Translational review: Neuroimmune mechanisms in cough and emerging therapeutic targets

• Published in: Journal of allergy and clinical immunology Vol. 142; no. 5; pp. 1392 - 1402
• Main Authors: McGovern, Alice E., Short, Kirsty R., Kywe Moe, Aung Aung, Mazzone, Stuart B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018; Elsevier Limited
• Subjects: Asthma; Central nervous system; Clinical trials; Cough; Cough hypersensitivity syndrome; Defensive behavior; Disease; Human subjects; Hypersensitivity; Inflammation; Information processing; Lungs; Nerve endings; Nervous system; Neurons; Neuropeptides; Patients; Respiratory tract; Rodents; sensitization; sensory; Sensory neurons; Therapeutic applications; vagal; ASIC; TSLP; Cough hypersensitivity syndrome; sensory; inflammation; P2X; sensitization; vagal; HMGB1; VIP; CGRP; CHS
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2018.09.004

Cough is an essential defensive behavior for maintaining airway patency and to protect the lungs from potentially harmful agents. However, inflammatory pathologies can sensitize and activate the neural pathways regulating cough, leading to excessive and nonproductive coughing that serves little protective utility. Problematic cough continues to be one of the most common reasons for seeking medical advice, yet for many patients, it can be refractory to disease-specific treatments and currently available antitussive therapies. The effect of inflammation on cough neural processing occurs not only at the level of the bronchopulmonary sensory nerve terminals but also within the nervous system at multiple peripheral and central sites. Sensory nerves also actively regulate inflammation, and it is therefore a complex interplay between the immune and nervous systems that contributes to chronic cough and the associated sensory hypersensitivities. In this review we provide a brief overview of cough neurobiology in health and disease and then explore the peripheral and central nervous system sites at which neuroimmune interactions can occur. We present advancements in the development of effective antitussive therapies and suggest novel targets for future consideration.