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
P2X3 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
P2X3 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.