Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults.Cochrane Database Syst Rev. 2005 Apr 18CD
Consensus statements recommend the addition of long-acting inhaled beta2-agonists only in asthmatic patients who are inadequately controlled on inhaled corticosteroids.
To compare the efficacy of initiating anti-inflammatory therapy using the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS+LABA) as compared to inhaled corticosteroids alone (ICS alone) in steroid-naive children and adults with persistent asthma.
We identified randomised controlled trials (RCTs) through electronic database searches (Cochrane Airways Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL) until April 2004, bibliographies of identified RCTs and correspondence with manufacturers.
RCTs comparing the combination of inhaled corticosteroids and long-acting beta2-agonists (ICS + LABA) to inhaled corticosteroids (ICS) alone in steroid-naive children and adults with asthma.
DATA COLLECTION AND ANALYSIS
Studies were assessed independently by each reviewer for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of asthma exacerbations requiring systemic corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptoms, use of other measures of asthma control, adverse events, and withdrawal rates.
Eighteen trials met the inclusion criteria; nine (totaling 1061 adults) contributed sufficient data to be analysed. Baseline forced expiratory volume in one minute (FEV1) was less than 80% predicted value in four trials and equal to or greater than 80% in five trials. The long-acting beta2-agonists (LABA) formoterol (N=2) or salmeterol (N=7) were added to a dose of at least 800 microg/day of beclomethasone dipropionate (BDP) equivalent of inhaled corticosteroids (ICS) in three trials and to at least 400 microg/day in the six remaining trials. Treatment with ICS plus LABA was not associated with a lower risk of exacerbations requiring oral corticosteroids than ICS alone (relative risk (RR) 1.2; 95% confidence interval (CI) 0.8 to 1.9). FEV1 improved significantly with LABA (weighted mean difference (WMD) 210 ml; 95% CI 120 to 300), as did symptom-free days (WMD 10.74%; 95% CI 1.86 to 19.62), but the change in use of rescue fast-acting beta2-agonists was not significantly different between the groups (WMD -0.4 puff/day, 95% CI -0.9 to 0.1). There was no significant group difference in adverse events (RR 1.1; 95% CI 0.8 to 1.5), withdrawals (RR 0.9; 95% CI 0.6 to 1.2), or withdrawals due to poor asthma control (RR 1.3; 95% CI 0.5 to 3.4).