Ineffectiveness of Breath Methane Excretion as a Diagnostic Test for Lactose Malabsorption.docx

Ineffectiveness of Breath Methane Excretion as a Diagnostic Test for Lactose Malabsorption.docx

《Ineffectiveness of Breath Methane Excretion as a Diagnostic Test for Lactose Malabsorption.docx》由会员分享，可在线阅读，更多相关《Ineffectiveness of Breath Methane Excretion as a Diagnostic Test for Lactose Malabsorption.docx（10页珍藏版）》请在冰豆网上搜索。

IneffectivenessofBreathMethaneExcretionasaDiagnosticTestforLactoseMalabsorption

IneffectivenessofBreathMethaneExcretionasaDiagnosticTestforLactoseMalabsorption

Myo-Khin;Bolin,TerryD.*;Khin-Mar-Oo†;Tin-Oo;Kyaw-Hla,S.†;Thein-Myint,Thein†

AuthorInformation

DepartmentofMedicalResearch,YangonMyanmar;*GastrointestinalUnit,PrinceofWalesHospital,Randwick,NewSouthWales,Australia;and†DepartmentofChildHealth,InstituteofMedicineI,Yangon,Myanmar

AddresscorrespondenceandreprintrequeststoProfessorTerryD.Bolin,GastrointestinalUnit,PrinceofWalesHospital,HighStreet,Randwick,NSW2031,Australia.

ABSTRACT 

Background:

Inclinicalandfieldconditions,breathgasanalysishasbeenwidelyusedinevaluatingcarbohydratedigestion.AfieldstudywasperformedtodeterminetheprevalenceoflactosemalabsorptioninMyanmarchildrenandtoevaluatethepossibilityofusingbreathmethaneexcretiontoindicatelactosemalabsorptioninafieldsituation. 

Methods:

Thestudypopulationconsistedof118childrenaged1to12years.Ahydrogenbreathtestafteralactosemeal（2g/kg,maximum50g）wasusedasastandardtest. 

Results:

Lactosemalabsorptionwasdetectedin16.7%ofchildrenaged1to2.9years,withtheprevalenceincreasingwithagefrom40.5%ofthoseaged3to5.9yearsto88.5%ofthoseaged6to8.9yearsandreaching91.7%inthoseaged9to11.9years.Lactosemalabsorptionwasmoreprevalentwhenchildrenwereweanedbefore4monthsofage（87.2vs.41.1%; p <0.01）.Comparedwithlactose-tolerantchildren,thosewithlactosemalabsorptionhadsignificantlyhigherconcentrationsofbreathhydrogenexcretion60minutesafterthelactosetestmeal.Breathmethaneexcretionwasalsosignificantlyhigherinsamplesat120minutesinchildrenwithlactosemalabsorption.Breathmethaneexcretionofgreaterthanorequalto2partspermillionat180minutesasadiagnostictestforlactosemalabsorptionhadasensitivityof61.5%andaspecificityof84.6%. 

Conclusion:

Thebreathmethanetestforlactosemalabsorptionhasalowersensitivityandspecificitythanthebreathhydrogentestandthereforedoesnotreplacethelactosebreathhydrogentest. 

Lactasedeficiencywithresultantlactosemalabsorptionisprevalentinmanypartsoftheworld,especiallyinnonwhitepopulations.Thediagnosisisideallyestablishedbysensitiveandspecificnoninvasivetests,suchasthehydrogenbreathtest.Theadministrationofthistest,however,istimeconsuming.Abreathanalysis,suchasmethane,maybemoreappropriate,becauseasinglebreathtestat180minutesafterlactoseingestionmaybediagnostic.Thisreducestheneedformultiplebreathanalysessuchasarenecessarywithhydrogen. 

Inclinicalandfieldconditions,breathhydrogenanalysishasbeenwidelyusedinevaluatinglactosedigestion.Ithasbeenshownthatthechangeinbreathhydrogenexcretion2hoursafterlactoseingestionperfectlydiscriminateslactase-deficientsubjectsfromthosewithnormallactaselevels 

（1）.BondandLevitt 

（2） reviewedotherstudiesandconcludedbreathhydrogentestsareasaccurateasothertolerancetestsinidentifyingsugarmalabsorption,withtheadvantagethatisnoninvasive. 

Recently,ithasbeenreportedthatanincreaseinbreathmethaneexcretionoccursamongchildrenwithlactoseintolerance.Breathmethaneexcretioninnormalchildrenaverages1.6partspermillion（ppm）from0to120minutes.Incontrast,thebreathmethaneexcretionbylactose-intolerantchildrenaverages5.1ppmat90minutesand,by120minutes,levelsincreasesignificantlycomparedwiththoseincontrolsubjects （3）.Methaneisproducedintheleftcolonbyreductionofhydrogenandcarbondioxide.Anincreasedcarbohydrateloadmayprovideincreasedsubstrateforhydrogenandcarbondioxideproductioninlactose-intolerantpeople,andthismayincreasesubstrateformethanogenicbacteriaintheleftcolon.Withitspotentialforgreatersimplicity,useofbreathmethaneexcretiontoindicatelactosemalabsorptioninafieldsituationwarrantsevaluation. 

Lactosemalabsorptionmaybesecondaryandtransientorprimaryandpermanent.Althoughprimarylactasedeficiencyhasageneticcomponent （4）,anothermajorfactormaybetheabsenceofcontinuedstimulationoftheenzymewhenlactoseisnolongeringestedafterweaning （5-9）.Lactosemalabsorptionmaydevelopsecondarytoacutediarrheaorparasiticinfestation （10-12） andisinfluencedintheratbyirondeficiency,proteindeficiency,andparasiteinfestation （13）.Lactosemalabsorptionusuallyappearsinchildrenafter3to5yearsoflife.StudiesfromAsiareportahighprevalenceoflactosemalabsorptionamongchildrenandadults,withtheconditionhavinganearlyonset （6,14,15）.Brownetal., （16） usingalactosebreathhydrogentest,diagnosedlactosemalabsorptioninmorethan80%ofchildrenmorethan3yearsofageinastudypopulationof234Bangladeshichildren.Noseetal. （17） studiedtheprevalenceoflactosemalabsorptioninJapanesechildrenandadultsandfoundthattheprevalencewas30%inthoseaged3yearsandincreasedsharply,reaching86%inthoseaged6years.Tingetal. （18） alsoreportedanabruptincreaseinlactosemalabsorptioninChinesechildren6to7yearsofage.Theprevalenceincreasesfrom12%to43%at6to7yearsofageandbyadolescence,70%ofTaiwanesehavelactoseintolerance.AsimilarpatternoflactosemalabsorptionwasalsoobservedinHongKongChinesechildren （19）. 

ThepresentstudywasperformedtoinvestigatetheprevalenceoflactosemalabsorptioninMyanmarchildrenandthepossibilitythatbreathmethaneexcretionmightbediagnostic. 

BacktoTop 

SUBJECTSANDMETHODS 

Thestudyinvolved125children,65boysand60girls,aged1to12years（meanage,5.4years）fromasemiurbanareainYangon,Myanmar.Allwereapparentlyhealthy,hadtakennoantibiotics,andhadnogastrointestinaldiseasesduringtheprevious2weeks.Theparentsofthechildrenwereinformedofthenatureofthestudyandgavetheirconsent.Interviewersrecordeddetailsofsocioeconomicstatusofthefamily,thechild'spastandpresenthealth,anddietaryandweaningpractices.Clinicalexaminationofthechildincludedweightandmidarmcircumferencemeasurement. 

BacktoTop 

LactoseBreathHydrogenTest 

Afteranovernightfast,eachchildwasadministered2g/kglactose（maximum,50g）in10%aqueoussolution（maximum,250ml）.Breathsamplesweretakenimmediatelybeforelactosewasadministeredandevery30minutesthereafterfor3hours. 

Breathsampleswerecollected（GaSampler;QuintronInstrumentsCo.,Milwaukee,WI,U.S.A.）withasystemthatconsistsofanalveolarair-collectionbag（volume,750ml）,adead-spacediscardbag（modifiedtoacapacityof50ml）,aT-valve,andamouthpiece.Thechildrenwereaskedtobreathonceintoacollectionbag.T-valve-fittedplasticbagsforbreathsamplingallowexpiredairfromthedeadspacetobediscarded. 

Thesampleswerethenimmediatelytransferredforstorageinsilicone-greased,30-mlairtightplasticsyringes（Terumo,Sydney;Australia）fittedwithplasticthree-waystopcocks;andtakentothelaboratoryoftheDepartmentofMedicalResearchwherehydrogen,oxygen,andmethanemeasurementsweremadewithin24hours.Thestoragesystempermitsstabilityofbreathsamplesfor24hours （20,21）. 

Usingthedefinitionsdescribedbelow,childrenwereclassifiedaslactoseabsorbers（LAs）orlactosemalabsorbers（LMs）.AllLAswereretestedwithin1week.Theyconsumedastandardtestmealof10glactulose（15mlDuphalac;DupharB.V.,TheNetherlands）todeterminetheirhydrogen-producingstatusandwereclassifiedastrueLAsornon-hydrogenproducers. 

BacktoTop 

AnalysisofHydrogenandOxygeninBreathSamples 

Agaschromatograph（model12MicroLyzer;Quintron）wasusedformeasuringhydrogeninbreathsamples.Analysisofoxygenconcentrationsinthesamebreathsampleswasperformedbyuseofaportableoxygenanalyzer,whichwasapotentiostaticoxygensensor（Oxywarn100I;DraegerInstrumentDivision,Blyth,Northumberland,England）. 

BacktoTop 

AnalysisofMethaneinBreathSamples 

Methanewasmeasuredwithadeviceequippedwithamolecularsievechromatographiccolumn（model16Microlyzer;Quintron）.Dryairwasusedasthecarriergasataflowrateof35mlperminute.Thechromatographwascalibratedwithamethane-referencedmixtureincompressedair（Quingas,Quintron）.Thesmallestdetectableconcentrationofmethanewas2µl/l,withalinearaccuracyresponserangeof2to200µl/l. 

BacktoTop 

WorkingDefinitions 

Lactosemalabsorption wasdefinedaspeakhydrogengreaterthanorequalto10ppmabovebaselinevaluesinsamplesobtained30to180minutesafteralactosetestmeal. Nonhydrogendetection wasdefinedaspeakhydrogenlessthan10ppmabovebaselinevaluesinthesamplesobtained30to180minutesafterlactulose.Peakhydrogenwascalculatedasthedifferencebetweenthehighestnormalizedbreathhydrogenvalueinanyoneofthebreathsamplescollectedafterlactoseorlactulosetestmealsandthebasalbreathhydrogenvalue.A methaneproducerwasdefinedasanysubjectwhoexcreted2ppmormoreofmethane. 

BacktoTop 

StatisticalAnalysis 

Dataanalysiswasperformedwithcommercialsoftware（StatisticalPackageforSocialScientists,ver.3.0;SPSSCorp.,Chicago,IL,U.S.A.）onacomputer（modelT3100e;Toshiba,Japan）Dataareexpressedasmean±standarderrorofthemean.Comparisonsbetweenbreathhydrogenandmethaneconcentrationsbetweengroups（LAsandLMs）weremadeusingStudent's t-testforunpairedsamples（two-tailed）.Temporaldifferencesinbreathhydrogenandmethaneconcent