Combined corticosteroid and longacting beta-agonist in one inhaler for chronic obstructive pulmonary disease

  • Review
  • Intervention


  • L Nannini,

  • CJ Cates,

  • TJ Lasserson,

  • P Poole

Dr Luis Javier Nannini, Head, Pulmonary Section, Hospital G. Baigorria, Ruta 11 Y Jm Estrada, G. Baigorria, Santa Fe - Rosario, 2152, ARGENTINA.



Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler is intended to facilitate adherence to medication regimens, and to improve efficacy.


To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to placebo or the individual components, in the treatment of adults with chronic obstructive pulmonary disease.

Search strategy

We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2005. Searches of LILACS and CENTRAL were also carried out.

Selection criteria

Studies were included if they were randomised and double-blind. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with either component preparation or placebo.

Data collection and analysis

Two reviewers independently assessed trial quality and extracted data. The primary outcome was exacerbations.

Main results

Six randomised trials with 4118 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were used. Combination treatment was more effective than placebo for mean exacerbation rates, quality of life and lung function. No trials were found comparing the combination of drugs in a single inhaler with the same drugs both given in separate inhalers.
Exacerbations: Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments in one large study. There was no significant difference when budesonide/formoterol was compared with budesonide. Budesonide/formoterol was more effective than formoterol in reducing exacerbations (Rate ratio: 0.78 [0.68 to 0.90], two studies). A pooled analysis of both combination therapies indicated that exacerbations were less frequent when compared with either placebo or long-acting beta-agonist (versus placebo Rate ratio: 0.76 [0.68, 0.84], three studies, versus beta-agonist, Rate ratio: 0.85 [0.77, 0.95], three studies), but not when compared with steroid. The clinical impact of this effect depends on the frequency of exacerbations experienced by patients. One full exacerbation was prevented for every two to four years of treatment in the type of patients included in the trials.
Quality of Life: There were conflicting findings in quality of life and symptoms when fluticasone/salmeterol was compared with inhaled steroids alone (three studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist in quality of life scores (three studies). Budesonide/formoterol improved symptoms when compared with budesonide but not with formoterol. There were conflicting findings in quality of life scores when budesonide/formoterol was compared with component inhaled corticosteroid or beta-agonist. These may be accounted for by different study design.
Lung Function: Treatment with either combination led to small, significant differences in lung function compared with component steroid medication. Fluticasone/salmeterol led to small improvements in FEV1 compared with salmeterol, but budesonide/formoterol treatment did not increase FEV1 significantly when compared with formoterol.

Authors' conclusions

Compared with placebo, combination therapy led to clinically meaningful differences in quality of life, symptoms and exacerbations. However, there were conflicting results when the different combination therapies were compared with the mono-components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.

Plain language summary

Plain language summary

Evidence shows that combination therapy can reduce exacerbations and improve quality of life in people with chronic obstructive pulmonary disease (COPD) over placebo treatment

Combinations of two classes of medication in one inhaler have been developed to treat people with COPD as it is thought that this approach may make it easier to take the medication than using separate inhalers. Two types of combined inhaler exist currently: budesonide/formoterol (BDF - 'Symbicort'), and fluticasone/salmeterol (FPS - 'Advair' or 'Seretide'). The results of the studies showed that BDF and FPS were effective and reduced the frequency of flare ups compared with dummy medication to a level of three quarters of the previous rates, with one exacerbation prevented every two to four years in the participants in the clinical trials. When the combination treatment was compared with one of the component drugs given as single treatments there was some meaningful benefit in quality of life for BDF and FPS in comparison to the inhaled steroid component alone. BDF was better than its component long-acting beta-agonist at reducing the frequency of flare-ups, but FPS did not show a significant advantage over long-acting beta-agonist in one large study. FPS led to improvements in lung function compared with its component treatments given singly, and was better than steroid in reducing the need for rescue medication. Future research is required to show whether the drugs work better together or separately, as well as head to head comparisons between the two types of drug.