Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Overlap of functional dyspepsia and GERD—diagnostic and treatment implications

Abstract

GERD and functional dyspepsia are the two most prevalent upper gastrointestinal disorders. Gastro-oesophageal reflux is most commonly diagnosed using the cardinal symptoms of heartburn and regurgitation. Patients might also be diagnosed using a questionnaire, after empiric treatment with an acid suppressant, after upper endoscopy or by pH testing. Functional dyspepsia is best diagnosed using symptoms outlined by the Rome committee in conjunction with a normal upper endoscopy. Theoretically, distinguishing these two populations should be easy for all health-care providers. In reality, however, carefully separating out these two populations can be quite difficult, as substantial overlap exists epidemiologically, symptomatically and even diagnostically. This overlap renders precise diagnosis a challenge; given the limited treatment options, the primary goal is to identify those patients who will respond to acid suppressive therapy. Despite the frequency with which functional dyspepsia and GERD overlap, remarkably few studies have investigated this overlap. Most recommendations are based on data derived from separate studies of functional dyspepsia and GERD. A further limitation of existing studies is their failure to differentiate between the various diagnostic categories into which the individual presenting with heartburn might belong.

Key Points

  • GERD and functional dyspepsia are common disorders in the community

  • GERD, functional dyspepsia and other functional gastrointestinal disorders commonly overlap in the same individual

  • A number of pathophysiological factors are common to GERD and functional dyspepsia

  • Although the pathophysiology of GERD and functional dyspepsia have been studied extensively, few studies have focused specifically on patients with both of these disorders

  • Overlapping functional dyspepsia and GERD might have important effects on therapeutic responses

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Flook, N. W. & Wiklund, I. Accounting for the effect of GERD symptoms on patients' health-related quality of life: supporting optimal disease management by primary care physicians. Int. J. Clin. Pract. 61, 2071–2078 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Camilleri, M. et al. Prevalence and socioeconomic impact of upper gastrointestinal disorders in the United States: results of the US Upper Gastrointestinal Study. Clin. Gastroenterol. Hepatol. 3, 543–552 (2005).

    Article  PubMed  Google Scholar 

  3. Everhart, J. E. & Ruhl, C. E. Burden of digestive diseases in the United States part 1: overall and upper gastrointestinal diseases. Gastroenterology 136, 376–386 (2009).

    Article  PubMed  Google Scholar 

  4. Brook, R. A. et al. Functional dyspepsia impacts absenteeism and direct and indirect costs. Clin. Gastroenterol. Hepatol. 8, 498–503 (2010).

    Article  PubMed  Google Scholar 

  5. Vakil, N. et al. The Montreal definition and classification of gastro-esophageal reflux disease (GERD): a global evidence-based consensus. Am. J. Gastroenterol. 101, 1900–2000 (2006).

    Article  PubMed  Google Scholar 

  6. Tack, J. et al. Functional gastroduodenal disorders. Gastroenterology 130, 1466–1479 (2006).

    Article  PubMed  Google Scholar 

  7. Choung, R. S. et al. Do distinct dyspepsia subgroups exist in the community? A population-based study. Am. J. Gastroenterol. 102, 1983–1989 (2007).

    Article  PubMed  Google Scholar 

  8. Bisschops, R. et al. Relationship between symptoms and ingestion of a meal in functional dyspepsia. Gut 57, 1495–1503 (2008).

    Article  CAS  PubMed  Google Scholar 

  9. Peery, A. F. et al. Burden of gastrointestinal diseases in the United States: update. Gastroenterology 143, 1179–1187 (2012) (2012).

    Article  PubMed  Google Scholar 

  10. Nebel, O. T., Fornes, M. F. & Castell, D. O. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am. J. Dig. Dis. 21, 953–956 (1976).

    Article  CAS  PubMed  Google Scholar 

  11. Sobieraj, D. M., Coleman, S. M. & Coleman, C. L. US prevalence of upper gastrointestinal symptoms: a systematic literature review. Am. J. Man. Care 17, 449–458 (2011).

    Google Scholar 

  12. Pace, F., Bollani, S., Molteni, P. & Bianchi Porro, G. Natural history of gastroesophageal reflux disease without esophagitis (NERD)—a reappraisal 10 years on. Dig. Liver Dis. 36, 111–115 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. El-Serag, H. B. & Talley, N. J. Systematic review: the prevalence and clinical course of functional dyspepsia. Aliment. Pharmacol. Ther. 19, 643–654 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. Castillo, E. J. et al. A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia. Clin. Gastroenterol. Hepatol. 2, 985–996 (2004).

    Article  PubMed  Google Scholar 

  15. Ford, A. C. et al. Initial poor quality of life and new onset of dyspepsia: results from a longitudinal 10-year follow-up study. Gut 56, 321–327 (2007).

    Article  PubMed  Google Scholar 

  16. Gerson, L. B., Kahrilas, P. J. & Fass, R. Insights into gastroesophageal reflux disease-associated dyspeptic symptoms. Clin. Gastroenterol. Hepatol. 9, 824–833 (2011).

    Article  PubMed  Google Scholar 

  17. Fass, R., Fennerty, M. B. & Vakil, N. Nonerosive reflux disease—current concepts and dilemmas. Am. J. Gastroenterol. 96, 303–314 (2001).

    CAS  PubMed  Google Scholar 

  18. Modlin, I. M. et al. Non-erosive reflux disease—defining the entity and delineating the management. Digestion 78 (Suppl. 1), 1–5 (2008).

    Article  PubMed  Google Scholar 

  19. Modlin, I. M. et al. Diagnosis and management of non-erosive reflux disease—the Vevey NERD Consensus Group. Digestion 80, 74–88 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Galmiche, J. P. et al. Functional esophageal disorders. Gastroenterology 130, 1459–1465 (2006).

    Article  PubMed  Google Scholar 

  21. Quigley, E. M. & Keohane, J. Dyspepsia. Curr. Opin. Gastroenterol. 24, 692–697 (2008).

    Article  PubMed  Google Scholar 

  22. Xiao, Y. L. et al. Prevalence and symptom pattern of pathologic esophageal acid reflux in patients with functional dyspepsia based on the Rome III criteria. Am. J. Gastroenterol. 105, 2626–2631 (2010).

    Article  PubMed  Google Scholar 

  23. Kaji, M. et al. Prevalence of overlaps between GERD, FD and IBS and impact on health-related quality of life. J. Gastroenterol. Hepatol. 25, 1151–1156 (2010).

    Article  PubMed  Google Scholar 

  24. de Vries, D. R., van Herwaarden, M. A., Smout, A. J. & Samsom, M. Patients with physiological acid exposure and positive symptom association scores: a distinct subgroup within the GORD spectrum. Neurogastroenterol. Motil. 21, 820–e53 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Noh, Y. W., Jung, H. K., Kim, S. E. & Jung, S. A. Overlap of erosive and non-erosive reflux diseases with functional gastrointestinal disorders according to Rome III criteria. J. Neurogastroenterol. Motil. 16, 148–156 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Savarino, E. et al. Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease. Gut 58, 1185–1191 (2009).

    Article  CAS  PubMed  Google Scholar 

  27. Fujiwara, Y. et al. Cigarette smoking and its association with overlapping gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome. Intern. Med. 50, 2443–2447 (2011).

    Article  PubMed  Google Scholar 

  28. Locke, G. R. 3rd, Zinsmeister, A. R., Talley, N. J., Fett, S. L. & Melton, L. J. 3rd. Familial association in adults with functional gastrointestinal disorders. Mayo Clin. Proc. 75, 907–912 (2000).

    Article  PubMed  Google Scholar 

  29. Gathaiya, N. et al. Novel associations with dyspepsia: a community-based study of familial aggregation, sleep dysfunction and somatization. Neurogastroenterol. Motil. 21, 922–e69 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jankowski, J. A. & Talley, N. J. Dissecting GI phenotype–genotype relationships in GERD and dyspepsia: an SNP here and an SNP there. Am. J. Gastroenterol. 104, 286–288 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Holtmann, G. et al. G-protein β3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology 126, 971–979 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Andresen, V. et al. Is there an association between GNβ3-C825T genotype and lower functional gastrointestinal disorders? Gastroenterology 130, 1985–1994 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Tahara, T. et al. Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia. Dig. Dis. Sci. 53, 642–646 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Oshima, T. et al. The G-protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med. Genet. 11, 13 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shimpuku, M. et al. G-protein β3 subunit 825CC genotype is associated with postprandial distress syndrome with impaired gastric emptying and with the feeling of hunger in Japanese. Neurogastroenterol. Motil. 23, 1073–1080 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. de Vries, D. R., ter Linde, J. J., van Herwaarden, M. A., Smout, A. J. & Samsom, M. Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein β3 subunit gene (GNB3). Am. J. Gastroenterol. 104, 281–285 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Arisawa, T. et al. Genetic polymorphisms of molecules associated with inflammation and immune response in Japanese subjects with functional dyspepsia. Int. J. Mol. Med. 20, 717–723 (2007).

    CAS  PubMed  Google Scholar 

  38. Tahara, T. et al. Serotonin-2A receptor gene T102C polymorphism in patients with dyspeptic symptoms. Hepatogastroenterology 55, 1921–1924 (2008).

    CAS  PubMed  Google Scholar 

  39. Tahara, T. et al. COMT gene val158met polymorphism in patients with dyspeptic symptoms. Hepatogastroenterology 55, 979–982 (2008).

    CAS  PubMed  Google Scholar 

  40. Arisawa, T. et al. Genetic polymorphisms of cyclooxygenase-1 (COX-1) are associated with functional dyspepsia in Japanese women. J. Womens Health (Larchmt) 17, 1039–1043 (2008).

    Article  Google Scholar 

  41. Tahara, T. et al. A genetic variant of the p22PHOX component of NADPH oxidase C242T is associated with reduced risk of functional dyspepsia in Helicobacter pylori-infected Japanese individuals. Eur. J. Gastroenterol. Hepatol. 21, 1363–1368 (2009).

    Article  PubMed  Google Scholar 

  42. Camilleri, M. et al. Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G510–G516 (2009).

    Article  CAS  PubMed  Google Scholar 

  43. Stec-Michalska, K. et al. Influence of cigarette smoking on the level of mRNA of somatostatin receptor 3 (SSTR3) in the gastric mucosa of patients with functional dyspepsia. Adv. Med. Sci. 55, 53–58 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Faure, C., Patey, N., Gauthier, C., Brooks, E. M. & Mawe, G. M. Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients. Gastroenterology 139, 249–258 (2010).

    Article  CAS  PubMed  Google Scholar 

  45. Tahara, T. et al. Homozygous TRPV1 315C influences the susceptibility to functional dyspepsia. J. Clin. Gastroenterol. 44, e1–e7 (2010).

    Article  CAS  PubMed  Google Scholar 

  46. Mujakovic, S. et al. Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia. BMC Med. Genet. 12, 140 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Toyoshima, F. et al. Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population. BMC Med. Genet. 12, 88 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Arisawa, T. et al. Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan. J. Gastroenterol. 47, 1091–1098 (2012).

    Article  CAS  PubMed  Google Scholar 

  49. Monnikes, H. et al. Randomised clinical trial: sustained response to PPI treatment of symptoms resembling functional dyspepsia and irritable bowel syndrome in patients suffering from an overlap with erosive gastro-esophageal reflux disease. Aliment. Pharmacol. Ther. 35, 1279–1289 (2012).

    Article  CAS  PubMed  Google Scholar 

  50. Sanaka, M., Yamamoto, T. & Kuyama, Y. Effects of proton pump inhibitors on gastric emptying: a systematic review. Dig. Dis. Sci. 55, 2431–2440 (2009).

    Article  CAS  PubMed  Google Scholar 

  51. Kriengkirakul, C., Patcharatrakul, T. & Gonlachanvit, S. The therapeutic and diagnostic value of 2-week high dose proton pump inhibitor treatment in overlapping non-erosive gastroesophageal reflux disease and functional dyspepsia patients. J. Neurogastroenterol. Motil. 18, 174–180 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Zerbib, F. et al. Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease. Gut 61, 501–506 (2012).

    Article  CAS  PubMed  Google Scholar 

  53. Mittal, R. K., Holloway, R. H., Penagini, R., Blackshaw, L. A. & Dent, J. Transient lower esophageal sphincter relaxation. Gastroenterology 109, 601–610 (1995).

    Article  CAS  PubMed  Google Scholar 

  54. Gilja, O. H., Hausken, T., Wilhelmsen, I. & Berstad, A. Impaired accommodation of proximal stomach to a meal in functional dyspepsia. Dig. Dis. Sci. 41, 689–696 (1996).

    Article  CAS  PubMed  Google Scholar 

  55. Tack, J., Piessevaux, H., Coulie, B., Caenepeel, P. & Janssens, J. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 115, 1346–1352 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Kim, D. Y. et al. Noninvasive measurement of gastric accommodation in patients with idiopathic nonulcer dyspepsia. Am. J. Gastroenterol. 96, 3099–3105 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Stanghellini, V. et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology 110, 1036–1042 (1996).

    Article  CAS  PubMed  Google Scholar 

  58. Tack, J., Bisschops, R. & Sarnelli, G. Pathophysiology and treatment of functional dyspepsia. Gastroenterology 127, 1239–1255 (2004).

    Article  PubMed  Google Scholar 

  59. Quigley, E. M. Review article: gastric emptying in functional gastrointestinal disorders. Aliment. Pharmacol. Ther. 20 (Suppl. 7), 56–60 (2004).

    Article  PubMed  Google Scholar 

  60. Penagini, R. et al. Motor function of the proximal stomach and visceral perception in gastro-oesophageal reflux disease. Gut 42, 251–257 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Vu, M. K. et al. Motor and sensory function of the proximal stomach in reflux disease and after laparoscopic Nissen fundoplication. Am. J. Gastroenterol. 94, 1481–1489 (1999).

    Article  CAS  PubMed  Google Scholar 

  62. Gonlachanvit, S., Maurer, A. H., Fisher, R. S. & Parkman, H. P. Regional gastric emptying abnormalities in functional dyspepsia and gastro-oesophageal reflux disease. Neurogastroenterol. Motil. 18, 894–904 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. van Lelyveld, N., Scheffer, R., Mundt, M. & Samsom, M. Partial gastric volumes and upper abdominal sensations in functional dyspeptic and GERD patients: a 3D ultrasonographic study. Am. J. Gastroenterol. 101, 1845–1852 (2006).

    Article  PubMed  Google Scholar 

  64. Miyamoto, M., Manabe, N. & Haruma, K. Efficacy of the addition of prokinetics for proton pump inhibitor (PPI) resistant non-erosive reflux disease (NERD) patients: significance of frequency scale for the symptom of GERD (SSG) on decision of treatment strategy. Intern. Med. 49, 1469–1476 (2010).

    Article  PubMed  Google Scholar 

  65. Futagami, S. et al. The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying. J. Gastroenterol. 45, 413–421 (2010).

    Article  CAS  PubMed  Google Scholar 

  66. Shindo, T. et al. Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease. Digestion 79, 65–72 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. Kindt, S. et al. Relationship between symptom pattern, assessed by the PAGI-SYM questionnaire, and gastric sensorimotor dysfunction in functional dyspepsia. Neurogastroenterol. Motil. 21, 1183–e105 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Keohane, J. & Quigley, E. M. Functional dyspepsia: the role of visceral hypersensitivity in its pathogenesis. World J. Gastroenterol. 12, 2672–2676 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  69. George, A. A., Tsuchiyose, M. & Dooley, C. P. Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Gastroenterology 101, 3–6 (1991).

    Article  CAS  PubMed  Google Scholar 

  70. Samsom, M., Verhagen, M. A., vanBerge Henegouwen, G. P. & Smout, A. J. Abnormal clearance of exogenous acid and increased acid sensitivity of the proximal duodenum in dyspeptic patients. Gastroenterology 116, 515–520 (1999).

    Article  CAS  PubMed  Google Scholar 

  71. Lee, K. J., Vos, R., Janssens, J. & Tack, J. Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G278–G284 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Cicala, M. et al. Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 18, 605–613 (2003).

    Article  CAS  PubMed  Google Scholar 

  73. Hopwood, D., Milne, G. & Logan, K. R. Electron. microscopic changes in human oesophageal epithelium in oesophagitis. J. Pathol. 129, 161–167 (1979).

    Article  CAS  PubMed  Google Scholar 

  74. Tobey, N. A., Carson, J. L., Alkiek, R. A. & Orlando, R. C. Dilated intercellular spaces: a morphological feature of acid reflux-damaged human esophageal epithelium. Gastroenterology 111, 1200–1205 (1996).

    Article  CAS  PubMed  Google Scholar 

  75. Vela, M. F., Craft, B. M., Sharma, N., Freeman, J. & Hazen-Martin, D. Refractory heartburn: comparison of intercellular space diameter in documented GERD vs. functional heartburn. Am. J. Gastroenterol. 106, 844–850 (2011).

    Article  PubMed  Google Scholar 

  76. Yang, M. et al. Quantitative assessment and characterization of visceral hyperalgesia evoked by esophageal balloon distention and acid perfusion in patients with functional heartburn, nonerosive reflux disease, and erosive esophagitis. Clin. J. Pain 26, 326–331 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Savarino, E. et al. The role of nonacid reflux in NERD: lessons learned from impedance-pH monitoring in 150 patients off therapy. Am. J. Gastroenterol. 103, 2685–2693 (2008).

    Article  PubMed  Google Scholar 

  78. Peura, D. A., Haber, M. M., Hunt, B. & Atkinson, S. Helicobacter pylori-negative gastritis in erosive esophagitis, nonerosive reflux disease or functional dyspepsia patients. J. Clin. Gastroenterol. 44, 180–185 (2010).

    Article  PubMed  Google Scholar 

  79. Marshall, J. K. et al. Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology 131, 445–450 (2006).

    Article  PubMed  Google Scholar 

  80. Zanini, B. et al. Incidence of post-infectious irritable bowel syndrome and functional intestinal disorders following a water-borne viral gastroenteritis outbreak. Am. J. Gastroenterol. 107, 891–899 (2012).

    Article  PubMed  Google Scholar 

  81. Hanevik, K., Dizdar, V., Langeland, N. & Hausken, T. Development of functional gastrointestinal disorders after Giardia lamblia infection. BMC Gastroenterol. 9, 27 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Mearin, F. et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one-year follow-up cohort study. Gastroenterology 129, 98–104 (2005).

    Article  PubMed  Google Scholar 

  83. Dizdar, V., Gilja, O. H. & Hausken, T. Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-antagonist ondansetron. Neurogastroenterol. Motil. 19, 977–982 (2007).

    CAS  PubMed  Google Scholar 

  84. Futagami, S. et al. Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia. Am. J. Gastroenterol. 105, 1835–1842 (2010).

    Article  PubMed  Google Scholar 

  85. Ford, A. C. et al. Prevalence of uninvestigated dyspepsia 8 years after a large waterborne outbreak of bacterial dysentery: a cohort study. Gastroenterology 138, 1727–1736 (2010).

    Article  PubMed  Google Scholar 

  86. Parry, S. D. et al. Does bacterial gastroenteritis predispose people to functional gastrointestinal disorders? A prospective, community-based, case–control study. Am. J. Gastroenterol. 98, 1970–1975 (2003).

    PubMed  Google Scholar 

  87. Tack, J. et al. Clinical and pathophysiological characteristics of acute-onset functional dyspepsia. Gastroenterology 122, 1738–1747 (2002).

    Article  PubMed  Google Scholar 

  88. Quigley, E. M. M. & Craig, O. F. Irritable bowel syndrome; update on pathophysiology and management. Turk. J. Gastroenterol. 23, 313–322 (2012).

    Article  PubMed  Google Scholar 

  89. Craig, O. F., Hyland, N. P. & Quigley, E. M. Functional dyspepsia: eosinophils, macrophages, and the postinfectious state. Gastroenterology 140, 1092–1095 (2011).

    Article  PubMed  Google Scholar 

  90. Talley, N. J. et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin. Gastroenterol. Hepatol. 5, 1175–1183 (2007).

    Article  PubMed  Google Scholar 

  91. Walker, M. M. et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment. Pharmacol. Ther. 29, 765–773 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Walker, M. M. et al. Implications of eosinophilia in the normal duodenal biopsy—an association with allergy and functional dyspepsia. Aliment. Pharmacol. Ther. 31, 1229–1236 (2010).

    Article  CAS  PubMed  Google Scholar 

  93. Ronkainen, J. et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut 56, 615–620 (2007).

    Article  PubMed  Google Scholar 

  94. Almansa, C., Devault, K. R. & Achem, S. R. A comprehensive review of eosinophilic esophagitis in adults. J. Clin. Gastroenterol. 45, 658–664 (2011).

    Article  PubMed  Google Scholar 

  95. Schäppi, M. G. et al. Mast cell–nerve interactions in children with functional dyspepsia. J. Pediatr. Gastroenterol. Nutr. 47, 472–480 (2008).

    Article  PubMed  Google Scholar 

  96. Gargala, G. et al. Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia. World J. Gastroenterol. 13, 2333–2338 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Kindt, S., Tertychnyy, A., de Hertogh, G., Geboes, K. & Tack, J. Intestinal immune activation in presumed post-infectious functional dyspepsia. Neurogastroenterol. Motil. 21, 832–e56 (2009).

    Article  CAS  PubMed  Google Scholar 

  98. Liebregts, T. et al. Small bowel homing T cells are associated with symptoms and delayed gastric emptying in functional dyspepsia. Am. J. Gastroenterol. 106, 1089–1098 (2011).

    Article  CAS  PubMed  Google Scholar 

  99. Ronkainen, J. et al. Lymphocytic oesophagitis, a condition in search of a disease? Gut 61, 1776 (2012).

    Article  PubMed  Google Scholar 

  100. Creed, F. Somatisation in functional dyspepsia: integrating gastric physiology with psychological state. Gut 57, 1642–1643 (2008).

    Article  PubMed  Google Scholar 

  101. Van Oudenhove, L. et al. Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation? Gut 57, 1666–1673 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. Oh, J. H. et al. Relationship between psychological factors and quality of life in subtypes of gastroesophageal reflux disease. Gut Liver 3, 259–265 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Lee, K. J., Kwon, H. C., Cheong, J. Y. & Cho, S. W. Demographic, clinical, and psychological characteristics of the heartburn groups classified using the Rome III criteria and factors associated with the responsiveness to proton pump inhibitors in the gastroesophageal reflux disease group. Digestion 79, 131–136 (2009).

    Article  CAS  PubMed  Google Scholar 

  104. Moayyedi, P., Talley, N. J., Fennerty, M. B. & Vakil, N. Can the clinical history distinguish between organic and functional dyspepsia? JAMA 295, 1566–1576 (2006).

    Article  CAS  PubMed  Google Scholar 

  105. Numans, M. E. & de Wit, N. J. Reflux symptoms in general practice: diagnostic evaluation of the Carlsson-Dent gastroesophageal reflux disease questionnaire. Aliment. Pharmacol. Ther. 17, 1049–1055 (2003).

    Article  CAS  PubMed  Google Scholar 

  106. Klauser, A. G., Schindlbeck, N. E. & Muller-Lissner, S. A. Symptoms in gastro-oesophageal reflux disease. Lancet 335, 205–208 (1990).

    Article  CAS  PubMed  Google Scholar 

  107. Moayyedi, P. & Axon, A. T. R. The usefulness of the likelihood ratio in the diagnosis of dyspepsia and gastro-oesophageal reflux disease. Am. J. Gastroenterol. 4, 3122–3125 (1999).

    Article  Google Scholar 

  108. Garcia-Rodriguez, L. A. et al. Natural history of chest pain in GERD [abstract]. Gut 54 (Suppl. VII), A75 (2005).

    Google Scholar 

  109. El-Serag, H. B. & Sonnenberg, A. Comorbid occurrence of laryngeal or pulmonary disease with esophagitis in US military veterans. Gastroenterology 113, 755–760 (1997).

    Article  CAS  PubMed  Google Scholar 

  110. Gislason, T. et al. Respiratory symptoms and nocturnal gastro-oesophageal reflux: a population based study of young adults in three European countries. Chest 121, 158–163 (2002).

    Article  PubMed  Google Scholar 

  111. Cremonini, F., Wise, J., Moayyedi, P. & Talley, N. Diagnostic and therapeutic use of PPIs in non-cardiac chest pain: a meta-analysis. Am. J. Gastroenterol. 100, 1226–1232 (2005).

    Article  CAS  PubMed  Google Scholar 

  112. Hammer, J., Eslick, G. D., Howell, S. C., Altiparmak, E. & Talley, N. J. Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia. Gut 53, 666–672 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Talley, N. J., Vakil, N. B. & Moayyedi, P. American Gastroenterological Association technical review on the evaluation of dyspepsia. Gastroenterology 129, 1756–1780 (2005).

    Article  PubMed  Google Scholar 

  114. Lacy, B. E. & Cash, B. D. A 32-year-old woman with chronic abdominal pain. JAMA 299, 555–565 (2008).

    Article  CAS  PubMed  Google Scholar 

  115. Greatorex, R. A. & Thorpe, J. A. Clinical assessment of gastro-oesophageal reflux by questionnaire. Br. J. Clin. Pract. 37, 133–135 (1983).

    CAS  PubMed  Google Scholar 

  116. Locke, G. R., Talley, N. J., Weaver, A. L. & Zinsmeister, A. R. A new questionnaire for gastroesophageal reflux disease. Mayo Clin. Proc. 69, 539–547 (1994).

    Article  CAS  PubMed  Google Scholar 

  117. Carlsson, R. et al. The usefulness of a structured questionnaire in the assessment of symptomatic gastroesophageal reflux disease. Scand. J. Gastroenterol. 33, 1023–1029 (1998).

    Article  CAS  PubMed  Google Scholar 

  118. Shaw, M. J. et al. Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease. Am. J. Gastroenterol. 96, 52–57 (2001).

    Article  CAS  PubMed  Google Scholar 

  119. Moreno Elola-Olaso, C., Rey, E., Rodriguez-Artalejo, F., Locke, G. R. 3rd & Diaz-Rubio, M. Adaptation and validation of a gastroesophageal reflux questionnaire for use on a Spanish population. Rev. Esp. Enferm. Dig. 94, 745–758 (2002).

    CAS  PubMed  Google Scholar 

  120. Wong, W. M. et al. A validated symptoms questionnaire (Chinese GERDQ) for the diagnosis of gastro-esophageal reflux disease in the Chinese population. Aliment. Pharmacol. Ther. 17, 1407–1413 (2003).

    Article  CAS  PubMed  Google Scholar 

  121. Wang, J. H. et al. Composite score of reflux symptoms in diagnosis of gastroesophageal reflux disease. World J. Gastroenterol. 10, 3332–3335 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  122. [No authors listed] Value of reflux diagnostic questionnaire in the diagnosis of gastroesophageal reflux disease. Chin. J. Dig. Dis. 5, 51–55 (2004).

  123. Zimmerman, J. Validation of a brief inventory for diagnosis and monitoring of symptomatic gastroesophageal reflux. Scand. J. Gastroenterol. 39, 212–216 (2004).

    Article  CAS  PubMed  Google Scholar 

  124. Shimoyama, Y. et al. Diagnosis of gastroesophageal reflux disease using a new questionnaire. J. Gastroenterol. Hepatol. 20, 643–647 (2005).

    Article  PubMed  Google Scholar 

  125. Horowitz, N., Moshkowitz, M., Halpern, Z. & Leshno, M. Applying data mining techniques in the development of a diagnostic questionnaire for GERD. Dig. Dis. Sci. 52, 1871–1878 (2007).

    Article  PubMed  Google Scholar 

  126. Ho, K. Y. et al. Validation of a graded response questionnaire for the diagnosis of gastroesophageal reflux disease in an Asian primary care population. J. Clin. Gastroenterol. 42, 680–686 (2008).

    Article  PubMed  Google Scholar 

  127. Kinekawa, F. et al. Is the questionnaire for the assessment of gastroesophageal reflux useful for diabetic patients? Scand. J. Gastroenterol. 40, 1017–1020 (2005).

    Article  PubMed  Google Scholar 

  128. Hung, C. S. et al. Clinical application of Carlsson's questionnaire to predict erosive GERD among healthy Chinese. J. Gastroenterol. Hepatol. 20, 1900–1095 (2005).

    Article  PubMed  Google Scholar 

  129. Lind, T. et al. Heartburn without esophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand. J. Gastroenterol. 32, 974–979 (1997).

    Article  CAS  PubMed  Google Scholar 

  130. Mantynen, T. et al. The impact of upper GI endoscopy referral volume on the diagnosis of gastroesophageal reflux disease and its complications: a 1-year cross-sectional study in a referral area with 260,000 inhabitants. Am. J. Gastroenterol. 97, 2524–2529 (2002).

    Article  PubMed  Google Scholar 

  131. Richter, J. E. Severe reflux esophagitis. Gastrointest. Endosc. Clin. N. Am. 4, 677–697 (1994).

    Article  CAS  PubMed  Google Scholar 

  132. Lundell, L. R. et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 45, 172–180 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vigneri, S. et al. A comparison of five maintenance therapies for reflux esophagitis. N. Engl. J. Med. 333, 1106–1110 (1995).

    Article  CAS  PubMed  Google Scholar 

  134. Kahrilas, P. J. et al. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease. Gastroenterology 135, 1383–1391 (2008).

    Article  PubMed  Google Scholar 

  135. Sharma, P. et al. A feasibility trial of narrow band imaging endoscopy in patients with gastroesophageal reflux disease. Gastroenterology 133, 454–464 (2007).

    Article  PubMed  Google Scholar 

  136. Amano, Y. et al. Does magnifying endoscopy improve the diagnosis of erosive esophagitis? J. Gastroenterol. Hepatol. 23, 1063–1068 (2008).

    Article  PubMed  Google Scholar 

  137. Small, P. K. et al. Importance of reflux symptoms in functional dyspepsia. Gut 36, 189–192 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Bolling-Sternevald, E. et al. Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial. Scand. J. Gastroenterol. 37, 1395–1402 (2002).

    Article  CAS  PubMed  Google Scholar 

  139. Tack, J. et al. Prevalence of acid reflux in functional dyspepsia and its association with symptom profile. Gut 54, 1370–1376 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Stacher, G. et al. Gastric emptying: a contributory factor in gastro-oesophageal reflux activity. Gut 47, 661–666 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. McCallum, R. W., Berkowitz, D. M. & Lerner, E. Gastric emptying in patients with gastroesophageal reflux. Gastroenterology 80, 285–291 (1981).

    Article  CAS  PubMed  Google Scholar 

  142. Keshavarzian, A., Bushnell, D. L., Sontag, S., Yegelwel, E. J. & Smid, K. Gastric emptying in patients with severe reflux esophagitis. Am. J. Gastroenterol. 86, 738–742 (1991).

    CAS  PubMed  Google Scholar 

  143. Sarnelli, G. et al. Symptoms associated with impaired gastric emptying of solids and liquids in functional dyspepsia. Am. J. Gastroenterol. 98, 783–788 (2003).

    Article  PubMed  Google Scholar 

  144. Maes, B. D., Ghoos, Y. F., Hiele, M. I. & Rutgeerts, P. J. Gastric emptying rate of solids in patients with nonulcer dyspepsia. Dig. Dis. Sci. 42, 1158–1162 (1997).

    Article  CAS  PubMed  Google Scholar 

  145. Lacy, B. E. Functional dyspepsia and gastroparesis: one disease or two? Am. J. Gastroenterol. 107, 1615–1620 (2012).

    Article  PubMed  Google Scholar 

  146. Sontag, S. J. Rolling review: gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 7, 293–298 (1993).

    Article  CAS  PubMed  Google Scholar 

  147. Bell, N. J. V. & Hunt, R. H. Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease. Gut 33, 118–125 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Moayyedi, P. et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD001960 http://dx.doi.org/10.1002/14651858.CD001960.pub3.

  149. Chiba, N., De Gara, C. J., Wilkinson, J. M. & Hunt, R. H. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology 112, 1798–1810 (1997).

    Article  CAS  PubMed  Google Scholar 

  150. Khan, M., Santana, J., Donnellan, C., Preston, C. & Moayyedi, P. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD003244 http://dx.doi.org/10.1002.CD003244.pub2.

  151. Kahrilas, P. J. Gastroesophageal reflux disease. N. Engl. J. Med. 359, 1700–1707 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Kahrilas, P. J., Howden, C. W. & Hughes, N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am. J. Gastroenterol. 106, 1419–1425 (2011).

    Article  PubMed  Google Scholar 

  153. Tominaga, K. et al. Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan. J. Gastroenterol. 47, 284–292 (2012).

    Article  CAS  PubMed  Google Scholar 

  154. Wong, W. M. et al. Double blind, randomised, placebo controlled study of four weeks of lansoprazole for the treatment of functional dyspepsia in Chinese patients. Gut 51, 502–506 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Peura, D. A. et al. Lansoprazole in the treatment of functional dyspepsia: two double-blind, randomized, placebo-controlled trials. Am. J. Med. 116, 740–748 (2004).

    Article  CAS  PubMed  Google Scholar 

  156. van Zanten, S. V. et al. Esomeprazole 40 mg once a day in patients with functional dyspepsia: the randomized, placebo-controlled “ENTER” trial. Am. J. Gastroenterol. 101, 2096–2106 (2008).

    Article  CAS  Google Scholar 

  157. van Rensburg, C. et al. Efficacy and safety of pantoprazole 20 mg once daily treatment in patients with ulcer-like functional dyspepsia. Curr. Med. Res. Opin. 24, 2009–2018 (2008).

    Article  CAS  PubMed  Google Scholar 

  158. Wang, W. H. et al. Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials. Clin. Gastroenterol. Hepatol. 5, 178–185 (2007).

    Article  CAS  PubMed  Google Scholar 

  159. Hameeteman, W. Clinical studies of sucralfate in reflux esophagitis: the European experience. J. Clin. Gastroenterol. 13 (Suppl. 2), 816–826 (1991).

    Google Scholar 

  160. Williams, R. M. et al. Multicenter trial of sucralfate suspension for the treatment of reflux esophagitis. Am. J. Med. 83 (Suppl. 3B), 61–71 (1987).

    Article  CAS  PubMed  Google Scholar 

  161. Misra, S. P., Dwivedi, M., Misra, V. & Agarwal, S. K. Sucralfate versus ranitidine in non-ulcer dyspepsia: results of a prospective, randomized, open, controlled trial. Indian J. Gastroenterol. 11, 7–8 (1992).

    CAS  PubMed  Google Scholar 

  162. McCallum, R. W., Kline, M. M., Curry, N. & Sturdevant, R. A. Comparative effects of metoclopramide and bethanechol on lower esophageal sphincter pressure in reflux patients. Gastroenterology 68, 1114–1118 (1975).

    CAS  PubMed  Google Scholar 

  163. McCallum, R. W., Fink, S. M., Lerner, E. & Berkowitz, D. M. Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients. Gastroenterology 84, 1573–1577 (1983).

    Article  CAS  PubMed  Google Scholar 

  164. Saco, L. S. et al. Double-blind controlled trial of bethanechol and antacid versus placebo and antacid in the treatment of erosive esophagitis. Gastroenterology 82, 1369–1373 (1982).

    Article  CAS  PubMed  Google Scholar 

  165. Orenstein, S. R., Lofton, S. W. & Orenstein, D. M. Bethanechol for pediatric gastroesophageal reflux: a prospective, blind, controlled study. J. Pediatr. Gastroenterol. Nutr. 5, 549–555 (1986).

    Article  CAS  PubMed  Google Scholar 

  166. Champion, G., Richter, J. E., Singh, S., Schan, C. & Nellans, H. Effects of oral erythromycin on esophageal pH and pressure profiles in patients with gastroesophageal reflux disease. Dig. Dis. Sci. 39, 129–137 (1994).

    Article  CAS  PubMed  Google Scholar 

  167. Pasricha, P. J., Pehlivanov, N., Sugumar, A. & Jankovic, J. Drug Insight: from disturbed motility to disordered movement—a review of the clinical benefits and medicolegal risks of metoclopramide. Nat. Clin. Pract. Gastroenterol. Hepatol. 3, 138–148 (2006).

    Article  CAS  PubMed  Google Scholar 

  168. Quigley, E. M. M. Cisapride. What can we learn from the rise and fall of a prokinetic? J. Dig. Dis. 12, 147–156 (2011).

    Article  CAS  PubMed  Google Scholar 

  169. Vakil, N. et al. Tegaserod treatment for dysmotility-like functional dyspepsia: results of two randomized, controlled trials. Am. J. Gastroenterol. 101, 1906–1919 (2008).

    Google Scholar 

  170. Holtmann, G., Talley, N. J., Liebregts, T., Adam, B. & Parow, C. A placebo-controlled trial of itopride in functional dyspepsia. N. Engl. J. Med. 354, 832–840 (2006).

    Article  CAS  PubMed  Google Scholar 

  171. Talley, N. J., Tack, J., Ptak, T., Gupta, R. & Giguère, M. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut 57, 740–746 (2008).

    Article  CAS  PubMed  Google Scholar 

  172. Hallerbäck, B. I. et al. Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study. Aliment. Pharmacol. Ther. 16, 959–967 (2002).

    Article  PubMed  Google Scholar 

  173. Tack, J. et al. A dose-ranging, placebo-controlled, pilot trial of acotiamide in patients with functional dyspepsia. Neurogastroenterol. Motil. 21, 272–280 (2009).

    Article  CAS  PubMed  Google Scholar 

  174. Matsueda, K. et al. Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia—100 mg t.i.d. is an optimal dose. Neurogastroenterol. Motil. 22, 618–e173 (2010).

    Article  CAS  PubMed  Google Scholar 

  175. Matsueda, K. et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut 61, 821–828 (2012).

    Article  CAS  PubMed  Google Scholar 

  176. Talley, N. J. et al. Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial. Aliment. Pharmacol. Ther. 14, 1653–1661 (2000).

    Article  CAS  PubMed  Google Scholar 

  177. Saarto, T. & Wiffen, P. J. Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews, Issue 4, Art. No.: CD005454. http://dx/doi.org/10.1002.14651858.CD005454.pub2.

  178. Ford, A. C., Talley, N., Schoenfeld, P. S., Quigley, E. M. & Moayyedi, P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58, 367–378 (2009).

    Article  CAS  PubMed  Google Scholar 

  179. Mertz, H. et al. Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. Am. J. Gastroenterol. 93, 160–165 (1998).

    Article  CAS  PubMed  Google Scholar 

  180. Otaka, M. et al. New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment. Pharmacol. Ther. 21 (Suppl. 2), 42–46 (2005).

    Article  CAS  PubMed  Google Scholar 

  181. Wu, J. C. et al. A randomized, double-blind, placebo-controlled trial of low dose imipramine for treatment of refractory functional dyspepsia (FD) [Abstact]. Gastroenterology 140 (Suppl. 1) S-50 (2011).

    Article  Google Scholar 

  182. Viazis, N. et al. Selective-serotonin reuptake inhibitors for the treatment of hypersensitive esophagus. A placebo controlled study using esophageal pH-impedance monitoring. Am. J. Gastroenterol. 107, 1662–1667 (2012).

    Article  CAS  PubMed  Google Scholar 

  183. van Kerkhoven, L. A. et al. Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double-blind, placebo-controlled trial. Clin. Gastroenterol. Hepatol. 6, 746–752 (2008).

    Article  CAS  PubMed  Google Scholar 

  184. Eisenberg, D. M. et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 280, 1569–1575 (1998).

    Article  CAS  PubMed  Google Scholar 

  185. Barnes, P. M., Powell-Griner, E., McFann, K. & Nahin, R. L. Complementary and alternative medicine use among adults: United States, 2002. Adv. Data 343, 1–19 (2004).

    Google Scholar 

  186. Dickman, R. et al. Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn. Aliment. Pharmacol. Ther. 26, 1333–1344 (2007).

    Article  CAS  PubMed  Google Scholar 

  187. Madisch, A., Holtmann, G., Mayr, G., Vinson, B. & Hotz, J. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion 69, 45–52 (2004).

    Article  CAS  PubMed  Google Scholar 

  188. von Arnim, U., Peitz, U., Vinson, B., Gundermann, K. J. & Malfertheiner, P. STW 5, a phytopharmacon for patients with functional dyspepsia: results of a multicenter, placebo-controlled double-blind study. Am. J. Gastroenterol. 102, 1268–1275 (2007).

    Article  CAS  PubMed  Google Scholar 

  189. Braden, B., Caspary, W., Borner, N., Vinson, B. & Schneider, A. R. J. Clinical effects of STW 5 (Iberogast) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis. Neurogastroenterol. Motil. 21, 632–639 (2009).

    Article  CAS  PubMed  Google Scholar 

  190. Holtmann, G. et al. Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six-week placebo-controlled, double-blind, multicentre trial. Aliment. Pharmacol. Ther. 18, 1099–1105 (2003).

    Article  CAS  PubMed  Google Scholar 

  191. May, B., Kohler, S. & Schneider, B. Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia. Aliment. Pharmacol. Ther. 14, 1671–1677 (2000).

    Article  CAS  PubMed  Google Scholar 

  192. Quigley, E. M. & DiBaise, J. K. Non-erosive reflux disease: the real problem in gastro-oesophageal reflux disease. Dig. Liver Dis. 33, 523–527 (2001).

    Article  CAS  PubMed  Google Scholar 

  193. Quigley, E. M. Functional dyspepsia (FD) and non-erosive reflux disease (NERD): overlapping or discrete entities? Best Pract. Res. Clin. Gastroenterol. 18, 695–706 (2004).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Both authors contributed equally to all aspects of this manuscript.

Corresponding author

Correspondence to Eamonn M. M. Quigley.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Box 1

Montreal Definition of GERD (DOC 30 kb)

Supplementary Box 2

Rome III Criteria for Functional Dyspepsia (DOC 33 kb)

Supplementary Table 1

NERD subgroups (DOC 38 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quigley, E., Lacy, B. Overlap of functional dyspepsia and GERD—diagnostic and treatment implications. Nat Rev Gastroenterol Hepatol 10, 175–186 (2013). https://doi.org/10.1038/nrgastro.2012.253

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2012.253

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing