RT Journal Article SR Electronic T1 Characterisation of cough evoked by inhaled treprostinil and treprostinil palmitil JF ERJ Open Research JO erjor FD European Respiratory Society SP 00592-2020 DO 10.1183/23120541.00592-2020 VO 7 IS 1 A1 Richard W. Chapman A1 Michel R. Corboz A1 Carlos Fernandez A1 Eugene Sullivan A1 Andy Stautberg A1 Adam J. Plaunt A1 Donna M. Konicek A1 Vladimir Malinin A1 Zhili Li A1 David Cipolla A1 Walter Perkins YR 2021 UL http://openres.ersjournals.com/content/7/1/00592-2020.abstract AB Cough is induced by inhaled prostacyclin analogues including treprostinil (TRE), and, at higher doses, treprostinil palmitil (TP), a prodrug of TRE. In this report, we have investigated mechanisms involved in TRE- and TP-induced cough, using a dry powder formulation of TP (TPIP) to supplement previous data obtained with an aqueous suspension formulation of TP (TPIS).Experiments in guinea pigs and rats investigated the prostanoid receptor subtype producing cough and whether it involved activation of sensory nerves in the airways and vasculature. Experiments involved treatment with prostanoid, tachykinin and bradykinin receptor antagonists, a cyclooxygenase inhibitor and TRE administration to the isolated larynx or intravenously.In guinea pigs, cough with inhaled TRE (1.23 µg·kg−1) was not observed with an equivalent dose of TPIP and required higher inhaled doses (12.8 and 35.8 µg·kg−1) to induce cough. TRE cough was blocked with IP and tachykinin NK1 receptor antagonists but not with EP1, EP2, EP3, DP1 or bradykinin B2 antagonists or a cyclooxygenase inhibitor. TRE administered to the isolated larynx or intravenously in rats produced no apnoea or swallowing, whereas citric acid, capsaicin and hypertonic saline had significant effects.The mechanisms inducing cough with inhaled TRE likely involves the activation of prostanoid IP receptors on jugular C-fibres in the tracheobronchial airways. Cough induced by inhaled dry powder and nebulised formulations of TP occurs at higher inhaled doses than TRE, presumably due to the slow, sustained release of TRE from the prodrug resulting in lower concentrations of TRE at the airway sensory nerves.Cough induced by inhaled treprostinil and treprostinil palmitil involves the activation of prostacyclin (IP) receptors located on airway tachykinin nerves https://bit.ly/37sXz1I