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

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

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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. 

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SUBJECTSANDMETHODS 

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

spastandpresenthealth,anddietaryandweaningpractices.Clinicalexaminationofthechildincludedweightandmidarmcircumferencemeasurement. 

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. 

AnalysisofHydrogenandOxygeninBreathSamples 

Agaschromatograph（model12MicroLyzer;

Quintron）wasusedformeasuringhydrogeninbreathsamples.Analysisofoxygenconcentrationsinthesamebreathsampleswasperformedbyuseofaportableoxygenanalyzer,whichwasapotentiostaticoxygensensor（Oxywarn100I;

DraegerInstrumentDivision,Blyth,Northumberland,England）. 

AnalysisofMethaneinBreathSamples 

Methanewasmeasuredwithadeviceequippedwithamolecularsievechromatographiccolumn（model16Microlyzer;

Quintron）.Dryairwasusedasthecarriergasataflowrateof35mlperminute.Thechromatographwascalibratedwithamethane-referencedmixtureincompressedair（Quingas,Quintron）.Thesmallestdetectableconcentrationofmethanewas2µ

l/l,withalinearaccuracyresponserangeof2to200µ

l/l. 

WorkingDefinitions 

Lactosemalabsorption 

wasdefinedaspeakhydrogengreaterthanorequalto10ppmabovebaselinevaluesinsamplesobtained30to180minutesafteralactosetestmeal. 

Nonhydrogendetection 

wasdefinedaspeakhydrogenlessthan10ppmabovebaselinevaluesinthesamplesobtained30to180minutesafterlactulose.Peakhydrogenwascalculatedasthedifferencebetweenthehighestnormalizedbreathhydrogenvalueinanyoneofthebreathsamplescollectedafterlactoseorlactulosetestmealsandthebasalbreathhydrogenvalue.A 

methaneproducerwasdefinedasanysubjectwhoexcreted2ppmormoreofmethane. 

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