What is Refractory Chronic Cough?
- Chronic cough is defined as a cough lasting for more than 8 weeks;
- Refractory chronic cough (RCC, also named idiopathic or unexplained chronic cough) is defined as a chronic cough that persists despite guideline-based treatment;
- RCC is a clinical syndrome with distinct intrinsic pathophysiology characterized by neuronal hypersensitivity, the cough hypersensitivity syndrome (CHS), similar to neuropathic pain;
- Distressful sensory symptoms are throat irritation, tickle or itch and persistent urge-to-cough;
- RCC has a substantial impact on quality of life, healthcare utilization, and patient productivity.
TRPM8 and Chronic Cough
- Activation of TRPM8-expressing sensory fibres has been shown to decrease irritation, itch and neuropathic pain in animal models;
- Converging evidences suggest that topical TRPM8 agonists by acting on sensory fibres innervating the surface of the upper respiratory and digestive tracts (e.g. oropharyngeal mucosa) can treat RCC by counterbalancing CHS:
- Decreasing/abolishing pathological coughing, by normalizing the cough reflex;
- Limiting/suppressing abnormal sensations.