A randomized prospective study to compare the efficacy and safety of budesonide plus formoterol and tiotropium plus formoterol in patients having mild to moderate chronic obstructive pulmonary disease

Chandra Veer Singh, Aditya Kumar Gautam, Alok Dixit, Amit Vikram Singh, Sandeep Kumar Singh


Background: Chronic obstructive pulmonary disease (COPD) is a leading respiratory illness affecting the quality of lives around the world. The present study aims to compare the efficacy and safety of combination of inhaled corticosteroid (ICS) and long acting β2 agonist (LABA) with long acting β2 agonist and long acting muscarinic antagonist (LAMA) in treatment of mild to moderate COPD in a tertiary care hospital.

Methods: Total 132 patients with COPD were recruited on the basis of inclusion and exclusion criteria for 8 weeks study from outpatient clinic. A complete pulmonary examination including spirometry examination was done to rule out severe and very severe forms of COPD. Spirometry was performed at the time of recruitment for evaluation of forced expiratory volume in one second (FEV1) and measurement of SpO2 at the time of recruitment at 2 weeks and 8 weeks. Appropriate statistical methods were used to compare the qualitative and quantitative primary and secondary efficacy end points, p value <0.05 was considered significant.

Results: On analysis, there was a significant difference (p<0.05) was observed in FEV1 and SpO2 from baseline in ICS plus LABA group (n=66). A similarly significant difference (p<0.05) was observed in LABA and LAMA group (n=66). On comparison between ICS plus LABA and LABA plus LAMA no significant difference in FEV1 and SpO2 was observed between the two groups.  More adverse drug reactions were observed in ICS plus LABA group than LAMA plus LABA group.

Conclusions: Combination of ICS and LABA combination is as effective as combination of LABA and LAMA in patients having mild to moderate COPD. However, LABA and LAMA combination is preferable because it is associated with fewer side effects.


COPD, Spirometry, FEV1, Oxygen saturation

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Chronic obstructive pulmonary disease (COPD). World Health Organization. Available at: Accessed on 25 November 2020

Jindal SK, Aggarwal AN, Gupta D. A review of population studies from India to estimate national burden of chronic obstructive pulmonary disease and its association with smoking. India J Chest Dis Allied Sci. 2001;43:139-47

ICMR-PHFI-IHME. India : Health of the Nation’s States; 2017

MacNee W. Pathology, pathogenesis, and pathophysiology. Bio Med J. 2006;332(7551):1202-4.

Chesnutt AN, Chesnutt MS, Prendergast TJ, Chronic Obstructive pulmonary disease. In: Maxine A. Papadakis, Stephen J. Mcphee, Associate editor Michel W. Rabow, Pulmonary disorders, 57th edition California; Mc Graw Hill Education. 2018; 263.

New GOLD global strategy for diagnosis, management and prevention of COPD. European Respiratory Society. Available from: Accessed on 20 November 2020.

Montuschi P. Pharmacological treatment of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulm Sisease. 2006;1(4):409.

Rabe KF. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am. J. Respire. 2007;176(6):532-55.

Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long acting beta (2) agonist in one inhaler versus long acting beta (2) agonist for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;9(9):CD006829.

Celli BR, Tashkin DP, Rennard SI. Bronchodilator responsiveness and onset of effect with budesonide/formoterol pMDI in COPD. Respir Med. 2011;105:1176–88

Ferguson GT, Tashkin DP, Skärby T. Effect of budesonide/formoterol pressurized metered-dose inhaler on exacerbations versus formoterol in chronic obstructive pulmonary disease: The 6-month, randomized RISE (Revealing the Impact of Symbicort in reducing Exacerbations in COPD) study. Respir Med. 2017;132:31–41.

Lofdahl CG, Ericsson A, Svensson K, Andreasson E. Cost effectiveness of budesonide/formoterol in a single inhaler for COPD compared with each monocomponent used alone. Pharmacoeconomics. 2005;23:365–75.

Tashkin DP, Varghese ST. Combined treatment with formoterol and tiotropium is more efficacious than treatment with tiotropium alone in patients with chronic obstructive pulmonary disease, regardless of smoking status, inhaled corticosteroid use, baseline severity, or gender. Pulm Pharmacol Ther. 2011;24(1):147-52.

Johnson M. Beta-2 agonists. Chron Obstruct Pulm Disease. 2007:669-84.

Cazzola M. The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD. Pulm Pharmacol Ther. 2004;17(1):35-9.

Rogliani P, Matera MG, Ora J. The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis. Int J Chron Obstruct Pulmon Dis. 2017;12:3469-85.

Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandström T, Taylor AF, et al. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respirat Medic. 2013;1(3):199-209.

Aaron SD, Fergusson D, Marks GB, Suissa S, Vandemheen KL, Doucette S, et al. Counting, analysing and reporting exacerbations of COPD in randomised controlled trials. Thorax. 2008;63(2):122-8.

Kruis AL, Ställberg B, Jones RC. Primary care COPD patients compared with large pharmaceutically-sponsored COPD studies: an UNLOCK validation study. PLoS One. 2014;9(3):e90145.

Suissa S, Dell’Aniello S, Ernst P. Comparative effectiveness and safety of LABA-LAMA vs LABA-ICS treatment of COPD in real-world clinical practice. Chest. 2019;155(6):1158-65.