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. 2002 Sep;57(9):799–803. doi: 10.1136/thorax.57.9.799

Effects of fluticasone propionate on inflammatory cells in COPD: an ultrastructural examination of endobronchial biopsy tissue

M Gizycki 1, K Hattotuwa 1, N Barnes 1, P Jeffery 1
PMCID: PMC1746422  PMID: 12200525

Abstract

Background: Inhaled corticosteroids (ICS) markedly reduce bronchial mucosal inflammation in asthma but whether they have an anti-inflammatory effect in airway tissue in chronic obstructive pulmonary disease (COPD) is unknown.

Methods: A study of endobronchial biopsy samples was conducted as part of a double blind, placebo controlled, randomised trial of parallel design. Patients had mild to moderately severe COPD (FEV1 25–80% of predicted) and were given 3 months treatment with ICS, fluticasone propionate (FP; 500 µg twice daily, n=14) or placebo (n=10). Biopsy tissue taken at baseline and after treatment was examined by transmission electron microscopy to count the numbers of all ultrastructurally distinct inflammatory cells.

Results: Compared with their baseline values, FP resulted in a significant decrease (on average 65%) in the numbers of mucosal mast cells (median 7.8 (range 1–33) v 2.8 (1–14), p<0.05). The reductive effect of FP held true when the post-treatment values of the placebo and FP groups were compared: 8.8 (1–24) v 2.8 (1–14) (p<0.05). Unexpectedly, there were significantly more neutrophils in the FP than in the placebo group: 4.0 (0–23) v 1.7 (0–8), respectively (p<0.05). There were no alterations to other cell types including mononuclear cells. Symptoms markedly improved in the patients treated with FP for 3 months.

Conclusion: Fluticasone propionate given for 3 months to patients with COPD has selective effects on the inflammatory cells in the bronchial mucosa: the reduction in mast cell numbers may account for the improvement in symptoms over this time.

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Selected References

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  1. Barnes P. J. Inhaled corticosteroids are not beneficial in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):342–344. doi: 10.1164/ajrccm.161.2.16125_2. [DOI] [PubMed] [Google Scholar]
  2. Bradding P., Roberts J. A., Britten K. M., Montefort S., Djukanovic R., Mueller R., Heusser C. H., Howarth P. H., Holgate S. T. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994 May;10(5):471–480. doi: 10.1165/ajrcmb.10.5.8179909. [DOI] [PubMed] [Google Scholar]
  3. Burge P. S., Calverley P. M., Jones P. W., Spencer S., Anderson J. A., Maslen T. K. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000 May 13;320(7245):1297–1303. doi: 10.1136/bmj.320.7245.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Calverley P. M. Inhaled corticosteroids are beneficial in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):341–344. doi: 10.1164/ajrccm.161.2.16125_1. [DOI] [PubMed] [Google Scholar]
  5. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol. 1995 May 1;154(9):4719–4725. [PubMed] [Google Scholar]
  6. Erjefält J. S., Andersson M., Greiff L., Korsgren M., Gizycki M., Jeffery P. K., Persson G. A. Cytolysis and piecemeal degranulation as distinct modes of activation of airway mucosal eosinophils. J Allergy Clin Immunol. 1998 Aug;102(2):286–294. doi: 10.1016/s0091-6749(98)70098-3. [DOI] [PubMed] [Google Scholar]
  7. Gizycki M. J., Adelroth E., Rogers A. V., O'Byrne P. M., Jeffery P. K. Myofibroblast involvement in the allergen-induced late response in mild atopic asthma. Am J Respir Cell Mol Biol. 1997 Jun;16(6):664–673. doi: 10.1165/ajrcmb.16.6.9191468. [DOI] [PubMed] [Google Scholar]
  8. Grashoff W. F., Sont J. K., Sterk P. J., Hiemstra P. S., de Boer W. I., Stolk J., Han J., van Krieken J. M. Chronic obstructive pulmonary disease: role of bronchiolar mast cells and macrophages. Am J Pathol. 1997 Dec;151(6):1785–1790. [PMC free article] [PubMed] [Google Scholar]
  9. Hattotuwa Keith L., Gizycki Mariusz J., Ansari Tareq W., Jeffery Peter K., Barnes Neil C. The effects of inhaled fluticasone on airway inflammation in chronic obstructive pulmonary disease: a double-blind, placebo-controlled biopsy study. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1592–1596. doi: 10.1164/rccm.2105025. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Jeffery P. K. Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. Novartis Found Symp. 2001;234:149–168. [PubMed] [Google Scholar]
  12. Jeffery P. K. Remodeling in asthma and chronic obstructive lung disease. Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S28–S38. doi: 10.1164/ajrccm.164.supplement_2.2106061. [DOI] [PubMed] [Google Scholar]
  13. Keatings V. M., Jatakanon A., Worsdell Y. M., Barnes P. J. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997 Feb;155(2):542–548. doi: 10.1164/ajrccm.155.2.9032192. [DOI] [PubMed] [Google Scholar]
  14. Lamb D., Lumsden A. Intra-epithelial mast cells in human airway epithelium: evidence for smoking-induced changes in their frequency. Thorax. 1982 May;37(5):334–342. doi: 10.1136/thx.37.5.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lams B. E., Sousa A. R., Rees P. J., Lee T. H. Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease. Eur Respir J. 2000 Mar;15(3):512–516. doi: 10.1034/j.1399-3003.2000.15.14.x. [DOI] [PubMed] [Google Scholar]
  16. Lange P., Nyboe J., Appleyard M., Jensen G., Schnohr P. Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes. Thorax. 1990 Aug;45(8):579–585. doi: 10.1136/thx.45.8.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Meagher L. C., Cousin J. M., Seckl J. R., Haslett C. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. J Immunol. 1996 Jun 1;156(11):4422–4428. [PubMed] [Google Scholar]
  18. Nadel J. A. Role of mast cell and neutrophil proteases in airway secretion. Am Rev Respir Dis. 1991 Sep;144(3 Pt 2):S48–S51. doi: 10.1164/ajrccm/144.3_pt_2.S48. [DOI] [PubMed] [Google Scholar]
  19. O'Shaughnessy T. C., Ansari T. W., Barnes N. C., Jeffery P. K. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med. 1997 Mar;155(3):852–857. doi: 10.1164/ajrccm.155.3.9117016. [DOI] [PubMed] [Google Scholar]
  20. Paggiaro P. L., Dahle R., Bakran I., Frith L., Hollingworth K., Efthimiou J. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group. Lancet. 1998 Mar 14;351(9105):773–780. doi: 10.1016/s0140-6736(97)03471-5. [DOI] [PubMed] [Google Scholar]
  21. Pauwels R. A., Löfdahl C. G., Laitinen L. A., Schouten J. P., Postma D. S., Pride N. B., Ohlsson S. V. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999 Jun 24;340(25):1948–1953. doi: 10.1056/NEJM199906243402503. [DOI] [PubMed] [Google Scholar]
  22. Pesci A., Rossi G. A., Bertorelli G., Aufiero A., Zanon P., Olivieri D. Mast cells in the airway lumen and bronchial mucosa of patients with chronic bronchitis. Am J Respir Crit Care Med. 1994 May;149(5):1311–1316. doi: 10.1164/ajrccm.149.5.8173772. [DOI] [PubMed] [Google Scholar]
  23. Saetta M., Baraldo S., Corbino L., Turato G., Braccioni F., Rea F., Cavallesco G., Tropeano G., Mapp C. E., Maestrelli P. CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Aug;160(2):711–717. doi: 10.1164/ajrccm.160.2.9812020. [DOI] [PubMed] [Google Scholar]
  24. Saetta M., Di Stefano A., Turato G., Facchini F. M., Corbino L., Mapp C. E., Maestrelli P., Ciaccia A., Fabbri L. M. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):822–826. doi: 10.1164/ajrccm.157.3.9709027. [DOI] [PubMed] [Google Scholar]
  25. Siafakas N. M., Vermeire P., Pride N. B., Paoletti P., Gibson J., Howard P., Yernault J. C., Decramer M., Higenbottam T., Postma D. S. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force. Eur Respir J. 1995 Aug;8(8):1398–1420. doi: 10.1183/09031936.95.08081398. [DOI] [PubMed] [Google Scholar]
  26. Sommerhoff C. P., Caughey G. H., Finkbeiner W. E., Lazarus S. C., Basbaum C. B., Nadel J. A. Mast cell chymase. A potent secretagogue for airway gland serous cells. J Immunol. 1989 Apr 1;142(7):2450–2456. [PubMed] [Google Scholar]
  27. Vestbo J., Prescott E., Lange P. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med. 1996 May;153(5):1530–1535. doi: 10.1164/ajrccm.153.5.8630597. [DOI] [PubMed] [Google Scholar]
  28. Wenzel S. E., Szefler S. J., Leung D. Y., Sloan S. I., Rex M. D., Martin R. J. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):737–743. doi: 10.1164/ajrccm.156.3.9610046. [DOI] [PubMed] [Google Scholar]
  29. van Grunsven P. M., van Schayck C. P., Derenne J. P., Kerstjens H. A., Renkema T. E., Postma D. S., Similowski T., Akkermans R. P., Pasker-de Jong P. C., Dekhuijzen P. N. Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis. Thorax. 1999 Jan;54(1):7–14. doi: 10.1136/thx.54.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]

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