title: How Do Dual Long-Acting Bronchodilators Prevent Exacerbations of Chronic Obstructive Pulmonary Disease?
abstract: Decreasing the frequency and severity of exacerbations is one of the main goals of treatment for patients with chronic obstructive pulmonary disease. Several studies have documented that long-acting bronchodilators can reduce exacerbation rate and/or severity, and others have shown that combinations of long-acting β2-adrenergic agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) provide greater reductions in exacerbation frequency than either their monocomponents or LABA/inhaled corticosteroid combinations in patients at low and high risk for these events. In this review, small groups of experts critically evaluated mechanisms potentially responsible for the increased benefit of LABA/LAMA combinations over single long-acting bronchodilators or LABA/inhaled corticosteroids in decreasing exacerbation. These included effects on lung hyperinflation and mechanical stress, inflammation, excessive mucus production with impaired mucociliary clearance, and symptom severity. The data assembled and analyzed by each group were reviewed by all authors and combined into this manuscript. Available clinical results support the possibility that effects of LABA/LAMA combinations on hyperinflation, mucociliary clearance, and symptom severity may all contribute to decreasing exacerbations. Although preclinical studies suggest LABAs and LAMAs have antiinflammatory effects, such effects have not been demonstrated yet in patients with chronic obstructive pulmonary disease.
authors.affiliation: 1 insaf Respiratory Research Institute, Wiesbaden, Germany.
authors.forename: Kai M
authors.initials: KM
authors.lastname: Beeh
authors.affiliation: 2 Department of Respiratory Diseases and Adult Cystic Fibrosis Centre, Hôpital Cochin, AP-HP and Paris Descartes University, Paris, France.
authors.forename: Pierre-Regis
authors.initials: PR
authors.lastname: Burgel
authors.affiliation: 3 Department of Research and Education, Centre of Expertise for Chronic Organ Failure, Horn, the Netherlands.
authors.forename: Frits M E
authors.initials: FME
authors.lastname: Franssen
authors.affiliation: 4 Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Sevilla, Spain.|5 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Lopez-Campos
authors.affiliation: 6 2nd Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Attiko University Hospital, Athens, Greece.
authors.forename: Stelios
authors.initials: S
authors.lastname: Loukides
authors.affiliation: 7 University College London Respiratory, University College London, London, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: Hurst
authors.affiliation: 8 University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Fležar
authors.affiliation: 9 Department of Pulmonary Medicine, Hvidovre Hospital, Copenhagen, Denmark.
authors.forename: Charlotte Suppli
authors.initials: CS
authors.lastname: Ulrik
authors.affiliation: 10 Dipartimento di Scienze della Salute, Università degli Studi di Milano, Ospedale San Paolo, Milan, Italy.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Di Marco
authors.affiliation: 11 Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
authors.affiliation: 12 Ludwig-Boltzmann-Institute for Chronic Obstructive Pulmonary Disease and Respiratory Epidemiology, Otto-Wagner-Spital, Vienna, Austria.
authors.forename: Arschang
authors.initials: A
authors.lastname: Valipour
authors.affiliation: 13 University Hospital, Limerick, Ireland.|14 Graduate Entry Medical School, University of Limerick, Limerick, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Casserly
authors.affiliation: 15 Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Ställberg
authors.affiliation: 16 Novartis, Basel, Switzerland; and.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostikas
authors.affiliation: 17 Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists
keywords: hyperinflation; inflammation; inhaled corticosteroid; mucus