Genetic factors

Figure A

Figure B

Figure C

References

Factors associated with the development of gastro-oesophageal reflux disease (brackets indicate inconsistent or preliminary evidence)

Genetic factors

Positive family history

Reflux disease or symptoms in a relative

Personal factors

Age

Pregnancy

Obesity

Behavioural factors

Smoking

(Alcohol consumption)

(Coffee consumption)

Dietary factors

Large volume meals

Rich energy dense meals

(High fat meals)

(Rapid intake of meals)

(High salt intake)

Low dietary fibre

Environmental

Helicobacter pylori—may inhibit or exacerbate GORD depending on effects on gastric acid secretion (little overall effect)

Drug therapy

Drugs that relax the lower oesophageal sphincter:

Calcium channel blockers

Anticholinergic drugs

Aminophylline

Nitrates

Drugs that slow gastrointestinal transit:

Opiates

Steroids

Non-steroidal anti-inflammatory drugs

(Oral contraceptives or hormone replacement therapy may be protective)

Fig A (Top) Incidence of Barrett’s columnar lined oesophagus in Tayside 1980-95. Adapted from Todd et al.w27 (Bottom) Incidence of oesophageal adenocarcinoma of the cardia and oesophagus, 1975-2001. Data from National Cancer Institute’s surveillance epidemiology and end results programme. Adapted from Pohl and Welchw28


 

Fig B Management flow chart for patients with reflux symptoms after endoscopy. Adapted from National Institute for Health and Clinical Excellence guideline 17 (www.nice.org.uk)

Fig C Investigation of chronic cough using a nasogastric catheter with inbuilt pH (acid), impedance (fluid movement), and manometry (pressure) sensors. These measurements clearly distinguish between reflux events that trigger coughing (left) and coughing that triggers reflux (right). Adapted from Sifrim et alw37


  1. Mohammed I, Cherkas LF, Riley SA, Spector TD, Trudgill NJ. Genetic influences in gastro-oesophageal reflux disease: a twin study. Gut 2003;52(8):1085-9.
  2. Cameron AJ, Lagergren J, Henriksson C, Nyren O, Locke GR, 3rd, Pedersen NL. Gastroesophageal reflux disease in monozygotic and dizygotic twins. Gastroenterology 2002;122(1):55-9.
  3. DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 2005;100(1):190-200.
  4. Schwizer W, Thumshirn M, Dent J, Guldenschuh I, Menne D, Cathomas G, et al. Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: a randomised controlled trial. Lancet 2001;357:1738-42.
  5. Moayyedi P, Bardhan C, Young L, Dixon MF, Brown L, Axon AT. Helicobacter pylori eradication does not exacerbate reflux symptoms in gastroesophageal reflux disease. Gastroenterology 2001;121:1120-6.
  6. Holloway RH, Hongo M, Berger K, McCallum RW. Gastric distention: a mechanism for postprandial gastroesophageal reflux. Gastroenterology 1985;89(4):779-84.
  7. Pandolfino JE, Shi G, Curry J, Joehl RJ, Brasseur JG, Kahrilas PJ. Esophagogastric junction distensibility: a factor contributing to sphincter incompetence. Am J Physiol Gastrointest Liver Physiol 2002;282:G1052-8.
  8. Emerenziani S, Zhang X, Blondeau K, Silny J, Tack J, Janssens J, et al. Gastric fullness, physical activity, and proximal extent of gastroesophageal reflux. Am J Gastroenterol 2005;100:1251-6.
  9. van Herwaarden MA, Samsom M, Smout AJ. Excess gastroesophageal reflux in patients with hiatus hernia is caused by mechanisms other than transient LES relaxations. Gastroenterology 2000;119(6):1439-46.
  10. Martinez SD, Malagon IB, Garewal HS, Cui H, Fass R. Non-erosive reflux disease (NERD)—acid reflux and symptom patterns. Aliment Pharmacol Ther 2003;17:537-45.
  11. Trimble KC, Pryde A, Heading RC. Lowered oesophageal sensory thresholds in patients with symptomatic but not excess gastro-oesophageal reflux: evidence for a spectrum of visceral sensitivity in GORD. Gut 1995;37(1):7-12.
  12. Pehlivanov N, Liu J, Mittal RK. Sustained esophageal contraction: a motor correlate of heartburn symptom. Am J Physiol Gastrointest Liver Physiol 2001;281(3):G743-51.
  13. Locke GR, 3rd, Zinsmeister AR, Fett SL, Melton LJ, 3rd, Talley NJ. Overlap of gastrointestinal symptom complexes in a US community. Neurogastroenterol Motil 2005;17(1):29-34.
  14. Castell DO, Kahrilas PJ, Richter JE, Vakil NB, Johnson DA, Zuckerman S, et al. Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol 2002;97(3):575-83.
  15. Lauritsen K, Deviere J, Bigard MA, Bayerdorffer E, Mozsik G, Murray F, et al. Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results. Aliment Pharmacol Ther 2003;17(3):333-41.
  16. Tharalson EF, Martinez SD, Garewal HS, Sampliner RE, Cui H, Pulliam G, et al. Relationship between rate of change in acid exposure along the esophagus and length of Barrett's epithelium. Am J Gastroenterol 2002;97(4):851-6.
  17. Shaker R, Milbrath M, Ren J, Toohill R, Hogan WJ, Li Q, et al. Esophagopharyngeal distribution of refluxed gastric acid in patients with reflux laryngitis. Gastroenterology 1995;109(5):1575-82.
  18. Hanson DG, Kamel PL, Kahrilas PJ. Outcomes of antireflux therapy for the treatment of chronic laryngitis. Ann Otol Rhinol Laryngol 1995;104(7):550-5.
  19. Williams RB, Szczesniak M, Maclean JC, Brake HM, Cole IE, Cook IJ. Predictors of Outcome in an Open Label, Therapeutic Trial of High-Dose Omeprazole in Laryngitis. Am J Gastroenterol 2004;99(5):777-85.
  20. Vaezi MF, Hicks DM, Ours TM. ENT manifestations of GERD: a large prospective study assessing treatment outcome and predictors of response. Gastroenterology 2001;120:A426.
  21. Katz PO. Ambulatory esophageal and hypopharyngeal pH monitoring in patients with hoarseness. Am J Gastroenterol 1990;85(1):38-40.
  22. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991;101(4 Pt 2 Suppl 53):1-78.
  23. Richter JE. Typical and atypical presentations of gastroesophageal reflux disease. The role of esophageal testing in diagnosis and management. Gastroenterol Clin North Am 1996;25(1):75-102.
  24. Wynne JW, Ramphal R, Hood CI. Tracheal mucosal damage after aspiration. A scanning electron Microscope study. Am Rev Respir Dis 1981;124(6):728-32.
  25. Little FB, Koufman JA, Kohut RI, Marshall RB. Effect of gastric acid on the pathogenesis of subglottic stenosis. Ann Otol Rhinol Laryngol 1985;94(5 Pt 1):516-9.
  26. Lagergren J. Adenocarcinoma of oesophagus: what exactly is the size of the problem and who is at risk? Gut 2005;54 Suppl 1:i1-5.
  27. Todd JA, Johnston DA, Dillon JF. The changing spectrum of gastroesophageal reflux disease. Eur J Cancer Prev 2002;11:215-9.
  28. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of eosphageal adenocarcinoma incidence. J Natl Cancer Inst 2005;97:142-6.
  29. Ouatu_Lascar R, Fitzgerald RC, Triadafilopoulos G. Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression. Gastroenterology 1999;117(2):327-35.
  30. Corley DA, Kerlikowske K, Verma R, Buffler P. Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 2003;124(1):47-56.
  31. Jankowski J, Sharma P. Review article: approaches to Barrett's oesophagus treatment-the role of proton pump inhibitors and other interventions. Aliment Pharmacol Ther 2004;19 Suppl 1:54-9.
  32. Van Pinxteren B, Numans M, Bonis P, Lau J. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2004:DOI:10.1002/14651858.CD002095.pub2.
  33. Donnellan C, Sharma N, Preston C, Moayyedi P. Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease. Cochrane Database Syst Rev 2004;(4):doi:10.1002/14651858.CD003245.pub2.
  34. Xue S, Katz PO, Banerjee P, Tutuian R, Castell DO. Bedtime H2 blockers improve nocturnal gastric acid control in GERD patients on proton pump inhibitors. Aliment Pharmacol Ther 2001;15(9):1351-6.
  35. Pandolfino JE, Richter JE, Ours T, Guardino JM, Chapman J, Kahrilas PJ. Ambulatory esophageal pH monitoring using a wireless system. Am J Gastroenterol 2003;98(4):740-9.
  36. Mainie I, Tutuian R, Agrawal A, Hila A, Highland KB, Adams DB, et al. Fundoplication eliminates chronic cough due to non-acid reflux identified by impedance pH monitoring. Thorax 2005;60(6):521-3.
  37. Sifrim D, Dupont L, Blondeau K, Zhang X, Tack J, Janssens J. Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring. Gut 2005;54:449-54.
  38. Olberg P, Johannessen R, Johnsen G, Myrvold HE, Bjerkeset T, Fjosne U, et al. Long-term outcome of surgically and medically treated patients with gastroesophageal reflux disease: a matched-pair follow-up study. Scand J Gastroenterol 2005;40(3):264-74.
  39. Nilsson G, Wenner J, Larsson S, Johnsson F. Randomized clinical trial of laparoscopic versus open fundoplication for gastro-oesophageal reflux. Brit J Surg 2004;91:552-9.
  40. Arguedas MR, Heudebert GR, Klapow JC, Centor RM, Eloubeidi MA, Wilcox CM, et al. Re-examination of the cost-effectiveness of surgical versus medical therapy in patients with gastroesophageal reflux disease: the value of long-term data collection. Am J Gastroenterol 2004;99:1023-8.
  41. Vakil N, Sharma P. Review article: endoscopic treatments for gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2003;17(12):1427-34.

 


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