Is combination therapy with inhaled anticholinergics and beta2-adrenoceptor agonists justified for chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is a debilitating condition characterised by progressive, irreversible airflow limitation. The economic and social burden of the disease is enormous. The treatment of COPD is guided by the stage of the disease and is aimed primarily at control of symptoms. Bronchodilators are the cornerstone of pharmacological management of COPD. Short-acting bronchodilators (beta(2)-adrenoceptor agonists and anticholinergics) have been available for many years and have been extensively studied as individual agents and in combination. When administered in combination, short-acting bronchodilators provide superior bronchodilation compared with individual agents given alone. However, the improvement in bronchodilation does not translate into an improvement in quality-of-life (QOL) indices. More recently, long-acting beta(2)-adrenoceptor agonists (LABAs) and anticholinergics have been introduced, and current guidelines recommend regular use of these agents in COPD of Global initiative for chronic Obstructive Lung Disease (GOLD) stage II or more. Combining short-acting anticholinergics with LABAs for daily use has been evaluated, but this combination does not confer any advantage in terms of subjective improvement or prevention of exacerbations. Combining the long-acting anticholinergic tiotropium bromide with formoterol given once or twice daily improves airway obstruction and hyperinflation. However, the effects of combinations of long-acting bronchodilators on patients' symptom scores, QOL and exacerbations remain to be studied. Ultra-LABAs, which are in development, may enable use of a combination of long-acting bronchodilators in a single inhaler for once-daily use, thus simplifying the regimen. This article discusses the results of various clinical trials comparing the efficacy of bronchodilators given alone or in combination to patients with COPD, with emphasis on the effects of these agents on bronchodilation, symptomatic and objective improvements in QOL and prevention of exacerbations.