Gastroesophageal Reflux Disease (GERD) and COPD

  • Nabid Zaer
  • John R. HurstEmail author


In this chapter we will consider the relevance of gastroesophageal reflux (GER) to Chronic Obstructive Pulmonary Disease (COPD), particularly with regard to COPD exacerbations. COPD is a long-term condition, progressive in its clinical course, characterised by persistent airflow limitation and chronic airway inflammation. Exacerbations contribute to the clinical severity in individual patients and are defined as episodic deteriorations in respiratory health. GERD, being common in the general population, is also highly prevalent in COPD. However, GERD has emerged as a potential risk factor for exacerbations of COPD in many studies employing diverse methodology.


  1. 1.
    Global initiative for chronic obstructive pulmonary disease [homepage on the Internet]. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2014.Google Scholar
  2. 2.
    Vos T, Flaxman A, Naghavi M. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–96.CrossRefGoogle Scholar
  3. 3.
    Mittal RK, Balaban DH. The esophagogastric junction. N Engl J Med. 1997;336:924–32.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101:1900–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Terada K, Muro S, Sato S, et al. Impact of gastro-oesophageal reflux disease symptoms on chronic obstructive pulmonary disease exacerbation. Thorax. 2008;63:951–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Martinez CH, Okajima Y, Murray S, COPDGene Investigators, et al. Impact of self-reported gastroesophageal reflux disease in subjects from COPD Gene cohort. Respir Res. 2014;15:62.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Liang B-M, Feng Y-L. Association of gastroesophageal reflux disease symptoms with stable chronic obstructive pulmonary disease. Lung. 2012;190:277–82.CrossRefPubMedGoogle Scholar
  8. 8.
    Rogha M, Behravesh B, Pourmoghaddas Z. Association of gastroesophageal reflux disease symptoms with exacerbations of chronic obstructive pulmonary disease. J Gastrointestin Liver Dis. 2010;19(3):253–6.PubMedGoogle Scholar
  9. 9.
    Rascon-Aguilar IE, Pamer M, Wludyka P, Cury J, Coultas D, Lambiase LR, et al. Role of gastroesophageal reflux symptoms in exacerbations of COPD. Chest. 2006;130:1096–101.CrossRefPubMedGoogle Scholar
  10. 10.
    Bor S, Kitapcioglu G, Solak Z, Ertilav M, Erdinc M. Prevalence of gastroesophageal reflux disease in patients with asthma and chronic obstructive pulmonary disease. J Gastroenterol Hepatol. 2010;25:309–13.CrossRefPubMedGoogle Scholar
  11. 11.
    Shimizu Y, Dobashi K, Kusano M, Mori M. Different gastroesophageal reflux symptoms of middle-aged to elderly asthma and chronic objective pulmonary disease patients. J Clin Biochem Nutr. 2011;50(2):169–75.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Takada K, Matsumoto S, Kojima E, et al. Prospective evaluation of the relationship between acute exacerbations of COPD and gastroesophageal reflux disease diagnosed by questionnaire. Respir Med. 2011;105:1531–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Phulpoto M, Ozyyum S, Rizvi N, Khuhaware S. Proportion of gastroesophageal symptoms in patients with chronic obstructive pulmonary disease. J Pak Med Assoc. 2005;55:276–9.PubMedGoogle Scholar
  14. 14.
    Sweet M, Patti M, Hoopes C, Hayes SR, Golden JA. Gastro-oesophageal reflux and aspiration in patients with advanced lung disease. Thorax. 2009;64:167–73.CrossRefPubMedGoogle Scholar
  15. 15.
    Barr RG, Celli BR, Mannino DM, Petty T, Rennard SI, Sciurba FC, et al. Comorbidities, patient knowledge, and disease management in a national sample of patients with COPD. Am J Med. 2009;122:348–55.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Mokhlesi B, Morris AL, Huang CF, Curcio AJ, Barrett TA, Kamp DW. Increased prevalence of gastroesophageal reflux symptoms in patients with COPD. Chest. 2001;119:1043–8.CrossRefPubMedGoogle Scholar
  17. 17.
    El-Serag H, Hill C, Jones R. Systematic review: the epidemiology of gastro-oesophageal reflux disease in primary care, using the UK general practice research database. Aliment Pharmacol Ther. 2009;29:470–80.CrossRefPubMedGoogle Scholar
  18. 18.
    García-Rodríguez LA, Ruigómez A, Martín-Merino E, Johansson S, Wallander MA. Relationship between gastroesophageal reflux disease and COPD in UK primary care. Chest. 2008;134:1223–30.CrossRefPubMedGoogle Scholar
  19. 19.
    Sweet MP, Herbella FA, Leard L, et al. The prevalence of distal and proximal gastroesophageal reflux in patients awaiting lung transplantation. Ann Surg. 2006;244(4):491–7.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Lee AL, Button B, Denehy L, et al. Proximal and distal gastro-oesophageal reflux in chronic obstructive pulmonary disease and bronchiectasis. Respirology. 2014;19(2):211–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Kamble N, Khan N, Kumar N, Nayak H, Daga M. Study of gastro-oesophageal reflux disease in patients with mild-to-moderate chronic obstructive pulmonary disease in India. Respirology. 2013;18:463–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Gadel AA, Mostafa M, Younis A, Haleem M. Esophageal motility pattern and gastroesophageal reflux in chronic obstructive pulmonary disease. Hepatogastroenterology. 2012;59(120):2498–502.PubMedGoogle Scholar
  23. 23.
    El-Serag H, Sweet S, Winchester C, Dent J. Update on the epidemiology of gastro-oesophageal disease: a systematic review. Gut. 2014;63(6):871–80.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Dent J, El-Serag H, Wallander M, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2005;54:710–7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Casanova C, Baudet JS, del Valle Velasco M, Martin JM, Aguirre-Jaime A, de Torres JP, et al. Increased gastro-oesophageal reflux disease in patients with severe COPD. Eur Respir J. 2004;23:841–5.CrossRefPubMedGoogle Scholar
  26. 26.
    Kempainen RR, Savik K, Whelan TP, Dunitz JM, Herrington CS, Billings JL. High prevalence of proximal and distal gastroesophageal reflux disease in advanced COPD. Chest. 2007;131:1666–71.CrossRefPubMedGoogle Scholar
  27. 27.
    Pauwels A, Blondeau K, Dupont L, Sifrim D. Mechanisms of increased gastroesophageal reflux in patients with cystic fibrosis. Am J Gastroenterol. 2012;107(9):1346–53.CrossRefPubMedGoogle Scholar
  28. 28.
    Turbyville J. Applying principles of physics to the airway to help explain the relationship between asthma and gastroesophageal reflux. Med Hypotheses. 2010;74:1075–80.CrossRefPubMedGoogle Scholar
  29. 29.
    Benson VS, Müllerová H, Vestbo J, Wedzicha JA, Patel A, Hurst JR, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Associations between gastro-oesophageal reflux, its management and exacerbations of chronic obstructive pulmonary disease. Respir Med. 2015;109(9):1147–54.CrossRefPubMedGoogle Scholar
  30. 30.
    Pandolfino JE, Kahrilas PJ. Smoking and gastro-esophageal reflux disease. Eur J Gastroenterol Hepatol. 2000;12:837–42.CrossRefPubMedGoogle Scholar
  31. 31.
    Kim J, Lee JH, Kim Y, et al. Association between chronic obstructive pulmonary disease and gastroesophageal reflux disease: a national cross-sectional cohort study. BMC Pulm Med. 2013;13:51.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Stein M, Towner T, Weber R. The effect of theophylline on the lower esophageal sphincter pressure. Ann Allergy. 1980;45:238.PubMedGoogle Scholar
  33. 33.
    Crowell M, Zayat E, Lacy B. The effects of an inhaled B2-adrenergic agonist on lower esophageal function: a dose-response study. Chest. 2001;121:1024–7.Google Scholar
  34. 34.
    Ruzkowski C, Sanowski R, Austin J, Rohwedder JJ, Waring JP. The effects of inhaled albuterol and oral theophylline on gastroesophageal reflux in patients with gastroesophageal reflux disease and obstructive lung disease. Arch Intern Med. 1992;152(4):783–5.CrossRefPubMedGoogle Scholar
  35. 35.
    Niklasson A, Strid H, Simren M, Engstrom C-P, Bjornsson E. Prevalence of gastrointestinal symptoms in patients with chronic obstructive pulmonary disease. Eur J Gastroenterol Hepatol. 2008;20(4):335–41.CrossRefPubMedGoogle Scholar
  36. 36.
    Sontag S, O’Connell S, Khandelwal S, Miller T, Nemchausky B, Schnell T. Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy. Gastroenterology. 1990;99:613–20.CrossRefPubMedGoogle Scholar
  37. 37.
    Emerenziani S, Sifrim D. Gastroesophageal reflux and gastric emptying, revisited. Curr Gastroenterol Rep. 2005;7:190–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Sifrim D, Silny J, Holloway R, Janssens J. Patterns of gas and liquid reflux during transient lower esophageal sphincter relaxation. A study using intraluminal electrical impedance. Gut. 1999;44:47–54.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Orr W, Elsenbruch S, Harnish M, Johnson L. Proximal migration of esophageal acid perfusions during waking and sleep. Am J Gastroenterol. 2000;95:37–42.CrossRefPubMedGoogle Scholar
  40. 40.
    Fortunato G, Machado M, Andrade C, Felicetti J, Camargo J, Cardoso P. Prevalence of gastroesophageal reflux in lung transplant candidates with advanced lung disease. J Bras Pneumol. 2008;34(10):772–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Terada K, Muro S, Ohara T, et al. Abnormal swallowing reflex and COPD exacerbations. Chest. 2010;137(2):326–32.CrossRefPubMedGoogle Scholar
  42. 42.
    Teramoto S, Kume H, Ouchi Y. Altered swallowing physiology and aspiration in COPD. Chest. 2002;122(3):1104–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Mokhlesi B, Logemann JA, Rademaker AW, Stangl CA, Corbridge TC. Oropharyngeal deglutition in stable COPD. Chest. 2002;121(2):361–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Wu DN, Tanifuji Y, Kobayashi H, Yamauchi K, Kato C, Suzuki K, et al. Effects of esophageal acid perfusion on airway hyperresponsiveness in patients with bronchial asthma. Chest. 2000;118:1553–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Wu DN, Yamauchi K, Kobayashi H, Tanifuji Y, Kato C, Suzuki K, et al. Effects of esophageal acid perfusion on cough responsiveness in patients with bronchial asthma. Chest. 2002;122:505–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Javorkova N, Varechova S, Pecova R, Tatar M, Balaz D, Demeter M, et al. Acidification of the oesophagus acutely increases the cough sensitivity in patients with gastro-oesophageal reflux and chronic cough. Neurogastroenterol Motil. 2008;20:119–24.PubMedGoogle Scholar
  47. 47.
    Sakae T, Pizzichini M, Teixeira P, de Silva R, Trevisol D, Pizzichini E. Exacerbations of COPD and symptoms of gastroesophageal reflux: a systematic review and meta-analysis. J Bras Pneumol. 2013;39(3):259–71.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128–38.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Ingebrigtsen T, Marott J, Vestbo J, Nordestgaard B, Hallas J, Lange P. Gastroesophageal reflux disease and exacerbations in chronic obstructive pulmonary disease. Respirology. 2015;20:101–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Katz PO, Gerson LB, Vela MF. Corrigendum: guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108:308–28.CrossRefPubMedGoogle Scholar
  51. 51.
    Stanghellini V, Armstrong D, Monnikes H, Bardhans K. Systematic review: do we need a new gastro-oesophageal reflux disease questionnaire? Aliment Pharmacol Ther. 2004;19:463–89.CrossRefPubMedGoogle Scholar
  52. 52.
    Fraser A, Delaney B, Moayyedi P. Symptom-based outcome measures for dyspepsia and GERD trials: a systematic review. Am J Gastroenterol. 2005;100:442–52.CrossRefPubMedGoogle Scholar
  53. 53.
    Modlin IM, Moss SF. Symptom evaluation in gastroesophageal reflux disease. J Clin Gastroenterol. 2008;42:558–63.CrossRefPubMedGoogle Scholar
  54. 54.
    Bytzer P, Jones R, Vakil N, Junghard O, Lind T, Wernersson B, et al. Limited ability of the proton-pump inhibitor test to identify patients with Gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2012;10(12):1360–6.CrossRefPubMedGoogle Scholar
  55. 55.
    Ronkainen J, Aro P, Storskrubb T, Johansson S-E, Lind T, Bolling-Sternevald E, et al. Prevalence of Barrett’s esophagus in the general population: an endoscopic study. Gastroenterology. 2005;129:1825–31.CrossRefPubMedGoogle Scholar
  56. 56.
    Pacheco-Galván A, Hart SP, Morice AH. Relationship between gastro-oesophageal reflux and airway diseases: the airway reflux paradigm. Arch Bronconeumol. 2011;47:195–203.CrossRefPubMedGoogle Scholar
  57. 57.
    Sasaki T, Nakayama K, Yasuda H, et al. A randomised, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc. 2009;57(8):1453–7.CrossRefPubMedGoogle Scholar
  58. 58.
    Kedika RR, Souza RF, Spechler SJ. Potential anti-inflammatory effects of proton pump inhibitors: a review and discussion of the clinical implications. Dig Dis Sci. 2009;54:2312–7.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Seemungal TAR, Wilkinson TMA, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 2008;178:1139–47.CrossRefPubMedGoogle Scholar
  60. 60.
    Albert RK, Connett J, Bailey WC, Casaburi R, JAD C Jr, Criner GJ, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689–98.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.UCL Respiratory MedicineUniversity College LondonLondonUK

Personalised recommendations