Role of ATP in Chronic Cough (360G-Wellcome-207504_B_17_Z)

The cough reflex is triggered by ion channels present on vagal nerve termini which can be activated by a wide variety of irritants. Utilising a P2X3 antagonist we have identified ATP as a driver of chronic idiopathic cough which is treatment refractory. However, the mechanisms are not known and it is not clear whether similar efficacy will be observed in chronic cough associated with common respiratory diseases. We have identified different neurophenotypes in patients with chronic cough associated with different lung diseases suggesting that a single therapeutic may not address cough across all indications and that mechanistic information will be required. Furthermore, upstream targets, involved in the release of ATP, may provide a broader efficacy profile as ATP has been shown to have a range of disease relevant biological effects in the lung mediated by purinoceptors. We will identify (1) whether ATP is a biomarker of treament sensitivity; (2) upstream targets involved in the release of ATP; (3) the contribution of the upper airway to ATP-induced sensations; (4) the role of ATP in mediating chronic cough across other airway diseases? This project will identify novel targets, biomarkers and the patient phenotypes that will respond to treatment.