Unexplained or Refractory Chronic Cough in Adults

This review outlines current concepts, diagnostic challenges, and evolving therapies for unexplained or refractory chronic cough, defined as cough persisting beyond 8 weeks without an identifiable cause or despite treatment of known causes. The condition is often linked to cough hypersensitivity syndrome a neuropathic process involving vagal sensory pathways. Despite past optimism around targeted treatments like gefapixant, FDA rejection of its marginal efficacy has left a therapeutic gap. The article emphasizes thorough evaluation per current guidelines, identification of diagnostic pitfalls, and use of multidisciplinary cough clinics. Recommended treatments for confirmed cases include multimodal speech therapy, centrally acting neuromodulators (e.g., amitriptyline, gabapentin), and psychosocial support. Novel pharmacologic agents targeting purinergic signaling (P2X3 antagonists) show promise but remain investigational. Clinicians are advised to rigorously exclude common causes (e.g., GERD, asthma, rhinosinusitis) before labeling a case unexplained.

This review outlines current concepts, diagnostic challenges, and evolving therapies for unexplained or refractory chronic cough, defined as cough persisting beyond 8 weeks without an identifiable cause or despite treatment of known causes. The condition is often linked to cough hypersensitivity syndrome a neuropathic process involving vagal sensory pathways. Despite past optimism around targeted treatments like gefapixant, FDA rejection of its marginal efficacy has left a therapeutic gap. The article emphasizes thorough evaluation per current guidelines, identification of diagnostic pitfalls, and use of multidisciplinary cough clinics. Recommended treatments for confirmed cases include multimodal speech therapy, centrally acting neuromodulators (e.g., amitriptyline, gabapentin), and psychosocial support. Novel pharmacologic agents targeting purinergic signaling (P2X3 antagonists) show promise but remain investigational. Clinicians are advised to rigorously exclude common causes (e.g., GERD, asthma, rhinosinusitis) before labeling a case unexplained.