Disclosures. GI Motility Disorders. Gastrointestinal Motility Disorders & Irritable Bowel Syndrome

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Gastrointestinal Motility Disorders & Irritable Bowel Syndrome None Disclosures Jasmine Zia, MD Acting Assistant Professor Division of Gastroenterology, University of Washington 6 th Asian Health Symposium October 6, 2017 GI Motility Disorders GI Motility Disorders: Highlighting Differences in Asians Organ GI Motility Disorders Esophagus GERD Achalasia Esophageal Spasms: DES, Nutcracker, Jackhammer Ineffective Esophageal Motility Stomach Gastroparesis Small Bowel Small Bowel Dysmotility Colon Slow Transit Constipation Organ GI Motility Disorders Any Differences in Asians Esophagus GERD Yes Achalasia No Esophageal Spasms??? Ineffective Esophageal Motility??? Stomach Gastroparesis??? Small Bowel Small Bowel Dysmotility??? Colon Slow Transit Constipation Possibly 1

Gastroesophageal Reflux Disease Lower Prevalence of GERD in Asians Ethnic Background GERD Prevalence (Weekly) Caucasians 28% Asians 8% Chinese 3% Taiwan 7% Hong Kong 3% Japanese 5% Malaysians 6% Koreans 8% Indians 8% Iranians 8% Turkish 20% J Clin Gastroenterol 2015;50(1):e1 e7. Journal of Gastroenterology and Hepatology, 2011;26: 816 824. GERD Related Complications in Asians Compared to Caucasians Barrett s Esophagus in Asians % Prevalence 40 35 30 25 20 15 10 5 0 Esophagitis Barrett's Esophagus White Hiatal Hernia Asian Stricture Ethnic Background Barrett s Esophagus Prevalence Asians 0.06% to 6% Indians 6 to 23.6%% Japanese 19.9% Chinese 1% Taiwan 0.8% Koreans 0.22% Dig Dis Sci. 2009;54(5): 964 71. Journal of Gastroenterology and Hepatology, 2011;26: 816 824. 2

Esophageal Adenocarcinoma in Asians Ethnic Background Prevalence Death Rate Japanese Increasing 3.7 to 6.9 per 100,000 population from 1960 to 1995 Singapore Increasing 0.03 to 0.13 per 100,000 population from 1968 to 2002 Chinese Hong Kong Decreasing 11.7% to 6.4% from 1988 to 2003 Taiwan Unchanged Korea Unchanged Why are Asians less likely to get GERD? Lower rates of hiatal hernias Lower rates of transient LES relaxations Smaller gastric parietal cell mass Lower gastric acid output Journal of Gastroenterology and Hepatology, 2011;26: 816 824. Dig Dis Sci. 2009;54(5): 964 71. Journal of Gastroenterology and Hepatology, 2011;26: 816 824. Why else is GERD less prevalent in Asians? Heartburn has no direct translation Lower awareness of GERD in Asian countries where peptic ulcer and gastric cancer are highly prevalent Less likely to seek medical attention for GERD 70 96% of survey participants with GERD do not consult their medical practitioner Prevalence of GERD is rising in Asians Ethnic Background Change in Weekly GERD Prevalence Asians 5.2% (2005) 8.5% (2010) Koreans 7.1% (2002) 7.9% (2007) Singapore 5.5% (1994) 10.5% (1999) Ethnic Background Change in Esophagitis Prevalence Taiwan 5% (1995) 12.6% (2002) Koreans 1.8% (1995) 9.1% (2005) Malaysians 2.7% (1992) 9.0% (2001) Singapore 3.9% (1992) 9.8% (2001) Philippines 2.9% (1992) 6.3% (2002) J Clin Gastroenterol 2015;50(1):e1 e7. Diseases of the Esophagus, 2011;24(1):18 24. J Clin Gastroenterol 2015;50(1):e1 e7. Journal of Gastroenterology and Hepatology, 2011;26: 816 824. 3

Why is GERD increasing amongst Asians? Increased awareness Increasing age Rapid urbanization Adoption of Western lifestyle Dietary habits Resultant obesity Decline in H pylori H pylori colonization decreases gastric acid output GERD symptoms present differently in Asians than Caucasians Caucasians Heartburn Acid regurgitation Diseases of the Esophagus, 2011;24(1):18 24. J Clin Gastroenterol 2015;50(1):e1 e7. Asians Non cardiac chest pain Dyspepsia/epigastric pain Feeling of stomach acidity Extra esophageal Typical acid reflux symptoms are uncommon (8 15%) Treatment Approach of GERD for Asians Start with: Upper endoscopy H pylori test and treat More cost effective than empirical PPI test as the initial diagnostic strategy for patients with reflux symptoms. Asians response to PPIs More profound gastric acid suppression Higher rate of healing of esophagitis Required lower maintenance dose of PPI Why??? Smaller parietal cell mass Higher prevalence of poor metabolizers due to cp450 2C19 polymorphism > higher plasma PPI levels Higher prevalence of H pylori: enhances acid suppressing effects of PPI through increased intensity of corpus gastritis, which further suppresses the acid secretory function 4

Asians are less likely to respond to PPIs H Pylori Eradication and GERD PPI Response Rates Asians Non Asians P value Week 4 44.3% 60.7% < 0.001 Week 8 63.6% 72.2% 0.010 Similar to Caucasians: Higher response rates for ERD (71.3%) versus NERD (48.5%) ERD and less severe GI symptoms predicted symptomatic response to PPIs. Unlike Caucasians: Lower BMI did not predict response to PPI therapy Caucasians Little effect on GERD severity (in terms of symptom relapse after withdrawal of acid suppressive therapy) Asians Higher failure rates of stepdown therapy compared to patients with persistent infection 43% vs 21%, P = 0.04 Increase in esophageal acid exposure Attributed to higher prevalence of CagA+ strain of H pylori and more severe corpus gastritis BMC Gastroenterology 2014;14:156. Recommendations for H pylori Achalasia Current consensus: eradicate H pylori before long term PPI in Asian patients with GERD. H pylori eradication prevents progression of atrophic gastritis (premalignant condition). This is a big deal where the incidence of gastric cancer is high. 5

Prevalence of Achalasia in Asians Equivalent to Non Asians In a Singapore Study, within Asians: Esophageal Manometry: Differences in Normal Values in Asians EMAN Value Caucasians Asians Integrated Relaxation Pressure < 15 mmhg < 20.5 mmhg Chinese Indian Malay Dig Dis Sci 1993;38(10):1920 5 Journal of Gastroenterology and Hepatology 1999;14:791 795. Journal of Gastroenterology and Hepatology 2013;28:1611 1615. Constipation Bowel transit times may be faster in Asians Ethnic Background Colon Transit Times (h) Caucasians Americans 56.2 Canadians 93 French 67 Asians Hong Kong 62 Japanese 33.9 Journal of Gastroenterology and Hepatology 2004;19:1270 1275. Lancet 1977;2(8029):110 1. 6

Asian Factors Affecting Colon Transit Times Prevalence of Constipation by Country Factor Lactose intolerance H pylori Effect on Colon Transit Times Reduction Reduction Eur J of Clin Investigation 2006;737 742. Best Practice & Research Clinical Gastroenterology 2011;25:3 18. Sex Differences in Constipation in Asians versus Non Asians Caucasians Asians Laxative Use Amongst Asians with Constipation 100 80 > = % using laxatives 60 40 20 Women Men 0 China Indonesia South Korea Aliment Pharmacol Ther. 2010;31(2):274 84. Aliment Pharmacol Ther. 2010;31(2):274 84. 7

Irritable Bowel Syndrome Irritable Bowel Syndrome (IBS) ROME IV Criteria: Recurrent abdominal pain at least 1 day/week in last 3 months associated with two or more of the following: 1. Related to defecation 2. Onset associated with change in stool frequency 3. Onset associated with a change in form (appearance of stool) *In absence of selected alarm features Rome IV Diagnostic Criteria for FGIDs Lower Prevalence of IBS in Asians? Prevalence of IBS is similar between Caucasians and Asians 2005 2016 Neurogastroenterol Motil 2005;17:317 324. J Gastroenterol Hepatol. 2017; ahead of print. 8

Prevalence of IBS in Asians Ethnic Background Prevalence of IBS Japanese 19 21% Chinese 5 20% Malaysians 16% Pakistan 13% Bangladesh 13% Singapore 9 11% Koreans 10% Indians 4 7% Iran 1% Cultural Differences in Symptom Interpretations Constipation, bloating, & fullness are difficult to define and differentiate from each other. Bloating is an English term. Post prandial fullness, bloating, and relative severity of abdominal pain may not be interpreted in the same way in different countries. J Gastroenterol Hepatol. 2017; ahead of print. Gender Distribution of IBS in Asians versus Non Asians Frequency of IBS Symptoms in Asians and Non Asians Non Asians Asians > = J Gastroenterol Hepatol. 2017; ahead of print. J Gastroenterol Hepatol. 2017; ahead of print. J Gastroenterol Hepatol 2007;22(8):1168 9. 9

Location of Abdominal Pain in Asian versus Non Asian IBS Patients Diet Highlights for Asian IBS Patients Rice Complete small bowel absorption, low gas production, low fiber Chili (Capsaicin) Can aggravate abdominal pain and burning May desensitize capsaicin receptors that play a role in gut irritability associated with FGIDs Vegetarians Vegetarianism is a risk factor for IBS in Northern India May make low FODMAP diet challenging Neurogastroenterol Motil 2005;17:317 324. Doctors in Asia are less likely to prescribe psychotropic agents. Non Asian Providers USA: 45 55% Asian Providers Asia: 20% 70% of Asian gastroenterologists would only use a psychotropic agent as second line therapy. Traditional Chinese Medicines for IBS Padma Lax Tumeric Tong Xie Yao Fang Xiaoyao San (MXS) Xinwei decoction Chang an I recipe Shugan Jianpi Zhixie Moxibustion Grundmann O et al. World J Gastroenterol 2014;20(2):346 362. Portincasa P et al. J Gastrointestin Liver Dis 2016;25(2):151 157. Bundy R et al. J of Alternative and Complementary Med 2004;10(6):1015 1018. Brinkhause B et al. Scandinavian J of Gastroenterology 2005;40:936 943. Qin F et al. J of Gastroenterol Hepatol 2009;24(8):1320 5. Dabos KJ et al. J of Ethanopharmacology 2010;127:205 209. Zhao L et al. Amer J of Chinese Medicine 2005;33(2):249 257. Efficacy:??? 10

Acupuncture for IBS Efficacy: Unlikely At least 4 double blind, sham controlled trials No differences in responder rates between acupuncture & sham acupuncture Adequate relief of IBS, IBS QOL, IBS SSS Real benefit: interaction between CAM provider and patient? Questions? JZia@medicine.washington.edu Chey WD et al. Gut and Liver. 2011;5(3):253 266. 11