RT Journal Article SR Electronic T1 Inhibition of ATP-gated P2X3 channels by AF-219: An effective anti-tussive mechanism in chronic cough JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1965 VO 42 IS Suppl 57 A1 Rayid Abdulqawi A1 Rachel Dockry A1 Kimberley Holt A1 Ashley Woodcock A1 Gary Layton A1 Bruce McCarthy A1 Anthony Ford A1 Smith Jaclyn YR 2013 UL http://erj.ersjournals.com/content/42/Suppl_57/1965.abstract AB BackgroundPre-clinical studies suggest that P2X3 receptors are expressed by airway vagal afferents and contribute to the hyperexcitability of sensory neurons. We hypothesized that P2X3 receptors play a role in the sensitisation of vagal pathways mediating the cough reflex leading to chronic cough (CC).ObjectiveTo investigate the efficacy of a first in class oral P2X3 antagonist, AF-219, in reducing daytime cough in idiopathic/treatment-resistant CC.Methods24 subjects (19 women, mean age 54.5 years) were randomised into a double blind, placebo-controlled, 2-period, crossover study, of AF-219, 600 mg bd. Cough was assessed at baseline and after 2 weeks of treatment; primary endpoint, daytime objective cough frequency (coughs/hr) (VitaloJAKā„¢); secondary endpoints, cough severity and urge to cough visual analogue scales (VAS), cough quality of life questionnaire (CQLQ).ResultsAF-219 markedly and significantly reduced cough (mean difference vs. placebo): daytime cough rate -75% (95%CI -50 to -88), p< 0.001 (Figure 1); daytime cough severity VAS -26mm (-10 to -42), p=0.003; urge to cough VAS -21mm (-2 to -41), p=0.035; and CQLQ -9.2 (-1.7 to -16.8), p=0.018. There were no significant period or carryover effects.ConclusionP2X3 receptors appear to play a key role in mediating cough neuronal hypersensitivity and their antagonists represent a promising new class of effective anti-tussives.