The heterogeneity of chronic cough: a case for endotypes of cough hypersensitivity

Cough is a troublesome and difficult-to-treat symptom that accompanies a diverse range of pulmonary and extrapulmonary conditions. Although considerable advances have been made over recent years in basic cough biology, this has not translated into improved clinical management. A major challenge has been in understanding the heterogeneity underlying the development and persistence of chronic cough in different patients. We present evidence that such heterogeneity begins with the multiple peripheral and central neural pathways capable of eliciting cough and associated respiratory behaviours, and extends to incorporate the diversity of diseases that underlie cough and the clinical phenotypic and pathological endotypic presentations that can vary substantially between individual patients with cough. A better understanding of how these sources of heterogeneity are expressed across individual patients with chronic cough is needed to better predict the efficacy of clinical management strategies and of specifically targeted therapies, which will facilitate the development of more personalised clinical approaches to treat patients with chronic cough.