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Combination inhaled steroid and long-acting beta2-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease

  • Review
  • Intervention




The long-acting bronchodilator tiotropium and single inhaler combination therapy of inhaled corticosteroids and long-acting beta2-agonists are both commonly used for maintenance treatment of chronic obstructive pulmonary disease. Combining these treatments, which have different mechanisms of action, may be more effective than the individual components. However, the benefits and risks of using tiotropium and combination therapy together for the treatment of chronic obstructive pulmonary disease are unclear.


To assess the relative effects of inhaled corticosteroid and long-acting beta2-agonist combination therapy in addition to tiotropium compared to tiotropium or combination therapy alone in patients with chronic obstructive pulmonary disease.

Search methods

We searched the Cochrane Airways Group Specialised Register of trials (July 2010) and reference lists of articles.

Selection criteria

We included parallel, randomised controlled trials of three months or longer, comparing inhaled corticosteroid and long-acting beta2-agonists combination therapy in addition to inhaled tiotropium against tiotropium alone or combination therapy alone.

Data collection and analysis

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

Main results

Three trials (1021 patients) were included comparing tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy to tiotropium alone. The duration, type of combination treatment and definition of outcomes varied. The limited data led to wide confidence intervals and there was no significant statistical difference in mortality, participants with one or more hospitalisations, episodes of pneumonia or adverse events. The results on exacerbations were heterogeneous and were not combined. The mean health-related quality of life and lung function were significantly different when combination therapy was added to tiotropium, although the size of the average benefits of additional combination therapy were small, St George's Respiratory Questionnaire (MD -2.49; 95% CI -4.04 to -0.94) and forced expiratory volume in one second (MD 0.06 L; 95% CI 0.04 to 0.08).

One trial (60 patients) compared tiotropium plus combination therapy to combination therapy alone. The results from the trial were insufficient to draw firm conclusions for this comparison.

Authors' conclusions

To date there is uncertainty regarding the long-term benefits and risks of treatment with tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy on mortality, hospitalisation, exacerbations of COPD and pneumonia. The addition of combination treatment to tiotropium has shown improvements in average health-related quality of life and lung function.

Plain language summary

Are tiotropium plus combination inhalers better than tiotropium or combination inhalers alone for the treatment of COPD?

Chronic obstructive pulmonary disease (COPD) is a lung disease which includes the conditions chronic bronchitis and/or emphysema. COPD is characterised by blockage or narrowing of the airways. The symptoms include breathlessness and chronic cough. COPD is an irreversible disease that is usually brought on by airway irritants, such as smoking or inhaled dust.

Inhalers with bronchodilators and/or anti-inflammatory agents are commonly used to ease symptoms and minimise the long-term decline in health caused by COPD. Examples of these treatments are tiotropium which is a bronchodilator and combination inhalers which contain another type of bronchodilator (long-acting beta-agonists) together with anti-inflammatory agents (steroids). These treatments work in different ways and therefore might be more beneficial if used together.

This review found three studies, involving 1021 patients, comparing the long-term efficacy and side effects of combining tiotropium with combination inhalers for treating COPD. In these studies there were not enough patients and the studies were too different from each other for us to be able to draw any firm conclusions as to whether combining tiotropium with combination inhalers is better or worse than using either drug alone for mortality, hospitalisation and pneumonia. The addition of combination inhalers to tiotropium did show small benefits in quality of life and lung function tests.

In order to better understand the effect of treatment with tiotropium and combination inhaler more long-term studies need to be done.

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