Abstract: 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.

Plain-language summary: This review has shown that regular use for at least seven days of inhaled beta-2 medicines that relieve airways obstruction and can also improve the symptoms associated with chronic obstructive pulmonary disease (COPD) in most patients but not all. Patients are far more likely to prefer treatment with these type of medicines than with placebo, and less likely to fail or drop-out from treatment when treated with such medicines. Regular treatment with such inhaled medicines should be reserved for those patients who report symptomatic and clinical benefit from their use. Newer, long acting bronchodilators are currently available, and they may be more practical and/or effective in these patients. However, this review indicates that these older inexpensive drugs are effective in the treatment of COPD.