The short, the long and the "ultra-long": why duration of bronchodilator action matters in chronic obstructive pulmonary disease

Abstract

Bronchodilators are the cornerstone of symptomatic treatment for all chronic obstructive pulmonary disease (COPD) severity stages when administered on a regular basis to prevent or reduce symptoms and exacerbations. The principal inhaled bronchodilator treatments are beta-2 agonists and anticholinergics, used singularly or in combination. There is good evidence that regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators. Long-acting agents include the twice-daily beta-2 agonists formoterol and salmeterol, the once-daily anticholinergic tiotropium, and, more recently, the once-daily beta-2 agonist indacaterol. Long-acting bronchodilators have been shown to improve multiple clinical outcomes in COPD in comparison to short-acting agents including lung function, symptoms, dyspnea, quality of life, and exacerbations. Studies of head-to-head comparisons of long-acting bronchodilators are scant but indicate superior bronchodilation of tiotropium over salmeterol, while preliminary data from trials with the novel once-daily beta-2 agonist indacaterol indicate superior bronchodilation and clinical efficacy over twice-daily long-acting beta-2 agonists and at least equipotent bronchodilation as once-daily tiotropium. These recent therapeutic developments in COPD represent a change of paradigm with a shift from short-acting bronchodilators with multiple dosing per day to reduced dosing frequency and prolonged duration of action including once-daily treatment. This review summarizes relevant data and landmark studies comparing the efficacy of short-acting versus longer-acting bronchodilators in COPD, including new data for once-daily indacaterol, and discusses potential mechanism underlying the improved efficacy of long-acting versus short-acting bronchodilators.