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In people with COPD, combined long-acting beta2-agonists + inhaled corticosteroids reduce worsening of condition but not hospitalizations

Nannini LJ, Poole P, Milan S, et al. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus inhaled corticosteroids alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013;8:CD006826.

Review question

How effective and safe are combined long-acting beta2-agonist (LABA) plus inhaled corticosteroid (ICS) drugs compared with ICSs alone for chronic obstructive pulmonary disease (COPD)?


COPD is a lung disease that significantly impairs breathing. Smoking is often the cause.

LABAs relax muscles in the airways that carry air to the lungs and make breathing easier. ICSs help control narrowing and inflammation in the lung tubes.

Guidelines for the treatment of COPD recommend combined LABA plus ICS drugs. A combined inhaler makes taking the medication easier and improves effectiveness.

How the review was done

A systematic review of 15 randomized controlled trials included 7814 adults with COPD. Publication period was 2002-2012. Duration of studies ranged from 4 to 156 weeks.

LABA + ICS combinations were fluticasone propionate plus salmeterol, budesonide plus formoterol, and mometasone furoate plus formoterol.

The combination inhaler of an LABA + ICS was compared with an ICS alone.

Outcomes assessed were exacerbations (worsening of symptoms), hospitalizations due to COPD exacerbation, mortality, and pneumonia.

What the researchers found

Exacerbation rates

  • Combined LABA + ICS reduced exacerbation rates significantly compared with an ICS alone. The LABA + ICS group had an average exacerbation rate of 1.05/person/year compared with 1.21/person/year in the ICS alone group.


  • Combined LABA + ICS and ICS alone did not differ for hospitalizations for COPD exacerbations. The LABA + ICS group had a hospitalization rate of 119/1,000 people treated compared with 127/1,000 people treated in the ICS group.


  • Combined LABA + ICS had lower death rates than ICS alone (56/1,000 people treated vs 71/1,000 people treated). A 3-year study of fluticasone propionate plus salmeterol influenced that difference. After removing it, there was no significant difference between the groups.

Lung function

  • Combined LABA + ICS was better than ICS alone for lung function, but the improvement was small.


In people with chronic obstructive pulmonary disease, combined long-acting beta2-agonists plus inhaled corticosteroids improve lung function and reduce exacerbations compared with ICS alone, but do not affect hospitalizations for exacerbations.


Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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