Efficacy of inhaled corticosteroids for patients with asthma: a descriptive review of randomized controlled trials

Main Article Content

Mostafa Alabousi
Abdullah Alabousi
Natalie Ambeault
John Riva


Objective: To evaluate the efficacy of inhaled corticosteroids (ICS) in patients with asthma based on changes in sputum eosinophil counts, through a review of relevant randomized controlled trials (RCTs).

Methods: Studies were retrieved from MEDLINE, EMBASE, the SYSTEM FOR INFORMATION ON GREY LITERATURE, and the INSTITUTE FOR SCIENTIFIC INFORMATION from February 1, 2003 to February 1, 2013 based on a comprehensive search strategy. Articles were screened through two stages: title and abstract; and full-text screening. RCTs enrolling patients with asthma, testing an ICS intervention, and reporting outcomes on changes in sputum eosinophil counts pre- and post-intervention were included. Following screening, data extraction, and quality appraisal, a descriptive synthesis of trials was conducted.

Results: The search strategy retrieved 447 articles, of which 66 articles underwent full-text screening, resulting in 37 RCTs that met the inclusion criteria for this review. The articles were stratified according to the type of ICS: budesonide, fluticasone propionate, ciclesonide, beclomethasone dipropionate, and mometasone.  Across trials, 9 of 16 budesonide, 5 of 14 fluticasone propionate, 4 of 9 of nine ciclesonide, 2 of 4 beclomethasone dipropionate, and 1 of 2 mometasone interventions demonstrated a statistically significant (p < 0.05) reduction in sputum eosinophil counts.

Conclusion: This study detected differences between ICS treatments however the clinical relevance is uncertain. There is insufficient evidence to suggest the superiority of one ICS treatment over another. Further research needs to be conducted to evaluate the relative impact of ICS products upon eosinophil counts, as well as in clarifying what quantitative level of change in baseline eosinophil counts is required to observe a change in symptom improvement and disease control.

Article Details

Review & Clinical Practice


1. Boulet LP, Becker A, Berube D, Beveridge R, Ernst P. (1999) Canadian asthma consensus report 1999. Canadian Asthma Consensus Group. CMAJ 161: Suppl. 11, S1–S61.

2. Djukanovic R, Roche WR, Wilson JW, et al. (1990) Mucosal inflammation in asthma: state of the art. Am Rev Respir Dis 142: 434–457.

3. Barnes PJ. (1996) Inhaled corticosteroids: new developments relevant to updating of asthma management guidelines. Respir Med 90: 379–384.

4. Barnes PJ. (1998) Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 94: 557–572.

5. Djukanovic R, Sterk PJ, Fahy JV, Hargreave FE. Standardized methodology of sputum induction and processing. Eur Respir J 2002; 20:Suppl. 37, 1s–55s.

6. Lemiere CM, FitzGerald M. (2012) Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can Respir J 19(2): 127-164.

7. Rank MA, Hagan JB, Park MA, Podjasek JC, Samant SA, Volcheck GW, et al. (2013) The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: A systematic review and meta-analysis of randomized controlled trials. J Allergy Clin Immunol 131(3): 724-729.

8. Gan WQ, Man SP, Sin DD. (2005) Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis. BMC pulmonary medicine 5(1): 3.

9. Moher D, Liberati A, Tetzlaff J, Altman DG. (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4): 264-269.

10. Landis JR, Koch GG. (1977) The measurement of observer agreement for categorical data. Biometrics 33(1): 159-175.

11. The Cochrane Collaboration. (2009) Cochrane Handbook for Systematic Reviews of Interventions (Version 5.0.2). Oxford: Cochrane Collaboration.

12. Boushey H, Sorkness C, King T. (2005) Intermittent therapy effective for mild persistent asthma. J Fam Pract 54(7): 577-84.

13. Cao WL, Sun YC, Yao WZ. (2007) A study on a therapeutic protocol to improve the control of persistent asthma by monitoring sputum eosinophil counts. Zhonghua Jie He He Hu Xi Za Zhi 30(5): 334-338.

14. Chlumský J, Striz I, Terl M, Vondracek J. (2006) Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma. J Int Med Res 34(2): 129-139.

15. Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. (2010) Simvastatin in the treatment of asthma: lack of steroid-sparing effect. Thorax 65(10): 891-896.

16. Dahl R, Nielsen L, Kips J, Foresi A, Cauwenberge P, Tudoric N, et al. (2005) Intranasal and inhaled fluticasone propionate for pollen‐induced rhinitis and asthma. Allergy 60(7): 875-881.

17. Deykin A, Lazarus SC, Fahy JV, Wechsler ME, Boushey HA, Chinchilli VM, et al. (2005) Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J Allergy Clin Immunol 115(4): 720-727.

18. Duong M, Amin R, Baatjes AJ, Kritzinger F, Qi Y, Meghji Z, et al. (2012) The effect of montelukast, budesonide alone, and in combination on exercise-induced bronchoconstriction. J Allergy Clin Immunol 130(2): 535-539.

19. Duong M, Gauvreau G, Watson R, Obminski G, Strinich T, Evans M, et al. (2007) The effects of inhaled budesonide and formoterol in combination and alone when given directly after allergen challenge. J Allergy Clin Immunol 119(2): 322-327.

20. Fagan HB, Harwood M. (2003) Use of sputum eosinophil count decreases asthma exacerbations. J Fam Pract 52(5): 353-354.

21. Heijink IH, Kauffman HF, Vellenga E, Veltman-Starkenburg CA, Postma DS, de Monchy JG. (2007) Effect of ciclesonide treatment on allergen-induced changes in T cell regulation in asthma. Int Arch Allergy Immunol 145(2): 111-121.

22. Horiguchi T, Hayashi N, Ohira D, Torigoe H, Ito T, Hirose M, et al. (2006) Usefulness of HFA-BDP for adult patients with bronchial asthma: randomized crossover study with fluticasone. J Asthma 43(7): 509-512.

23. Horiguchi T, Tachikawa S, Kondo R, Miyazaki J, Shiga M, Hirose M, et al. (2007) Comparative evaluation of the leukotriene receptor antagonist pranlukast versus the steroid inhalant fluticasone in the therapy of aged patients with mild bronchial asthma. Arzneimittelforschung 57(02): 87-91.

24. Hoshino M, Ohtawa J. (2012) Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration 83(6): 520-528.

25. Janson SL, Fahy JV, Covington JK, Paul SM, Gold WM, Boushey HA. (2003) Effects of individual self-management education on clinical, biological, and adherence outcomes in asthma. Am J Med 115(8): 620-626.

26. Jayaram L, Pizzichini M, Cook R, Boulet L, Lemiere C, Pizzichini E, et al. (2006) Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Resp J 27(3): 483-494.

27. Kawayama T, O'Byrne P, Watson R, Killian K, Duong M, Yoshida M, et al. (2006) Effects of inhaled ciclesonide on circulating T‐helper type 1/T‐helper type 2 cells in atopic asthmatics after allergen challenge. Clin Exp Allergy 36(11): 1417-1424.

28. Koopmans JG, Lutter R, Jansen HM, van der Zee, Jaring S. (2005) Adding salmeterol to an inhaled corticosteroid reduces allergen-induced serum IL-5 and peripheral blood eosinophils. J Allergy Clin Immunol 116(5): 1007-1013.

29. Lemière C, Tremblay C, FitzGerald M, Aaron SD, Leigh R, Boulet L, et al. (2011) Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic subjects. Can Respir J 18(5): 278-282.

30. Luijk B, Van Den Berge M, Kerstjens H, Postma D, Cass L, Sabin A, et al. (2008) Effect of an inhaled adenosine A2A agonist on the allergen‐induced late asthmatic response. Allergy 63(1): 75-80.

31. Ohbayashi H, Adachi M. (2008) Hydrofluoroalkane-beclomethasone dipropionate effectively improves airway eosinophilic inflammation including the distal airways of patients with mild to moderate persistent asthma as compared with fluticasone propionate in a randomized open double-cross study. Allergol Int 57(3): 231-239.

32. Ohbayashi H, Shibata N, Hirose T, Adachi M. (2009) Additional effects of pranlukast in salmeterol/fluticasone combination therapy for the asthmatic distal airway in a randomized crossover study. Pulm Pharmacol Ther 22(6): 574-579.

33. Ohbayashi H, Adachi M, Ichinose M, Ohta K, Kokubu F, Sano Y, et al. (2007) A multicenter, open-label, randomized comparison of suppressive effects on asthmatic inflammation of lower airways and improved effects on health-related QOL between HFA-BDP and fluticasone propionate. Arerugi 56(6): 577-586.

34. Palmqvist M, Bruce C, Sjöstrand M, Arvidsson P, Lötvall J. (2005) Differential effects of fluticasone and montelukast on allergen‐induced asthma. Allergy 60(1): 65-70.

35. Pavord ID, Jeffery PK, Qiu Y, Zhu J, Parker D, Carlsheimer Å, et al. (2009) Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol. J Allergy Clin Immunol 123(5): 1083-1089.

36. Pavord I, Woodcock A, Parker D, Rice L, SOLTA Study Group. (2007) Salmeterol plus fluticasone propionate versus fluticasone propionate plus montelukast: a randomised controlled trial investigating the effects on airway inflammation in asthma. Respir Res 8(1): 67.
37. Peroni D, Bodini A, Miraglia Del Giudice M, Loiacono A, Baraldi E, Boner A, et al. (2005) Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens. Allergy 60(2): 206-210.

38. Subbarao P, Dorman SC, Rerecich T, Watson RM, Gauvreau GM, O'Byrne PM. (2005) Protection by budesonide and fluticasone on allergen-induced airway responses after discontinuation of therapy. J Allergy Clin Immunol 115(4): 745-750.

39. ten Brinke A, Zwinderman AH, Sterk PJ, Rabe KF, Bel EH. (2004) “Refractory” eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids. Am J Respir Crit Care Med 170(6): 601-605.

40. Tien Nguyen L, Lim S, Oates T, Chung KF. (2005) Increase in airway neutrophils after oral but not inhaled corticosteroid therapy in mild asthma. Respir Med 99(2): 200-207.

41. Hoshino M. (2010) Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma. Allergol Int 59(1): 59-66.

42. Green R, Brightling C, McKenna S, Hargadon B, Neale N, Parker D, et al. (2006) Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness. Eur Respir J 27(6): 1144-1151.

43. Kelly MM, O'Connor TM, Leigh R, Otis J, Gwozd C, Gauvreau GM, et al. (2010) Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma. J Allergy Clin Immunol 125(2): 349-356.

44. Hoshino M, Ohtawa J. (2012) Effects of budesonide/formoterol combination therapy versus budesonide alone on airway dimensions in asthma. Respirology 17(4): 639-646.

45. Basyigit I, Yildiz F, Kacar Ozkara S, Boyaci H, Ilgazli A, Ozkarakas O. (2004) Effects of different anti‐asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics. Respirology 9(4): 514-520.

46. Hauber H, Taha R, Bergeron C, Migounov V, Hamid Q, Olivenstein R. (2006) Effects of hydrofluoroalkane and dry powder-formulated corticosteroids on sputum inflammatory markers in asthmatic patients. Can Respir J 13(2): 73.

47. Barnes N, Laviolette M, Allen D, Flood-Page P, Hargreave F, Corris P, et al. (2007) Effects of montelukast compared to double dose budesonide on airway inflammation and asthma control. Respir Med 101(8): 1652-1658.

48. Rytilä P, Pelkonen A, Metso T, Nikander K, Haahtela T, Turpeinen M. (2004) Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate. Allergy 59(8): 839-844.

49. Menezes MB, Teixeira AL, Vianna EO. (2008) Inflammatory and functional effects of increasing asthma treatment with formoterol or double dose budesonide. Respir Med 102(10): 1385-1391.

50. Perng D, Huang H, Lee Y, Perng R. (2004) Leukotriene Modifier vs Inhaled Corticosteroid in Mild-to-Moderate Asthma: Clinical and Anti-inflammatory Effects. Chest 125(5): 1693-1699.

51. Echevarria EMU, Maldonado CA, Echevaria AMU, Aoki A. (2011) Neutrophil predominance in induced sputum from asthmatic patients. Therapeutic implications and role of clara cell 16-KD protein. Medicana (B Aires) 71(4): 343-349.

52. Strauch E, Moske O, Thoma S. (2003) A randomized controlled trial on the effect of montelukast on sputum eosinophil cationic protein in children with corticosteroid-dependent asthma. Pediatr Res 54(2): 198-203.

53. Maneechotesuwan K, Ekjiratrakul W, Kasetsinsombat K, Wongkajornsilp A, Barnes PJ. (2010) Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase. J Allergy Clin Immunol 126(4): 754-762.

54. van Dalen CJ, Aldridge RE, Chan T, Senthilmohan R, Hancox RJ, Cowan JO, et al. (2009) Bromotyrosines in sputum proteins and treatment effects of terbutaline and budesonide in asthma. Ann Allergy Asthma Immunol 103(4): 348-353.

55. Boulet L, Lemière C, Gauvreau G, Olivenstein R, Lougheed D, Paradis B, et al. (2009) Safety, pharmacodynamics and pharmacokinetics of TPI 1020 in smokers with asthma. Respir Med 103(8): 1159-1166.

56. Maneechotesuwan K, Essilfie-Quaye S, Kharitonov SA, Adcock IM, Barnes PJ. (2007) Loss of control of asthma following inhaled corticosteroid withdrawal is associated with increased sputum interleukin-8 and neutrophils. Chest 132(1): 98-105.

57. Belda J, Margarit G, Martínez C, Bellido-Casado J, Casan P, Torrejón M, et al. (2007) Anti-inflammatory effects of high-dose inhaled fluticasone versus oral prednisone in asthma exacerbations. Eur Respir J 30(6): 1143-1149.

58. Kawayama T, Kinoshita T, Imaoka H, Gauvreau GM, O'Byrne PM, Aizawa H. (2008) Effects of inhaled fluticasone propionate on CTLA‐4‐positive CD4 CD25 cells in induced sputum in mild asthmatics. Respirology 13(7): 1000-1007.

59. Hoshino M, Handa H, Miyazawa T. (2009) Effects of salmeterol and fluticasone propionate combination versus fluticasone propionate on airway function and eosinophilic inflammation in mild asthma. Allergol Int 58: 357-363.

60. Hozawa S, Haruta Y, Terada M, Yamakido M. (2009) Effects of the addition of Beta2-agonist tulobuterol patches to inhaled corticosteroid in patients with asthma. Allergol Int 58: 509-518.

61. Giannini D, Di Franco A, Tonelli M, Bartoli M, Carnevali S, Cianchetti S, et al. (2003) Fifty μg bid of inhaled fluticasone propionate (FP) are effective in stable asthmatics previously treated with a higher dose of FP. Respir Med 97(5): 463-467.

62. Kanazawa H, Nomura S, Asai K. (2007) Roles of angiopoietin-1 and angiopoietin-2 on airway microvascular permeability in asthmatic patients. Chest 131(4): 1035-1041.

63. Di Franco A, Bacci E, Laura Bartoli M, Cianchetti S, Dente FL, Taccola M, et al. (2006) Inhaled fluticasone propionate is effective as well as oral prednisone in reducing sputum eosinophilia during exacerbations of asthma which do not require hospitalization. Pulm Pharmacol Ther 19(5): 353-360.

64. Koopmans JG, Lutter R, Jansen HM, van der Zee, Jaring S. (2006) Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma. Thorax 61(4): 306-313.

65. Jayaram L, Pizzichini E, Lemiere C, Man S, Cartier A, Hargreave F, et al. (2005) Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast. Thorax 60(2): 100-105.

66. Foresi A, Mastropasqua B, Chetta A, D’Ippolito R, Testi R, Olivieri D, et al. (2005) Step-down compared to fixed-dose treatment with inhaled fluticasone propionate in asthma. Chest 127(1): 117-124.

67. Bacci E, Latorre M, Cianchetti S, Bartoli M, Costa F, Di Franco A, et al. (2012) Transient sputum eosinophilia may occur over time in non‐eosinophilic asthma and this is not prevented by salmeterol. Respirology 17(8): 1199-1206.

68. Wilson A, Duong M, Pratt B, Dolovich M, O'Byrne P. (2006) Anti‐inflammatory effects of once daily low dose inhaled ciclesonide in mild to moderate asthmatic patients. Allergy 61(5): 537-542.

69. Gauvreau GM, Boulet LP, Postma DS, Kawayama T, Watson RM, Duong M, et al. (2005) Effect of low-dose ciclesonide on allergen-induced responses in subjects with mild allergic asthma. J Allergy Clin Immunol 116(2): 285-291.

70. Erin EM, Zacharasiewicz AS, Nicholson GC, Tan AJ, Neighbour H, Engelstätter R, et al. (2008) Rapid Effect of Inhaled Ciclesonide in AsthmaA Randomized, Placebo-Controlled Study. Chest 134(4): 740-745.

71. van den Berge M, Arshad S, Ind P, Magnussen H, Hamelmann E, Kanniess F, et al. (2009) Similar efficacy of ciclesonide versus prednisolone to treat asthma worsening after steroid tapering. Respir Med 103(8): 1216-1223.

72. Duong M, Subbarao P, Adelroth E, Obminski G, Strinich T, Inman M, et al. (2008) Sputum eosinophils and the response of exercise-induced bronchoconstriction to corticosteroid in asthma. Chest 133(2): 404-411.

73. Negro RD, Micheletto C, Tognella S, Turco P, Rossetti A, Cantini L. (2003) Assessment of inhaled BDP‐dose dependency of exhaled nitric oxide and local and serum eosinophilic markers in steroids‐naive nonatopic asthmatics. Allergy 58(10): 1018-1022.

74. Wang Y, Wang C, Lin K, Qian G, Zhuo W, Li S, et al. (2005) Comparison of inhaled corticosteroid combined with theophylline and double‐dose inhaled corticosteroid in moderate to severe asthma. Respirology 10(2): 189-195.

75. Lazarus SC, Chinchilli VM, Rollings NJ, Boushey HA, Cherniack R, Craig TJ, et al. (2007) Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Crit Care Med 175(8):783-790.

76. Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, et al. (2007) Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 62(12): 1043-1049.

77. Nelson HS, Gallegos CM, Silveira LJ, Newell JD, Gelfand EW. (2009) Effect of the inhaled corticosteroid mometasone on small airway patency in patients with asthma. Allerg Asthma Proc 30(3): 284-92.

78. Davies AR, Hancox RJ. (2013) Induced sputum in asthma: diagnostic and therapeutic implications. Curr Opin Pulm Med 19: 60-65.

79. Condemi JJ, Chervinsky P, GoldsteinMF, Ford LB, Berger WE, Ayars GH, et al. (1997) Fluticasone propionate powder administered through Diskhaler versus triamcinolone acetonide aerosol administered through metered-dose inhaler in patients with persistent asthma. J Allergy Clin Immunol 100: 467-474.

80. Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, et al. (2001) Long-acting b2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA 285: 2583-2593.