title: Combination therapy of inhaled corticosteroids and long-acting beta2-adrenergics in management of patients with chronic obstructive pulmonary disease.
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 beta(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 beta(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 mono-therapy 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.
authors.affiliation: James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Room 368A, 1081 Burrard Street, Vancouver, BC. V6Z 1Y6, Canada. dsin@mrl.ubc.ca
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.forename: Wen Qi
authors.initials: WQ
authors.lastname: Gan
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000336:Aerosols; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000336:Aerosols; D003692:Delayed-Action Preparations; D018343:Receptors, Adrenergic, beta-2; D011965:Receptors, Glucocorticoid