Breath Tests, pH-Metry and
Impedance
Michael J. Lentze
Zentrum für Kinderheilkunde
University Hospitals Bonn
Oct 2013
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
Clinical Use of H2-Breath Test
Substrate
Utility
Glucose H2-breath test
Glucose
Lactulose H2-breath test
Lactulose
Lactose H2-breath test
Lactose
Fructose H2-breath test
Fructose
Sucrose H2-breath test
Sucrose
Small intestinal
overgrowth
Glucose
malabsorption
Oro-cecal transit time
Small intestinal
overgrowth
Lactose
malabsorption
Fructose
malabsorption
Sucrase-Isomaltase
Defiency
Clinical Case: 10 year old Boy
• Healthy until his 6 th year of life, than episodes of vomiting and
•
•
•
•
•
•
•
diarrhea
These episodes occur in intervals of weeks
When diarrhea occurs he had 17-20 liquid stools per day
During these episodes he lost weight
In between episodes he was completely normal and healthy
During the last episode he had a complete workup in the refering
hospital. Normal: red and white blood count, BSR, liver
transaminases, creatinine, TTG-antibodies, H2-Lactose breath test,
sonography of abdomen, coloscopy, histology, upper GI-series
It was suggested to the parents to see a child psychologist
Before he was refered for a second opinion to us
Nutrition
• The boy’s nutrition consisted in:
Morning: Milk, cornflakes, honey, bred
with marmelade
Noon: from the table, in addition plenty
of fruits, drinks Coca-Cola
Afternoon: Chocolate, Fruitcake
Dinner: bred, salad, fruits
• When I asked his brother whether he also
liked sweets and fruits, he answered: yes,
but his brother was eating up everything ,
so nothing was left for himself
Lactose-Intolerance in the World
Genetic Variant of Adult Hypolactasia
on Chromosome 2q21
8 kb
14 kb
Promot
Lactase-Phlorizin Hydrolase
C/C - 13910
G/G - 22018
Function?
Found in 229/236 cases from Finland, Germany, Italy, Korea
Enattah NS et al Nat Genet 30: 233, 2002
Adult Hypolactasia
Ratio Lactase/Sucrase
Kokkanen M et al Gut 52: 647-52, 2003
Expression of Lactase Gene
Decline of Lactase in C/C-13910 Individuals
Finnish Children
Rasinperä H et al Gut 53: 1571-76,2004
African Children
Phenotype- Genotype-Correlation
A-22018
C-14010
G-13915
G-13907
Tishkoff SA et al, Nature Genet 39: 31-40,2007
Malabsorption of Lactose and Fructose and RAP
220 children with RAP had Lactose and Fructose H2-Breath Test
(double blind testing):
Lactose-Malabsorption
Fructose-Malabsorption
Pain disappeared (Lac-Malabs)
Pain disappeared (Fruc-Malabs)
Open provocation + Lact.: positive
Open provocation + Fruct.:postive
57/210
79/121
24/38
32/49
7/23
13/31
Conclusion: Neither Lactose- nor Fructose intolerance could be
established as cause for RAP
Gijsbers CFM et al 2012
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
Interaction of Hydrolysis and Absorption
of Glucose and Fructose
Intestinal
Lumen
Sucrose
Brush Border Membrane
Cytoplasm
Sucrase-Isomaltase
Glucose
+
Na+
SGLT1
+
Fructose
GLUT5
+
Glycin
Na+
Na+-Glycine Transporter
Age Dependency of Fructose and Lactose
Intolerance
Fructose H2-BT
Jones HF JPGN 52:581-84, 2011
Lactose H2-BT
Lactose Intolerance in IBD
Relationship between Symptoms and Genotype
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.pylori
Infection in Children- Meta-Analysis
Children 6 years and younger
95%
Leal YA et al. Helicobacter 16:327-37, 2011
94%
13C-Urea
Breath test for the Diagnosis of H.pylori
Infection in Children- Meta-Analysis
Children 6 years and older
97%
Leal YA et al. Helicobacter 16:327-37, 2011
98%
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. Breath
Tests
Zevit N et al Eur J Clin Invest 41: 767-72,2011
Shall we use 13C Urea Breath Test for the
Diagnosis of RAP?
The test would 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 the
Management of H.pylori Infection
1. For the diagnosis of H. pyloris 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 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. Test 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: 230-243, 2011
Algorithm for Treatment of H.pylori Infection in Children
Koletzko S et al. JPGN 53: 230-243, 2011
Has the 13C-Urea Breath Test a Future?
13CO
2
13C-Urea
M.tuberculosis
+ NH3
Urease
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
Predicted Outcome of Breath Test for active
Tuberculosis
Philipps M et al. Tuberculosis 92: 414-20, 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 Impedance
And pH-Metry
Wenzl, T. G. et al. Pediatrics 2003;111:e355-e359
Detection of GER in 700 Children using
Multichannel Intraluminal Impedance (MII) and pHMetry
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 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: 3664-6, 2009
Arguments contra MII-pH-Metry
• What does an non-acid reflux mean?
• Automated detection overestimates the
number of reflux episodes
• More difficult to read
• Nasal catheter is uncomfortable
• Outcome studies are missing, e.g. after
fundoplication
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 cannot be advocated at present
Loots CM et al. J Pediatrics 160: 441-6, 2012
Reflux Events by pH-MMI do not determine
Fundoplication Outcome
Rosen R et al. JPGN 50: 251-255, 2010
Reflux Events by pH-MMI do not determine
Fundoplication Outcome
Rosen R et al. JPGN 50: 251-255, 2010
Diagnostic Steps in GERD
for an Infant with recurrent
Regurgitation and vomiting
Evaluate further
Evaluate further
ESPGHAN-NASPGHAN guidelines JPGN 49: 498-547, 2009
Diagnostic Steps in GERD
for an Infant with recurrent
Regurgitation and Weight Loss
ESPGHAN-NASPGHAN guidelines on GERD
JPGN 49: 498-547, 2009
Diagnostic Steps in GERD
for an older Child or Adolescent
with Heartburn
ESPGHAN-NASPGHAN guidelines on GERD
JPGN 49: 498-547, 2009
Diagnostic Steps in GERD
for a Child with Asthma that
might be worsened by GERD
ESPGHAN-NASPGHAN guidelines on GERD
JPGN 49: 498-547, 2009
Recommendation for Treatment of GERD
ESPGHAN-NASPGHAN guidelines on GERD
JPGN 49: 498-547, 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