Short-acting beta2-agonists for stable chronic obstructive pulmonary disease

Piersante Sestini, E Renzoni, Stewart Robinson, Phillippa Poole, Felix SF Ram

Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta-2 bronchodilator medication. Short-acting beta-2 bronchodilators are used in the management of both stable and acute exacerbations of COPD. 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. A search was carried out using the Cochrane Airways Group database. In addition, the reference lists of review articles and the randomised controlled trials (RCTs) retrieved in full text were searched for other potentially relevant citations. RCTs of at least one week in duration comparing treatment with inhaled short-acting beta-2 agonists with placebo in patients with stable COPD. Data extraction and study quality assessment was performed independently by two reviewers. Where further or missing data was required, authors of studies were contacted. The data was analysed using the Cochrane Review Manager 4.1. Thirteen studies were included in this review. All studies used a crossover design and were of high quality. Spirometry performed at the end of the study period and after the administration of treatment (post-bronchodilator) showed a slight but significant increase in FEV1 and FVC when compared to placebo (WMD=0.14 L; 95%CI=0.04,0.25 & WMD=0.30 L; 95%CI=0.02,0.58, respectively). In addition, both morning and evening PEFR were significantly better during active treatment than during placebo (WMD=29.17 L/min; 95%CI=0.25,58.09 & WMD=36.75 L/min; 95%CI=2.56,70.94, respectively). A significant improvement in daily breathlessness score was observed during treatment with beta-2 agonist when compared to placebo (SMD=1.33; 95%CI=1.0,1.65). The risk of dropping out of the study (treatment failure) when on treatment with placebo was almost twice that of patients on treatment with beta-2 agonists (RR=0.49; 95%CI=0.33,0.73). Patients preferred beta-2 agonists almost 10 times more frequently to placebo (OR=9.04; 95%CI=4.64,17.61). One study that used a validated questionnaire for 'quality of life' assessment, found highly significant improvements in the scores for dyspnoea (p=0.003) and fatigue (p=0.0003) during treatment with salbutamol. No studies reported serious side effects during treatment with inhaled beta-agonists. However, none of the studies were of sufficient length or size in order to allow any meaningful information on long-term occurrence of side effects. Use of short-acting beta-2 agonists on a regular basis for at least seven days in stable COPD is associated with improvements in post bronchodilator lung function and a decrease in breathlessness. Patients are far more likely to prefer treatment with beta-2 agonists than placebo, and less likely to drop out from such treatment. None of the studies included in this review reported sufficient data or were of sufficient length or size in order to provide reliable information on adverse effects. Therefore large scale, parallel, longer term studies would be needed to investigate the effect of treatment with regular inhaled beta-2 agonists on mortality, disease progression and side effects. Newer, long acting bronchodilators (including long-acting beta-2 agonists) are currently available and they may be more practical and/or effective in these patients. However, this review indicates that treatment with these older, inexpensive drugs is beneficial in patients with COPD.