Proton pump inhibitors (PPIs) are the most widely used drugs for treatment of gastroesophageal reflux disease. However, approximately 20% of patients with reflux esophagitis and 40% of those with nonerosive reflux diseases complain of troublesome symptoms, even during treatment with PPIs. In patients with reflux esophagitis, dose escalation and co-administration with a histamine H2-receptor antagonist are potential approaches, since the major cause of PPI resistance is incomplete suppression of gastric acid secretion. On the other hand, for patients with nonerosive reflux disease, switching from PPIs to pain modulators is often necessary for improvement of symptoms, since 25% of patients with nonerosive reflux disease have symptoms not caused by gastroesophageal acid reflux. Therapeutic approaches for PPI-resistant patients with reflux esophagitis and nonerosive reflux diseases are considered according to pathogenesis.
Adachi, K., Katsube, T., Kawamura, A., Takashima, T., Yuki, M., Amano, K. et al. (2000) CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole. Aliment Pharmacol Ther14: 1259-1266.
2.
Adachi, K., Fujishiro, H., Katsube, T., Yuki, M., Ono, M., Kawamura, A. et al. (2001) Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis. J Gastroenterol Hepatol16: 1191-1196.
3.
Adachi, K., Komazawa, Y., Fujishiro, H., Mihara, T., Ono, M., Yuki, M. et al. (2003) Nocturnal gastric acid breakthrough during the administration of rabeprazole and ranitidine in Helicobacter pylori-negative subjects: effects of different regimens. J Gastroenterol38: 830-835.
4.
Adachi, K., Komazawa, Y., Mihara, T., Fujishiro, H., Ishihara, S., Amano, Y. et al. (2004) Administration of H2 receptor antagonist with proton pump inhibitor is effective for long-term control of refractory reflux esophagitis. J Clin Gastroenterol38: 297-298.
5.
Broekaert, D., Fischler, B., Sifrim, D., Janssens, J. and Tack, J. (2006) Influence of citalopram, a selective serotonin reuptake inhibitor, on oesophageal hypersensitivity: a double-blind, placebo-controlled study. Aliment Pharmacol Ther23: 365-370.
6.
Castell, D.O., Kahrilas, P.J., Richter, J.E., Vakil, N.B., Johnson, D.A., Zuckerman, S. et al. (2002)
7.
Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis. Am J Gastroenterol97: 575-583.
8.
Cho, Y.K., Choi, M.G., Han, H.W., Park, J.M., Oh, J.H., Jeong, J.J. et al. (2006) The effect of mosapride on esophageal motility and bolus transit in asymptomatic volunteers. J Clin Gastroenterol40: 286-292.
9.
de Groen, P.C., Lubbe, D.F., Hirsch, L.J., Daifotis, A., Stephenson, W., Freedholm, D. et al. (1996) Esophagitis associated with the use of alendronate. N Engl J Med335: 1016-1021.
10.
Ekström, T. and Tibbling, L. (1988) Influence of theophylline on gastro-oesophageal reflux and asthma. Eur J Clin Pharmacol35: 353-356.
11.
Emerenziani, S., Sifrim, D., Habib, F.I., Ribolsi, M., Guarino, M.P., Rizzi, M. et al. (2008) Presence of gas in the refluxate enhances reflux perception in nonerosive patients with physiological acid exposure of the oesophagus. Gut57: 443-447.
12.
Fass, R., Shapiro, M., Dekel, R. and Sewell, J. (2005) Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease - where next? Aliment Pharmacol Ther22: 79-94.
13.
Fass, R., Naliboff, B.D., Fass, S.S., Peleg, N., Wendel, C., Malagon, I.B. et al. (2008) The effect of auditory stress on perception of intraesophageal acid in patients with gastroesophageal reflux disease. Gastroenterology134: 696-705.
14.
Fujisawa, T., Adachi, K., Komazawa, Y., Mihara, T., Azumi, T., Katsube, T. et al. (2004) Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of histamine H2 receptor antagonists . Aliment Pharmacol Ther20: 559-565.
15.
Fujishiro, H., Adachi, K., Kawamura, A., Katsube, T., Ono, M., Yuki, M. et al. (2001) Influence of Helicobacter pylori infection on the prevalence of reflux esophagitis in Japanese patients. J Gastroenterol Hepatol16: 1217-1221.
16.
Furuta, T., Ohashi, K., Kosuge, K., Zhao, X.J., Takashima, M., Kimura, M. et al. (1999) CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther65: 552-561.
17.
Galmiche, J.P., Clouse, R.E., Bálint, A., Cook, I.J., Kahrilas, P.J., Paterson, W.G. et al. (2006) Functional esophageal disorders. Gastroenterology130: 1459-1465.
18.
Gunaratnam, N.T., Jessup, T.P., Inadomi, J. and Lascewski, D.P. (2006) Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastro-oesophageal reflux disease. Aliment Pharmacol Ther23: 1473-1477.
19.
Hatlebakk, J.G., Katz, P.O., Camacho-Lobato, L. and Castell, D.O. (2000) Proton pump inhibitors: better acid suppression when taken before a meal than without a meal. Aliment Pharmacol Ther14: 1267-1272.
20.
Hershcovici, T. and Zimmerman, J. (2008) Functional heartburn vs. non-erosive reflux disease: similarities and differences. Aliment Pharmacol Ther27: 1103-1109.
21.
Hirakawa, K., Adachi, K., Amano, K., Katsube, T., Ishihara, S., Fukuda, R. et al. (1999) Prevalence of non-ulcer dyspepsia in the Japanese population. J Gastroenterol Hepatol14: 1083-1087.
22.
Hongo, M., Kinoshita, Y. and Haruma, K. (2008) A randomized, double-blind, placebo-controlled clinical study of the histamine H2-receptor antagonist famotidine in Japanese patients with nonerosive reflux disease. J Gastroenterol43: 448-456.
23.
Iwakiri, K., Hayashi, Y., Kotoyori, M., Tanaka, Y., Kawami, N., Sano, H. et al. (2007) Defective triggering of secondary peristalsis in patients with non-erosive reflux disease. J Gastroenterol Hepatol22: 2208-2211.
24.
Kataoka, H., Horie, Y., Koyama, R., Nakatsugi, S. and Furukawa, M. (2000) Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a preferential COX-2 inhibitor in the stomach. Dig Dis Sci45: 1366-1375.
25.
Katsube, T., Adachi, K., Kawamura, A., Amano, K., Uchida, Y., Watanabe, M. et al. (2000) Helicobacter pylori infection influences nocturnal gastric acid breakthrough. Aliment Pharmacol Ther14: 1049-1056.
26.
Kawamura, M., Ohara, S., Koike, T., Iijima, K., Suzuki, J., Kayaba, S. et al. (2003) The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism. Aliment Pharmacol Ther17: 965-973.
27.
Kim, S.L., Hunter, J.G., Wo, J.M., Davis, L.P. and Waring, J.P. (1999) NSAIDs, aspirin, and esophageal strictures: are over-the-counter medications harmful to the esophagus?J Clin Gastroenterol29: 32-34.
28.
Kinoshita, Y., Kawanam, C., Kishi, K.Nakata, H., Seino, Y. and Chiha, T. (1997) Helicobacter pylo: independent chronological change in gastric acid secretion in the Japanese. Gut41: 457-408.
29.
Kinoshita, Y., Kobayashi, T., Kato, M., Asahina, K., Haruma, K., Shimatani, T. et al. (2006) The pharmacodynamic effect of omeprazole 10 mg and 20 mg once daily in patients with nonerosive reflux disease in Japan . J Gastroenterol41: 554-561.
30.
Knowles, C.H. and Aziz, Q. (2008) Visceral hypersensitivity in non-erosive reflux disease. Gut57: 674-683.
31.
Komazawa, Y., Adachi, K., Mihara, T., Ono, M., Kawamura, A., Fujishiro, H. et al. (2003) Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection. J Gastroenterol Hepatol18: 678-682.
32.
Kusano, M., Ino, K., Yamada, T., Kawamura, O., Toki, M., Ohwada, T. et al. (1999) Interobserver and intraobserver variation in endoscopic assessment of GERD using the ``Los Angeles'' classification . Gastrointest Endosc49: 700-704.
33.
Labenz, J., Armstrong, D., Lauritsen, K., Katelaris, P., Schmidt, S., Schütze, K. et al. (2005) A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study. Aliment Pharmacol Ther21: 739-746.
34.
Lind, T., Havelund, T., Carlsson, R., Anker-Hansen, O., Glise, H., Hernqvist, H. et al. (1997) Heartburn without oesophagitis: efficacy of omeprazole therapy and features determining therapeutic response. Scand J Gastroenterol32: 974-979.
35.
Lundell, L., Miettinen, P., Myrvold, H.E., Pedersen, S.A., Thor, K., Lamm, M. et al. (2000) Long-term management of gastro-oesophageal reflux disease with omeprazole or open antireflux surgery: results of a prospective, randomized clinical trial. Eur J Gastroenterol Hepatol12: 879-887.
36.
Lundell, L.R., Dent, J., Bennett, J.R., Blum, A.L., Armstrong, D., Galmiche, J.P. et al. (1999) Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification . Gut45: 172-180.
37.
Miki, M., Adachi, K., Azumi, T., Koshino, K., Furuta, K. and Kinoshita, Y. (2006) A comparative study of intragastric acidity during post-breakfast and pre-dinner administration of low-dose proton pump inhibitors: a randomized three-way crossover study. Aliment Pharmacol Ther24: 1445-1451.
38.
Mishima, I., Adachi, K., Arima, N., Amano, K., Takashima, T., Moritani, M. et al. (2005) Prevalence of endoscopically negative and positive gastroesophageal reflux disease in the Japanese. Scand J Gastroenterol40: 1005-1009.
39.
Miwa, H., Sasaki, M., Furuta, T., Koike, T., Habu, Y., Ito, M. et al. (2007) Efficacy of rabeprazole on heartburn symptom resolution in patients with non-erosive and erosive gastro-oesophageal reflux disease: a multicenter study from Japan. Aliment Pharmacol Ther26: 69-77.
40.
Nojkov, B., Rubenstein, J.H., Adlis, S.A., Shaw, M.J., Saad, R., Rai, J. et al. (2008) The influence of co-morbid IBS and psychological distress on outcomes and quality of life following PPI therapy in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther27: 473-482.
41.
Richter, J.E., Dalton, C.B., Buice, R.G. and Castell, D.O. (1985) Nifedipine: a potent inhibitor of contractions in the body of the human esophagus. Studies in healthy volunteers and patients with the nutcracker esophagus. Gastroenterology89: 549-554.
42.
Robertson, D., Aldersley, M., Shepherd, H. and Smith, C.L. (1987) Patterns of acid reflux in complicated oesophagitis . Gut28: 1484-1488.
43.
Ruth, M., Hamelin, B., Röhss, K. and Lundell, L. (1998) The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther12: 35-40.
44.
Ruth, M., Finizia, C., Cange, L. and Lundell, L. (2003) The effect of mosapride on oesophageal motor function and acid reflux in patients with gastro-oesophageal reflux disease. Eur J Gastroenterol Hepatol15: 1115-1121.
45.
Savarino, V., Mela, G.S., Zentilin, P., Cimmino, M.A., Parisi, M., Mele, M.R. et al. (1998) Effect of one-month treatment with nonsteroidal antiinflammatory drugs (NSAIDs) on gastric pH of rheumatoid arthritis patients . Dig Dis Sci43: 459-463.
46.
Schey, R., Dickman, R., Parthasarathy, S., Quan, S.F., Wendel, C., Merchant, J. et al. (2007) Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease. Gastroenterology133: 1787-1795.
47.
Shirota, T., Kusano, M., Kawamura, O., Horikoshi, T., Mori, M. and Sekiguchi, T. (1999) Helicobacter pylori infection correlates with severity of reflux esophagitis: with manometry findings. J Gastroenterol34: 553-559.
48.
Soga, T., Matsuura, M., Kodama, Y., Fujita, T., Sekimoto, I., Nishimura, K. et al. (1999) Is a proton pump inhibitor necessary for the treatment of lower-grade reflux esophagitis? J Gastroenterol34: 435-440.
49.
Sontag, S.J., Sonnenberg, A., Schnell, T.G., Leya, J. and Metz, A. (2006) The long-term natural history of gastroesophageal reflux disease. J Clin Gastroenterol40: 398-404.
50.
Tack, J. and Fass, R. (2004) Review article: approaches to endoscopic-negative reflux disease: part of the GERD spectrum or a unique acid-related disorder ? Aliment Pharmacol Ther19(suppl.1): 28-34.
51.
Taha, A.S., Angerson, W.J., Knill-Jones, R.P. and Blatchford, O. (2006) Upper gastrointestinal mucosal abnormalities and blood loss complicating low-dose aspirin and antithrombotic therapy. Aliment Pharmacol Ther23: 489-495.
52.
Tobey, N.A., Carson, J.L., Alkiek, R.A. and Orlando, R.C. (1996) Dilated intercellular spaces: a morphological feature of acid reflux-damaged human esophageal epithelium. Gastroenterology111: 1200-1205.
53.
Vakil, N., Shaw, M. and Kirby, R. (2003) Clinical effectiveness of laparoscopic fundoplication in a U.S. community. Am J Med114: 1-5.
54.
Vakil, N., van Zanten, S.V., Kahrilas, P., Dent, J. and Jones, R. (2006) The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol101: 1900-1920.
55.
Vakil, N. (2007) Review article: the role of surgery in gastro-oesophageal reflux disease. Aliment Pharmacol Ther25: 1365-1372.
56.
Vandenplas, Y., De Wolf, D. and Sacre, L. (1986) Influence of xanthines on gastroesophageal reflux in infants at risk for sudden infant death syndrome. Pediatrics77: 807-810.
57.
Wong, B.C. and Kinoshita, Y. (2006) Systematic review on epidemiology of gastroesophageal reflux disease in Asia. Clin Gastroenterol Hepatol4: 398-407.
58.
Wu, J.C., Cheung, C.M., Wong, V.W. and Sung, J.J. (2007) Distinct clinical characteristics between patients with nonerosive reflux disease and those with reflux esophagitis. Clin Gastroenterol Hepatol5: 690-695.
59.
Yamada, S., Onda, M., Kato, S., Matsuda, N., Matsuhisa, T., Yamada, N. et al. (2001) Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian po pulations. J Gastroenterol36: 669-672.
