Unraveling the neuro-immune axis in cough hypersensitivity: from pathogenesis to synergistic management

Cough Hypersensitivity Syndrome (CHS) stands as the definitive pathological phenotype of refractory chronic cough, characterized by a sensory nervous system that over-reacts to even trivial, low-threshold stimuli. This condition is not merely a clinical symptom but a profound burden that erodes a patient's quality of life. This narrative review synthesizes the latest breakthroughs in CHS pathogenesis and clinical management. We first unpack the neuro-immune dialogue within the airway microenvironment, detailing how a compromised epithelial barrier recruits alarmins to drive peripheral vagal sensitization via P2X3 and TRP ion channels. Moving beyond the periphery, we map the central sensitization cascade, where the remodeling of cortical inhibitory networks leads to a failure of the "cough brake." To address the inherent clinical heterogeneity of CHS, we evaluate a necessary paradigm shift toward precision assessment-leveraging AI-powered acoustic monitoring and multidimensional, patient-reported outcomes to quantify the cough burden. Furthermore, we critically review the evolution of mechanism-based therapies, balancing the therapeutic promise of highly selective P2X3 antagonists against their safety profiles. Finally, we advocate for a multidisciplinary framework that marries targeted pharmacology with behavioral interventions like speech-language pathology (SLP), offering a forward-looking strategy for personalized care. This review aims to provide a systematic overview of the pathogenesis of CHS, with a particular focus on the neuro-immune axis, to offer a theoretical framework for personalized treatment, and to emphasize the importance of comprehensive, multidisciplinary diagnosis and treatment.