Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2004 Jan;59(1):16–20.

Clinical dose-response relationship of fluticasone propionate in adults with asthma

M Masoli 1, M Weatherall 1, S Holt 1, R Beasley 1
PMCID: PMC1758851  PMID: 14694240

Abstract

Background: A study was undertaken to examine the dose-response relation of inhaled fluticasone in adolescents and adults with asthma.

Methods: A meta-analysis was carried out of randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two doses of fluticasone given twice daily. The main outcome measures were forced expiratory volume in 1 second (FEV1), morning peak expiratory flow (amPEF), ß agonist use, and withdrawals due to exacerbations of asthma.

Results: Seven studies of 2431 adolescents and adults with moderate to severe asthma met the inclusion criteria for the meta-analysis. Four studies examined a dose of >500 µg/day. For all outcome measures there were no statistically significant differences between a dose of 200 v 500 µg/day, 500 v 1000 µg/day, and 200 v ⩾500 µg/day, although the point estimates favoured the higher doses. The mean improvement for FEV1 and amPEF resulting from an increase in dose from 200 to ⩾500 µg/day was 0.07 l (95% CI -0.01 to 0.14) and 5.9 l/min (95% CI -3.0 to 15.3), respectively. The odds ratio for withdrawals with 200 µg/day compared with ⩾500 µg/day was 1.27 (95% CI 0.78 to 2.07).

Conclusions: In adolescents and adults with asthma, most of the therapeutic benefit of fluticasone is achieved with a total daily dose of 200 µg/day with minimal further clinical benefit achieved with higher doses. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids in asthma, which would suggest that some patients may obtain a greater clinical benefit at higher doses.

Full Text

The Full Text of this article is available as a PDF (327.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ayres J. G., Bateman E. D., Lundbäck B., Harris T. A. High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate, 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. International Study Group. Eur Respir J. 1995 Apr;8(4):579–586. [PubMed] [Google Scholar]
  2. Barnes N. C., Hallett C., Harris T. A. Clinical experience with fluticasone propionate in asthma: a meta-analysis of efficacy and systemic activity compared with budesonide and beclomethasone dipropionate at half the microgram dose or less. Respir Med. 1998 Jan;92(1):95–104. doi: 10.1016/s0954-6111(98)90039-7. [DOI] [PubMed] [Google Scholar]
  3. Boni E., Corda L., Franchini D., Chiroli P., Damiani G. P., Pini L., Grassi V., Tantucci C. Volume effect and exertional dyspnoea after bronchodilator in patients with COPD with and without expiratory flow limitation at rest. Thorax. 2002 Jun;57(6):528–532. doi: 10.1136/thorax.57.6.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bousquet Jean, Ben-Joseph Rami, Messonnier Mark, Alemao Evo, Gould A. Lawrence. A meta-analysis of the dose-response relationship of inhaled corticosteroids in adolescents and adults with mild to moderate persistent asthma. Clin Ther. 2002 Jan;24(1):1–20. doi: 10.1016/s0149-2918(02)85002-0. [DOI] [PubMed] [Google Scholar]
  5. Busse W. W., Brazinsky S., Jacobson K., Stricker W., Schmitt K., Vanden Burgt J., Donnell D., Hannon S., Colice G. L. 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 Dec;104(6):1215–1222. doi: 10.1016/s0091-6749(99)70016-3. [DOI] [PubMed] [Google Scholar]
  6. Chervinsky P., van As A., Bronsky E. A., Dockhorn R., Noonan M., LaForce C., Pleskow W. Fluticasone propionate aerosol for the treatment of adults with mild to moderate asthma. The Fluticasone Propionate Asthma Study Group. J Allergy Clin Immunol. 1994 Oct;94(4):676–683. doi: 10.1016/0091-6749(94)90174-0. [DOI] [PubMed] [Google Scholar]
  7. Gershman N. H., Wong H. H., Liu J. T., Fahy J. V. Low- and high-dose fluticasone propionate in asthma; effects during and after treatment. Eur Respir J. 2000 Jan;15(1):11–18. doi: 10.1183/09031936.00.15101100. [DOI] [PubMed] [Google Scholar]
  8. Holt S., Suder A., Weatherall M., Cheng S., Shirtcliffe P., Beasley R. Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis. BMJ. 2001 Aug 4;323(7307):253–256. doi: 10.1136/bmj.323.7307.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kerrebijn K. F., van Essen-Zandvliet E. E., Neijens H. J. Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma. J Allergy Clin Immunol. 1987 Apr;79(4):653–659. doi: 10.1016/s0091-6749(87)80163-x. [DOI] [PubMed] [Google Scholar]
  10. Lawrence M., Wolfe J., Webb D. R., Chervinsky P., Kellerman D., Schaumberg J. P., Shah T. Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):744–751. doi: 10.1164/ajrccm.156.3.9608058. [DOI] [PubMed] [Google Scholar]
  11. Pauwels R. A., Löfdahl C. G., Postma D. S., Tattersfield A. E., O'Byrne P., Barnes P. J., Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997 Nov 13;337(20):1405–1411. doi: 10.1056/NEJM199711133372001. [DOI] [PubMed] [Google Scholar]
  12. Pearlman D. S., Noonan M. J., Tashkin D. P., Goldstein M. F., Hamedani A. G., Kellerman D. J., Schaberg A. Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma. Ann Allergy Asthma Immunol. 1997 Apr;78(4):356–362. doi: 10.1016/S1081-1206(10)63196-1. [DOI] [PubMed] [Google Scholar]
  13. Raphael G. D., Lanier R. Q., Baker J., Edwards L., Rickard K., Lincourt W. R. A comparison of multiple doses of fluticasone propionate and beclomethasone dipropionate in subjects with persistent asthma. J Allergy Clin Immunol. 1999 May;103(5 Pt 1):796–803. doi: 10.1016/s0091-6749(99)70422-7. [DOI] [PubMed] [Google Scholar]
  14. Santanello N. C., Zhang J., Seidenberg B., Reiss T. F., Barber B. L. What are minimal important changes for asthma measures in a clinical trial? Eur Respir J. 1999 Jul;14(1):23–27. doi: 10.1034/j.1399-3003.1999.14a06.x. [DOI] [PubMed] [Google Scholar]
  15. Sheffer A. L., LaForce C., Chervinsky P., Pearlman D., Schaberg A. Fluticasone propionate aerosol: efficacy in patients with mild to moderate asthma. Fluticasone Propionate Asthma Study Group. J Fam Pract. 1996 Apr;42(4):369–375. [PubMed] [Google Scholar]
  16. Shrewsbury S., Pyke S., Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ. 2000 May 20;320(7246):1368–1373. doi: 10.1136/bmj.320.7246.1368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Szefler S. J., Boushey H. A., Pearlman D. S., Togias A., Liddle R., Furlong A., Shah T., Knobil K. Time to onset of effect of fluticasone propionate in patients with asthma. J Allergy Clin Immunol. 1999 May;103(5 Pt 1):780–788. doi: 10.1016/s0091-6749(99)70420-3. [DOI] [PubMed] [Google Scholar]
  18. Szefler Stanley J., Martin Richard J., King Tonya Sharp, Boushey Homer A., Cherniack Reuben M., Chinchilli Vernon M., Craig Timothy J., Dolovich Myrna, Drazen Jeffrey M., Fagan Joanne K. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002 Mar;109(3):410–418. doi: 10.1067/mai.2002.122635. [DOI] [PubMed] [Google Scholar]
  19. Wasserman S. I., Gross G. N., Schoenwetter W. F., Munk Z. M., Kral K. M., Schaberg A., Kellerman D. J. A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma. J Asthma. 1996;33(4):265–274. doi: 10.3109/02770909609055367. [DOI] [PubMed] [Google Scholar]
  20. Wolfe J. D., Selner J. C., Mendelson L. M., Hampel F., Jr, Schaberg A. Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study. Clin Ther. 1996 Jul-Aug;18(4):635–646. doi: 10.1016/s0149-2918(96)80214-1. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES