Skip to main content
Log in

The Cough Hypersensitivity Syndrome: A Novel Paradigm for Understanding Cough

  • Published:
Lung Aims and scope Submit manuscript

Abstract

For many years patients with chronic cough have been investigated in an attempt to diagnose the cause of the cough. Here I suggest that the overwhelming majority of patients with chronic cough have a single diagnosis: cough hypersensitivity syndrome. This is demonstrated by the homogeneous nature of the clinical history and investigational results of patients attending cough clinics. The hypersensitivity facet of the syndrome is demonstrated by objective testing with capsaicin and other protussive agents. Within the cough hypersensitivity syndrome there are different phenotypes. Those patients with a predominantly Th2-type immune response will develop eosinophilic inflammation and either cough-variant asthma or eosinophilic bronchitis. Those with predominantly heartburn symptoms will have a phenotype that reflects GERD and cough. However, the similarities between the different phenotypes far outweigh differences in a unifying diagnosis of the cough hypersensitivity syndrome, providing a more rational understanding of chronic cough.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Irwin RS, Corrao WM, Pratter MR (1981) Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy. Am Rev Respir Dis 123(4 Pt 1):413–417

    CAS  PubMed  Google Scholar 

  2. Corrao WM, Braman SS, Irwin RS (1979) Chronic cough as the sole presenting manifestation of bronchial asthma. N Engl J Med 300(12):633–637

    CAS  PubMed  Google Scholar 

  3. Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave FE (1989) Chronic cough: eosinophilic bronchitis without asthma. Lancet 1(8651):1346–1348

    Article  CAS  PubMed  Google Scholar 

  4. Joo JH, Park SJ, Park SW, Lee JH, Kim DJ, Uh ST, Kim YH, Park CS (2002) Clinical features of eosinophilic bronchitis. Korean J Intern Med 17(1):31–37

    PubMed  Google Scholar 

  5. Brightling CE, Ward R, Goh KL, Wardlaw AJ, Pavord ID (1999) Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med 160(2):406–410

    CAS  PubMed  Google Scholar 

  6. Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID (2002) Mast cell infiltration of airway smooth muscle in asthma. N Engl J Med 346:1699–1705

    Article  PubMed  Google Scholar 

  7. Pratter MR (2006) Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines. Chest 129(1 Suppl):63S–71S

    Article  PubMed  Google Scholar 

  8. Sanu A, Eccles R (2008) Postnasal drip syndrome. Two hundred years of controversy between UK and USA. Rhinology 46(2):86–91

    CAS  PubMed  Google Scholar 

  9. Sadofsky LR, Campi B, Trevisani M, Compton SJ, Morice AH (2008) Transient receptor potential vanilloid-1-mediated calcium responses are inhibited by the alkylamine antihistamines dexbrompheniramine and chlorpheniramine. Exp Lung Res 34(10):681–693

    Article  CAS  PubMed  Google Scholar 

  10. Johnson LF, DeMeester TR (1986) Development of the 24-hour intraesophageal pH monitoring composite scoring system. J Clin Gastroenterol 8(Suppl 1):52–58

    Article  PubMed  Google Scholar 

  11. Blondeau K, Dupont LJ, Mertens V, Tack J, Sifrim D (2007) Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough. Aliment Pharmacol Ther 25(6):723–732

    CAS  PubMed  Google Scholar 

  12. Haque RA, Usmani OS, Barnes PJ (2005) Chronic idiopathic cough: a discrete clinical entity? Chest 127(5):1710–1713

    Article  PubMed  Google Scholar 

  13. Millqvist E, Bende M, Lowhagen O (1998) Sensory hyperreactivity—a possible mechanism underlying cough and asthma-like symptoms. Allergy 53(12):1208–1212

    Article  CAS  PubMed  Google Scholar 

  14. Millqvist E (2000) Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms. Allergy 55(6):546–550

    Article  CAS  PubMed  Google Scholar 

  15. Kastelik JA, Thompson R, Aziz I, Ojoo J, Redington AE, Morice AH (2002) Gender related differences in cough reflex sensitivity in patients with chronic cough. Am J Respir Crit Care Med 166:961–964

    Article  PubMed  Google Scholar 

  16. Morice AH, Geppetti P (2004) Cough. 5: the type 1 vanilloid receptor: a sensory receptor for cough. Thorax 59(3):257–258

    Article  CAS  PubMed  Google Scholar 

  17. Groneberg DA, Niimi A, Dinh QT, Cosio B, Hew M, Fischer A, Chung KF (2004) Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough. Am J Respir Crit Care Med 170(12):1276–1280

    Article  PubMed  Google Scholar 

  18. Mitchell JE, Campbell AP, New NE, Sadofsky LR, Kastelik JA, Mulrennan SA, Compton SJ, Morice AH (2005) Expression and characterization of the intracellular vanilloid receptor (TRPV1) in bronchi from patients with chronic cough. Exp Lung Res 31(3):295–306

    Article  CAS  PubMed  Google Scholar 

  19. MacPherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A (2007) Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445(7127):541–545

    Article  CAS  PubMed  Google Scholar 

  20. Everett CF, Morice AH (2007) Clinical history in gastroesophageal cough. Respir Med 101(2):345–348

    Article  PubMed  Google Scholar 

  21. Irwin RS, Ownbey R, Cagle PT, Baker S, Fraire AE (2006) Interpreting the histopathology of chronic cough: a prospective, controlled, comparative study. Chest 130(2):362–367

    Article  PubMed  Google Scholar 

  22. Birring SS, Parker D, Brightling CE, Bradding P, Wardlaw AJ, Pavord ID (2004) Induced sputum inflammatory mediator concentrations in chronic cough. Am J Respir Crit Care Med 169(1):15–19

    Article  PubMed  Google Scholar 

  23. Forsythe P, McGarvey LP, Heaney LG, MacMahon J, Ennis M (2000) Sensory neuropeptides induce histamine release from bronchoalveolar lavage cells in both nonasthmatic coughers and cough variant asthmatics. Clin Exp Allergy 30(2):225–232

    Article  CAS  PubMed  Google Scholar 

  24. Chung KF, Pavord ID (2008) Prevalence, pathogenesis, and causes of chronic cough. Lancet 371(9621):1364–1374

    Article  PubMed  Google Scholar 

  25. O’Connell F, Thomas VE, Studham JM, Pride NB, Fuller RW (1996) Capsaicin cough sensitivity increases during upper respiratory infection. Resp Med 90:279–286

    Article  Google Scholar 

  26. Morice AH, Lowry R, Brown MJ, Higenbottam T (1987) Angiotensin converting enzyme and the cough reflex. Lancet 2(8568):1116–1118

    Article  CAS  PubMed  Google Scholar 

  27. Benini L, Ferrari M, Sembenini C, Olivieri M, Micciolo R, Zuccali V, Bulighin GM, Fiorino F, Ederle A, Cascio VL, Vantini I (2000) Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage. Gut 46(6):762–767

    Article  CAS  PubMed  Google Scholar 

  28. Ford AC, Forman D, Moayyedi P, Morice AH (2006) Cough in the community: a cross sectional survey and the relationship to gastrointestinal symptoms. Thorax 61:975–979

    Article  CAS  PubMed  Google Scholar 

  29. Faruqi S, Brook H, Hunter V, Fathi H, Morice AH (2009) Reproducibility and sensitivity of the Hull Reflux Cough Questionnaire (HRCQ). Am J Respir Crit Care Med 179:A5756

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alyn H. Morice.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morice, A.H. The Cough Hypersensitivity Syndrome: A Novel Paradigm for Understanding Cough. Lung 188 (Suppl 1), 87–90 (2010). https://doi.org/10.1007/s00408-009-9185-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-009-9185-z

Keywords

Navigation