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. 2011 Sep 7;2011(9):CD009039.
doi: 10.1002/14651858.CD009039.pub2.

The effect of adding inhaled corticosteroids to tiotropium and long-acting beta(2)-agonists for chronic obstructive pulmonary disease

Charlotta Karner  1 , Christopher J Cates
Affiliations

The effect of adding inhaled corticosteroids to tiotropium and long-acting beta(2)-agonists for chronic obstructive pulmonary disease

Charlotta Karner et al. Cochrane Database Syst Rev. .

Abstract

Background: Long-acting bronchodilators comprising long-acting beta(2)-agonists and the anticholinergic agent tiotropium are commonly used, either on their own or in combination, for managing persistent symptoms of chronic obstructive pulmonary disease. Patients with severe chronic obstructive pulmonary disease who are symptomatic and who suffer repeated exacerbations are recommended to add inhaled corticosteroids to their bronchodilator treatment. However, the benefits and risks of adding inhaled corticosteroid to tiotropium and long-acting beta(2)-agonists for the treatment of chronic obstructive pulmonary disease are unclear.

Objectives: To assess the relative effects of adding inhaled corticosteroids to tiotropium and long-acting beta(2)-agonists treatment in patients with chronic obstructive pulmonary disease.

Search strategy: We searched the Cochrane Airways Group Specialised Register of trials (February 2011) and reference lists of articles.

Selection criteria: We included parallel group, randomised controlled trials of three months or longer comparing inhaled corticosteroid and long-acting beta(2)-agonist combination therapy in addition to inhaled tiotropium against tiotropium and long-acting beta(2)-agonist treatment for patients with chronic obstructive pulmonary disease (COPD).

Data collection and analysis: Two review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials.

Main results: One trial (293 patients) was identified comparing tiotropium in addition to inhaled corticosteroid and long-acting beta(2)-agonist combination therapy to tiotropium plus long-acting beta(2)-agonist. The study was of good methodological quality, however it suffered from high and uneven withdrawal rates between the treatment arms. There is currently insufficient evidence to know how much difference the addition of inhaled corticosteroids makes to people who are taking tiotropium and a long-acting beta(2)-agonist for COPD.

Authors' conclusions: The relative efficacy and safety of adding inhaled corticosteroid to tiotropium and a long-acting beta(2)-agonist for chronic obstructive pulmonary disease patients remains uncertain and additional trials are required to answer this question.

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Conflict of interest statement

None known

Update of

  • doi: 10.1002/14651858.CD009039

References

References to studies included in this review

Aaron 2007 {published data only}
    1. Aaron SD, Vandemheen K, Ferguson D, FitzGerald M, Maltais F, Boureau J, et al. The Canadian optimal therapy of COPD trial: Design, organization and patient recruitment. Canadian Respiratory Journal 2004;11(8):581‐5. - PubMed
    1. Aaron SD, Vandemheen KL, Fergusson D, Maltais F, Bourbeau J, Goldstein R, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone‐salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. [see comment] [summary for patients in Annals of Internal Medicine 2007 Apr 17;146(8):I12; PMID: 17310044]. Annals of Internal Medicine 2007;146(8):545‐55. - PubMed
    1. Kaplan A. Effects of tiotropium combined with either salmeterol or salmeterol/fluticasone in moderate to severe COPD. Primary Care Respiratory Journal 2007;16(4):258‐60. - PMC - PubMed
    1. Najafzadeh M, Marra CA, Sadatsafavi M, Aaron SD, Sullivan SD, Vandemheen KL, et al. Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD. Thorax 2008;63(11):962‐7. - PubMed
    1. Roisman G. Tiotropium in combination with placebo, salmeterol, or fluticasone‐salmeterol for treatment of chronic obstructive pulmonary disease. A randomized trial. Revue de Pneumologie Clinique 2007;63(6):390‐1. - PubMed

References to studies excluded from this review

Golabi 2006 {published data only}
    1. Golabi P, Topaloglu N, Karakurt S, Celikel T. Effects of tiotropium and salmeterol/fluticasone combination on lung hyperinflation dyspnea and exercise tolerance in COPD [Abstract]. European Respiratory Journal. 2006; Vol. 28, issue Suppl 50:33s [E304].
Hara 2007 {published data only}
    1. Hara K, Kurashima K, Tokunaga D, Ueno M, Aoyagi K, Isobe Z, et al. Single blind comparison of tiotropium and salmeterol plus fluticasone propionate of treatment in patients with chronic obstructive pulmonary disease (COPD) [Abstract]. American Thoracic Society International Conference, May 18‐23, 2007, San Francisco, California, USA. 2007:Poster #A1.
Mittmann 2010 {published data only}
    1. Mittmann N, Hernandez P, Mellström C, Brannman L, Welte T. Cost‐effectiveness of budesonide/formoterol added to tiotropium in COPD patients in Canada, Australia and Sweden [Abstract]. European Respiratory Society Annual Congress, Barcelona, Spain, September 18‐22. 2010:[5183].
Singh 2008 {published data only}
    1. Singh D, Brooks J, Hagan G, Cahn A, O'Connor BJ. Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 2008;63(7):592‐8. - PubMed
    1. Singh D, Hagan G, Cahn A, Leonard TB, Riley JH, O'Connor BJ. Individual and combined responses to salmeterol/fluticasone propionate combination (SFC) and tiotropium (Tio) shown in a COPD clinical trial [Abstract]. American Thoracic Society International Conference, May 16‐21, 2008, Toronto. 2008:A648[#F10].

Additional references

Agarwal 2010
    1. Agarwal R, Aggarwal AN, Gupta D, Jindal SK. Inhaled corticosteroids vs placebo for preventing COPD exacerbations. Chest 2010;137(2):318‐25. - PubMed
Akazawa 2008
    1. Akazawa M, Hayflinger DC, Stanford RH, Blanchette CM. Economic assessment of initial maintenance therapy for chronic obstructive pulmonary disease. The American Journal of Managed Care 2008;14(7):438‐48. - PubMed
Appleton 2006
    1. Appleton S, Poole P, Smith B, Veale A, Lasserson TJ, Chan MMK, et al. Long‐acting beta2‐agonists for poorly reversible chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD001104.pub2] - DOI - PMC - PubMed
Barr 2005
    1. Barr RG, Bourbeau J, Camargo Carlos A. Tiotropium for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD002876.pub2] - DOI - PMC - PubMed
Beeh 2010
    1. Beeh KM, Beier J. The short, the long, and the "ultra‐long": Why duration of bronchodilator action matters in chronic obstructive pulmonary disease. Advances in Therapy 2010;27(3):150‐9. - PubMed
Berger 2008
    1. Berger WE, Nadel JA. Efficacy and safety of formoterol for the treatment of chronic obstructive pulmonary disease. Respiratory Medicine 2008;102(2):173‐88. - PubMed
Briggs 2010
    1. Briggs AH, Glick HA, Lozano‐Ortega G, Spencer M, Calverley PMA, Jones PW, et al. Is treatment with ICS and LABA cost‐effective for COPD? Multinational economic analysis of the TORCH study. European Respiratory Journal 2010;35(3):532‐9. - PubMed
Calverley 2007
    1. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. The New England Journal of Medicine 2007;356(8):775‐89. - PubMed
Dalal 2010
    1. Dalal AA, Charles M, Petersen HV, Roberts MH, Blanchette CM, Manavi‐Zieverink K. Cost‐effectiveness of combination fluticasone propionate‐salmeterol 250/50 microg versus salmeterol in severe COPD patients. International Journal of Chronic Obstructive Pulmonary Disease 2010;5:179‐87. - PMC - PubMed
Effing 2007
    1. Effing T, Monninkhof EEM, Valk PPDLPM, Zielhuis GGA, Walters EH, Palen JJ, et al. Self‐management education for patients with chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD002990.pub2] - DOI - PubMed
GOLD
    1. Global Initiative for Chronic Obstructive Lung Disease. http://www.goldcopd.com [Accessed 14th December 2009].
Higgins 2011
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration. Available from www.cochrane‐handbook.org, 2011.
Hutchinson 2010
    1. Hutchinson A, Brand C, Irving L, Roberts C, Thompson P, Campbell D. Acute care costs of patients admitted for management of chronic obstructive pulmonary disease exacerbations: contribution of disease severity, infection and chronic heart failure. Internal Medicine Journal 2010;40(5):364‐71. - PubMed
Johnson 1998
    1. Johnson M. The beta‐adrenoceptor. American Journal of Respiratory and Critical Care Medicine 1998;158(5 Pt 3):S146‐53. - PubMed
Lacasse 2006
    1. Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/14651858.CD003793.pub2] - DOI - PubMed
Najafzadeh 2008
    1. Najafzadeh M, Marra CA, Sadatsafavi M, Aaron SD, Sullivan SD, Vandemheen KL, et al. Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD. Thorax 2008;63(11):962‐7. - PubMed
Nannini 2007
    1. Nannini L, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid and long‐acting beta‐agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD003794.pub3] - DOI - PMC - PubMed
Nannini 2007a
    1. Nannini Luis J, Cates Christopher J, Lasserson Toby J, Poole P. Combined corticosteroid and long‐acting beta‐agonist in one inhaler versus long‐acting beta‐agonists for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006829] - DOI - PubMed
NICE 2010
    1. National Clinical Guideline Centre. Chronic obstructive pulmonary disease: Management of chronic obstructive pulmonary disease in adults in primary and secondary care. Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre, 2010. [URL: http://guidance.nice.org.uk/CG101/Guidance/pdf/English]
Proskocil 2005
    1. Proskocil BJ, Fryer AD. Beta2‐agonist and anticholinergic drugs in the treatment of lung disease. Proceedings of the American Thoracic Society 2005;2(4):305‐10; discussion 311‐2. - PubMed
Review Manager 5 [Computer program]
    1. The Nordic Cochrane Centre; Cochrane Collaboration. Review Manager (RevMan) Version 5. Copenhagen: The Nordic Cochrane Centre; Cochrane Collaboration, 2008.
Rodrigo 2008
    1. Rodrigo GJ, Nannini LJ, Rodríguez‐Roisin R. Safety of long‐acting β‐agonists in stable COPD: A systematic review. Chest 2008;133(5):1079‐87. - PubMed
Rodrigo 2009
    1. Rodrigo GJ, Castro‐Rodriguez JA, Plaza V. Safety and efficacy of combined long‐acting beta‐agonists and inhaled corticosteroids vs long‐acting beta‐agonists monotherapy for stable COPD: a systematic review. Chest 2009;136(4):1029‐38. - PubMed
SGRQ‐C manual 2008
    1. Jones P. St George's Respiratory Questionnaire for COPD Patients (SGRQ‐C). St George’s, University of London 2008.
Singh 2010
    1. Singh S, Loke YK. An overview of the benefits and drawbacks of inhaled corticosteroids in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease 2010;5:189‐95. - PMC - PubMed
Tanaka 2005
    1. Tanaka Y, Horinouchi T, Koike K. New insights into beta‐adrenoceptors in smooth muscle: distribution of receptor subtypes and molecular mechanisms triggering muscle relaxation. Clinical and Experimental Pharmacology and Physiology 2005;32(7):503‐14. - PubMed
Tashkin 2008
    1. Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M, UPLIFT Study Investigators. A 4‐year trial of tiotropium in chronic obstructive pulmonary disease. The New England Journal of Medicine 2008;359(15):1543‐54. - PubMed
van der Meer 2001
    1. Meer RM, Wagena E, Ostelo RWJG, Jacobs AJE, Schayck O. Smoking cessation for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/14651858.CD002999] - DOI - PMC - PubMed
Wallukat 2002
    1. Wallukat G. The beta‐adrenergic receptors. Herz 2002;27(7):683‐90. - PubMed
Welsh 2010
    1. Welsh EJ, Cates CJ, Poole P. Combination inhaled steroid and long‐acting beta2‐agonist versus tiotropium for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2010, Issue 5. [DOI: 10.1002/14651858.CD007891] - DOI - PubMed
WHO
    1. World Health Organization. Chronic Respiratory Diseases. www.who.int.
Yang 2007
    1. Yang IA, Fong K, Sim EHA, Black PN, Lasserson TJ. Inhaled corticosteroids for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2007, Issue 2. [DOI: 10.1002/14651858.CD002991.pub2] - DOI - PubMed

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