Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterised by progressive airflow limitation that is at best partially reversible. Despite the lack of reversibility patients with stable often report symptomatic improvement with short-acting beta-2 bronchodilator medication. OBJECTIVES: To determine the clinical effectiveness and assess the adverse effects of regular treatment with short-acting beta-2 agonists bronchodilators in patients with stable COPD. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group database. In addition, reference lists of review articles and retrieved studies were searched for other potentially relevant citations. SELECTION CRITERIA: Randomised controlled trials of at least one week in duration that compared treatment with inhaled short-acting beta-2 agonists delivered by metered dose inhaler or nebuliser with placebo in patients with stable COPD. DATA COLLECTION AND ANALYSIS: Data extraction and study quality assessment were performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. The data were analysed using the Cochrane Review Manager 4.0.4. MAIN RESULTS: Thirteen studies were included. All used a cross-over design and were of high quality. Post-bronchilator spirometry performed at the end of the study period showed a significant increase in FEV1 compared to placebo; weighted mean difference (WMD) =0.14 L; 95% Confidence Interval (CI) 0.04 to 0.25. This effect was only seen in studies in which the drug was delivered by metered dose inhaler. Post-bronchodilator morning and evening PEFR were significantly better during active treatment than during placebo; WMD=29.2 L/min; 95%CI 0.3 to 58.1 & WMD = 36.8 L/min; 95%CI: 2.6 to 70.9 respectively. A significant improvement in daily breathlessness score was observed during treatment with beta-2 agonist when compared to placebo; standardised mean difference (SMD) =1.33; 95%CI: 1.0 to 1.65. There was no improvement in exercise performance. The risk of dropping out of the study (ie treatment failure) when on treatment with placebo was almost twice that of patients on treatment with beta-2 agonists; Relative Risk =0.49; 95%CI 0.33-0.73). Patients preferred beta-2 agonist therapy more frequently than placebo; Odds Ratio = 9.04; 95%CI 4.6 to 17.61). No studies reported serious side effects during treatment with inhaled beta-agonists, but none were of sufficient size or length to allow any meaningful information on long-term occurrence of side effects. REVIEWER'S CONCLUSIONS: Short-acting beta-2 agonists delivered by metered dose inhaler on a regular basis improve lung function. Breathlessness but not exercise performance are also improved. There are insufficient data to provide reliable information on long-term adverse effects. Use of these drugs as first line agents for symptomatic treatment of COPD is supported by this review.