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Dual bronchodilation in COPD: lung function and patient-reported outcomes – a review

Authors Price D, Østrem A, Thomas M, Welte T

Received 7 July 2016

Accepted for publication 3 November 2016

Published 30 December 2016 Volume 2017:12 Pages 141—168


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 4

Editor who approved publication: Dr Richard Russell

David Price,1,2 Anders Østrem,3 Mike Thomas,4 Tobias Welte5

1Department of Primary Care Respiratory Medicine, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 2Observational and Pragmatic Research Institute, Singapore; 3Gransdalen Legesenter, Oslo, Norway; 4Department of Primary Care Research, University of Southampton, Southampton, UK; 5Department of Pulmonary Medicine, Hannover Medical School, Hannover, Germany

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.

Keywords: chronic obstructive pulmonary disease, combination therapy, dyspnea, forced expiratory volume, health status, spirometry

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