Breath Tests, ph-metry and Impedance

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1 Breath Tests, ph-metry and Impedance Michael J. Lentze ESPGHAN goes Africa Course March 2015

2 Clinical Use of H 2 -Breath Test Ghoshal UC J Neurogastroenterol Motil 17: , 2011

3 Typical Exhalation Curves in CH H 2 -Breath Tests Ghoshal UC J Neurogastroenterol Motil 17: , 2011

4 Clinical Use of H 2 -Breath Test Substrate Utility Glucose H2-breath test Glucose Small intestinal overgrowth Glucose malabsorption Lactulose H2-breath test Lactulose Oro-cecal transit time Small intestinal overgrowth Lactose H2-breath test Lactose Lactose malabsorption Fructose H2-breath test Fructose Fructose malabsorption Sucrose H2-breath test Sucrose Sucrase-Isomaltase Defiency

5 Lactose-Intolerance in the World

6 Genetic Variant of Adult Hypolactasia on Chromosome 2q21 8 kb 14 kb Promot Lactase-Phlorizin Hydrolase C/C G/G Function? Found in 229/236 cases from Finland, Germany, Italy, Korea Enattah NS et al Nat Genet 30: 233, 2002

7 Adult Hypolactasia Ratio Lactase/Sucrase Expression of Lactase Gene CC CT TT CC CT Kokkanen M et al Gut 52: , 2003

8 Decline of Lactase in C/C Individuals Finnish Children African Children Rasinperä H et al Gut 53: ,2004

9 Malabsorption of Lactose and Fructose and RAP 220 children with RAP had Lactose and Fructose H2-Breath Test (double blind testing): Lactose-Malabsorption 57/210 Fructose-Malabsorption 79/121 Pain disappeared (Lac-Malabs) 24 / 38 Pain disappeared (Fruc-Malabs) 32 / 49 Open provocation + Lact.: positive 7 / 23 Open provocation + Fruct.:postive 13 / 31 Conclusion: Neither Lactose- nor Fructose intolerance could be established as cause for RAP Gijsbers CF et al Acta Paediatrica 2012, 101: e

10 Secondary Lactose Intolerance in PEM 196 severely malnourished childen Lactose intolerance in 50 children (25%): 27/75 with Kwashiorkor 6/25 Marasmic Kwashiorkor 17/96 Marasmus Assessment: stool ph, reducing substances in stool Nyeko R et al. BMC Pediatrics 10:31, 2010

11 Intestinal Lumen Sucrose Interaction of Hydrolysis and Absorption of Glucose and Fructose Brush Border Membrane Cytoplasm Sucrase-Isomaltase Glucose + Fructose Glycin Na + + Na + + SGLT1 GLUT5 Na + -Glycine Transporter

12 Age Dependency of Fructose and Lactose Intolerance Fructose H2-BT Lactose H2-BT Jones HF JPGN 52:581-84, 2011

13 Lactose Intolerance in IBD Relationship between Symptoms and Genotype after Lactose Challenge Eadala P et al. Aliment Pharmacol Ther 34: , 2011

14 Principle of 13 C-Urea Breath Test

15 13 C-Urea Breath test for the Diagnosis of H.pylori Infection in Children- Meta-Analysis Children 6 years and younger 95% 94% Leal YA et al. Helicobacter 16:327-37, 2011

16 13 C-Urea Breath test for the Diagnosis of H.pylori Infection in Children- Meta-Analysis Children 6 years and older 97% 98% Leal YA et al. Helicobacter 16:327-37, 2011

17 Prevalence of H.pylori Infection in a Population: People in Denmark by Home 13 C-Breath Test Dahlerup S et al. Helicobacter 16: , 2011

18 Age and Gender Differences in H.P. Breath Tests Zevit N et al Eur J Clin Invest 41: ,2011

19 Shall we use 13C Urea Breath Test for the Diagnosis of H.P.-Infection in RAP? The test would be applicable, if the symptoms would correlate to positive findings, but there is no correlation between RAP and H.P.-Infection Spee LAA et al. Pediatrics 125: , 2010

20 H. pylori Antigen in Stool Guarner J et al. Eur J Pediatrics 169: 15-25, 2010

21 ESPGHAN-NASPGHAN Guidelines for the Management of H.pylori Infection 1. For the diagnosis of H. pylori infection during EGD, it is recommended that gastric biopsies (antrum and corpus) for histopathology be obtained 2. It is recommended that the initial diagnosis of H.p. be based on either histopathology plus positive rapid urease test or a positive culture 3. The 13 C-urea breath test is a reliable noninvasive test to determine whether H.p. has been eradicated. 4. A validated ELISA test for detection of H.p. in stool is a reliable noninvasive test to determine whether H.p. has been eradicated 5. Tests based on the detection of antibodies (IgG, IgA) against H.p. in serum, hwole blood, urine and saliva are not reliable for use in the clinical setting Koletzko S et al. JPGN 53: , 2011

22 Has the 13 C-Urea Breath Test a Future? 13 CO 2 13 C-Urea M.tuberculosis Urease + NH3

23 High Burden Countries for Tuberculosis Maiga M et al. Indian J Med Res 135: , 2012

24 Rabbits infected with M. tuberculosis 13 C-Urea Breath Test Maiga M et al. Indian J Med Res 135: , 2012

25 Utility of 13 C-Breath Tests Braden B Best Pract Res Clin Gastroenterol 23: , 2009

26 ph-metry in the Diagnosis of GERD

27 Multichannel intraluminal Impedance And ph-metry Wenzl, T. G. et al. Pediatrics 2003;111:e355-e359

28 Comparison between ph Monitoring and Impedance Wenzl TG et al. JPGN 55: , 2012

29 Indications for Multichannel intraluminal Impedance (MII)-pH-Metry Quantification of reflux episodes Measure reflux in patients not responding to antireflux therapy Research Wenzl TG et al. JPGN 55: , 2012

30 Detection of GER in 700 Children using Multichannel Intraluminal Impedance (MII) and ph- Metry Number of abnormal Measurements Pilic D et al. J Pediatrics 158: 650-4, 2011

31 Arguments pro MII-pH-Metry MII + ph- is most sensitive method to detect acidic, weakly acidic and alkaline refluxes Is the best method to correlate symptoms with reflux events Diagnostic gain for combining the 2 methods is 22% - 32% MII detects the proximal extent of refluate which is important for increased risk of aspiration In children with asthma it can show also weakly acidic refluxes (51%) In preterm infants apnea episodes occur more frequently after a reflux event of which 57% are non-acidic. Outcome studies are lacking Blondeau K et al Am J Gastroenterol 104: , 2009

32 Arguments contra MII-pH-Metry What does an non-acid reflux mean? No medical treatment available Automated detection overestimates the number of reflux episodes More difficult to read Nasal catheter is uncomfortable Large outcome studies are missing, e.g. after fundoplication Richter JE Am J Gastroenterol 104: , 2009

33 Intraobserver Variability in MII + ph Metry 10 experienced observers in the world had to read 1242 liquid and mixed GER 490 GER were scored by all observers = 42%!! Agreement for gas GER was poor Automated analysis was better than that of observers Widespread use is debatable Loots CM et al. J Pediatrics 160: 441-6, 2012

34 Reflux Events by ph-mmi do not determine Fundoplication Outcome Rosen R et al. JPGN 50: , 2010

35 Reflux Events by ph-mmi do not determine Fundoplication Outcome Rosen R et al. JPGN 50: , 2010

36 MII-pH results fail to identify parameters correlating with the presence of esophagitis

37 Macroscopy Abnormal MII-pH abnormal Macroscopy Normal MII-pH normal Macroscopy Normal MII-pH abnormal JPGN 2013, 56:

38 Correlation in infants but not in children! JPGN 60:

39 Diagnostic Steps in GERD for an Infant with recurrent Regurgitation and vomiting Evaluate further Evaluate further ESPGHAN-NASPGHAN guidelines JPGN 49: , 2009

40 Diagnostic Steps in GERD for an Infant with recurrent Regurgitation and Weight Loss ESPGHAN-NASPGHAN guidelines on GERD JPGN 49: , 2009

41 Diagnostic Steps in GERD for an older Child or Adolescent with Heartburn ESPGHAN-NASPGHAN guidelines on GERD JPGN 49: , 2009

42 Diagnostic Steps in GERD for a Child with Asthma that might be worsened by GERD ESPGHAN-NASPGHAN guidelines on GERD JPGN 49: , 2009

43 Recommendation for Treatment of GERD ESPGHAN-NASPGHAN guidelines on GERD JPGN 49: , 2009 In infants try extensively hydrolysed formula for 2-4 weeks (Eosinophilic Esophagitis?) Thicken formula Supine position during sleep In adolescents with GERD left-side sleeping and elevation of the head decreases GERD PPI s are more effective than H2RAs Insufficient support for metoclopramide, erythromycin, bethanechol or domperidone Buffering agent as sucralfate, alginates are not recommended Antireflux surgery should only be considered in failure of optimized medical therapy or life-threatening complications

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