Title: Combination Therapy of Inhaled Corticosteroids and Long-Acting β2- Adrenergics In Management of Patients with Chronic Obstructive Pulmonary Disease
Volume: 10
Issue: 28
Author(s): Don D. Sin, Malcolm Johnson, Wen Qi Gan and S. F. Paul Man
Affiliation:
Keywords:
chronic obstructive pulmonary disease, long-acting agonists, corticosteroid, glucocorticoid receptors, aerosols, combination therapy, randomized trials
Abstract: Chronic obstructive pulmonary disease (COPD) affects over 5% of the adult population and is the only major cause of death in the United States where morbidity and mortality are increasing. Clinically, COPD is characterized by irreversible airflow obstruction and airway inflammation that eventually lead to dyspnea, cough and sputum production. Long-acting β2-agonists (LABAs) are effective in reducing patient symptoms through their bronchodilatory action on airway smooth muscle. More importantly, when LABAs are given in conjunction with inhaled corticosteroids, they appear to provide added benefits for patients. While the mechanisms for this observation are not entirely clear, there is emerging evidence to indicate that LABAs and corticosteroids attenuate different but complementary components of the inflammatory cascade related to COPD. Moreover, LABAs and corticosteroids may beneficially interact to prevent downregulation of β2-receptors in airway cells (and thereby preventing tachyphylaxis) and to facilitate translocation of glucocorticoid receptors into the nucleus of inflammatory cells (thereby, amplifying the anti-inflammatory activity of the corticosteroid). Regardless of the mechanism, several large, high-quality randomized controlled clinical trials indicate that combination therapy of LABA with inhaled corticosteroids improves patient symptoms, and reduces exacerbations by a third (compared to placebo). More importantly, combination therapy produces superior health outcomes than monotherapy with inhaled corticosteroids or LABA, suggesting added clinical benefits of these two compounds in COPD. This article will present a comprehensive overview of the currently available clinical evidence for the use of combination therapy as well as the potential mechanisms of their actions in COPD.
