Peripheral and central neuroinflammatory mechanisms regulating vagal sensory circuit processing and cough in lung disease.

BACKGROUND: The pulmonary system can be exposed to a diverse range of injurious insults which drive pathological events including inflammation, tissue damage and structural remodelling within the airways and lungs. SUMMARY: Patients with lung inflammation and injury often experience sensory neurological complications, suggesting that the pathological processes in the lung either impact or extend into the nervous system. KEY MESSAGES: Cough is a common presenting neurological symptom in patients with lung disease and there is growing evidence that neuroinflammation, either within the vagal nerves innervating the airways and lungs or within the central sensory neural circuits regulating cough, is involved in the development of cough disorders. We review and summarise the evidence that lung inflammation and injury drive regional neuroinflammation along peripheral and central vagal sensory pathways, co-ordinated by inflammatory cell recruitment and activation, resulting in altered gene and protein expression, vascular disruption and neurophysiological changes. We also discuss the current therapies in development for chronic cough and highlight the need to consider disease modifying therapeutics that target neuroinflammation.