Breath Tests, pH-Metryand Impedance

Michael J. LentzeESPGHAN goes Africa Course

March 2015

Clinical Use of H2-Breath Test

Ghoshal UC J Neurogastroenterol Motil 17: 312-17, 2011

Typical Exhalation Curves in CH H2-Breath Tests

Ghoshal UC J Neurogastroenterol Motil 17: 312-17, 2011

Substrate Utility

Glucose H2-breath test Glucose Small intestinalovergrowth

Glucose malabsorption

Lactulose H2-breath test Lactulose Oro-cecal transit time

Small intestinalovergrowth

Lactose H2-breath test Lactose Lactosemalabsorption

Fructose H2-breath test Fructose Fructosemalabsorption

Sucrose H2-breath test Sucrose Sucrase-IsomaltaseDefiency

Clinical Use of H2-Breath Test

Lactose-Intolerance in the World

Genetic Variant of Adult Hypolactasiaon Chromosome 2q21

Promot Lactase-Phlorizin Hydrolase

C/C - 13910

14 kb8 kb

G/G - 22018

Found in 229/236 cases from Finland, Germany, Italy, Korea

Enattah NS et al Nat Genet 30: 233, 2002

Function?

Adult Hypolactasia

Ratio Lactase/Sucrase Expression of Lactase Gene

Kokkanen M et al Gut 52: 647-52, 2003

CC CT TT CC CT

Decline of Lactase in C/C-13910 Individuals

Finnish Children African Children

Rasinperä H et al Gut 53: 1571-76,2004

Malabsorption of Lactose and Fructose and RAP

220 children with RAP had Lactose and Fructose H2-Breath Test (double blind testing):

Lactose-Malabsorption 57/210Fructose-Malabsorption 79/121Pain disappeared (Lac-Malabs) 24 / 38Pain disappeared (Fruc-Malabs) 32 / 49Open provocation + Lact.: positive 7 / 23Open provocation + Fruct.:postive 13 / 31

Conclusion: Neither Lactose- nor Fructose intolerancecould be established as cause for RAP

Gijsbers CF et al Acta Paediatrica 2012, 101: e411-415

Secondary Lactose Intolerance in PEM

• 196 severely malnourished childenLactose 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

BrushBrush BorderBorder MembraneMembraneIntestinalIntestinalLumenLumen

CytoplasmCytoplasm

SGLT1SGLT1

GLUT5GLUT5

NaNa++--GlyciGlycinene TransporterTransporter

SucroseSucroseSucraseSucrase--IsomaltaseIsomaltase

GlucoseGlucose

FructoseFructose

NaNa++++

GlycinGlycinNaNa++

++

++

Interaction of Interaction of HydrolysisHydrolysis and Absorptionand Absorptionof Glucose and Fructoseof Glucose and Fructose

Age Dependency of Fructose and LactoseIntolerance

Fructose H2-BT Lactose H2-BT

Jones HF JPGN 52:581-84, 2011

Lactose Intolerance in IBD Relationship between Symptoms and Genotype after Lactose Challenge

Eadala P et al. Aliment Pharmacol Ther 34: 735-46, 2011

Principle of 13C-Urea Breath Test

13C-Urea Breath test for the Diagnosis of H.pyloriInfection in Children- Meta-Analysis

Children 6 years and younger

Leal YA et al. Helicobacter 16:327-37, 2011

95% 94%

13C-Urea Breath test for the Diagnosis of H.pyloriInfection in Children- Meta-Analysis

Children 6 years and older

97% 98%

Leal YA et al. Helicobacter 16:327-37, 2011

Prevalence of H.pylori Infection in a Population:36.629 People in Denmark by Home 13C-Breath Test

Dahlerup S et al. Helicobacter 16: 468-74, 2011

Age and Gender Differences in H.P. BreathTests

Zevit N et al Eur J Clin Invest 41: 767-72,2011

Shall we use 13C Urea Breath Test for theDiagnosis 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: 651-69, 2010

H. pylori Antigen in Stool

Guarner J et al. Eur J Pediatrics 169: 15-25, 2010

ESPGHAN-NASPGHAN Guidelines for theManagement of H.pylori Infection

1. For the diagnosis of H. pylori infection during EGD, it isrecommended that gastric biopsies (antrum and corpus) for histopathology be obtained

2. It is recommended that the initial diagnosis of H.p. bebased on either histopathology plus positive rapid ureasetest or a positive culture

3. The 13C-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 arenot reliable for use in the clinical setting

Koletzko S et al. JPGN 53: 230-243, 2011

Has the 13C-Urea Breath Test a Future?

13C-Urea

M.tuberculosis Urease

+ NH3

13CO2

High Burden Countries for Tuberculosis

Maiga M et al. Indian J Med Res 135: 731-36, 2012

Rabbits infected with M. tuberculosis

13C-Urea Breath Test

Maiga M et al. Indian J Med Res 135: 731-36, 2012

Utility of 13C-Breath Tests

Braden B Best Pract Res Clin Gastroenterol 23: 337-52, 2009

pH-Metry in the Diagnosis of GERD

Multichannel intraluminal ImpedanceAnd pH-Metry

Wenzl, T. G. et al. Pediatrics 2003;111:e355-e359

Comparison between pH Monitoringand Impedance

Wenzl TG et al. JPGN 55:230-234, 2012

Indications for Multichannel intraluminalImpedance (MII)-pH-Metry

• Quantification of reflux episodes• Measure reflux in patients not

responding to antireflux therapy• Research

Wenzl TG et al. JPGN 55:230-234, 2012

Detection of GER in 700 Children usingMultichannel Intraluminal Impedance (MII) and pH-

Metry

Number of abnormal Measurements

Pilic D et al. J Pediatrics 158: 650-4, 2011

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 refluxevents

• Diagnostic gain for combining the 2 methods is 22% -32%

• MII detects the proximal extent of refluate which isimportant for increased risk of aspiration

• In children with asthma it can show also weakly acidicrefluxes (51%)

• In preterm infants apnea episodes occur more frequentlyafter a reflux event of which 57% are non-acidic.

• Outcome studies are lacking

Blondeau K et al Am J Gastroenterol 104: 3664-6, 2009

• What does an non-acid reflux mean?No medical treatment available

• Automated detection overestimates the numberof reflux episodes

• More difficult to read• Nasal catheter is uncomfortable• Large outcome studies are missing, e.g. after

fundoplication

Arguments contra MII-pH-Metry

Richter JE Am J Gastroenterol 104: 2667-69, 2009

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

Reflux Events by pH-MMI do not determineFundoplication Outcome

Rosen R et al. JPGN 50: 251-255, 2010

Reflux Events by pH-MMI do not determineFundoplication Outcome

Rosen R et al. JPGN 50: 251-255, 2010

MII-pH results fail to identify parameters correlatingwith the presence of esophagitis

JPGN 2013, 56:196-200

MacroscopyNormalMII-pH normal

MacroscopyAbnormalMII-pH abnormal

MacroscopyNormalMII-pH abnormal

Correlation in infants but not in children!JPGN 60:224-229

Diagnostic Steps in GERDfor an Infant with recurrentRegurgitation and vomiting

Evaluate further

Evaluate further

ESPGHAN-NASPGHAN guidelines JPGN 49: 498-547, 2009

Diagnostic Steps in GERDfor an Infant with recurrent

Regurgitation and Weight Loss

ESPGHAN-NASPGHAN guidelines on GERDJPGN 49: 498-547, 2009

Diagnostic Steps in GERDfor an older Child or Adolescent

with Heartburn

ESPGHAN-NASPGHAN guidelines on GERDJPGN 49: 498-547, 2009

Diagnostic Steps in GERDfor a Child with Asthma thatmight be worsened by GERD

ESPGHAN-NASPGHAN guidelines on GERDJPGN 49: 498-547, 2009

Recommendation for Treatment of GERD

• 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-threateningcomplications

ESPGHAN-NASPGHAN guidelines on GERDJPGN 49: 498-547, 2009