{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:38:46Z","timestamp":1784126326994,"version":"3.55.0"},"reference-count":19,"publisher":"European Respiratory Society (ERS)","issue":"5","funder":[{"name":"Verona Pharma"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2018,8,22]]},"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p>We investigated the short-term bronchodilator effects of RPL554 (an inhaled dual phosphodiesterase 3 and 4 inhibitor) combined with other bronchodilators in chronic obstructive pulmonary disease patients with reversibility (&gt;150\u2005mL to short-acting bronchodilators).<\/jats:p><jats:p>Study 1 was a six-way, placebo-controlled crossover study (n=36) with single doses of RPL554 (6\u2005mg), salbutamol (200\u2005\u00b5g), ipratropium (40\u2005\u00b5g), RPL554 (6\u2005mg)+salbutamol (200\u2005\u00b5g), RPL554 (6\u2005mg)+ipratropium (40\u2005\u00b5g) or placebo. Study 2 was a three-way crossover study (n=30) of tiotropium (18\u2005\u00b5g) combined with RPL554 (1.5 or 6\u2005mg) or placebo for 3\u2005days. Forced expiratory volume in 1\u2005s (FEV<jats:sub>1<\/jats:sub>), lung volumes and specific airway conductance (s<jats:italic>G<\/jats:italic><jats:sub>aw<\/jats:sub>) were measured.<\/jats:p><jats:p>In study 1, peak FEV<jats:sub>1<\/jats:sub>change compared with placebo was similar with RPL554, ipratropium and salbutamol (mean 223, 199 and 187\u2005mL, respectively). The peak FEV<jats:sub>1<\/jats:sub>was higher for RPL554+ipratropium<jats:italic>versus<\/jats:italic>ipratropium (mean difference 94\u2005mL; p&lt;0.0001) and RPL554+salbutamol<jats:italic>versus<\/jats:italic>salbutamol (mean difference 108\u2005mL; p&lt;0.0001). In study 2 (day 3), both RPL554 doses caused greater peak FEV<jats:sub>1<\/jats:sub>effects than placebo. The average FEV<jats:sub>1<\/jats:sub><jats:sub>(0\u201312\u2005h)<\/jats:sub>increase was greater with RPL554 6\u2005mg only<jats:italic>versus<\/jats:italic>placebo (mean difference 65\u2005mL; p=0.0009). In both studies, lung volumes and s<jats:italic>G<\/jats:italic><jats:sub>aw<\/jats:sub>showed greater RPL554 combination treatment effects<jats:italic>versus<\/jats:italic>monotherapy.<\/jats:p><jats:p>RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.<\/jats:p>","DOI":"10.1183\/13993003.01074-2018","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T13:09:46Z","timestamp":1535634586000},"page":"1801074","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":62,"title":["The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD"],"prefix":"10.1183","volume":"52","author":[{"given":"Dave","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine","family":"Abbott-Banner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bengtsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"2024102100361682000_52.5.1801074.1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.099192"},{"key":"2024102100361682000_52.5.1801074.2","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S2213-2600(13)70187-5","article-title":"Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials","volume":"1","author":"Franciosi","year":"2013","journal-title":"Lancet Respir Med"},{"key":"2024102100361682000_52.5.1801074.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14451.x"},{"key":"2024102100361682000_52.5.1801074.4","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1998.t01-1-00689.x"},{"key":"2024102100361682000_52.5.1801074.5","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.160.3.9812065"},{"key":"2024102100361682000_52.5.1801074.6","doi-asserted-by":"crossref","unstructured":"Page CP , Spina D . 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