.
    Bateman E, Nelson H, Bousquet J, et al. Meta-analysis: effects of adding salmeterol to inhaled corticosteroids on serious asthma-related events. Ann Intern Med. 2008;149:33–42.CrossRefGoogle Scholar
  39. 39.
    Sears MR, Ottosson A, Radner F, Suissa S. Long-acting beta-agonists: a review of formoterol safety data from asthma clinical trials. Eur Respir J. 2009;33:21–32.CrossRefGoogle Scholar
  40. 40.
    Nelson H, Bonuccelli C, Radner F, et al. Safety of formoterol in patients with asthma: combined analysis of data from double-blind, randomized controlled trials. J Allergy Clin Immunol. 2010;125:390–6 e8.CrossRefGoogle Scholar
  41. 41.
    M. L. Long-acting beta agonists and adverse asthma events meta-analysis. Statistical briefing package for Joint Meeting of the FDA Pulmonary-Allergy Drugs Advisory Committee; December 10–11 2008.Google Scholar
  42. 42.
    Stempel DA, Raphiou IH, Kral KM, et al. Serious asthma events with fluticasone plus salmeterol versus fluticasone alone. N Engl J Med. 2016;374:1822.CrossRefGoogle Scholar
  43. 43.
    Stempel DA, Szefler SJ, Pedersen S, et al. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016;375:840–9.CrossRefGoogle Scholar
  44. 44.
    Peters SP, Bleecker ER, Canonica GW, et al. Serious asthma events with Budesonide plus Formoterol vs Budesonide Alone. N Engl J Med. 2016;375:850–60.CrossRefGoogle Scholar
  45. 45.
    Weinstein CLJGD, Ryan N, et al. Serious asthma outcomes with mometasone furoate plus formoterol versus mometasone alone. Washington, DC: American Thoracic Society; 2017.Google Scholar
  46. 46.
    Busse WW, Bateman ED, Caplan AL, et al. Combined analysis of asthma safety trials of long-acting beta2-agonists. N Engl J Med. 2018;378:2497–505.CrossRefGoogle Scholar
  47. 47.
    Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. 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:CD005535.Google Scholar
  48. 48.
    Israel E, Roche N, Martin RJ, et al. Increased dose of inhaled corticosteroid versus add-on long-acting beta-agonist for step-up therapy in asthma. Ann Am Thorac Soc. 2015;12:798–806.CrossRefGoogle Scholar
  49. 49.
    Thomas M, von Ziegenweidt J, Lee AJ, Price D. High-dose inhaled corticosteroids versus add-on long-acting beta-agonists in asthma: an observational study. J Allergy Clin Immunol. 2009;123:116–21 e10.CrossRefGoogle Scholar
  50. 50.
    Jabbal S, Manoharan A, Anderson W, Lipworth J, Lipworth B. Real-life effect of long-acting beta2-agonist withdrawal in patients with controlled step 3 asthma. Ann Allergy Asthma Immunol. 2016;117:430–1.CrossRefGoogle Scholar
  51. 51.
    Jackson D, Bacharier LB, Mauger DT, et al. Quintupling inhaled glucocorticoids to prevent childhood asthma exacerbations. N Engl J Med. 2018;378:891–901.CrossRefGoogle Scholar
  52. 52.
    Chung K, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–73.CrossRefGoogle Scholar
  53. 53.
    Toogood J, Baskerville J, Jennings B, et al. Bioequivalent doses of budesonide and prednisone in moderate and severe asthma. J Allergy Clin Immunol. 1989;84:688–700.CrossRefGoogle Scholar
  54. 54.
    Bardin P. Escalating inhaled glucocorticoids to prevent asthma exacerbations. N Engl J Med. 2018;378:950–2.CrossRefGoogle Scholar
  55. 55.
    Boulet LP, Gupta S, FitzGerald JM. Inhaled glucocorticoids in asthma. N Eng J Med. 2018;378:2049–52.Google Scholar
  56. 56.
    Reddel H, Bateman ED, Becker A, et al. A summary of the new GINA strategy: a roadmap to asthma control. Eur Respir J. 2015;46:622–39.CrossRefGoogle Scholar
  57. 57.
    Vogelmeier C, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Am J Respir Crit Care Med. 2017;195:557–82.CrossRefGoogle Scholar
  58. 58.
    Fardon T, Haggart K, Lee DKC, et al. A proof of concept study to evaluate stepping down the dose of fl uticasone in combination with salmeterol and tiotropium in severe persistent asthma. Respir Med. 2007;101:1218–28.CrossRefGoogle Scholar
  59. 59.
    Peters S, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010;363:1715–26.CrossRefGoogle Scholar
  60. 60.
    Kerstjens H, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367:1198–207.CrossRefGoogle Scholar
  61. 61.
    Rodrigo G, Castro-Rodríguez JA. What is the role of tiotropium in asthma? A systematic review with meta-analysis. Chest. 2015;147:388–96.CrossRefGoogle Scholar
  62. 62.
    Sobieraj D, Baker WL, Nguyen E, 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;319:1473–84.CrossRefGoogle Scholar
  63. 63.
    Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180:388–95.CrossRefGoogle Scholar
  64. 64.
    Petsky HL, Kew KM, Turner C, Chang AB. Exhaled nitric oxide levels to guide treatment for adults with asthma. Cochrane Database Syst Rev. 2016;9:CD011440.PubMedGoogle Scholar
  65. 65.
    Petsky HL, Cates CJ, Kew KM, Chang AB. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis. Thorax. 2018;73:1110.CrossRefGoogle Scholar
  66. 66.
    Magnussen H, Watz H, Kirsten A, et al. Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation: WISDOM study design and rationale. Respir Med. 2014;108:593–9.CrossRefGoogle Scholar
  67. 67.
    Crossingham I, Evans DJ, Halcovitch NR, Marsden PA. Stepping down the dose of inhaled corticosteroids for adults with asthma. Cochrane Database Syst Rev. 2017;2:CD011802.PubMedGoogle Scholar
  68. 68.
    Xue Z, Zhang L, Liu Y, Gunst SJ, Tepper RS. Chronic inflation of ferret lungs with CPAP reduces airway smooth muscle contractility in vivo and in vitro. J Appl Physiol. 2008;104:610–5.CrossRefGoogle Scholar
  69. 69.
    Ahmad S, Kew KM, Normansell R. Stopping long-acting beta2-agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015:CD011306.Google Scholar
  70. 70.
    Brozek JL, Kraft M, Krishnan JA, et al. Long-acting beta2-agonist step-off in patients with controlled asthma. Arch Intern Med. 2012;172:1365–75.CrossRefGoogle Scholar
  71. 71.
    Rogers L, Sugar EA, Blake K, et al. Step-down therapy for asthma well controlled on inhaled corticosteroid and long-acting beta-agonist: a randomized clinical trial. J Allergy Clin Immunol Pract. 2018;6:633–43 e1.CrossRefGoogle Scholar
  72. 72.
    Papi A, Corradi M, Pigeon-Francisco C, et al. Beclometasone-formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir Med. 2013;1:23–31.CrossRefGoogle Scholar
  73. 73.
    Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev. 2013:CD009019.Google Scholar
  74. 74.
    Sobieraj DM, Weeda ER, Nguyen E, et al. Association of inhaled corticosteroids and long-acting beta-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: a systematic review and meta-analysis. JAMA. 2018;319:1485–96.CrossRefGoogle Scholar
  75. 75.
    Jorup C, Lythgoe D, Bisgaard H. Budesonide/formoterol maintenance and reliever therapy in adolescent patients with asthma. Eur Respir J. 2018;51.CrossRefGoogle Scholar
  76. 76.
    O'Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined Budesonide-Formoterol as needed in mild asthma. N Engl J Med. 2018;378:1865–76.CrossRefGoogle Scholar
  77. 77.
    Bateman ED, Reddel HK, FitzGerald JM. As-needed Budesonide-Formoterol in mild asthma. N Engl J Med. 2018;379:898.PubMedGoogle Scholar
  78. 78.
    Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2019. Available from: www.ginasthma.org.
  79. 79.
    Pedersen S, Bateman ED, Boulet LP, et al. Global Initiative for asthma: global strategy for Asthma Management and Prevention, 2017. wwwginaasthmaorg. Accessed 2 Sept 2018.Google Scholar
  80. 80.
    Sobieraj D, Weeda ER, Nguyen E, et al. Association of inhaled corticosteroids and long-acting-B-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: a systematic review and meta-analysis. JAMA. 2018;319:1485–96.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Aaron B. Holley
    • 1
  • Linda Rogers
    • 2
    • 3
  1. 1.Walter Reed National Military Medical CenterBethesdaUSA
  2. 2.Adult Asthma Program, Mount Sinai National Jewish Health Respiratory InstituteNew YorkUSA
  3. 3.Icahn School of Medicine at Mount SinaiNew YorkUSA

Personalised recommendations