The role of ATP in cough hypersensitivity syndrome: new targets for treatment

Clinically, chronic cough can be effectively controlled in most patients by etiological treatment; however, there remain a small number of patients whose cough has unidentifiable etiology or where treatment efficacy is poor following etiology identification, whose condition is described as unexplained chronic cough or refractory chronic cough. Patients with refractory chronic or unexplained chronic cough commonly have increased cough reflex sensitivity, which has been described as cough hypersensitivity syndrome. The adenosine triphosphate (ATP)-gated P2X(3) receptor may be a key link in the activation of sensory neurons that regulate cough reflexes and has recently draw attention as a potential target for the treatment of refractory chronic cough, with a number of clinical studies validating the therapeutic effects of P2X(3) receptor antagonists in patients with this condition. As the energy source for various cells in vivo, ATP localizes within cells under normal physiological conditions, and has physiological functions, including in metabolism; however, under some pathological circumstances, ATP can act as a neuromodulator and is released into the extracellular space in large quantities as a signal transduction molecule. In addition, ATP is involved in regulation of airway inflammation and the cough reflex. Here, we review the generation, release, and regulation of ATP during airway inflammation and its role in the etiology of cough hypersensitivity syndrome, including the potential underlying mechanism.