13C Breath Test

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enzyme saturation (50100 mg in thesestudies, according to body size), and the col-lection of a second breath sample 3045minutes after the test dose. The comparisonin 13C enrichment of expired breath betweenthe first and second breath samples issuYcient to provide the diagnosis. Theabstracts show that a range of adaptationscan be made to the test provided that thesecore components are preserved. The selec-

tion of the test meal, timing of breath samplecollection, and dose of13C urea administeredcan be altered to suit local requirements,which enhances the usefulness of the test inclinical practice

x The appropriate cut oV can be establishedfrom within each data set, and can beverified if necessary by empirical comparisonso that conventional approaches to validat-ing the test need not be employed. Assign-ment of a binary value to the test resultsremains consistent between diVerent centreseven with modifications to protocols, whichallows true comparability of results through-out Europe in all ages

x

The

13

C UBT can be used to diagnosegastric H pyloricolonisation in all age groupsin epidemiological studies, and as a reliablemeans of assessing eradication after treat-ment

x The role of non-invasive tests in primarydiagnosis of H pylori colonisation is morecontroversial. A full evaluation of this interms of its influence upon clinical decisionmaking needs to be undertaken.

1 Taylor DN, Blaser MJ. The epidemiology of Helicobacterpylori infection. Epidemiol Rev 1991;13:4259.

2 Andersen LP, Espersen F, Souckova A, et al. Isolation andpreliminary evaluation of a low molecular mass antigenpreparation for improved detection of Helicobacter pyloriimmunoglobulin G antibodies. Clin Diagn Lab Immunol1995;2:1569.

3 Wu JC, Liu GL, Zhang ZH, et al. L.(NH4+)-N15 excretiontest - a new method for detection of Helicobacter pyloriinfection. J Clin Microbiol1992;30:181184.

4 Logan RPH. The 13C urea breath test. In Lee A, Mgraud F(eds) Helicobacter pylori : techniques for clinical diagnosis andbasic research. New York: WB Saunders, 1996:7481.

5 Vandenplas Y, Blecker U, Devreker T, et al. Contribution ofthe 13C urea breath test to the detection of Helicobacterpylori gastritis in children. Pediatrics 1992;90:60811.

(1) Helicobacter pylori infection diagnosis andtreatment control in Leipzig children using the[15N

2]urea urine test

P KRUMBIEGEL, C H LEICHT, T H RICHTER, B TEICHMANDepartment of Human Exposure Research and Epidemi-ology, UFZ-Centre for Environmental Research,Depart-ment of Paediatrics, University Hospital, and Private

Paediatric Practice, Leipzig, GermanyAim: To investigate the use of the [15N2]urea urinetest to diagnose Helicobacter pylori colonisation inchildren after producing a standardised protocolsuitable for use among infants.

Two groups of children (aged 317 years) beinginvestigated for symptoms of chronic abdominalpain were studied: (a) day patients at the paediatricpoliclinic of the University of Leipzig; and (2)ambulatory patients of a local paediatrician.

On study mornings, fasting children were given atest meal of 100 g warm, slightly acidic instant pud-ding mixed with 3 mg [15N2] urea/kg body mass.Urine samples were collected one, two, and threehours later.The two hour sample was used to analyse

the 15N content in the urinary ammonium using anon-mass spectrometric 15N analyser (NOI-6PC,Fischer FAN, Leipzig).

Values above 0.06 for a quotient 15N ammonium/15N urea in the urine samples were considered posi-tive based on a previous study of comparisons withendoscopic diagnosis. Those children with positiveresults had the test repeated four weeks aftertreatment.

129 children with chronic abdominal pain weretested, and 49 (38%) had positive tests. Repeat test-

ing was undertaken to check reproducibility, and adiVerent result on the second test was only obtainedin three cases. This non-invasive test has beenshown to be acceptable among young children, anda study comparing the [15N2]urea urine test with the13C urea breath test in a population sample includ-ing young children is about to begin in Leipzig togain an accurate picture of the sensitivity andspecificity of the urine test, and to gain furtherinformation on the natural history ofH pylori infec-tion and its sources.

(2) 13C urea breath test for the diagnosis of

Helicobacter pylori in childrenM ROWLAND, I LAMBERT, S GORMALLY, 2L E DALY,2J E THOMAS, 2C HETHERINGTON, M DURNIN, B DRUMMDepartment of Paediatrics and Department of PublicHealth Medicine and Epidemiology, University CollegeDublin, Childrens Research Centre, Our Ladys Hospi-tal for Sick Children, Dublin, Ireland, 2Department ofChild Health, University of Newcastle upon Tyne, UK

Aims: To determine if the 13C urea breath test(UBT) can be used in children by evaluating (a) itssensitivity and specificity compared with eitherbiopsy culture or both biopsy rapid urease test andhistology; (b) if a test meal or a prolonged fast arerequired; (c) its usefulness after treatment for Helico-bacter pylori.

Eighty eight children (mean (SD) age 10.6 (4.19))undergoing upper endoscopy were studied. Testswere performed fasting, non-fasting, and after treat-ment. Children were given 50 mg 13C urea (50 kg) with 50 mg of a glucosepolymer solution in 7.5 ml of water. Breath sampleswere collected at baseline 15, 30, 45, and 60minutes.

In 63 fasting children the UBT was 100%sensitive and 97% specific at 30 minutes using a cutoV value of 3.5 baseline enrichment. Non-fasting tests in 23 children performed between oneand two hours after their usual meal were 100% sen-sitive and 91.6% specific. In 13 children fed directlybefore the UBT the sensitivity of the test wasreduced to 50%. Thirty minutes was the optimalsampling time. There was a significant decrease inspecificity when samples were obtained at 15minutes, possibly due to the interference of oralurease producing organisms. The test was 100%sensitive and specific in 20 infected children aftertreatment for H pylori.

The UBT is a useful test for the diagnosis of Hpylori infection in children. Neither a prolonged fastnor a test meal is required. The UBT is an ideal testfor studies on the epidemiology of H pylori inchildren.

(3) 13C urea breath test is a very accurateclinical tool in the diagnosis of intragastric

Helicobacter pylori infectionF PERRI, R CLEMENTE, M QUITADAMO, V ANNESE,A ANDRIULLI

Division of GastroenterologyCasa Sollievo della Sof-ferenzaHospital, IRCCS,San Giovanni Rotondo, Italy

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Aim: To evaluate the accuracy of the UBT by means

of receiver operating characteristic (ROC) curveanalysis.

A total of 172 consecutive outpatients (mean(SD) age: 39.7 (14.1) years, M/F: 1.12) referred forendoscopy because of abdominal symptoms wereenrolled. After an overnight fast, endoscopy wasperformed. Three biopsy specimens were takenfrom the antrum and two from the fundus of thestomach. Four specimens were stained with haema-toxylin and eosin and cresyl-violet, and one antralbiopsy was used for culture. A blood sample wastaken from all subjects and measurement of specificcirculating IgG made using a commercial kit(Helori-test, Eurospital, Trieste, Italy). Patientswere considered infected if they were positive onhistology or culture, or both. The UBT was done

the day after endoscopy. After an overnight fast,each subject received 200 ml of full cream milk fol-lowed five minutes later by a 50 ml solution with 75mg of [13C] urea (13C: 99%, Isotec, Ohio, USA).Breath samples were taken before the meal andevery 15 minutes for one hour after ingestion of theurea solution. The 13C enrichment was determinedby isotope ratio mass spectrometry (ANCA-NT,Europa Scientific, Crewe, UK). The analytical datawere expressed as percentages of 13CO2 recovery perhour of the administered dose (%DH) at 15, 30, 45,and 60 minutes. The percentage of 13CO2 cumula-tive values at 60 minutes (%CD) was calculated.The diVerence between the delta value at 30minutes and the delta value at baseline (DOB30 ordelta over baseline at 30 minutes) was alsomeasured.To evaluate the accuracy of the UBT, aROC curve was plotted using both the %CD valuesat 60 minutes and the DOB30 values.

One hundred and twenty six (73.2%) patients(M/F: 1.13) were infected. There were 125 (99.2%)patients positive on histology and one (0.8%) patientpositive on culture but negative on histology. Eightyfour (66.6%) patients were positive on culture. Onehundred and thirteen (89.7%) patients were H pyloripositive on serology. There were four serologicallypositive patients who were negative on histology andculture. The table shows the sensitivity and specifi-city of histology, culture, and serology. We classified126 H pylori positive and 46 H pylori negativesubjects. ROC analysis showed that the best cut oVvalue for CD60 was 1.15%. Using this threshold,121 (96.03%) patients were positive on UBT, with

only one false positive and five false negative results.For DOB30, ROC analysis showed that the best cutoV value was 3.3. This threshold produced 124positive patients with three false positive results andfive false negative results. The table shows the sensi-tivity, specificity, and accuracy of these two cut oVs,and the commonly used cut oV of 5 baselineenrichment.

When the UBT is performed with a low dose ofsubstrate (75 mg of13C urea) and a simple test meal(200 ml full cream cows milk) the accuracy of thetest is about 95% and can be further increased byusing an analytical method for calculating theappropriate cut oVvalue.

(4) Determination of the cut oVpoint of 13C

urea breath test in adults by cluster analysisF MION, G ROSNER, M ROUSSEAU

Fdration des Spcialits Digestives, Hpital E Herriot,Lyon, France and Inbiomed, Passage du Vercours, Lyon,

FranceAlthough the 13C urea breath test (UBT) is nowwidely used for non-invasive diagnosis ofHelicobacter

pylori infection, there is still some controversy aboutthe adequate cut oV point to use. Using receiveroperating characteristic (ROC) curve analysis ofUBT results v histology of gastric biopsies in 95patients, we have recently reported the best cut oVpoint to be +3 . The goal of the present studywas to confirm this cut oVpoint by statistical analy-sis of a larger set of data. UBTs were performed in696 individuals to establish the diagnosis of H pyloriinfection (diagnosis group), and in 1056 patients to

control the eYcacy of an anti-H pylori treatment(post-treatment group). A statistical technique wasused to determine the UBT value best separating H

pylorinegative and H pyloripositive subjects withoutknowledge of actual H pylori status. The followingsteps were applied: (a) render the presumed H pylorinegative and H pylori positive distributions gaussianby logarithmic transformation of UBT values; (b)perform cluster analysis on the variable Ln (UBTvalue); (c) estimate the values of H pylori negativeand H pyloripositive distributions; (d) determine thecut oVpoint of these two populations by generatingtheir density of probability curves using the formulaof the normal distribution.

This statistical study gave two optimal cut oVpoints for UBT: one of +3.25 , when the UBT isused for the initial diagnosis of H pylori infection,

and the second of +2.75

when the UBT is usedto control the eYcacy of an anti-H pylori treatment.In both cases, the sensitivity and specificity of theUBT was more than 97%.

(5) The 13C urea breath test to assess

Helicobacter pylori eradication in childhood HpylorigastritisG ODERDA, 3M HARDING, 4J E THOMAS, 3W A COWARD,1F BAZZOLI, 1M ZAGARI, 1P POZZATO, 1E CHIORBOLI,

2P MARTELLI, 2P LERRO, 2P GARISIO, 2G BONA

Universita di Novara, Italy; 1Universita di Bologna,Italy; 2Universita di Torino, Italy; 3MRC Human

Nutrition Research, Cambridge, UK; 4Department ofChild Health, University of Newcastle upon Tyne, UK

Aim: To assess accuracy of13

C urea breath test(UBT) to diagnose Helicobacter pylori eradicationwhen performed one or two weeks (early) and sixor 10 weeks after treatment has been stopped(late).

In 78 children (41 boys, 37 girls, median age 10.6years, range 415) with H pylori gastritis antibiotictreatment (with omeprazole, amoxicillin, and met-ronidazole or clarithromicin) was given for one ortwo weeks. Six to 10 weeks later eradication wasconfirmed by gastroscopy with histology (Giemsastain) and urease test, and 13C UBT (late) was per-formed. In half of the children an additional 13CUBT was performed with a test meal of 100 ml of a10% solution of polycose (glucose polymer: Abbott,

Abstract 3, Table 1

Histology Culture Serology UBT (CD60)UBT(DOB >3.3)

UBT(DOB >5)

Sensitivity 99.2 66.6 89.7 96.0 96.0 90.5Specificity 100 100 91.3 97.8 93.5 97.8Accuracy 99.4 75.6 90.1 96.5 95.3 92.4

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UK) and 50 mg of 13C urea, breath samples werecollected before and 30 minutes later in vacutainertubes and shipped to Cambridge (UK) and Bologna(Italy).

Endoscopy based tests showed H pylori eradica-tion in 54 (69%).Early 13C UBT was performed atone week in 32 patients, and at two weeks in 36 (10patients did not show up for early 13C UBT) andthe test was repeated at six weeks in 56 and at 10weeks in 16 (in six patients results were not availableeither due to test tubes broken during shipping orthe breath collection was insuYcient). Of 68 early13

C UBTs 52 were negative (Excess 13

CO2 excretion< 5 ) with five false negative (10%) and 16 werepositive with one false positive (6%). Of 72 late 13CUBTs, 52 were negative with two false negative (4%both at six weeks) and 20 were positive without falsepositive results.

The 13C UBT is a simple and non-invasive testthat can be used to assess H pylori eradication inchildren.Its sensitivity and specificity are satisfactoryeven one or two weeks after treatment has beenstopped, but 10% false negative or 6% false positiveresults can occur. False negative results decrease to4% when performed six weeks after treatment, butthe best accuracy is obtained 10 weeks aftertreatment.

(6) Helicobacter pylori and duodenal ulcer

SHEE V, M QUINAClinica Universitria de Medicina Interna e Gastroen-trologia, Hospital de Pulido Valente, Lisboa, Portugal

Aim: To compare diVerent diagnostic techniques fordiagnosing Helicobacter pylori colonisation within abusy department of adult gastroenterology, and tomonitor patient progress after treatment.

Patients with endoscopically proved duodenalulcer had H pylori infection detected by biopsyurease test, biopsy culture, histology, and 13C ureabreath test (UBT). The use of several techniquesbefore treatment allowed the correct definition ofinfection and thus the validation of these tests. Com-

pared with biopsy culture, the sensitivity and specifi-city of the other tests were as table 1 shows.After diagnosis and treatment, assessment of H

pylori eradication was made by 13C UBT, four weeksafter treatment was stopped (table 2).

Follow up endoscopy was performed at 12 and 24months after treatment, or when clinical relapse wassuspected. Additional 13C UBT was performed atthree, six, 12, and 24 months.

During a follow up period of 14 to 24 monthsamong 132 patients the ulcer relapse rate was 35.2%for those who remained positive for H pyloriinfectionand 3.7% in H pylori negative patients. Reinfectionwas detected in only two patients (2.5%) with anannual rate of 1.2%.

(7) Helicobacter pyloriinfection and failure tothrive among pre-school childrenJ A WALKER-SMITH, A PHILLIPS, A HOLLAND,N MEADOWS

Queen Elizabeth Hospital for Children, London,UK

Children aged < 5 years (mean age 25 months)attending for small bowel biopsy to investigatesymptoms of persistent diarrhoea and growth falter-ing, without other abdominal symptoms, were stud-ied. On the day of their biopsy, these children alsounderwent a 13C urea breath test (UBT), taking 50mg of urea with a glucose polymer test meal, withbreath samples collected at baseline and 30 minuteslater. 13C enrichment in expired CO2 was measuredby isotope ratio mass spectrometry, (SIRA 10, VGIsotech, UK or ANCA, Europa Scientific, UK). Theappropriate cut oV was determined by comparisonwith age-matched children undergoing diagnosticendoscopy and using the same breath test protocolsfrom other centres participating in the BIOMEDcollaboration. Collecting adequate breath samplesfrom such young children on the same day as theyattended hospital for an invasive procedure proveddiYcult. Successful breath tests, with suYcientvolume of expired CO2 collected to allow reliableanalysis, were performed on 52 children undergoingsmall bowel biopsy: 50 were aged


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Our results support the hypothesis that duringchildhood, H pylori infection may be a fluctuatingdisease with spontaneous eradications and recur-rences.

(9) Helicobacter pylori infection is associatedwith short stature, low socioeconomicconditions, and household overcrowdingF PERRI, 1M R PASTORE, R CLEMENTE, A LATIANO,M QUITADAMO, A ANDRIULLIDivisions of Gastroenterology and 1PaediatricsCasaSollievo della SoVerenza Hospital, IRCCS, SanGiovanni Rotondo, Italy

Aims: To evaluate the prevalence rate ofHelicobacterpylori infection in Italian children and to search forany diVerence in body weight and height betweenchildren with positive and negative H pylori. A totalof 216 Italian children (M/F: 105/111, aged 314years) were tested for H pylori infection by means ofa 13C urea breath test (UBT; 200 ml of milk and 75mg of13C urea (13C: 99%);13C enrichment in breath

determined by isotope ratio mass spectrometry(ANCA-NT, Europa Scientific, Crewe, UK)). Theheight and weight of each subject were recorded andcentile values were calculated. Composite indexesfor socioeconomic class and household crowdingwere also determined.

Forty nine out of 216 (22.7%) children wereinfected. The prevalence rate of infection increasedwith age. Eight out of 49 (16.3%) H pylori positivechildren v 13 out of 167 (7.8%) H pylori negativechildren were below the 25th centile of height(p=0.09). This diVerence became significant in chil-dren aged 8.5 to 14 years; in this group (n=127),eight out of 31 (25.8%) infected subjects v eight outof 96 (8.3%) non-infected ones were below the 25thcentile of height (p=0.024). Significant correlationswere found between socioeconomic conditions,

household overcrowding, and H pylori status. Byusing stepwise logistic regression analysis, only thecentile value of height (but not weight) wassignificantly related with H pylori status in olderchildren.

The overall prevalence rate ofH pyloriinfection inItalian children aged 314 years is 23%and increaseswith age. A significant diVerence in height was found

between H pyloripositive and H pylori negative chil-dren aged 8.514 years. The H pylori infection isassociated with low socioeconomic condition andhousehold overcrowding. All these findings are con-sistent with the hypothesis that childhood acquiredH pylori infection may be one of the environmentalfactors capable of aVecting growth.

(10) Urea breath test in the initial assessmentof patients with upper gastrointestinalsymptoms

F PERRI, R CLEMENTE, M QUITADAMO, A ANDRIULLIDivision of Gastroenterology,CSS Hospital, San Gio-vanni Rotondo, Italy

Aim: To relatethe 13C urea breathtest (UBT) resultsto endoscopic and histological findings in patientswith upper gastrointestinal symptoms, and to evalu-ate the role of the UBT in clinical decision making.

A total of 172 consecutive outpatients (mean(SD) age 39.7 (14.1) years, M/F 1.12) referred fordyspepsia, and never previously endoscoped, werestudied. Symptoms were scored using a question-naire. All patients underwent endoscopy withbiopsies (histology with haematoxylin and eosin andcresyl violet, Sydney score) and UBT. One antralbiopsy was used for culture. Patients positive on his-tology and/or culture were considered infected.

Results: 126 (73.2%) patients were H pyloriposi-tive. Of these, 124 were H pylori positive on antralbiopsies. The sensitivity and specificity of the UBTwere 96% and 97.8%. Table 1 gives the endoscopicfindings.

Either gastroduodenal ulcers or cancers andhistologically severe lesions (panmucosal gastritis;mononuclear and PMN infiltration; metaplasia andatrophic changes) were almost exclusively observedin H pylori positve patients. In H pylori negativepatients, the only endoscopic abnormalities seenwere non-specific gastritis or duodenitis with super-ficial inflammation on histology (table 2).

A significant association was found between Hpylori positivity and belching, and between H pylorinegativity and mucus in the stool. Conclusions:The syndrome of dyspepsia is generally associatedwith gastritis, peptic ulcer, or gastric cancer. Because

the risk of gastric cancer is estimated as extremelylow in people aged


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international 13C standard PDB above baseline at 30minutes were considered positive, although adjustingthis cut oVtoany value between 4 and 5.5 did not sig-nificantly aVect the results. Table 1 shows the numberof children with positive identification of H pyloricompared with UBT results.

Only one H pylori positive child was aged

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