Airway sensory nerve density is increased in chronic cough

Clare O. Shapiro, Becky J. Proskocil, Laura J. Oppegard, Emily D. Blum, Nicole L. Kappel, Christopher H. Chang, Allison D. Fryer, David B. Jacoby, Richard W. Costello, Matthew G. Drake

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Rationale: 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. Objectives: To measure airway nerve density (axonal length) and complexity (nerve branching, neuropeptide expression) in humans with and without chronic cough. Methods: 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. Measurements and Main Results: Nerve length and the number of branch points were significantly increased in epithelium, but not subepithelium, in chronic cough compared with healthy airways. Substance P expression was scarce and was similar in chronic cough and healthy airways. Nerve length and branching were not associated with eosinophil peroxidase nor with demographics such as age and sex in either group. Conclusions: Airway epithelial sensory nerve density is increased in chronic cough, suggesting sensory neuroplasticity contributes to cough hypersensitivity.

Original languageEnglish (US)
Pages (from-to)348-355
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Issue number3
StatePublished - Feb 1 2021


  • Cough
  • Eosinophil peroxidase
  • Nerve
  • Substance P

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'Airway sensory nerve density is increased in chronic cough'. Together they form a unique fingerprint.

Cite this