Future Directions in Chronic Cough

Abstract

Introduction: Refractory/unexplained chronic cough (RUCC) is a highly prevalent debilitating condition. The characteristics of RUCC suggest neuronal excitability. The biological mechanisms leading to this in humans are uncertain but are thought to involve changes in both the peripheral and central nervous system. Efficacy of P2X purinoceptor 3 (P2X3) antagonists suggests a role for extracellular adenosine triphosphate (ATP) in RUCC. In guinea pigs, ATP release occurs in response to hypotonic saline, through a transient receptor potential cation channel subfamily V member 4 (TRPV4)−ATP−P2X3 axis. Aims: In this review we discuss data from two European Respiratory Society 2022 abstracts in RUCC, as well as current insights and future directions in chronic cough. Results: We show that hypotonic saline cough challenge, measured by maximum evoked cough response, effectively discriminates RUCC from healthy volunteers. We show that low-dose morphine is efficacious in up to 75% of patients with RUCC and that side effects, experienced in around 38% of cases, can usually be managed. Further areas: We discuss treatable traits in chronic cough, existing pharmacological management options and future antitussives.