Mucociliary dysfunction in COPD: effect of current pharmacotherapeutic options

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. COPD comprises multiple components which, as well as a systemic component, include pulmonary inflammation, airway remodelling and mucociliary dysfunction. The latter features contribute to the development of chronic, progressive airflow limitation. The mucociliary dysfunction component of COPD is due to mucus hypersecretion coupled with a decrease in mucus transport, and represents an important pathophysiological feature requiring appropriate treatment. Current international guidelines do not recommend the use of mucolytics in the treatment of stable COPD. In contrast, bronchodilators are central to symptomatic management of COPD, and include beta(2)-adrenoceptor agonists, anti-cholinergics and methylxanthines. Interestingly, long-acting beta(2)-agonists (LABAs), rather than short-acting beta(2)-agonists, have the potential to improve the mucociliary component of COPD, in addition to providing symptomatic treatment by their bronchodilator action. Combination therapy with a LABA and an inhaled corticosteroid has the potential to more fully address the multicomponent nature of COPD by providing important anti-inflammatory activity, which may indirectly further improve mucociliary clearance. Theoretically, anti-cholinergics are likely to have mixed effects on mucociliary function, but clinically these effects have been difficult to demonstrate. Finally, a number of novel targets for the treatment of airway mucociliary dysfunction have been identified, and targeting agents are currently in development.