Saudi J Gastroenterol.docx

Saudi J Gastroenterol.docx

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SaudiJGastroenterol

SaudiJGastroenterol. 2011Nov-Dec; 17（6）:

371–375.

SmallIntestinalBacterialOvergrowthandLactoseIntoleranceContributetoIrritableBowelSyndromeSymptomatologyinPakistan

JavedYakoob, ZaighamAbbas, RustamKhan, SaeedHamid, SafiaAwan, and WasimJafri

Abstract

Background/Aim:

Thesymptomsofirritablebowelsyndromeresemblethoseofsmallintestinalbacterialovergrowth（SIBO）.TheaimofthisstudywastodeterminethefrequencyofSIBOandlactoseintolerance（LI）occurrenceinpatientswithdiarrhea-predominantirritablebowelsyndrome（IBS-D）accordingtoRomeIIIcriteria.

PatientsandMethods:

Inthisretrospectivecase-controlstudy,patientsover18yearsofagewithalteredbowelhabit,bloating,andpatientswhohadlactoseHydrogenbreathtest（H2BT）donewereincluded.The“cases”weredefinedaspatientswhofulfillRomeIIIcriteriaforIBS-D,while“controls”werethosehavingchronicnonspecificdiarrhea（CNSD）whodidnotfulfillRomeIIIcriteriaforIBS-D.Demographicdata,predominantbowelhabitpattern,concurrentuseofmedications,etc.,werenoted.

Results:

PatientswithIBS-Dwere119（51%）withameanageof35±13years,whilethosewithCNSDwere115（49%）withmeanage36±15years.PatientsinbothIBS-DandCNSDwerecomparableingender,withmale87（74%）andfemale77（64%）.SIBOwasdocumentedbylactoseH2BTin32/234（14%）cases.Itwaspositivein22/119（19%）caseswithIBS-D,while10/115（9%）caseshadCNSD（P =0.03）.LIwaspositivein43/234（18%）cases.Ofthese,25/119（21%）caseshadIBS-Dand18/115（16%）caseshadCNSD（P =0.29）.

Conclusion:

SIBOwasseeninasignificantnumberofourpatientswithIBS-D.TherewasnosignificantageorgenderdifferenceinpatientswithorwithoutSIBO.

Keywords:

 Hydrogenbreathtest,IBS-diarrhea,lactoseintolerance,RomeIIIcriteria,smallintestinalbacterialovergrowth,youngage

Irritablebowelsyndrome（IBS）isthemostcommonlydiagnosedchronicfunctionalgastrointestinaldisorderworldwideincludingAsia.[1,2]IBSaffectsfemalesapproximatelytwiceasoftenasmalesandismostfrequentlydiagnosedinindividualsbetweentheagesof30and50years.[1,2]However,thereisalackoffemaledominanceinAsianstudies.[3]SymptomsofIBScansubstantiallyimpactpatients’qualityoflife,andtheeffectofIBSonphysicalandpsychologicalhealthcannegativelyimpacttheworkplace.[4–6]TheeconomicburdenofIBSissubstantialandincludesdirectphysicians’costsaswellasindirectcostsintermsofemployeeabsenteeism.IBSischaracterizedbyabdominaldiscomfortassociatedwithalteredbowelhabitsincludingconstipation,diarrhea,oralternatingperiodsofconstipationanddiarrhea.

Anemerginghypothesissuggeststhatsmallintestinalbacterialovergrowth（SIBO）maycontributetoIBSpathophysiology.[7]SIBOisaconditioncharacterizedbyabnormallyhighbacterialcount（≥105colony-formingunits/ml）intheproximalsmallintestine,resemblingdistributionofbacterianormallyfoundinthecolon.[8,9]SymptomsofSIBOincludeabdominalpain,bloating,flatulence,anddiarrhea,similartothoseobservedinpatientswithIBS.[10,11]SIBOwasdetectedin17to84%ofpatientswhometRomeIorRomeII[12–16]criteriaforIBSusingHydrogenbreathtesting（H2BT）withglucoseorlactulose.Furthermore,treatmentwithantibioticscanreduceoreradicateSIBO[16–21]andimprovesymptomsofIBS[22,23]whichsupportstheroleofSIBOinIBS.AsdiagnosisofIBSisbasedonacombinationofsymptomsthatarealsocommoninpatientswithmalabsorptiondisorders,itispossiblethatsomeofthesepatientsmaybemisdiagnosedasIBS,particularlyifspecifictestsarenotperformed.[7]ThiswassupportedbythereportsofdiagnosisofceliacdiseaseinpatientspresentingasIBS.[19–21]AsH2BTissimplertoadminister,ismorecost-effective,anddoesnotexposethepatienttoradiation,ithasbecomethenoninvasivegoldstandardinthediagnosisofSIBO.Previously,SIBOinIBSwasshowntobeassociatedwithpositivelactoseH2BT.[15]Inastudyof98consecutiveIBSpatients,apositivelactulosebreathtestwasfoundin64of98（65%）subjects;theseSIBOpatientsshowedasignificantlyhigherprevalenceofpositivitytothelactosebreathtest（P<0.05）.[15]ClinicalstudiesevaluatingcharacteristicsassociatedwithSIBOinpatientswithIBS-diarrhea（IBS-D）accordingtoRomeIIIcriteriaarelacking.Therefore,thepurposeofthisstudywastodeterminethefrequencyofSIBOandlactoseintolerance（LI）occurrenceinpatientswithIBS-DaccordingtoRomeIIIcriteriaanddeterminethepredictorsofSIBOinthesepatients.

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PATIENTSANDMETHODS

Patients

Inthisretrospectivecase-controlledstudy,themedicalrecordsofpatientsover18yearsofagewhoattendedgastroenterologyclinicsupervisedbytheinvestigatorsattheUniversityHospitalwithalteredbowelhabitandbloating,wereincluded.TheyhadlactoseH2BTdonebetweenJanuary2007andOctober2010.TheEthicsReviewCommitteeattheUniversityapprovedthestudy.The“cases”had,overthepastthreemonthsormore,atleastthreebowelmovementsperdaydescribedaslooseorwaterystoolsassociatedwithurgency,andfulfilledtheRomeIIIcriteriaforIBS-D,[2]while“controls”werethosehavingchronicnonspecificdiarrhea（CNSD）definedasabdominalpainordiscomfortassociatedwithintermittentdiarrheawithmorethan3stoolsadayforatleast4weeksandlessthan12weeksanddidnotfulfillRomeIIIcriteriaforIBS-D.[24]Demographicdata,predominantbowelhabitpattern,andconcurrentuseofmedicationswerenoted.Thesepatientsunderwentthoroughhistory,physicalexamination,completebloodcount,serumcreatinine,electrolytes,andstoolmicroscopy.Allthepatientshadcolonoscopywithrectalbiopsytoexcludeinflammatoryboweldiseaseandmicroscopiccolitis.Exclusioncriteriawereconcurrentuseofopiatesanalgesics,prokineticdrugs,andPPI,havinginfectionwith Giardialamblia,Entamebahistolytica,Blastocystishominis,positiveserologyforceliacdiseaseasdeterminedbytissuetransglutaminaseantibody-IgAandtransglutaminaseantibody-IgGandabnormalthyroidactivityassuggestedbyserumthyroxinandthyroid-stimulatinghormonelevel.PatientswithpredisposingconditionsforSIBO,e.g.,priorsmallintestinalsurgery,scleroderma,diabetesmellitus,livercirrhosis,formsofautonomicneuropathy,historyofpepticulcerandtherapywithH2antagonists/PPIsduringthepreceding8weeks,hypothyroidism,intestinalpseudo-obstruction,colonoscopywithinaweekbeforeH2BT,anddrugsknowntointerferewithgastrointestinalmotility,e.g.,anticholinergicsandantidepressantswerealsoexcluded.

Hydrogenbreathtest

AllpatientsunderwentalactoseH2BTatthebeginningofthestudy.ImmediatelybeforetheH2BT,patientsusedamouthwashcontaining40mlof1%chlorhexidine.TheH2BTwasdonewithpatientfastingovernightfor12hours.Patientswereaskedtorefrainfromsmokingafterthelastmealtilltheendofthetestandfromexercise30minutesbeforeandduringthetest.Antibioticswerestopped4weeksbeforeadministeringtheSIBObreathtest.Patientsalsoavoidedlaxatives,stoolsofteners,orstoolbulkingagentsoneweekpriortothetest.Foodwithhighfibercontent,e.g.,beans,pasta,meats,fiberorbrancereals,coladrinks,butter,ormargarine,wasavoided24hourspriortothetest.Samplesofexpiredairwerecollected.Fivesampleswerecollectedincludingonefastingsample（0minute）afterthedoseof50glactoseforadult,andfoursamplesat30,60,90,and120minutesinterval.Expiratorybreathsamplesobtainedwereanalyzedimmediatelyaftercollection,usingacommercialdevice（GaSampler;QuinTronInstrumentCompany,Milwaukee,Wisconsin）.Gaschromatography（ModelDP;QuinTronInstrumentCompany,Milwaukee,Wisconsin）wasemployedtomeasuretheconcentrationinpartspermillion（ppm）ofhydrogenintheair.ThediagnosticcriteriaforapositiveSIBOwasariseabovebaselineof20ppmin30or60-minutebreathsample,whileisolatedpositivebreathtestat90or120-minutesamplescorrespondingtothepassageoflactoseintothecolonwastakenasLIratherthanSIBO.[23,24]Definitionsofnormalandabnormalresultsofbreathtestsarevariableandthereisalackofgenerallyaccepteddefinitions.ThesensitivityandspecificityofthelactuloseH2BTindetectingSIBOhasbeenreportedtobeonly68%and44%,respectively.[25]However,sensitivityingeneralisacceptable,becauseofthelowspecificityfordiagnosingSIBOcomparedwithjejunalcultures.[26]

Samplesize

ThesoftwareEPIInfowasutilisedforsamplesizeestimation.Assuminga30%prevalenceofSIBOinIBS-Dand8%inCNSD,[27]atwo-sidedalphaof0.05andoddsratioof2withan80%powertodetectadifference,therequiredsamplesizeforthisobjectivewas115forthecasesand115forcontrol.

Statisticalmethod

Resultswereexpressedasmean±standarddeviationforcontinuousvariables（e.g.,age）andnumber（percentage）forcategoricaldata（e.g.,gender,diarrhea,etc.）.ComparisonofIBS-DpatientsandCNSDpatientswithothercovariateslikeage,gender,hydrogentest,hemoglobin,andserologyofceliacdiseasewasdonebyusingtheindependentsample t-test,PearsonChi-squaretest,andFisherExacttestwhereappropriate.ThepatientswerefurtherdividedintoSIBOpositiveandSIBOnegativeandacomparisonwasdonewithothercovariates.A P valueof<0.05wasconsideredasstatisticallysignificant.All P valuesweretwosided.StatisticalinterpretationofdatawasperformedbyusingthecomputerizedsoftwareprogramSPSSversion17.0.

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RESULTS

PatientswithIBS-D（119,51%）hadameanageof35±13yearsandmale:

fema