title: Dual bronchodilation in COPD: lung function and patient-reported outcomes - a review.
abstract: Several fixed-dose combinations (FDCs) of long-acting bronchodilators (a long-acting muscarinic antagonist [LAMA] plus a long-acting β2-agonist [LABA]) are available for the treatment of COPD. Studies of these FDCs have demonstrated substantial improvements in lung function (forced expiratory volume in 1 second) in comparison with their respective constituent monocomponents. Improvements in patient-reported outcomes (PROs), such as symptoms and health status, as well as exacerbation rates, have been reported compared with a LABA or LAMA alone, but results are less consistent. The inconsistencies may in part be owing to differences in study design, methods used to assess study end points, and patient populations. Nevertheless, these observations tend to support an association between improvements in forced expiratory volume in 1 second and improvements in symptom-based outcomes. In order to assess the effects of FDCs on PROs and evaluate relationships between PROs and changes in lung function, we performed a systematic literature search of publications reporting randomized controlled trials of FDCs. Results of this literature search were independently assessed by two reviewers, with a third reviewer resolving any conflicting results. In total, 22 Phase III randomized controlled trials of FDC bronchodilators in COPD were identified, with an additional study including a post-literature search (ten for indacaterol-glycopyrronium once daily, eight for umeclidinium-vilanterol once daily, three for tiotropium-olodaterol once daily, and two for aclidinium-formoterol twice daily). Results from these studies demonstrated that the LAMA-LABA FDCs significantly improved lung function compared with their component monotherapies or other single-agent treatments. Furthermore, LABA-LAMA combinations also generally improved symptoms and health status versus monotherapies, although some discrepancies between lung function and PROs were observed. Overall, the safety profiles of the FDCs were similar to placebo. Further research is required to examine more closely any relationship between lung function and PROs in patients receiving LABA-LAMA combinations.
authors.affiliation: Department of Primary Care Respiratory Medicine, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; Observational and Pragmatic Research Institute, Singapore.
authors.forename: David
authors.initials: D
authors.lastname: Price
authors.affiliation: Gransdalen Legesenter, Oslo, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Østrem
authors.affiliation: Department of Primary Care Research, University of Southampton, Southampton, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Department of Pulmonary Medicine, Hannover Medical School, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic / Q000379:methods; D018450:Disease Progression; D004338:Drug Combinations; D005541:Forced Expiratory Volume; D006304:Health Status; D006801:Humans; D016018:Least-Squares Analysis; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D016017:Odds Ratio; D000071066:Patient Reported Outcome Measures; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D004338:Drug Combinations; D018727:Muscarinic Antagonists
keywords: chronic obstructive pulmonary disease; combination therapy; dyspnea; forced expiratory volume; health status; spirometry