#4-17E. Beyond the Reflex: Decoding the Neuropathic Endotypes of Chronic Cough (AAAI, 2026)

How should we approach patients with refractory chronic cough who fail to respond to standard therapies? This episode reviews the complex neurobiology of cough, highlighting that chronic cough is not merely a prolonged reflex but a heterogeneous neuropathic disorder involving vagal sensory neurons and central brain circuits. The authors summarize how disordered cough manifests through peripheral sensitization and central neural amplification. A critical clinical takeaway is the identification of distinct cough endotypes—such as peripheral vagal neuroinflammation and the loss of central inhibitory control—which paves the way for precision medicine. However, when critically appraising these concepts, it is important to note that much of the evidence for vagal neuroinflammation relies heavily on preclinical animal models, as direct physiological evidence in humans remains limited. For clinicians, recognizing chronic cough as a primary neuropathic condition rather than just a secondary symptom is vital. This paradigm shift directly informs daily practice by encouraging the use of emerging targeted neuromodulators, like P2X3 and NMDA receptor antagonists, thereby enabling a personalized, endotype-driven approach to managing treatment-resistant patients.

Citation: Mazzone SB, Pflaumer L, Richards A. Neurological mechanisms regulating cough in health and disease. Annals of Allergy, Asthma & Immunology. 2026. DOI: 10.1016/j.anai.2026.04.005

Disclaimer: This audio summary is based on personal interpretation and does not guarantee the exact content of the original paper. Please refer to the original article for details.