TY - JOUR T1 - The short-term bronchodilator effects of the dual phosphodiesterase 3 and 4 inhibitor RPL554 in COPD JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01074-2018 VL - 52 IS - 5 SP - 1801074 AU - Dave Singh AU - Katharine Abbott-Banner AU - Thomas Bengtsson AU - Kenneth Newman Y1 - 2018/11/01 UR - http://erj.ersjournals.com/content/52/5/1801074.abstract N2 - 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 (>150 mL to short-acting bronchodilators).Study 1 was a six-way, placebo-controlled crossover study (n=36) with single doses of RPL554 (6 mg), salbutamol (200 µg), ipratropium (40 µg), RPL554 (6 mg)+salbutamol (200 µg), RPL554 (6 mg)+ipratropium (40 µg) or placebo. Study 2 was a three-way crossover study (n=30) of tiotropium (18 µg) combined with RPL554 (1.5 or 6 mg) or placebo for 3 days. Forced expiratory volume in 1 s (FEV1), lung volumes and specific airway conductance (sGaw) were measured.In study 1, peak FEV1 change compared with placebo was similar with RPL554, ipratropium and salbutamol (mean 223, 199 and 187 mL, respectively). The peak FEV1 was higher for RPL554+ipratropium versus ipratropium (mean difference 94 mL; p<0.0001) and RPL554+salbutamol versus salbutamol (mean difference 108 mL; p<0.0001). In study 2 (day 3), both RPL554 doses caused greater peak FEV1 effects than placebo. The average FEV1(0–12 h) increase was greater with RPL554 6 mg only versus placebo (mean difference 65 mL; p=0.0009). In both studies, lung volumes and sGaw showed greater RPL554 combination treatment effects versus monotherapy.RPL554 combined with standard bronchodilators caused additional bronchodilation and hyperinflation reduction.The dual PDE3 and PDE4 inhibitor RPL554 causes additional bronchodilation when combined with commonly used short- or long-acting bronchodilators http://ow.ly/CUYi30lDcYW ER -