Skip to main content
Thorax logoLink to Thorax
. 2003 Jun;58(6):500–504. doi: 10.1136/thorax.58.6.500

Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment

A Sovijarvi 1, T Haahtela 1, H Ekroos 1, A Lindqvist 1, A Saarinen 1, T Poussa 1, L Laitinen 1
PMCID: PMC1746689  PMID: 12775860

Abstract

Background: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks.

Methods: Twenty six asthmatic patients aged 21–59 years were selected for this randomised, double blind, parallel group study. The effect of 250 µg inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV1) by 15% (PD15FEV1) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD15FEV1 were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves.

Results: The increase in PD15FEV1 from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD15FEV1 was 1.85–2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment.

Conclusions: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 µg. The effect tapered within 2 weeks of cessation of treatment.

Full Text

The Full Text of this article is available as a PDF (130.7 KB).

Selected References

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

  1. Convery R. P., Leitch D. N., Bromly C., Ward R. J., Bartlett G., Hendrick D. J. Effect of inhaled fluticasone propionate on airway responsiveness in treatment-naive individuals--a lesser benefit in females. Eur Respir J. 2000 Jan;15(1):19–24. doi: 10.1183/09031936.00.15101900. [DOI] [PubMed] [Google Scholar]
  2. Crapo R. O., Casaburi R., Coates A. L., Enright P. L., Hankinson J. L., Irvin C. G., MacIntyre N. R., McKay R. T., Wanger J. S., Anderson S. D. Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med. 2000 Jan;161(1):309–329. doi: 10.1164/ajrccm.161.1.ats11-99. [DOI] [PubMed] [Google Scholar]
  3. Dupont L. J., Rochette F., Demedts M. G., Verleden G. M. Exhaled nitric oxide correlates with airway hyperresponsiveness in steroid-naive patients with mild asthma. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):894–898. doi: 10.1164/ajrccm.157.3.9709064. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Gibson P. G., Saltos N., Fakes K. Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial. Am J Respir Crit Care Med. 2001 Jan;163(1):32–36. doi: 10.1164/ajrccm.163.1.9807061. [DOI] [PubMed] [Google Scholar]
  6. Jatakanon A., Kharitonov S., Lim S., Barnes P. J. Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma. Thorax. 1999 Feb;54(2):108–114. doi: 10.1136/thx.54.2.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jatakanon A., Lim S., Kharitonov S. A., Chung K. F., Barnes P. J. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax. 1998 Feb;53(2):91–95. doi: 10.1136/thx.53.2.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kharitonov S. A., Yates D. H., Barnes P. J. Inhaled glucocorticoids decrease nitric oxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med. 1996 Jan;153(1):454–457. doi: 10.1164/ajrccm.153.1.8542158. [DOI] [PubMed] [Google Scholar]
  9. Kraan J., Koëter G. H., van der Mark T. W., Boorsma M., Kukler J., Sluiter H. J., De Vries K. Dosage and time effects of inhaled budesonide on bronchial hyperreactivity. Am Rev Respir Dis. 1988 Jan;137(1):44–48. doi: 10.1164/ajrccm/137.1.44. [DOI] [PubMed] [Google Scholar]
  10. Nunn A. J., Gregg I. New regression equations for predicting peak expiratory flow in adults. BMJ. 1989 Apr 22;298(6680):1068–1070. doi: 10.1136/bmj.298.6680.1068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Quanjer P. H., Lebowitz M. D., Gregg I., Miller M. R., Pedersen O. F. Peak expiratory flow: conclusions and recommendations of a Working Party of the European Respiratory Society. Eur Respir J Suppl. 1997 Feb;24:2S–8S. [PubMed] [Google Scholar]
  12. Sherrington C. A., Mallol J. Early effects of inhaled steroids on airway hyperreactivity and pulmonary function in asthma. Pediatr Pulmonol. 1999 Jun;27(6):376–382. doi: 10.1002/(sici)1099-0496(199906)27:6<376::aid-ppul3>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
  13. Sont J. K., Willems L. N., Bel E. H., van Krieken J. H., Vandenbroucke J. P., Sterk P. J. Clinical control and histopathologic outcome of asthma when using airway hyperresponsiveness as an additional guide to long-term treatment. The AMPUL Study Group. Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1043–1051. doi: 10.1164/ajrccm.159.4.9806052. [DOI] [PubMed] [Google Scholar]
  14. Sovijärvi A. R., Malmberg L. P., Reinikainen K., Rytilä P., Poppius H. A rapid dosimetric method with controlled tidal breathing for histamine challenge. Repeatability and distribution of bronchial reactivity in a clinical material. Chest. 1993 Jul;104(1):164–170. doi: 10.1378/chest.104.1.164. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Vathenen A. S., Knox A. J., Wisniewski A., Tattersfield A. E. Time course of change in bronchial reactivity with an inhaled corticosteroid in asthma. Am Rev Respir Dis. 1991 Jun;143(6):1317–1321. doi: 10.1164/ajrccm/143.6.1317. [DOI] [PubMed] [Google Scholar]
  17. Viljanen A. A., Halttunen P. K., Kreus K. E., Viljanen B. C. Spirometric studies in non-smoking, healthy adults. Scand J Clin Lab Invest Suppl. 1982;159:5–20. [PubMed] [Google Scholar]
  18. Woodruff P. G., Khashayar R., Lazarus S. C., Janson S., Avila P., Boushey H. A., Segal M., Fahy J. V. Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. J Allergy Clin Immunol. 2001 Nov;108(5):753–758. doi: 10.1067/mai.2001.119411. [DOI] [PubMed] [Google Scholar]
  19. van Grunsven P. M., van Schayck C. P., Molema J., Akkermans R. P., van Weel C. Effect of inhaled corticosteroids on bronchial responsiveness in patients with "corticosteroid naive" mild asthma: a meta-analysis. Thorax. 1999 Apr;54(4):316–322. doi: 10.1136/thx.54.4.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. van Rensen E. L., Straathof K. C., Veselic-Charvat M. A., Zwinderman A. H., Bel E. H., Sterk P. J. Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma. Thorax. 1999 May;54(5):403–408. doi: 10.1136/thx.54.5.403. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES