Physiological mechanisms and therapeutic targets in chronic cough

Cough is a vital defensive reflex that safeguards the airways; however, it can become maladaptive and pathological. Chronic cough (>8 weeks in duration) affects up to 10% of the global adult population and is associated with considerable health status impairment. The understanding of cough physiology remains limited. Cough reflex hypersensitivity is conventionally considered to underpin the pathophysiology of chronic cough, primarily mediated by peripheral nerve dysfunction. Whilst this framework has led to important mechanistic insights and effective pharmacotherapies, recent functional neuroimaging studies have demonstrated equally important central mechanisms. Taken together, cough reflex hypersensitivity may not be mediated exclusively by peripheral nerve dysfunction, and the answer may lie within a complex interplay of central and peripheral neural physiology. In the pathophysiology of chronic cough, impaired voluntary suppression also appears to be important. This review will provide an overview of the physiology and pathophysiology of chronic cough and attempts in pharmacotherapy to date.