, Volume 192, Issue 1, pp 39–46 | Cite as

A Causal Relationship Between Cough and Gastroesophageal Reflux Disease (GERD) has been Established: A Pro/Con Debate

  • Peter J. Kahrilas
  • Jaclyn A. Smith
  • Peter V. Dicpinigaitis


Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of nonacid or weakly acidic reflux. Further contributing to the controversy are recent studies that demonstrate that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The fourth American Cough Conference (New York, June 2013) provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough.


Gastroesophageal reflux disease Cough pH monitoring Impedance-pH monitoring Proton pump inhibitors Reflux testing Esophagus 


Conflict of interest

Dr. Kahrilas is supported by R01 DK56033 and R01 DK092217 from the Public Health Service; Dr. Smith is an inventor on a patent describing novel methods for acoustic cough detection, licensed to a medical device company with which she collaborates to develop a commercial cough monitoring system; Dr. Dicpinigaitis reports no conflicts relevant to the content of this manuscript.


  1. 1.
    Irwin RS (2006) Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest 129(1):80S–94SCrossRefPubMedGoogle Scholar
  2. 2.
    Morice AH, Fontana GA, Sovijarvi ARA, Pistolesi M, Chung KF, Widdicombe J et al (2004) The diagnosis and management of chronic cough. Eur Respir J 24:481–492CrossRefPubMedGoogle Scholar
  3. 3.
    Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA (2011) Gastro-oesophageal reflux treatment for prolonged nonspecific cough in children and adults. Cochrane Database Syst Rev 1:CD004823PubMedGoogle Scholar
  4. 4.
    Faruqi S, Molyneux ID, Fathi H, Wright C, Thompson R, Morice AH (2011) Chronic cough and esomeprazole: a double-blind placebo-controlled parallel study. Respirology 16:1150–1156CrossRefPubMedGoogle Scholar
  5. 5.
    Shaheen NJ, Crockett SD, Bright SD, Madanick RD, Buckmire R, Couch M et al (2011) Randomised clinical trial: high-dose acid suppression for chronic cough—a double-blind, placebo-controlled study. Aliment Pharmacol Ther 33:225–234PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Irwin RS, Zawacki JK, Wilson MM, French CT, Callery MP (2002) Chronic cough due to gastroesophageal reflux disease: failure to resolve despite total/near-total elimination of esophageal acid. Chest 121:1132–1140CrossRefPubMedGoogle Scholar
  7. 7.
    Poe RH, Kallay MC (2003) Chronic cough and gastroesophageal reflux disease: experience with specific therapy for diagnosis and treatment. Chest 123:679–684CrossRefPubMedGoogle Scholar
  8. 8.
    Vakil N, Veldhuyzen van Zanten S, Kahrilas P et al (2006) The Montreal definition and classification of gastro-esophageal reflux disease (GERD)—a global evidence-based consensus. Am J Gastroenterol 101:1900–1920CrossRefPubMedGoogle Scholar
  9. 9.
    Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd (1997) Prevalence and clinical spectrum of gastro-oesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology 112:1448–1456CrossRefPubMedGoogle Scholar
  10. 10.
    El-Serag HB, Sonnenberg A (1997) Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in United States military veterans. Gastroenterology 113:755–760CrossRefPubMedGoogle Scholar
  11. 11.
    Gislason T, Janson C, Vermeire P et al (2002) Respiratory symptoms and nocturnal gastro-esophageal reflux: a population based study of young adults in three European countries. Chest 121:158–163CrossRefPubMedGoogle Scholar
  12. 12.
    Sackett DL, Straus SE, Richardson WS et al (2000) Evidence-based medicine: how to practice and teach EBM, 2nd edn. Churchill Livingstone, EdinburghGoogle Scholar
  13. 13.
    Ing AJ, Ngu MC, Breslin AB (1994) Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. Am J Respir Crit Care Med 149:160–167CrossRefPubMedGoogle Scholar
  14. 14.
    Irwin RS, French CL, Curley FJ et al (1993) Chronic cough due to gastroesophageal reflux. Clinical, diagnostic, and pathogenetic aspects. Chest 104:1511–1517CrossRefPubMedGoogle Scholar
  15. 15.
    Dicpinigaitis PV (2003) Short- and long-term reproducibility of capsaicin cough challenge testing. Pulm Pharmacol Ther 16:61–65CrossRefPubMedGoogle Scholar
  16. 16.
    Javorkova N, Varechova S, Pecova R et al (2008) Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough. Neurogastroenterol Motil 20:119–124PubMedGoogle Scholar
  17. 17.
    Vaezi MF, Hicks DM, Abelson TI et al (2003) Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol 1:333–344CrossRefPubMedGoogle Scholar
  18. 18.
    Irwin RS, Ownbey R, Cagle PT et al (2006) Interpreting the histopathology of chronic cough: a prospective, controlled, comparative study. Chest 130:362–370CrossRefPubMedGoogle Scholar
  19. 19.
    Patterson N, Mainie I, Rafferty G et al (2009) Nonacid reflux episodes reaching the pharynx are important factors associated with cough. J Clin Gastroenterol 43:414–419CrossRefPubMedGoogle Scholar
  20. 20.
    Oelschlager BK, Quiroga E, Isch JA, Cuenca-Abente F (2006) Gastroesophageal and pharyngeal reflux detection using impedance and 24-h pH monitoring in asymptomatic subjects: defining the normal environment. J Gastrointest Surg 10:54–62CrossRefPubMedGoogle Scholar
  21. 21.
    Decalmer S, Stovold R, Houghton LA et al (2012) Chronic cough: relationship between microaspiration, gastroesophageal reflux, and cough frequency. Chest 142:958–964CrossRefPubMedGoogle Scholar
  22. 22.
    Bohman JK, Kor DJ, Kashyap R, Gajic O, Festic E, He Z, Lee AS (2013) Airway pepsin levels in otherwise healthy surgical patients receiving general anesthesia with endotracheal intubation. Chest 143:1407–1413PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Kahrilas PJ (2008) When proton pump inhibitors fail (editorial). Clin Gastroenterol Hepatol 6:482–483PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Ing AJ, Ngu MC, Breslin AB (1991) Chronic persistent cough and gastro-oesophageal reflux. Thorax 46:479–483PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Ours TM, Kavuru MS, Schilz RJ et al (1999) A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough. Am J Gastroenterol 94:3131–3138CrossRefPubMedGoogle Scholar
  26. 26.
    Paterson WG, Murat BW (1994) Combined ambulatory esophageal manometry and dual-probe pH-metry in evaluation of patients with chronic unexplained cough. Dig Dis Sci 39:1117–1125CrossRefPubMedGoogle Scholar
  27. 27.
    Blondeau K, Dupont LJ, Mertens V et al (2007) Improved diagnosis of gastro-oesophageal reflux in patients with unexplained chronic cough. Aliment Pharmacol Ther 25:723–732CrossRefPubMedGoogle Scholar
  28. 28.
    Sifrim D, Dupont L, Blondeau K et al (2005) Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut 54:449–454PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Bogte A, Bredenoord AJ, Smout AJ (2008) Diagnostic yield of oesophageal pH monitoring in patients with chronic unexplained cough. Scand J Gastroenterol 43:13–19CrossRefPubMedGoogle Scholar
  30. 30.
    Smith JA, Decalmer S, Kelsall A et al (2010) Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms. Gastroenterology 139:754–762CrossRefPubMedGoogle Scholar
  31. 31.
    Kunsch S, Gross V, Neesse A et al (2011) Combined lung-sound and reflux-monitoring: a pilot study of a novel approach to detect nocturnal respiratory symptoms in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 33:592–600CrossRefPubMedGoogle Scholar
  32. 32.
    Chang AB, Lasserson TJ, Kiljander TO et al (2006) Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux. BMJ 332:11–17PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA (2006) Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev 4:CD004823PubMedGoogle Scholar
  34. 34.
    Kahrilas PJ, Howden CW, Hughes N et al (2013) Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest 143:605–612PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Kiljander TO, Salomaa ER, Hietanen EK, Terho EO (2000) Chronic cough and gastro-oesophageal reflux: a double-blind placebo-controlled study with omeprazole. Eur Respir J 16:633–638CrossRefPubMedGoogle Scholar
  36. 36.
    Noordzij JP, Khidr A, Evans BA et al (2001) Evaluation of omeprazole in the treatment of reflux laryngitis: a prospective, placebo-controlled, randomized, double-blind study. Laryngoscope 111:2147–2151CrossRefPubMedGoogle Scholar
  37. 37.
    Ing AJ, Ngu MC, Breslin ABX (1992) A randomised double blind placebo controlled cross-over study of ranitidine in patients with chronic persistent cough (CPC) associated with gastroesophageal reflux (GOR) [abstract]. Am Rev Resp Dis 145(4 pt 2):A11Google Scholar
  38. 38.
    Vaezi MF, Richter JE, Stasney CR et al (2006) Treatment of chronic posterior laryngitis with esomeprazole. Laryngoscope 116:254–260CrossRefPubMedGoogle Scholar
  39. 39.
    Francis DO, Goutte M, Slaughter JC et al (2011) Traditional reflux parameters and not impedance monitoring predict outcome after fundoplication in extraesophageal reflux. Laryngoscope 121:1902–1909CrossRefPubMedGoogle Scholar
  40. 40.
    Allen CJ, Anvari M (1998) Gastro-oesophageal reflux related cough and its response to laparoscopic fundoplication. Thorax 53:963–968PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Allen CJ, Anvari M (2002) Preoperative symptom evaluation and esophageal acid infusion predict response to laparoscopic Nissen fundoplication in gastroesophageal reflux patients who present with cough. Surg Endosc 16:1037–1041CrossRefPubMedGoogle Scholar
  42. 42.
    Brouwer R, Kiroff GK (2003) Improvement of respiratory symptoms following laparoscopic Nissen fundoplication. ANZ J Surg 73:189–193CrossRefPubMedGoogle Scholar
  43. 43.
    Ziora D, Jarosz W, Dzielicki J et al (2005) Citric acid cough threshold in patients with gastroesophageal reflux disease rises after laparoscopic fundoplication. Chest 128:2458–2464CrossRefPubMedGoogle Scholar
  44. 44.
    So JB, Zeitels SM, Rattner DW (1998) Outcomes of atypical symptoms attributed to gastro-esophageal reflux treated by laparoscopic fundoplication. Surgery 124:28–32CrossRefPubMedGoogle Scholar
  45. 45.
    Faruqi S, Sedman P, Jackson W, Molyneux I, Morice AH (2012) Fundoplication in chronic intractable cough. Cough 8:3PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Hoppo T, Komatsu Y, Jobe BA (2013) Antireflux surgery in patients with chronic cough and abnormal proximal exposure as measured by hypopharyngeal multichannel intraluminal impedance. JAMA Surg 148:608–615CrossRefPubMedGoogle Scholar
  47. 47.
    Trinick R, Johnston N, Dalzell AM, McNamara PS (2012) Reflux aspiration in children with neurodisability—a significant problem, but can we measure it? J Pediatr Surg 47:291–298CrossRefPubMedGoogle Scholar
  48. 48.
    Grabowski M, Kasran A, Seys S, Pauwels A, Medrala W, Dupont L, Panaszek B, Bullens D (2011) Pepsin and bile acids in induced sputum of chronic cough patients. Respir Med 105:1257–1261CrossRefPubMedGoogle Scholar
  49. 49.
    Pauwels A, Decraene A, Blondeau K, Mertens V, Farre R, Proesmans M, Van Bleyenbergh P, Sifrim D, Dupont LJ (2012) Bile acids in sputum and increased airway inflammation in patients with cystic fibrosis. Chest 141:1568–1574CrossRefPubMedGoogle Scholar
  50. 50.
    Zerbib F, Roman S, Bruley Des Varannes S, Gourcerol G, Coffin B, Ropert A, Lepicard P, Mion F (2013) Normal values of pharyngeal and esophageal twenty-four-hour ph impedance in individuals on and off therapy and interobserver reproducibility. Clin Gastroenterol Hepatol 11:366–372CrossRefPubMedGoogle Scholar
  51. 51.
    Kawamura O, Shimoyama Y, Hosaka H, Kuribayashi S, Maeda M, Nagoshi A, Zai H, Kusano M (2011) Increase of weakly acidic gas esophagopharyngeal reflux (epr) and swallowing-induced acidic/weakly acidic epr in patients with chronic cough responding to proton pump inhibitors. Neurogastroenterol Motil 23(411–418):e172Google Scholar
  52. 52.
    Ummarino D, Vandermeulen L, Roosens B, Urbain D, Hauser B, Vandenplas Y (2013) Gastroesophageal reflux evaluation in patients affected by chronic cough: restech versus multichannel intraluminal impedance/ph metry. Laryngoscope 123:980–984CrossRefPubMedGoogle Scholar
  53. 53.
    Becker V, Graf S, Schlag C, Schuster T, Feussner H, Schmid RM, Bajbouj M (2012) First agreement analysis and day-to-day comparison of pharyngeal ph monitoring with ph/impedance monitoring in patients with suspected laryngopharyngeal reflux. J Gastrointest Surg 16:1096–1101CrossRefPubMedGoogle Scholar
  54. 54.
    Koch OO, Kaindlstorfer A, Antoniou SA, Asche KU, Granderath FA, Pointner R (2012) Laparoscopic nissen versus Toupet fundoplication: objective and subjective results of a prospective randomized trial. Surg Endosc 26:413–422CrossRefPubMedGoogle Scholar
  55. 55.
    Galmiche JP, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund S, Langstrom G, Lind T, Lundell L (2011) Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the lotus randomized clinical trial. JAMA 305:1969–1977CrossRefPubMedGoogle Scholar
  56. 56.
    Campos GM, Peters JH, DeMeester TR, Oberg S, Crookes PF, Tan S, DeMeester SR, Hagen JA, Bremner CG (1999) Multivariate analysis of factors predicting outcome after laparoscopic nissen fundoplication. J Gastrointest Surg 3:292–300CrossRefPubMedGoogle Scholar
  57. 57.
    Novitsky YW, Zawacki JK, Irwin RS, French CT, Hussey VM, Callery MP (2002) Chronic cough due to gastroesophageal reflux disease: efficacy of antireflux surgery. Surg Endosc 16:567–571CrossRefPubMedGoogle Scholar
  58. 58.
    Kirkby-Bott J, Jones E, Perring S, Hosking SW (2011) Proximal acid reflux treated by fundoplication predicts a good outcome for chronic cough attributable to gastro-oesophageal reflux disease. Langenbecks Arch Surg 396:167–171CrossRefPubMedGoogle Scholar
  59. 59.
    Mainie I, Tutuian R, Agrawal A, Hila A, Highland KB, Adams DB, Castell DO (2005) Fundoplication eliminates chronic cough due to non-cid reflux identified by impedance pH monitoring. Thorax 60:521–523PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Thoman DS, Hui TT, Spyrou M, Phillips EH (2002) Laparoscopic antireflux surgery and its effect on cough in patients with gastroesophageal reflux disease. J Gastrointest Surg 6:17–21CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Peter J. Kahrilas
    • 1
  • Jaclyn A. Smith
    • 2
  • Peter V. Dicpinigaitis
    • 3
  1. 1.Division of Gastroenterology and HepatologyNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Centre for Respiratory and AllergyUniversity of ManchesterManchesterUK
  3. 3.Department of MedicineAlbert Einstein College of Medicine and Montefiore Medical CenterBronxUSA

Personalised recommendations