title: How phosphodiesterase 4 inhibitors work in patients with chronic obstructive pulmonary disease of the severe, bronchitic, frequent exacerbator phenotype.
abstract: Current international guidelines recommend that roflumilast be added on to an inhaled corticosteroid/long-acting β2-adrenoceptor agonist (LABA) combination therapy in high-risk patients with severe, bronchitic chronic obstructive pulmonary disease who have frequent acute exacerbations. This article presents evidence that a glucocorticoid, LABA, and phosphodiesterase (PDE) 4 inhibitor in combination can interact in a complex manner to induce a panel of genes that could act collectively to suppress inflammation and improve lung function. The possibility that multivalent ligands may deliver superior efficacy is also being explored. Single molecules that inhibit PDE4 and activate β2-adrenoceptors at similar concentrations have been described.
authors: Department of Physiology & Pharmacology, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 3280 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada. Electronic address: giembycz@ucalgary.ca.
authors: Mark A
authors: MA
authors: Giembycz
authors: Department of Cell Biology & Anatomy, Airways Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, 3280 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada.
authors: Robert
authors: R
authors: Newton
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast
keywords: Acute exacerbations; COPD phenotypes; Combination therapies; Gene transactivation; Phosphodiesterase 4 inhibitors; Roflumilast