Treatments in Respiratory Medicine

, Volume 5, Issue 6, pp 385–391

Inhaled Glucocorticosteroid and Long-Acting β2-Adrenoceptor Agonist Single-Inhaler Combination for Both Maintenance and Rescue Therapy

A Paradigm Shift in Asthma Management
Current Opinion

Abstract

Despite aggressive fixed-dose (FD) combination therapy with inhaled glucocorticosteroids (ICS) and long acting β2-adrenoceptor agonists (LABA), many patients with asthma remain suboptimally controlled, based on the need for rescue therapy and rates of severe exacerbations. The strategy of adjustable maintenance dosing (AMD) involves adjustment of the maintenance dose, (using a single combination [budesonide/formoterol] inhaler, Symbicort®) in response to variability of asthma control over time. The AMD strategy, like the FD approach, involves the use of a short-acting β2-adrenoceptor agonist (SABA) for rapid relief of bronchospasm. The dose-response characteristics of budesonide/formoterol make the AMD strategy a feasible option that cannot be exploited with the combination of salmeterol/fluticasone propionate (Advair®). Several studies suggest that the AMD strategy is superior to a FD approach in terms of overall asthma control.

Budesonide/formoterol in a single inhaler is as effective as albuterol (salbutamol) for relief of acute asthma episodes, a feature that makes it possible to use this combination for both maintenance and reliever therapy without the need for the use of a SABA. The single-inhaler strategy has been shown to be safe and more efficacious than FD therapy. In particular, the COSMOS study has demonstrated that exacerbation burden is reduced more effectively when the combination (budesonide/formoterol) single inhaler is used for both maintenance and relief compared with FD therapy with salmeterol/fluticasone and albuterol for rescue in patients with moderate-to-severe asthma. These findings suggest that we will have to reconsider our definition of reliever therapy for patients that require long-term therapy with combination ICS and LABA.

The concept of single-inhaler therapy represents a paradigm shift in asthma management that has been validated in several large studies involving thousands of patients. The single-inhaler strategy represents one of the most significant advances in asthma management in many years, and one that appears ideal for adoption in primary care.

References

  1. 1.
    American Thoracic Society (ATS). Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 1987; 136: 225–44CrossRefGoogle Scholar
  2. 2.
    Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Publication No. 02-3659. Bethesda (MD): National Institutes of Health, 2002Google Scholar
  3. 3.
    Greening AP, Ind PW, Northfield M, et al. Added salmeterol versus higher-doses of corticosteroid in asthma patients with symptoms on existing ICS. Lancet 1994; 344: 219–24PubMedCrossRefGoogle Scholar
  4. 4.
    Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroid with doubling the dose of inhaled steroid. Am J Respir Crit Care Med 1996; 153: 1481–8PubMedGoogle Scholar
  5. 5.
    Pauwels RA, Lafdahl C-G, Postma DS, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997; 337: 1405–11PubMedCrossRefGoogle Scholar
  6. 6.
    O’Byrne PM, Barnes PJ, Rodrigues-Roisin R, et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 2001; 164: 1392–7PubMedGoogle Scholar
  7. 7.
    Bateman ED, Boushey HA, Bousquet J, et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma Control study. Am J Respir Crit Care Med 2004; 170: 836–44PubMedCrossRefGoogle Scholar
  8. 8.
    Balanag VM, Yunus F, Yang PC, et al. Budesonide/formoterol in a single inhaler is as effective and well tolerated as salbutamol in relieving acute asthma in adults and adolescents. Eur Respir J 2003; 22 Suppl. 45: 445sGoogle Scholar
  9. 9.
    Busse WW, Chervinsky P, Condemi J, et al. Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma. J Allergy Clin Immunol 1998; 101: 457–63PubMedCrossRefGoogle Scholar
  10. 10.
    D’Urzo AD, Chapman KR, Cartier A, et al. Effectiveness and safety of salmeterol in nonspecialist practice settings. Chest 2001 Mar; 119(3): 719Google Scholar
  11. 11.
    Fitzgerald JM, Sears MR, Boulet LP, et al. for the Canadian Investigators. Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a five month multicentre Canadian study. Can Respir J 2003; 10: 427–34Google Scholar
  12. 12.
    Aalbers R, Backer V, Kava TT, et al. Adjustable maintenance dosing with budesonide/formoterol compared to fixed-dose salmeterol/fluticasone in moderate to severe asthma. Curr Med Res Opin 2004; 20: 225–40PubMedCrossRefGoogle Scholar
  13. 13.
    Stallberg B, Olsson P, Jorgensen LA, et al. Budesonide/formoterol adjustable maintenance dosing reduces asthma exacerbations versus fixed dosing. Int J Clin Pract 2003; 57: 656–61PubMedGoogle Scholar
  14. 14.
    Buhl R, Kardos P, Richter K, et al. The effect of adjustable dosing with budesonide/formoterol on health-related quality of life and asthma control compared with fixed dosing. Curr Med Res Opin 2004 Aug; 20(2): 1209–20PubMedCrossRefGoogle Scholar
  15. 15.
    Canonica GW, Castellani P, Cazzola M, et al. The CAST (Control Of Asthma By Symbicort Turbuhaler) Study Group. Adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma symptom control at a lower dose than fixed maintenance dosing. Pulm Pharmacol Ther 2004; 17(4): 239–47Google Scholar
  16. 16.
    Ind PW, Haughney J, Price D, et al. Adjustable and fixed dosing with budesonide/formoterol via a single inhaler in asthma patients: the ASSURE study. Respir Med 2004 May; 98(5): 464–75PubMedCrossRefGoogle Scholar
  17. 17.
    Leuppi JD, Salzberg M, Meyer L, et al. An individual, adjustable maintenance regimen of budesonide/formoterol provides effective asthma symptom control at a lower overall dose than fixed dosing. Swiss Med Wkly 2003; 133: 302–9PubMedGoogle Scholar
  18. 18.
    Fitzgerald JM, Boulet LP, Follows RM. The CONCEPT trial: a 1 year, multicentre, randomized, double-blind, double dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma. Clin Ther 2005; 27: 393–406PubMedCrossRefGoogle Scholar
  19. 19.
    Pauwels RA, Sears MR, Campbell M, et al. for the RELIEF Study investigators. Formoterol Turbuhaler compared with salbutamol as reliever medication in asthma: outcomes from the RELIEF study in patients across different severities and age groups. Eur Resp J 2003; 22: 787–94Google Scholar
  20. 20.
    Tattersfield AE, Postma DS, Barnes PJ, et al. Exacerbations of asthma: a descriptive study of 425 severe exacerbations: FACET International Study Group. Am J Respir Crit Care Med 1999; 160: 594–9PubMedGoogle Scholar
  21. 21.
    Tattersfield AE, Löfdahl CG, Postma DS, et al. Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomized trial. Lancet 2001; 357: 257–61PubMedCrossRefGoogle Scholar
  22. 22.
    O’Byrne PM, Bisgaard H. Godard PP, et al. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am J Respir Crit Care Med 2005; 171: 129–36Google Scholar
  23. 23.
    Scicchitano R, Aalbers R, Ukena D, et al. Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma. Curr Med Res Opin 2004; 20: 1403–18PubMedCrossRefGoogle Scholar
  24. 24.
    Vogelmeier C, D’Urzo AD, Pauwels RA, et al. Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option? Eur Respir J 2005; 26: 819–28PubMedCrossRefGoogle Scholar
  25. 25.
    Currie GP, Lee DK. The GOAL study: designed to favor a long-acting β2-agonist? Am J Respir Crit Car Med 2005; 171: 1060–1Google Scholar
  26. 26.
    Woude VD, Boursma M, Bergqvist PB, et al. Budesonide/formoterol in a single inhaler rapidly relieves methacholine-induced moderate-to-severe bronchoconstriction. Pulm Pharmacol Ther 2004; 17(2): 89–95PubMedCrossRefGoogle Scholar
  27. 27.
    Rabe KF, Pizzichini E, Ställberg B, et al. Single inhaler therapy with budesonide/formoterol provides superior asthma control compared with fixed dosing with budesonide plus terbutaline as needed [abstract no. 360]. J Allergy Clin Immunol 2004; 113 Suppl. 2: S116CrossRefGoogle Scholar
  28. 28.
    Engel T, Dirksen A, Heing JH, et al. Single-dose inhaled budesonide in subjects with chronic asthma. Allergy 1991; 46: 547–53PubMedCrossRefGoogle Scholar
  29. 29.
    Rodrigo G, Rodrigo C. Inhaled flunisolide for acute severe asthma. Am J Respir Crit Care Med 1998; 157: 698–703PubMedGoogle Scholar
  30. 30.
    Gibson PG, Saltos N, Fakes K. Acute anti-inflammatory effects of inhaled budesonide in asthma. Am J Respir Crit Care Med 2001; 163: 32–6PubMedGoogle Scholar
  31. 31.
    Spoelstra FM, Postma DS, Hovenga H, et al. Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts. Eur Respir J 2000; 15: 68–74PubMedCrossRefGoogle Scholar
  32. 32.
    Usmani OS, Ito K, Maneechotesuwan K, et al. Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. Am J Respir Crit Care Med 2005; 172: 704–12PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Department of Family and Community MedicineUniversity of Toronto, Faculty of MedicineTorontoCanada
  2. 2.Primary Care Lung ClinicTorontoCanada

Personalised recommendations