Current Allergy and Asthma Reports

, Volume 4, Issue 2, pp 144–148 | Cite as

The dose-response relationship of inhaled corticosteroids in asthma

  • Matthew Masoli
  • Shaun Holt
  • Mark Weatherall
  • Richard Beasley


Inhaled corticosteroids are the only class of asthma medication that can reduce symptoms, improve lung function, reduce the frequency of severe exacerbations, including hospital and ICU admissions, and decrease the risk of mortality. The therapeutic dose range for all clinical outcome measures in adults is 100 to 1000 ώg/d of beclomethasone dipropionate or budesonide, or 50 to 500 ώg/d of fluticasone propionate. Doses in excess of this range are not recommended for routine use because they are likely to increase the risk of systemic side-effects without further major improvement in efficacy. The recommendations are qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients might obtain greater benefit at higher doses, just as some might obtain maximum benefit at lower doses.


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References and Recommended Reading

  1. 1.
    Global Initiative for Asthma: Global strategy for asthma management and prevention NHLBI/WHO Workshop Report. National Institutes of Health, National Heart, Lung and Blood Institute, 2002; 1–299.Google Scholar
  2. 2.
    British Thoracic Society and Scottish Intercollegiate Guidelines Network: British Guideline on Asthma Management: a national clinical guideline. Thorax 2003, 58(Suppl 1):i1-i94.Google Scholar
  3. 3.
    Barnes PJ: Inhaled glucocorticoids for asthma. N Engl J Med 1995, 332:868–875.PubMedCrossRefGoogle Scholar
  4. 4.
    Barnes PJ, Pedersen S, Busse W: Efficacy and safety of inhaled corticosteroids: new developments. Am J Respir Crit Care Med 1998, 157(3 Pt 2):S1-S39.PubMedGoogle Scholar
  5. 5.
    Holt S, Suder A, Weatherall M, et al.: Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ 2001, 323:1–8. This meta-analysis of placebo-controlled studies of the dose-response relationship of the inhaled corticosteroid fluticasone in adults and adolescents with asthma showed that for all clinical outcome measures, at least 90% of the maximum efficacy can be achieved with a dose of approximately 200 mcg per day.CrossRefGoogle Scholar
  6. 6.
    Masoli M, Weatherall M, Holt S, Beasley R: The clinical doseresponse relationship of fluticasone propionate in adults with asthma. Thorax, In press.Google Scholar
  7. 7.
    Masoli M, Holt S, Weatherall M, et al.: Dose-response relation of inhaled budesonide in adolescents and adults with asthma. Thorax 2002, 57(Supp3):S28.Google Scholar
  8. 8.
    Busse WW, Brazinsky S, Jacobson K, et al.: Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999, 104:1215–1222.PubMedCrossRefGoogle Scholar
  9. 9.
    Welch MJ, Levy S, Smith JA, et al.: Dose-ranging study of the clinical efficacy of twice-daily triamcinolone acetonide inhalation aerosol in moderately severe asthma. Chest 1997, 112:597–606.PubMedGoogle Scholar
  10. 10.
    Sharpe M, Jarvis B: Inhaled mometasone: a review of its use in adults and adolescents with persistent asthma. Drugs 2001, 61:1325–1350.PubMedCrossRefGoogle Scholar
  11. 11.
    Szefler SJ, Martin RJ, King TS, et al.: Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 2002, 109:410–418. This study demonstrated that there is considerable interindividual variability in response to inhaled corticosteroids in asthma, a finding that should be considered when the dose-responsive relationships of inhaled corticosteroids are reviewed.PubMedCrossRefGoogle Scholar
  12. 12.
    Nelson HS, Busse WW, de Boisblanc BP, et al.: Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma. J Allergy Clin Immunol 1999, 103:267–275.PubMedCrossRefGoogle Scholar
  13. 13.
    Noonan M, Chervinsky P, Busse W, et al.: Fluticasone propionate reduces oral prednisone use while it improves asthma control. Am J Ther 1996, 3:497–505.PubMedCrossRefGoogle Scholar
  14. 14.
    Miyamoto T, Takahashi T, Nakajima S, et al.: A double blind placebo-controlled steroid-sparing study with budesonide turbuhaler in Japanese oral steroid-dependent asthma patients. Respirology 2000, 5:231–240.PubMedCrossRefGoogle Scholar
  15. 15.
    Levy ML, Stevenson C, Maslen T: Comparison of short courses of oral prednisone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care. Thorax 1996, 51:1087–1092.PubMedCrossRefGoogle Scholar
  16. 16.
    Fitzgerald JM, Shragge D, Haddon J, et al.: A randomized controlled trial of high dose inhaled budesonide versus oral prednisone in patients discharged from the emergency department following an acute asthma exacerbation. Can Respir J 2000, 7:61–67.PubMedGoogle Scholar
  17. 17.
    Edmonds ML, Camargo CA Jr, Pollack CV Jr, Rowe BH: Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev 2003, 3:CD002308. This preliminary meta-analysis study suggests that high doses of inhaled corticosteroids might be as effective as oral steroids in the treatment of moderate to severe exacerbations of asthma.PubMedGoogle Scholar
  18. 18.
    Suissa S, Ernst P, Benayoun S, et al.: Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000, 343:332–336. This epidemiologic study demonstrates a dose-response relationship for inhaled corticosteroids in reducing the risk of asthma mortality. These findings also indicated the importance of compliance with inhaled corticosteroid therapy to obtain the benefits in terms of reducing the risk of life-threatening asthma.PubMedCrossRefGoogle Scholar
  19. 19.
    Ernst P, Walter O, Spitzer MD, et al.: Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. JAMA 1992, 268:3462–3464.PubMedCrossRefGoogle Scholar
  20. 20.
    Lanes SF, Rodriguez LAG, Huerta C: Respiratory medications and risk of asthma death. Thorax 2002, 57:683–686.PubMedCrossRefGoogle Scholar
  21. 21.
    Gershman N, Wong H, Liu J, Fahy J: Low and high dose fluticasone propionate in asthma: effects during and after treatment. Eur Respir J 2000, 15:11–18.PubMedCrossRefGoogle Scholar
  22. 22.
    Visser M, Postma D, Arends L, et al.: One year treatment with different dosing schedules of fluticasone propionate in childhood asthma. Am J Respir Crit Care Med 2001, 164:2073–2077.PubMedGoogle Scholar
  23. 23.
    Wallin A, Sue-Chu M, Bjermer L, et al.: Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma. J Allergy Clin Immunol 2003, 112:72–78.PubMedCrossRefGoogle Scholar
  24. 24.
    O’Sullivan S, Cormican L, Murphy M, et al.: Effects of varying doses of fluticasone propionate on the physiology and bronchial wall immunopathology in mild-to-moderate asthma. Chest 2002, 122:1966–1972. This study provides evidence that the dose-response relationship of inhaled corticosteroids for reducing airway inflammation is similar to that for the major clinical outcome measures.PubMedCrossRefGoogle Scholar
  25. 25.
    Aaronson D, Kaiser H, Dockhorn R, et al.: Effects of budesonide by means of the Turbuhaler on the hypothalamicpituitary-adrenal axis in asthmatic subjects: a dose-response study. J Allergy Clin Immunol 1998, 101:312–319. This study, which utilized sensitive measures of adrenal function, demonstrates that the marked increase in systemic effects of inhaled corticosteroids occurs at higher doses than previously considered (>2000 mcg of budesonide or equivalent).PubMedCrossRefGoogle Scholar
  26. 26.
    Brown PH, Blundell G, Greening AP, Crompton GK: Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids. Resp Med 1991, 85:501–510.CrossRefGoogle Scholar
  27. 27.
    Wong C, Walsh L, Smith C, et al.: Inhaled corticosteroid use and bone-mineral density in patients with asthma. Lancet 2000, 355:1399–1403.PubMedCrossRefGoogle Scholar
  28. 28.
    Elmst⇘hl S, Ekström H, Galvard H, et al.: Is there an association between inhaled corticosteroids and bone density in postmenopausal women? J Allergy Clin Immunol 2003, 111:91–96.CrossRefGoogle Scholar
  29. 29.
    Walsh LJ, Lewis SA, Wong CA, et al.: The impact of oral corticosteroid use on bone mineral density and vertebral fracture. Am J Respir Crit Care Med 2002, 166:691–695.PubMedCrossRefGoogle Scholar
  30. 30.
    Hubbard RB, Smith CJP, Smeeth L, et al.: Inhaled corticosteroids and hip fracture. Am J Respir Crit Care Med 2002, 166:1563–1566. This study showed that the dose-response relationship for inhaled corticosteroids in terms of fracture risk is similar to adrenal suppression, with a marked increase occurring at doses at least >1600 mcg per day of BDP or equivalent.PubMedCrossRefGoogle Scholar
  31. 31.
    Todd GRG, Acerini CL, Buck JJ, et al.: Acute adrenal crisis in asthmatics treated with high-dose fluticasone propionate. Eur Respir J 2002, 19:1207–1209.PubMedCrossRefGoogle Scholar
  32. 32.
    Drake AJ, Howells RJ, Shield JPH, et al.: Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with asthma receiving high dose inhaled fluticasone propionate. BMJ 2002, 324:1081–1082.PubMedCrossRefGoogle Scholar
  33. 33.
    Patel L, Wales JK, Kibirige MS, et al.: Symptomatic adrenal insufficiency during inhaled corticosteroid treatment. Arch Dis Child 2001, 85:330–333.PubMedCrossRefGoogle Scholar
  34. 34.
    Masoli M, Weatherall M, Holt S, Beasley R: Systematic review of the dose-response relation of inhaled fluticasone propionate. Arch Dis Child, In press. This study shows that lower doses are required in children than in adults to achieve the maximum clinical benefit, and that children are more sensitive to adrenal suppression.Google Scholar
  35. 35.
    Pedersen S, Ramsgaard-Hansen O: Budesonide treatment of moderate and severe asthma in children: a dose-response study. J Allergy Clin Immunol 1995, 95:29–33.PubMedCrossRefGoogle Scholar
  36. 36.
    Shapiro G, Bronsky EA, LaForce CF, et al.: Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. J Pediatr 1998, 132:976–982.PubMedCrossRefGoogle Scholar
  37. 37.
    Shrewsbury S, Pyke S, Britton M: Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000, 320:1368–1373.PubMedCrossRefGoogle Scholar
  38. 38.
    Pauwels RA, Lofdahl C-G, Postma DS, et al.: Effect of inhaled formoterol and budesonide on exacerbations of asthma (FACET). N Engl J Med 1997, 337:1405–1411.PubMedCrossRefGoogle Scholar
  39. 39.
    Masoli M, Holt S, Beasley R: What to do at step 3 of the asthma guidelines: increase the dose of inhaled corticosteroids or add a long-acting beta-agonist drug? [editorial] J Allergy Clin Immunol 2003, 112:10–11.PubMedCrossRefGoogle Scholar
  40. 40.
    Barnes P: Scientific rationale for inhaled combination therapy with long-acting beta2-agonists and corticosteroids. Eur Respir J 2002, 19:182–191.PubMedCrossRefGoogle Scholar
  41. 41.
    Verberne AAPH, Frost C, Duiverman EJ, et al.: Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998, 158:213–219.PubMedGoogle Scholar
  42. 42.
    Abramson MJ, Bailey MJ, Couper FJ, et al.: Are asthma medications and management related to deaths from asthma? Am J Respir Crit Care Med 2001, 163:12–18.PubMedGoogle Scholar
  43. 43.
    Gibson PG, Coughlan J, Wilson, et al.: Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev 2003, 1:CD001117. This meta-analysis conclusively demonstrates that the greatest benefits with long-term inhaled corticosteroid therapy are achieved when their use is incorporated within the structure of an asthma self-management plan system of care.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Matthew Masoli
    • 1
  • Shaun Holt
    • 1
  • Mark Weatherall
    • 1
  • Richard Beasley
    • 1
  1. 1.Medical Research Institute of New ZealandWellingtonNew Zealand

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