Advertisement

Treatments in Respiratory Medicine

, Volume 5, Issue 5, pp 305–315 | Cite as

Performance of Turbuhaler® in Patients with Acute Airway Obstruction and COPD, and in Children with Asthma

Understanding the Clinical Importance of Adequate Peak Inspiratory Flow, High Lung Deposition, and Low In Vivo Dose Variability
  • Olof Selroos
  • Lars Borgström
  • Jarl Ingelf
Review Article

Abstract

The dry-powder inhaler (DPI) Turbuhaler® has been on the market for nearly two decades. Products containing terbutaline, formoterol, budesonide, and the combination budesonide/formoterol are widely used by patients with asthma and COPD. Most patients and physicians find Turbuhaler® easy to use, and local side effects are rare. This is thought to arise from the lack of additives or only small amounts in the formulation, in addition to minimal deposition of the drug in the oropharynx and on the vocal cords during inspiration.

The function of Turbuhaler® has frequently been questioned. This article aims to review and clarify some key issues that have been challenged in the literature (e.g. the effectiveness of Turbuhaler® in patients with more restricting conditions), to discuss the importance of lung deposition, and to explain the low in vivo variability associated with Turbuhaler® and the lack of correlation with the higher in vitro variability.

Turbuhaler®, like other DPIs, is flow dependent to some degree. However, a peak inspiratory flow (PIF) through Turbuhaler® of 30 L/min gives a good clinical effect. These PIF values can be obtained by patients with conditions thought to be difficult to manage with inhalational agents, such as asthmatic children and adult patients with acute severe airway obstruction and COPD. Excellent clinical results with Turbuhaler® in large controlled studies in patients with COPD and acute severe airway obstruction provide indirect evidence that medication delivered via Turbuhaler® reaches the target organ.

Due to the large amount of small particles and the moderate inbuilt resistance in Turbuhaler®, which opens up the vocal cords during inhalation, Turbuhaler® is associated with a high lung deposition (25–40% of the delivered dose) compared with pressurized metered-dose inhalers (pMDIs) and other DPIs. A good correlation has been found between lung deposition and clinical efficacy. A high lung deposition always results in the best ratio between clinical efficacy and risk of unwanted systemic activity. Studies with Turbuhaler® also show that the in vivo variation in lung deposition is significantly lower compared with a pMDI or, for example, the Diskus® inhaler, and much lower than the in vitro dose variability seen in laboratory tests.

Turbuhaler® appears to be a reliable DPI which can be used with confidence by patients with airway diseases, including those with clinical conditions believed to be difficult to manage with inhalational therapy.

Keywords

Salbutamol Budesonide Fluticasone Propionate Terbutaline Formoterol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Lars Borgström and Jarl Ingelf are fulltime employees at AstraZeneca, Lund, Sweden. Olof Selroos was employed by AstraZeneca up to 2001, and since then has performed consultancy work for the company.

References

  1. 1.
    Hilton S. An audit of inhaler technique among asthma patients of 34 general practitioners. Br J Gen Pract 1990; 40: 505–6PubMedGoogle Scholar
  2. 2.
    Goren A, Noviski N, Springer C, et al. The ability of young children to use a powder inhalation device (Bricanyl Turbuhaler) efficiently. Eur Respir J 1991; 4 (Suppl. 14): 242sGoogle Scholar
  3. 3.
    Sinninghe Damsté HEJ. Turbuhaler: a clinical overview. In: Turbuhaler — a non-CFC metered dose inhaler. Report of a symposium held at the 8th Congress of The International Society for Aerosols in Medicine; 1991 Jun 12–13; Davos, Switzerland. Amsterdam: Exerpta Medica, 1992Google Scholar
  4. 4.
    Vogel H, Wettmarshausen C. Auswirkungen der Inhalation eines Glukokortikoids mittels Treibgasdosieraerosol und mittels Turbohaler® — eine Röntgenpilot-studie. Pneumologie 1995; 49: 559–60PubMedGoogle Scholar
  5. 5.
    Engel T, Heinig JH, Madsen F, et al. Peak inspiratory flow and inspiratory vital capacity of patients with asthma measured with and without a new dry-powder inhaler device (Turbuhaler®). Eur Respir J 1990; 3: 1037–41PubMedGoogle Scholar
  6. 6.
    Pedersen S, Hansen O, Fuglsang G. Influence of inspiratory flow rate upon the effect of a Turbuhaler. Arch Dis Child 1990; 65: 308–10PubMedCrossRefGoogle Scholar
  7. 7.
    Borgström L. On the use of dry powder inhalers in situations perceived as constrained. J Aerosol Med 2001; 14: 281–7PubMedCrossRefGoogle Scholar
  8. 8.
    McNeill K, Malcolm G, Rhink Brown W. A comparison of expiratory and inspiratory flow rates in health and in chronic pulmonary disease. Thorax 1959; 14: 225–31CrossRefGoogle Scholar
  9. 9.
    Brown PH, Ning ACWS, Greening AP, et al. Peak inspiratory flow through Turbuhaler in acute asthma. Eur Respir J 1995; 8: 1940–1PubMedCrossRefGoogle Scholar
  10. 10.
    Nana A, Youngchaiyud P, Maranetra N, et al. β2-Agonists administered by a dry powder inhaler can be used in acute asthma. Respir Med 1998; 92: 167–72PubMedCrossRefGoogle Scholar
  11. 11.
    Meijer RJ, van der Mark TW, Aalders DS, et al. Home assessment of peak inspiratory flow through the Turbohaler in asthmatic patients. Thorax 1996; 51: 433–4PubMedCrossRefGoogle Scholar
  12. 12.
    Dewar MH, Jamieson A, McLean A, et al. Peak inspiratory flow through Turbuhaler® in chronic obstructive airways disease. Respir Med 1999; 93: 342–4PubMedCrossRefGoogle Scholar
  13. 13.
    Bisgaard H. Delivery of inhaled medication to children. J Asthma 1995; 34: 443–67CrossRefGoogle Scholar
  14. 14.
    Agertoft L, Pedersen S. Importance of training for correct Turbuhaler use in preschool children. Acta Paediatr 1998; 87: 842–7PubMedCrossRefGoogle Scholar
  15. 15.
    Turpeinen M, Pelkonen A, Nikander K, et al. Asthmatic children from 5 years of age can generate sufficient peak inspiratory flows through Turbuhaler. AstraZeneca. (Data on file)Google Scholar
  16. 16.
    Tönnesen F, Laursen LC, Evald T, et al. Bronchodilating effect of terbutaline powder in acute severe bronchial obstruction. Chest 1994; 105: 697–700PubMedCrossRefGoogle Scholar
  17. 17.
    Borgström L, Derom E, Ståhl E, et al. Inhalation device influences lung deposition and bronchodilating effect of terbutaline. Am J Respir Crit Care Med 1996; 153: 1636–40PubMedGoogle Scholar
  18. 18.
    Malolepszy J, Böszörményi Nagy G, Selroos O, et al. Safety of formoterol Turbuhaler® at cumulative dose of 90μg in patients with acute bronchial obstruction. Eur Respir J 2001; 18: 928–34PubMedCrossRefGoogle Scholar
  19. 19.
    Boonsawat W, Charoenratanakul S, Pothiratana S, et al. Formoterol (Oxis®) Turbuhaler as a rescue therapy compared with salbutamol by pMDI plus spacer in patients with acute severe asthma. Respir Med 2003; 97: 1067–74PubMedCrossRefGoogle Scholar
  20. 20.
    Rubinfeld A, Scicchitano R, Hunt A, et al. Formoterol Turbuhaler as reliever medication in patients with acute asthma. Eur Respir J 2006; 27: 735–41PubMedCrossRefGoogle Scholar
  21. 21.
    Ahlström H, Svenonius E, Svensson M. Treatment of asthma in pre-school children with inhalation of terbutaline in Turbuhaler compared with Nebuhaler. Allergy 1989; 44: 515–8PubMedCrossRefGoogle Scholar
  22. 22.
    Hultquist C, Ahlström H, Kjellman N-IM, et al. A double-blind comparison between a new multi-dose powder inhaler (Turbuhaler®) and metered dose inhaler in children with asthma. Allergy 1989; 44: 467–70PubMedCrossRefGoogle Scholar
  23. 23.
    Rufin P, Benoist M, Panqueva P, et al. Efficacy of a powder inhaler (Turbuhaler) in moderate asthmatic crises in children. Rev Mal Respir 1993; 10: 545–50PubMedGoogle Scholar
  24. 24.
    Drblik S, Lapierre G, Thivierge R, et al. Comparative efficacy of terbutaline sulphate delivered by Turbuhaler dry powder inhaler or pressurised metered dose inhaler with Nebuhaler spacer in children during an acute asthmatic episode. Arch Dis Child 2003; 88: 319–23PubMedCrossRefGoogle Scholar
  25. 25.
    Llanos-Ackert J-P, Vargas-Castillo R, Gutierrez M, et al. Formoterol in acute asthma in children 6–14 years old. Eur Respir J 2003; 22 (Suppl. 45): 133sGoogle Scholar
  26. 26.
    Cazzola M, Centanni S, Regorda C, et al. Onset of action of single doses of formoterol administered via Turbuhaler in patients with stable COPD. Pulm Pharmacol Ther 2001; 14: 41–5PubMedCrossRefGoogle Scholar
  27. 27.
    Cazzola M, Di Perna F, D’Amato M, et al. Formoterol Turbuhaler for as-needed therapy in patients with mild acute exacerbations of COPD. Respir Med 2001; 95: 917–21PubMedCrossRefGoogle Scholar
  28. 28.
    Wadbo M, Löfdahl CG, Larsson K, et al. Effects of formoterol and ipratropium bromide in COPD: a 3-month placebo-controlled study. Eur Respir J 2002; 20: 1138–46PubMedCrossRefGoogle Scholar
  29. 29.
    Bogdan M, Eliraz A, Mckinnon C, et al. Formoterol Turbuhaler is an effective maintenance and maintenance plus reliever therapy in patients with chronic obstructive pulmonary disease (COPD) irrespective of the level of lung function impairment and reversibility. Eur Respir J 2002; 20 Suppl. 38: 243sGoogle Scholar
  30. 30.
    Campbell M, Eliraz A, Johansson G, et al. Formoterol for maintenance and asneeded treatment of chronic obstructive pulmonary disease. Respir Med 2005; 99: 1511–20PubMedCrossRefGoogle Scholar
  31. 31.
    Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/ formoterol in a single inhaler in the management of COPD. Eur Respir J 2003; 21: 74–8PubMedCrossRefGoogle Scholar
  32. 32.
    Calverley P, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22: 912–9PubMedCrossRefGoogle Scholar
  33. 33.
    Pauwels R, Newman S, Borgström L. Airway deposition and airway effects of anti-asthma drugs delivered from metered-dose inhalers. Eur Respir J 1997; 10: 2127–38PubMedCrossRefGoogle Scholar
  34. 34.
    Selroos O, Pietinalho A, Riska H. Delivery devices for inhaled asthma medication: clinical implications of differences in effectiveness. Clin Immunother 1996; 6: 273–99CrossRefGoogle Scholar
  35. 35.
    Thorsson L, Edsbäcker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered dose inhaler P-MDI. Eur Respir J 1994; 7: 1839–44PubMedCrossRefGoogle Scholar
  36. 36.
    Thorsson L, Edsbäcker S, Källén A, et al. Pharmacokinetics and systemic activity of fluticasone propionate and budesonide. Br J Clin Pharmacol 2001; 52: 1–15CrossRefGoogle Scholar
  37. 37.
    Fuller RW, Sharma RK, Cripps A. Letter to the editor: lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler (P-MDI). Eur Respir J 1995; 8: 2194–5PubMedCrossRefGoogle Scholar
  38. 38.
    Osterman K, Norborg AM, Ståhl E. A multidose powder inhaler (Turbuhaler®) compared with a conventional aerosol. Allergy 1989; 44: 294–7PubMedCrossRefGoogle Scholar
  39. 39.
    Hetta L, Larsson LG, Nikander K. A comparative clinical study of inhaled budesonide delivered either via a pressurized metered-dose inhaler or via Turbuhaler. Eur Respir J 1989; 2: 832sGoogle Scholar
  40. 40.
    Persson G, Gruvstad E, Ståhl E. A new multiple dose powder inhaler (Turbuhaler®) compared with a pressurized inhaler in a study of terbutaline in asthmatics. Eur Respir J 1988; 1: 681–4PubMedGoogle Scholar
  41. 41.
    Arvidsson P, Meilén A, Palmqvist M, et al. Equivalent therapeutic ratio of salbutamol given by Turbuhaler and Diskus. Respir Med 2000; 94: 574–7PubMedCrossRefGoogle Scholar
  42. 42.
    Britton J, Tattersfield A. Comparison of cumulative and non-cumulative techniques to measure dose-response curves for beta agonists in patients with asthma. Thorax 1984; 39: 597–9PubMedCrossRefGoogle Scholar
  43. 43.
    Fishwick D, Bradshaw L, Macdonald C, et al. Cumulative and single-dose design to assess the bronchodilator effects of β2-agonists in individuals with asthma. Am J Respir Crit Care Med 2001; 163: 474–7PubMedGoogle Scholar
  44. 44.
    Löfdahl C-G, Andersson L, Bondesson E, et al. Differences in bronchodilating potency of salbutamol in Turbuhaler® as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction. Eur Respir J 1997; 10: 2474–8CrossRefGoogle Scholar
  45. 45.
    Böllert FGE, Matusiewicz SP, Dewar MH, et al. Comparative efficacy and potency of ipratropium via Turbuhaler® and pressurized metered-dose inhaler in reversible airflow obstruction. Eur Respir J 1997; 10: 1824–8PubMedCrossRefGoogle Scholar
  46. 46.
    Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J 1998; 12: 1346–53PubMedCrossRefGoogle Scholar
  47. 47.
    van Schayck CP, Donnell D. The efficacy and safety of QVAR (hydrofluoroalkane-beclomethasone dipropionate extrafine aerosol) in asthma (Part 1): an update of clinical experience in adults. Int J Clin Pract 2004; 58: 678–88PubMedCrossRefGoogle Scholar
  48. 48.
    Fairfax A, Hall I, Spelman R. A randomised, double-blind comparison of beclomethasone dipropionate extrafine aerosol and fluticasone propionate. Ann Allergy Asthma Immunol 2001; 86: 575–82PubMedCrossRefGoogle Scholar
  49. 49.
    Reichel W, Dahl R, Ringdal N, et al. Extrafine beclomethasone dipropionate breath-actuated inhaler (400 (μg/day) versus budesonide dry powder inhaler (800 μg/day) in asthma. Int J Clin Pract 2001; 55: 100–6PubMedGoogle Scholar
  50. 50.
    Worth H, Muir J, Pieters W. Comparison of hydrofluoroalkane beclomethasone dipropionate Autohaler with budesonide Turbuhaler in asthma control. Respiration 2001; 68: 517–26PubMedCrossRefGoogle Scholar
  51. 51.
    Beasley R, Sterk PJ, Kerstjens HAM, et al. Comparative studies of inhaled corticosteroids in asthma. Eur Respir J 2001; 17: 579–80PubMedCrossRefGoogle Scholar
  52. 52.
    Bethke TD, Boudreau RJ, Hasselquist BE, et al. High lung deposition of ciclesonide in 2D- and 3D-imaging. Eur Respir J 2002; 20 (Suppl. 38): 109sGoogle Scholar
  53. 53.
    Hansel T, Engelstätter R, Benezet O, et al. Once daily ciclesonide (80μg and 320(μg) is equally effective as budesonide 200μg given twice daily: a 12-week study in asthma patients. Eur Respir J 2003; 22 (Suppl. 45): 410sGoogle Scholar
  54. 54.
    Wilson AM, Sims EJ, Orr LC, et al. Differences in lung bioavailability between different propellants for fluticasone propionate. Lancet 1999; 354: 1357–8PubMedCrossRefGoogle Scholar
  55. 55.
    Kunka R Andrews S, Pimazzoni M, et al. Dose proportionality of fluticasone propionate from hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and comparability with chlorofluorocarbon pMDIs. Respir Med 2000; 94 (Suppl. B): S10–6Google Scholar
  56. 56.
    Agertoft L, Pedersen S. Importance of the inhalation device on the effect of budesonide. Arch Dis Child 1993; 69: 130–3PubMedCrossRefGoogle Scholar
  57. 57.
    Johnson M. Anti-inflammatory properties of fluticasone propionate. Int Arch Allergy Immunol 1995; 107: 439–40PubMedCrossRefGoogle Scholar
  58. 58.
    Kuna P, Joubert JR, Greefhorst LAPM, et al. A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma. Clin Ther 2003; 25: 2182–97PubMedCrossRefGoogle Scholar
  59. 59.
    Agertoft L, Pedersen S. A randomized double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler. J Allergy Clin Immunol 1997; 99: 773–80PubMedCrossRefGoogle Scholar
  60. 60.
    Agertoft L, Pedersen, S. Lung deposition and systemic availability of drug from two different dry powder inhalers in children with asthma. Am J Respir Crit Care Med 2003; 168: 779–82PubMedCrossRefGoogle Scholar
  61. 61.
    Borgström L, Nilsson M. A method for determination of the absolute pulmonary bioavailability of inhaled drugs: terbutaline. Pharm Res 1990; 7: 1068–70PubMedCrossRefGoogle Scholar
  62. 62.
    Thorsson L, Edsbäcker S. Less variability in lung deposition of budesonide via Turbuhaler® than of fluticasone via Diskus®/Accuhaler® and pMDI in adults. Am J Respir Crit Care Med 2003; 167: A896Google Scholar
  63. 63.
    Bisgaard H, Klug H, Sumby BS, et al. Fine particle mass from Diskus inhaler and Turbuhaler inhaler in children with asthma. Eur Respir J 1998; 11: 1111–5PubMedCrossRefGoogle Scholar
  64. 64.
    Svartengren K, Lindestad P-A, Svartengren M, et al. Added external resistance reduces oropharyngeal deposition and increases lung deposition of aerosol particles in asthmatics. Am J Respir Crit Care Med 1995; 152: 32–7PubMedGoogle Scholar
  65. 65.
    Singh SD, Whale C, Houghton N, et al. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 2003; 55: 375–81PubMedCrossRefGoogle Scholar
  66. 66.
    Harrison TW, Tattersfield AE. Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects. Thorax 2003; 58: 258–60PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.SEMECO ABLundSweden
  2. 2.AstraZeneca R&DLundSweden

Personalised recommendations