P2X3: a new target for treating chronic cough

A substantial proportion of patients with chronic cough (lasting longer than 8 weeks) have no obvious cause after extensive investigation and their symptoms persist despite commonly prescribed antitussive medication. P2X3 receptors are expressed by airway vagal afferent nerves and contribute to the hypersensitisation of sensory neurons. This randomised, double-blind, placebo-controlled UK based phase II study (Lancet, doi:10.1016/S0140-6736(14)61255-1) aimed to investigate the efficacy of a first-in-class oral P2X3 antagonist, AF-219, to reduce cough frequency in patients with refractory chronic cough. After 2 weeks of treatment, cough frequency was reduced by 75% when patients were allocated to AF-219 compared with placebo (p=0.0003). Taste disturbance was reported by all patients taking AF-219, leading to six patients withdrawing from the study. Inhibition of P2X3 receptors, by antagonists such as AF-219, seems to have significant effect on cough neuronal hypersensitivity and is a promising new …