Chronic cough is characterized by frequent urges to cough and a heightened sensitivity to inhaled irritants. Airway sensory nerves trigger cough. We hypothesized that sensory nerve density is increased in chronic cough, which may contribute to excessive and persistent coughing.
To measure airway nerve density (axonal length) and complexity (nerve branching, neuropeptide expression) in humans with and without chronic cough.
Bronchoscopic human airway biopsies were immunolabeled for nerves and the sensory neuropeptide substance P. Eosinophil peroxidase was also quantified given previous reports showing associations between eosinophils and nerve density. Three-dimensional image z-stacks of epithelium and subepithelium were generated using confocal microscopy and from these z-stacks, total nerve length, the number of nerve branch points, substance P expression, and eosinophil peroxidase were quantified within each airway compartment.
Nerve length and the number of branch points were significantly increased in epithelium, but not subepithelium, in chronic cough compared to healthy airways. Substance P expression was scarce and was similar in chronic cough and healthy airways. Nerve length and branching was not associated with eosinophil peroxidase or with demographics such as age or gender in either group.
Airway epithelial sensory nerve density is increased in chronic cough, suggesting sensory neuroplasticity contribute to cough hypersensitivity.