Therapeutic and Mechanistic Advances in Chronic Cough

Cough is one of the most common reasons patients seek medical care in the outpatient setting. Chronic cough (CC) in adults is defined as a cough lasting more than 8 weeks, with a global prevalence of approximately 10%. CC significantly impairs quality of life, affecting physical, social, and psychological well-being. In most cases, CC is attributed to one or more of three key conditions: upper airway cough syndrome, gastroesophageal or laryngopharyngeal reflux, and asthma or non-asthmatic eosinophilic bronchitis-assuming a normal chest X-ray and no use of ACE inhibitors. If the cough persists despite thorough guideline-based evaluation and treatment, it is classified as refractory chronic cough (RCC). RCC is thought to arise from neuronal dysregulation involving both peripheral and central mechanisms, termed cough hypersensitivity syndrome. This is typically characterized by a tickle or itch sensation in the throat, leading to an urge to cough in response to seemingly harmless stimuli. Current treatment options for RCC include "off-label" use of centrally acting neuromodulators and speech therapy. Additionally, a new peripherally acting oral P2×3 receptor antagonist, gefapixant, has been approved in the EU, UK, Switzerland, and Japan, though not in the USA or Canada. Emerging treatments hold promise for improving management in the future.