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In the second episode of this three-part series, we delve into the science behind Refractory Chronic Cough (RCC), focusing on the role of neuronal hypersensitivity and how the cough reflex becomes dysregulated.1 Join leading experts as they explain the neurobiology of RCC, discuss the latest research, and share practical insights for identifying RCC in clinical practice.
Speakers:
Anju Peters1
Matt Drake2
Stuart B. Mazzone3
1. Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2. Oregon Health & Science University, Portland, OR, USA
3. University of Melbourne, Melbourne, Victoria, Australia
Reference
1. Chung KF et al. Cough hypersensitivity and chronic cough. Net Rav Dis Primers. 2022;8(1):45.
2. Mazzone SB, Undem BJ. Vagal afferent innervation of the airways in health and disease. Physiol Rev 2016;96(3):975-1024.
3. Shannon R et al. Ventrolateral medullary respiratory network and a model of cough motor pattern generation. J Appl Physiol (1985). 1998;84(6):2020-35.
4. Lee KK et al.; CHEST Expert Cough Panel. Global physiology and pathophysiology of cough Part 1: cough phenomenology – CHEST guideline and expert panel report. Chest. 2021;159(1):282-93.
5. Magni C et al. Voluntary and reflex cough: similarities and differences. Pulm Pharmacol Ther. 2011;24(3):308-311.
6. Hegland KW et al. Volitional control of reflex cough. J Appl Physiol (1985). 2012;113(1):39-46.
7. Hilton E et al. Clinical features of the urge-to-cough in patients with chronic cough. Respir Med. 2015;109(6):701-7.
8. Eccles R. The powerful placebo effect in cough: relevance to treatment and clinical trials. Lung. 2020;198(1):13-21.
9. Leech J et al. The effect of placebo conditioning on capsaicin-evoked urge to cough. Chest. 2012;142(4):951-7.
10. Leech J et al. Brain activity associated with placebo suppression of the urge-to-cough in humans. Am J Respir Crit Care Med. 2013;188(9):1069-75.
11. Moe AAK al. Brainstem processing of cough sensory inputs in chronic cough hypersensitivity. EBioMedicine. 2024;100:104976
12. Mazzone SB et al. Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med. 2007;176(4):327-32.
13. Ando A et al. Cough-related neural processing in the brain: a roadmap for cough dysfunction? Neurosci Biobehav Rev. 2014;47:457-68.
14. Ando A et al. Neural correlates of cough hypersensitivity in humans. Thorax. 2016;71:323-9.
15.Shapiro CO et al. Airway sensory nerve density is increased in chronic cough. Am J Respir Crit Care Med. 2021;203(3):348-55.
16. Zhang M et al. The role of ATP in cough hypersensitivity syndrome: new targets for treatment. J Thorac Dis. 2020;12(5):2781-90.
17. Guilleminault L et al. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype. ERJ Open Res. 2024;10(4):1-11.
18. Honey CR. The vagal rhizopathies. Front Neurol. 2025;15:1513160.
19. Cho PSP et al. Impaired cough suppression in chronic refractory cough. Eur Respir J. 2019;53(5):1802203.
20. Taylor-Clark TE, Undem BJ. Neural control of the lower airways: role in cough and airway inflammatory disease. Handb Clin Neurol. 2022;188:373-91.
21. Morice AH et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J. 2020;55(1):1901136.
22. Alhajjaj MS et al. Chronic Cough [Internet]. (2024) Oct 7. Treasure Island: StatPearls. Available at: https://www.ncbi.nlm.nih.gov/books/NBK430791/. Last accessed: 10 November 2025.
NX-GBL-CML-WCNT-250010 | November 2025.
