title: Combined corticosteroid and long-acting beta-agonist in one inhaler versus inhaled steroids for chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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. Two preparations are currently available, fluticasone/salmeterol (FPS) and budesonide/formoterol (BDF).
  
  
  OBJECTIVE
  To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to inhaled corticosteroids, in the treatment of adults with chronic obstructive pulmonary disease.
  
  
  METHODS
  We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007.
  
  
  METHODS
  Studies were included if they were randomised and double-blind. Studies compared combined inhaled corticosteroids and long-acting beta-agonist preparations with the inhaled corticosteroid component.
  
  
  METHODS
  Two reviewers independently assessed trial quality and extracted data. The primary outcome were exacerbations, mortality and pneumonia. Health-related quality of life (measured by validated scales), lung function and side-effects were secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios (OR), and continuous data as mean differences and 95% confidence intervals (CI).
  
  
  RESULTS
  Seven studies of good methodological quality met the inclusion criteria randomising 5708 participants with predominantly poorly reversible, severe COPD. Exacerbation rates were significantly reduced with combination therapies (Rate ratio 0.91; 95% confidence interval 0.85 to 0.97, P = 0.0008). Data from two FPS studies indicated that exacerbations requiring oral steroids were reduced with combination therapy. Data from one large study suggest that there is no significant difference in the rate of hospitalisations. Mortality was also lower with combined treatment (odds ratio 0.77; 95% confidence interval 0.63 to 0.94). Quality of life, lung function and withdrawals due to lack of efficacy favoured combination treatment. Adverse event profiles were similar between the two treatments. No significant differences were found between FPS and BDP in the primary outcomes, but the confidence intervals for the BDP results were wide as smaller numbers of patients have been studied.
  
  
  CONCLUSIONS
  Combination ICS and LABA significantly reduces morbidity and mortality in COPD when compared with mono component steroid. Adverse events were not significantly different between treatments, although evidence from other sources indicates that inhaled corticosteroids are associated with increased risk of pneumonia. Assessment of BDF in larger, long-term trials is required. Dose response data would provide valuable evidence on whether efficacy and safety outcomes are affected by different steroid loads.
authors.affiliation: Hospital G. Baigorria, Pulmonary Section, Ruta 11 Y Jm Estrada, G. Baigorria, Santa Fe - Rosario, Argentina, 2152. nanninilj@cimero.org.ar
authors.forename: L J
authors.initials: LJ
authors.lastname: Nannini
authors.forename: C J
authors.initials: CJ
authors.lastname: Cates
authors.forename: T J
authors.initials: TJ
authors.lastname: Lasserson
authors.forename: P
authors.initials: P
authors.lastname: Poole
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D009330:Nebulizers and Vaporizers; D011014:Pneumonia / Q000139:chemically induced; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D013256:Steroids