{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:18:25Z","timestamp":1776788305293,"version":"3.51.2"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"GSK","award":["201749 [NCT03034915]"],"award-info":[{"award-number":["201749 [NCT03034915]"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The double-blind, double-dummy EMAX trial randomised patients to umeclidinium\/vilanterol 62.5\/25\u00a0\u00b5g once daily, umeclidinium 62.5\u00a0\u00b5g once daily, or salmeterol 50\u00a0\u00b5g twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1\u00a0s (FEV<jats:sub>1<\/jats:sub>) of\u2009\u2265\u200912% and\u2009\u2265\u2009200\u00a0mL 10\u221230\u00a0min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV<jats:sub>1<\/jats:sub> and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21\u201324, and rescue medication use (puffs\/day) over Weeks 1\u201324. Analyses were conducted across the full range of reversibility (\u2212850\u2013896\u00a0mL); however, results are presented for the range \u2212100\u2013400\u00a0mL because there were few participants with values outside this range.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The mean (standard deviation) reversibility was 130\u00a0mL (156) and the median was 113\u00a0mL; 625\/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV<jats:sub>1<\/jats:sub>, SAC-TDI, E-RS and rescue medication use with umeclidinium\/vilanterol with higher reversibility. Improvements in trough FEV<jats:sub>1<\/jats:sub> and reductions in rescue medication use were greater with umeclidinium\/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium\/vilanterol versus monotherapy in the middle of the reversibility range.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium\/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium\/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-021-01859-w","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T10:03:10Z","timestamp":1635415390000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of umeclidinium\/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial"],"prefix":"10.1186","volume":"22","author":[{"given":"Claus F.","family":"Vogelmeier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward M.","family":"Kerwin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle H.","family":"Boucot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7ois","family":"Maltais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Tombs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Compton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Lipson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif H.","family":"Bjermer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"issue":"5","key":"1859_CR1","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1183\/09031936.05.00035205","volume":"26","author":"R Pellegrino","year":"2005","unstructured":"Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948\u201368.","journal-title":"Eur Respir J"},{"key":"1859_CR2","doi-asserted-by":"crossref","unstructured":"Calverley PM, Albert P, Walker PP. Bronchodilator reversibility in chronic obstructive pulmonary disease: use and limitations. Lancet Respir Med. 2013; 1(7): 564\u201373.","DOI":"10.1016\/S2213-2600(13)70086-9"},{"issue":"3","key":"1859_CR3","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1378\/chest.14-0437","volume":"146","author":"JE Hansen","year":"2014","unstructured":"Hansen JE, Porszasz J. Counterpoint: is an increase in FEV1 and\/or FVC \u2265 12% of control and \u2265 200 mL the best way to assess positive bronchodilator response? No. Chest. 2014;146(3):538\u201341.","journal-title":"Chest"},{"key":"1859_CR4","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021. https:\/\/goldcopd.org\/wp-content\/uploads\/2019\/12\/GOLD-2020-FINAL-ver1.2-03Dec19_WMV.pdf. Accessed Dec 2020."},{"issue":"3","key":"1859_CR5","doi-asserted-by":"publisher","first-page":"1900561","DOI":"10.1183\/13993003.00561-2019","volume":"54","author":"C Janson","year":"2019","unstructured":"Janson C, Malinovschi A, Amaral AFS, et al. Bronchodilator reversibility in asthma and COPD: findings from three large population studies. Eur Respir J. 2019;54(3):1900561.","journal-title":"Eur Respir J"},{"key":"1859_CR6","doi-asserted-by":"publisher","first-page":"461","DOI":"10.2147\/COPD.S194102","volume":"14","author":"JA Ohar","year":"2019","unstructured":"Ohar JA, Bowling A, Goodin T, et al. Efficacy and safety of glycopyrrolate in patients with COPD by reversibility: pooled analysis of GEM1 and GEM2 12-week studies. 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All patients provided written informed consent at either the pre-screening or screening visit.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CFV has received grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Grifols, Mundipharma, Novartis, and the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), and has received personal fees from AstraZeneca, Boehringer Ingelheim, Berlin Chemie\/Menarini, Chiesi, CSL Behring, GSK, Grifols, MedUpdate, Novartis and Teva. EMK has served on advisory boards, speaker panels or received travel reimbursement for Amphastar, AstraZeneca, Boehringer Ingelheim, Connect Biopharma, GSK, Mylan, Novartis, Pearl, Sunovion, Teva and Theravance, and has received consulting fees from Cipla and GSK. IHB, DAL, CC and PWJ are employees of GSK and hold stock and shares in GSK. FM has received research grants for participating in multicentre trials for AstraZeneca, Boehringer Ingelheim, GSK, Sanofi and Novartis, and has received unrestricted research grants and personal fees from Boehringer Ingelheim, Grifols and Novartis. LT is a contingent worker on assignment at GSK. LHB has received honoraria for giving a lecture or attending an advisory board for Airsonett, ALK-Abell\u00f3, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Meda, Novartis and Teva. DISKUS and ELLIPTA are owned by\/licensed to the GSK group of companies.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"279"}}