Authors: Sin, Don D.; Johnson, Malcolm; Gan, Wen Q.; Man, S. F. P.a.u.l.

Source: Current Pharmaceutical Design, Volume 10, Number 28, November 2004 , pp. 3547-3560(14)

Publisher: Bentham Science Publishers

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 2-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 2-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.

Keywords: chronic obstructive pulmonary disease; long-acting agonists; corticosteroid; glucocorticoid receptors; aerosols; combination therapy; randomized trials

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1381612043382990

Affiliations: 1: James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Room 368A, 1081 Burrard Street, Vancouver, BC., V6Z 1Y6.

Publication date: 2004-11-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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