Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1998 Sep;53(9):753–761. doi: 10.1136/thx.53.9.753

Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time

J Faul 1, C Leonard 1, C Burke 1, V Tormey 1, L Poulter 1
PMCID: PMC1745308  PMID: 10319057

Abstract

BACKGROUND—Inhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time.
METHODS—A randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12placebo.
RESULTS—FEV1, ΔFEV1, FEF25-75, and FEV1/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC20FEV1 showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment.
CONCLUSIONS—These results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.



Full Text

The Full Text of this article is available as a PDF (173.6 KB).

Selected References

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

  1. Azzawi M., Bradley B., Jeffery P. K., Frew A. J., Wardlaw A. J., Knowles G., Assoufi B., Collins J. V., Durham S., Kay A. B. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407–1413. doi: 10.1164/ajrccm/142.6_Pt_1.1407. [DOI] [PubMed] [Google Scholar]
  2. Barnes P. J. Effect of corticosteroids on airway hyperresponsiveness. Am Rev Respir Dis. 1990 Feb;141(2 Pt 2):S70–S76. [PubMed] [Google Scholar]
  3. Barnes P. J. Inhaled glucocorticoids for asthma. N Engl J Med. 1995 Mar 30;332(13):868–875. doi: 10.1056/NEJM199503303321307. [DOI] [PubMed] [Google Scholar]
  4. Bentley A. M., Menz G., Storz C., Robinson D. S., Bradley B., Jeffery P. K., Durham S. R., Kay A. B. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis. 1992 Aug;146(2):500–506. doi: 10.1164/ajrccm/146.2.500. [DOI] [PubMed] [Google Scholar]
  5. Booth H., Richmond I., Ward C., Gardiner P. V., Harkawat R., Walters E. H. Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. Am J Respir Crit Care Med. 1995 Jul;152(1):45–52. doi: 10.1164/ajrccm.152.1.7599861. [DOI] [PubMed] [Google Scholar]
  6. Bousquet J., Chanez P., Lacoste J. Y., Barnéon G., Ghavanian N., Enander I., Venge P., Ahlstedt S., Simony-Lafontaine J., Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. doi: 10.1056/NEJM199010113231505. [DOI] [PubMed] [Google Scholar]
  7. Bradley B. L., Azzawi M., Jacobson M., Assoufi B., Collins J. V., Irani A. M., Schwartz L. B., Durham S. R., Jeffery P. K., Kay A. B. Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J Allergy Clin Immunol. 1991 Oct;88(4):661–674. doi: 10.1016/0091-6749(91)90160-p. [DOI] [PubMed] [Google Scholar]
  8. Burke C., Power C. K., Norris A., Condez A., Schmekel B., Poulter L. W. Lung function and immunopathological changes after inhaled corticosteroid therapy in asthma. Eur Respir J. 1992 Jan;5(1):73–79. [PubMed] [Google Scholar]
  9. Chapman I. D., Foster A., Morley J. The relationship between inflammation and hyperreactivity of the airways in asthma. Clin Exp Allergy. 1993 Mar;23(3):168–171. doi: 10.1111/j.1365-2222.1993.tb00877.x. [DOI] [PubMed] [Google Scholar]
  10. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992 Mar;145(3):669–674. doi: 10.1164/ajrccm/145.3.669. [DOI] [PubMed] [Google Scholar]
  11. Djukanović R., Wilson J. W., Lai C. K., Holgate S. T., Howarth P. H. The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma. Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):772–777. doi: 10.1164/ajrccm/143.4_Pt_1.772. [DOI] [PubMed] [Google Scholar]
  12. Fabbri L., Burge P. S., Croonenborgh L., Warlies F., Weeke B., Ciaccia A., Parker C. Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group. Thorax. 1993 Aug;48(8):817–823. doi: 10.1136/thx.48.8.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Faul J. L., Tormey V. J., Leonard C., Burke C. M., Farmer J., Horne S. J., Poulter L. W. Lung immunopathology in cases of sudden asthma death. Eur Respir J. 1997 Feb;10(2):301–307. doi: 10.1183/09031936.97.10020301. [DOI] [PubMed] [Google Scholar]
  14. Haahtela T., Järvinen M., Kava T., Kiviranta K., Koskinen S., Lehtonen K., Nikander K., Persson T., Reinikainen K., Selroos O. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med. 1991 Aug 8;325(6):388–392. doi: 10.1056/NEJM199108083250603. [DOI] [PubMed] [Google Scholar]
  15. Hoekstra M. O., Grol M. H., Bouman K., Stijnen T., Köeter G. H., Kauffman H. F., Gerritsen J. Fluticasone propionate in children with moderate asthma. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1039–1044. doi: 10.1164/ajrccm.154.4.8887604. [DOI] [PubMed] [Google Scholar]
  16. Hutter C., Poulter L. W. The balance of macrophage subsets may be customised at mucosal surfaces. FEMS Microbiol Immunol. 1992 Dec;5(5-6):309–315. doi: 10.1111/j.1574-6968.1992.tb05915.x. [DOI] [PubMed] [Google Scholar]
  17. Jeffery P. K., Godfrey R. W., Adelroth E., Nelson F., Rogers A., Johansson S. A. Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):890–899. doi: 10.1164/ajrccm/145.4_Pt_1.890. [DOI] [PubMed] [Google Scholar]
  18. Jeffery P. K., Wardlaw A. J., Nelson F. C., Collins J. V., Kay A. B. Bronchial biopsies in asthma. An ultrastructural, quantitative study and correlation with hyperreactivity. Am Rev Respir Dis. 1989 Dec;140(6):1745–1753. doi: 10.1164/ajrccm/140.6.1745. [DOI] [PubMed] [Google Scholar]
  19. Kay A. B., Barata L., Meng Q., Durham S. R., Ying S. Eosinophils and eosinophil-associated cytokines in allergic inflammation. Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):196–199. doi: 10.1159/000237545. [DOI] [PubMed] [Google Scholar]
  20. Laitinen L. A., Laitinen A., Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta 2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol. 1992 Jul;90(1):32–42. doi: 10.1016/s0091-6749(06)80008-4. [DOI] [PubMed] [Google Scholar]
  21. Lundgren R., Söderberg M., Hörstedt P., Stenling R. Morphological studies of bronchial mucosal biopsies from asthmatics before and after ten years of treatment with inhaled steroids. Eur Respir J. 1988 Dec;1(10):883–889. [PubMed] [Google Scholar]
  22. Nadel J. A. Inflammation and asthma. J Allergy Clin Immunol. 1984 May;73(5 Pt 2):651–653. doi: 10.1016/0091-6749(84)90299-9. [DOI] [PubMed] [Google Scholar]
  23. Noonan M., Chervinsky P., Busse W. W., Weisberg S. C., Pinnas J., de Boisblanc B. P., Boltansky H., Pearlman D., Repsher L., Kellerman D. Fluticasone propionate reduces oral prednisone use while it improves asthma control and quality of life. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1467–1473. doi: 10.1164/ajrccm.152.5.7582278. [DOI] [PubMed] [Google Scholar]
  24. Poulter L. W., Norris A., Power C., Condez A., Burnes H., Schmekel B., Burke C. T cell dominated inflammatory reactions in the bronchioles of asymptomatic asthmatics are also present in the nasal mucosa. Postgrad Med J. 1991 Aug;67(790):747–753. doi: 10.1136/pgmj.67.790.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Poulter L. W., Power C., Burke C. The relationship between bronchial immunopathology and hyperresponsiveness in asthma. Eur Respir J. 1990 Jul;3(7):792–799. [PubMed] [Google Scholar]
  26. Power C. K., Burke C. M., Sreenan S., Hurson B., Poulter L. W. T-cell and macrophage subsets in the bronchial wall of clinically healthy subjects. Eur Respir J. 1994 Mar;7(3):437–441. doi: 10.1183/09031936.94.07030437. [DOI] [PubMed] [Google Scholar]
  27. Reed C. E. Aerosol steroids as primary treatment of mild asthma. N Engl J Med. 1991 Aug 8;325(6):425–426. doi: 10.1056/NEJM199108083250610. [DOI] [PubMed] [Google Scholar]
  28. Robinson D. S., Bentley A. M., Hartnell A., Kay A. B., Durham S. R. Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness. Thorax. 1993 Jan;48(1):26–32. doi: 10.1136/thx.48.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sont J. K., Han J., van Krieken J. M., Evertse C. E., Hooijer R., Willems L. N., Sterk P. J. Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids. Thorax. 1996 May;51(5):496–502. doi: 10.1136/thx.51.5.496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sterk P. J., Fabbri L. M., Quanjer P. H., Cockcroft D. W., O'Byrne P. M., Anderson S. D., Juniper E. F., Malo J. L. Airway responsiveness. Standardized challenge testing with pharmacological, physical and sensitizing stimuli in adults. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:53–83. [PubMed] [Google Scholar]
  31. Trigg C. J., Manolitsas N. D., Wang J., Calderón M. A., McAulay A., Jordan S. E., Herdman M. J., Jhalli N., Duddle J. M., Hamilton S. A. Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. Am J Respir Crit Care Med. 1994 Jul;150(1):17–22. doi: 10.1164/ajrccm.150.1.8025745. [DOI] [PubMed] [Google Scholar]
  32. 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]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES