Skip to main content
PMC home page
Thorax logoLink to Thorax
. 2005 Feb;60(2):100–105. doi: 10.1136/thx.2004.021634

Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast

L Jayaram 1, E Pizzichini 1, C Lemiere 1, S Man 1, A Cartier 1, F Hargreave 1, M Pizzichini 1
PMCID: PMC1747311  PMID: 15681495

Abstract

Background: Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma.

Methods: A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of ⩾3.5%.

Results: Eighteen patients received low dose fluticasone (250 µg/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV1 (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not.

Conclusions: Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naïve eosinophilic asthma.

Full Text

The Full Text of this article is available as a PDF (145.6 KB).

Selected References

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

  1. Barnes N. C., Miller C. J. Effect of leukotriene receptor antagonist therapy on the risk of asthma exacerbations in patients with mild to moderate asthma: an integrated analysis of zafirlukast trials. Thorax. 2000 Jun;55(6):478–483. doi: 10.1136/thorax.55.6.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Belda J., Leigh R., Parameswaran K., O'Byrne P. M., Sears M. R., Hargreave F. E. Induced sputum cell counts in healthy adults. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):475–478. doi: 10.1164/ajrccm.161.2.9903097. [DOI] [PubMed] [Google Scholar]
  3. Bisgaard Hans, Study Group on Montelukast and Respiratory Syncytial Virus A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med. 2002 Oct 3;167(3):379–383. doi: 10.1164/rccm.200207-747OC. [DOI] [PubMed] [Google Scholar]
  4. Boulet L. P., Becker A., Bérubé D., Beveridge R., Ernst P. Canadian Asthma Consensus Report, 1999. Canadian Asthma Consensus Group. CMAJ. 1999 Nov 30;161(11 Suppl):S1–61. [PMC free article] [PubMed] [Google Scholar]
  5. Bousquet J., Chanez P., Lacoste J. Y., White R., Vic P., Godard P., Michel F. B. Asthma: a disease remodeling the airways. Allergy. 1992 Feb;47(1):3–11. doi: 10.1111/j.1398-9995.1992.tb02242.x. [DOI] [PubMed] [Google Scholar]
  6. Brusasco V., Hodder R., Miravitlles M., Korducki L., Towse L., Kesten S. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax. 2003 May;58(5):399–404. doi: 10.1136/thorax.58.5.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Busse W. W., Chervinsky P., Condemi J., Lumry W. R., Petty T. L., Rennard S., Townley R. G. Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 1):457–463. doi: 10.1016/S0091-6749(98)70353-7. [DOI] [PubMed] [Google Scholar]
  8. Busse W., Raphael G. D., Galant S., Kalberg C., Goode-Sellers S., Srebro S., Edwards L., Rickard K., Fluticasone Proprionate Clinical Research Study Group Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial. J Allergy Clin Immunol. 2001 Mar;107(3):461–468. doi: 10.1067/mai.2001.114657. [DOI] [PubMed] [Google Scholar]
  9. Crapo R. O., Morris A. H., Gardner R. M. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981 Jun;123(6):659–664. doi: 10.1164/arrd.1981.123.6.659. [DOI] [PubMed] [Google Scholar]
  10. Donohue James F., van Noord Jan A., Bateman Eric D., Langley Stephen J., Lee Angela, Witek Theodore J., Jr, Kesten Steven, Towse Lesley. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest. 2002 Jul;122(1):47–55. doi: 10.1378/chest.122.1.47. [DOI] [PubMed] [Google Scholar]
  11. Dutoit J. I., Salome C. M., Woolcock A. J. Inhaled corticosteroids reduce the severity of bronchial hyperresponsiveness in asthma but oral theophylline does not. Am Rev Respir Dis. 1987 Nov;136(5):1174–1178. doi: 10.1164/ajrccm/136.5.1174. [DOI] [PubMed] [Google Scholar]
  12. Gibson P. G., Wong B. J., Hepperle M. J., Kline P. A., Girgis-Gabardo A., Guyatt G., Dolovich J., Denburg J. A., Ramsdale E. H., Hargreave F. E. A research method to induce and examine a mild exacerbation of asthma by withdrawal of inhaled corticosteroid. Clin Exp Allergy. 1992 May;22(5):525–532. doi: 10.1111/j.1365-2222.1992.tb00161.x. [DOI] [PubMed] [Google Scholar]
  13. Green R. H., Brightling C. E., Woltmann G., Parker D., Wardlaw A. J., Pavord I. D. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax. 2002 Oct;57(10):875–879. doi: 10.1136/thorax.57.10.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Green Ruth H., Brightling Christopher E., McKenna Susan, Hargadon Beverley, Parker Debbie, Bradding Peter, Wardlaw Andrew J., Pavord Ian D. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715–1721. doi: 10.1016/S0140-6736(02)11679-5. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Haahtela T., Klaukka T. Societal and health care benefits of early use of inhaled steroids. Thorax. 1998 Dec;53(12):1005–1006. doi: 10.1136/thx.53.12.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Homer R. J., Elias J. A. Consequences of long-term inflammation. Airway remodeling. Clin Chest Med. 2000 Jun;21(2):331-43, ix. doi: 10.1016/s0272-5231(05)70270-7. [DOI] [PubMed] [Google Scholar]
  18. Jayaram L., Parameswaran K., Sears M. R., Hargreave F. E. Induced sputum cell counts: their usefulness in clinical practice. Eur Respir J. 2000 Jul;16(1):150–158. doi: 10.1034/j.1399-3003.2000.16a27.x. [DOI] [PubMed] [Google Scholar]
  19. Juniper E. F., Kline P. A., Vanzieleghem M. A., Ramsdale E. H., O'Byrne P. M., Hargreave F. E. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Am Rev Respir Dis. 1990 Oct;142(4):832–836. doi: 10.1164/ajrccm/142.4.832. [DOI] [PubMed] [Google Scholar]
  20. Leckie M. J., ten Brinke A., Khan J., Diamant Z., O'Connor B. J., Walls C. M., Mathur A. K., Cowley H. C., Chung K. F., Djukanovic R. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000 Dec 23;356(9248):2144–2148. doi: 10.1016/s0140-6736(00)03496-6. [DOI] [PubMed] [Google Scholar]
  21. Leff J. A., Busse W. W., Pearlman D., Bronsky E. A., Kemp J., Hendeles L., Dockhorn R., Kundu S., Zhang J., Seidenberg B. C. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998 Jul 16;339(3):147–152. doi: 10.1056/NEJM199807163390302. [DOI] [PubMed] [Google Scholar]
  22. Leigh Richard, Vethanayagam Dilini, Yoshida Makoto, Watson Richard M., Rerecich Tracy, Inman Mark D., O'Byrne Paul M. Effects of montelukast and budesonide on airway responses and airway inflammation in asthma. Am J Respir Crit Care Med. 2002 Nov 1;166(9):1212–1217. doi: 10.1164/rccm.200206-509OC. [DOI] [PubMed] [Google Scholar]
  23. Louis R., Sele J., Henket M., Cataldo D., Bettiol J., Seiden L., Bartsch P. Sputum eosinophil count in a large population of patients with mild to moderate steroid-naive asthma: distribution and relationship with methacholine bronchial hyperresponsiveness. Allergy. 2002 Oct;57(10):907–912. doi: 10.1034/j.1398-9995.2002.23608.x. [DOI] [PubMed] [Google Scholar]
  24. Malmstrom K., Rodriguez-Gomez G., Guerra J., Villaran C., Piñeiro A., Wei L. X., Seidenberg B. C., Reiss T. F. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999 Mar 16;130(6):487–495. doi: 10.7326/0003-4819-130-6-199903160-00005. [DOI] [PubMed] [Google Scholar]
  25. Minoguchi Kenji, Kohno Yasurou, Minoguchi Hideko, Kihara Norio, Sano Yasuyuki, Yasuhara Hajime, Adachi Mitsuru. Reduction of eosinophilic inflammation in the airways of patients with asthma using montelukast. Chest. 2002 Mar;121(3):732–738. doi: 10.1378/chest.121.3.732. [DOI] [PubMed] [Google Scholar]
  26. O'Byrne P. M., Inman M. D., Parameswaran K. The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol. 2001 Oct;108(4):503–508. doi: 10.1067/mai.2001.119149. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Pavord I. D., Brightling C. E., Woltmann G., Wardlaw A. J. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999 Jun 26;353(9171):2213–2214. doi: 10.1016/S0140-6736(99)01813-9. [DOI] [PubMed] [Google Scholar]
  29. Pedersen S., Hansen O. R. Budesonide treatment of moderate and severe asthma in children: a dose-response study. J Allergy Clin Immunol. 1995 Jan;95(1 Pt 1):29–33. doi: 10.1016/s0091-6749(95)70149-4. [DOI] [PubMed] [Google Scholar]
  30. Pizzichini E., Leff J. A., Reiss T. F., Hendeles L., Boulet L. P., Wei L. X., Efthimiadis A. E., Zhang J., Hargreave F. E. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. Eur Respir J. 1999 Jul;14(1):12–18. doi: 10.1034/j.1399-3003.1999.14a04.x. [DOI] [PubMed] [Google Scholar]
  31. Pizzichini E., Pizzichini M. M., Efthimiadis A., Evans S., Morris M. M., Squillace D., Gleich G. J., Dolovich J., Hargreave F. E. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308–317. doi: 10.1164/ajrccm.154.2.8756799. [DOI] [PubMed] [Google Scholar]
  32. Pizzichini E., Pizzichini M. M., Gibson P., Parameswaran K., Gleich G. J., Berman L., Dolovich J., Hargreave F. E. Sputum eosinophilia predicts benefit from prednisone in smokers with chronic obstructive bronchitis. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1511–1517. doi: 10.1164/ajrccm.158.5.9804028. [DOI] [PubMed] [Google Scholar]
  33. Pizzichini M. M. M. Is sputum eosinophilia a good or poor predictor of benefit from inhaled corticosteroid therapy in asthma? Eur Respir J. 2002 Dec;20(6):1359–1361. doi: 10.1183/09031936.02.00068102. [DOI] [PubMed] [Google Scholar]
  34. Pizzichini M. M., Popov T. A., Efthimiadis A., Hussack P., Evans S., Pizzichini E., Dolovich J., Hargreave F. E. Spontaneous and induced sputum to measure indices of airway inflammation in asthma. Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):866–869. doi: 10.1164/ajrccm.154.4.8887576. [DOI] [PubMed] [Google Scholar]
  35. Reiss T. F., Chervinsky P., Dockhorn R. J., Shingo S., Seidenberg B., Edwards T. B. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group. Arch Intern Med. 1998 Jun 8;158(11):1213–1220. doi: 10.1001/archinte.158.11.1213. [DOI] [PubMed] [Google Scholar]
  36. Reiss T. F., Sorkness C. A., Stricker W., Botto A., Busse W. W., Kundu S., Zhang J. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax. 1997 Jan;52(1):45–48. doi: 10.1136/thx.52.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Reiss T. F., Sorkness C. A., Stricker W., Botto A., Busse W. W., Kundu S., Zhang J. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax. 1997 Jan;52(1):45–48. doi: 10.1136/thx.52.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Suissa S., Ernst P., Benayoun S., Baltzan M., Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000 Aug 3;343(5):332–336. doi: 10.1056/NEJM200008033430504. [DOI] [PubMed] [Google Scholar]
  39. Suissa S., Ernst P., Kezouh A. Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma. Thorax. 2002 Oct;57(10):880–884. doi: 10.1136/thorax.57.10.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Turner M. O., Johnston P. R., Pizzichini E., Pizzichini M. M., Hussack P. A., Hargreave F. E. Anti-inflammatory effects of salmeterol compared with beclomethasone in eosinophilic mild exacerbations of asthma: a randomized, placebo controlled trial. Can Respir J. 1998 Jul-Aug;5(4):261–268. doi: 10.1155/1998/868379. [DOI] [PubMed] [Google Scholar]
  41. Yudkin P. L., Stratton I. M. How to deal with regression to the mean in intervention studies. Lancet. 1996 Jan 27;347(8996):241–243. doi: 10.1016/s0140-6736(96)90410-9. [DOI] [PubMed] [Google Scholar]
  42. 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