Functional heartburnWord文件下载.docx

Functional heartburnWord文件下载.docx

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Functionalheartburnhasmoreincommonwithfunctionaldyspepsiathanwithnon-erosiverefluxdisease

ESavarino1,DPohl2,PZentilin1,PDulbecco1,GSammito1,LSconfienza1,SVigneri3,GCamerini4,RTutuian2,VSavarino1

1DivisionofGastroenterology,DepartmentofInternalMedicine,UniversityofGenoa,Genoa,Italy

2DivisionofGastroenterologyandHepatology,DepartmentofInternalMedicine,UniversityHospitalZurich,Zurich,Switzerland

3DivisionofGastroenterology,DepartmentofInternalMedicine,UniversityofPalermo,Palermo,Italy

4DivisionofSurgery,DepartmentofInternalMedicine,UniversityofGenoa,Genoa,Italy

Correspondenceto:

CorrespondencetoDrESavarino,CattedradiGastroenterologia,Università

diGenova,VialeBenedettoXV,16100Genova,Italy;

edoardo.savarino@unige.it

Revisedversionreceived6April2009

Accepted16April2009

ABSTRACT

TOP

ABSTRACT

Methods

Results

Discussion

REFERENCES

Introduction:

Functionaldyspepsiaandnon-erosiverefluxdisease（NERD）areprevalentgastrointestinalconditionswithaccumulatingevidenceregardinganoverlapbetweenthetwo.Still,patientswithNERDrepresentaveryheterogeneousgroupandlimiteddataondyspepticsymptomsinvarioussubgroupsofNERDareavailable.

Aim:

ToevaluatetheprevalenceofdyspepticsymptomsinpatientswithNERDsubclassifiedbyusing24himpedance-pHmonitoring（MII-pH）.

Methods:

Patientswithtypicalrefluxsymptomsandnormalendoscopyunderwentimpedance-pHmonitoringoffprotonpumpinhibitortreatment.Oesophagealacidexposuretime（AET）,typeofacidandnon-acidrefluxepisodes,andsymptomassociationprobability（SAP）werecalculated.Avalidateddyspepsiaquestionnairewasusedtoquantifydyspepticsymptomspriortorefluxmonitoring.

Results:

Of200patientswithNERD（105female;

medianage,48years）,81（41%）hadanabnormaloesophagealAET（NERDpH-POS）,65（32%）hadnormaloesophagealAETandpositiveSAPforacidand/ornon-acidreflux（hypersensitiveoesophagus）,and54（27%）hadnormaloesophagealAETandnegativeSAP（functionalheartburn）.Patientswithfunctionalheartburnhadmorefrequent（p<

0.01）postprandialfullness,bloating,earlysatietyandnauseacomparedtopatientswithNERDpH-POSandhypersensitiveoesophagus.

Conclusion:

Theincreasedprevalenceofdyspepticsymptomsinpatientswithfunctionalheartburnreinforcestheconceptthatfunctionalgastrointestinaldisordersextendbeyondtheboundariessuggestedbytheanatomicallocationofsymptoms.Thisshouldberegardedasafurtherargumenttotestpatientswithsymptomsofgastro-oesophagealrefluxdiseaseinordertoseparatepatientswithfunctionalheartburnfrompatientswithNERDinwhomsymptomsareassociatedwithgastro-oesophagealreflux.

Gastro-oesophagealrefluxdisease（GORD）isoneofthemostcommonchronicgastrointestinaldiseasesinWesterncountries.12Recentstudiesdocumentedthatupto70%ofrefluxpatientshavetypicalrefluxsymptoms（ie,heartburnand/orregurgitation）intheabsenceofendoscopicallyvisibleoesophagealmucosalinjuries,makingnon-erosiverefluxdisease（NERD）themorecommonformofGORD.34TheNERDpatientgroupincorporatessubgroupswhichdiffersignificantlyintermsofpresentation,pathophysiologyandmanagement.PatientsexperiencingtypicalrefluxsymptomswithoutevidenceofoesophagitisonupperendoscopyareclassifiedonthebasisofoesophagealpHmonitoringresultsandsymptomassociationanalysisassufferingeitherfromNERD,whenexcessiveacidrefluxorapositivesymptomassociationwithacidrefluxisdemonstrated,orfromfunctionalheartburn（FH）,when,inagreementwithRomeIIIcriteria,distaloesophagealacidexposureisnormalandanegativeresponsetoacidsuppressionisfound.56Recognisingthatstimuliotherthanacidcanevoketypicalrefluxsymptoms,7ourgrouppreviouslyproposedsubclassifyingpatientswithtypicalrefluxsymptomsandnormaluppergastrointestinalendoscopyasfollows:

（1）NERDpH-POSpatientswithnormalendoscopyandabnormaldistaloesophagealacidexposure;

（2）hypersensitiveoesophagus–patientswithnormalendoscopy,normaldistaloesophagealacidexposureandpositivesymptomassociationforeitheracidornon-acidreflux;

and（3）functionalheartburn–patientswithnormalendoscopy,normaldistaloesophagealacidexposureandnegativesymptomassociationforacidandnon-acidreflux.8

PatientswithGORD,bothwitherosiveoesophagitisandNERD,frequentlyreportdyspepticsymptoms.9EpidemiologicalstudiesinvestigatingtheprevalenceofdyspepticandoesophagealsymptomshavereportedahigherprevalenceofdyspepticsymptomsinpatientswithGORD,suggestingthatthedegreeofoverlapisgreaterthancouldbepredictedbychancealone.10Moreover,itwasrecentlydemonstratedthatpatientswithfunctionalheartburnandpoorresponsetoacidsuppressivetherapyaremorelikelytohavepsychopathologysimilarlytopatientswithfunctionaldyspepsia.11Last,butnotleast,abdominalsymptomsappeartobeindependentpredictorsoftheseverityofrefluxsymptomsinpatientswithNERDwhencomparedtonormalcontrols.12

GivenpreviousreportsindicatinganinverserelationshipbetweendyspepticsymptomsandtheobjectivecriteriaforGORDwehypothesisedthatinpatientswithfunctionalheartburndyspepticsymptomsshouldbemoreprevalentcomparedtotherestofNERDpatients.Totestthishypothesis,weevaluatedtheprevalenceofdyspepticsymptomsinpatientswithNERDsubclassifiedintothreedistinctgroupsbyusing24hMII-pHmonitoring.

Methods

Studysubjects

BetweenJune2004andSeptember2008,patientspresentingtotheoutpatientmotilitycentreattheUniversityofGenoawithpredominanttypicalGORDsymptoms（ie,heartburnandregurgitation）lastingformorethan6monthsandoccurringatleastthreetimesweekly,wereprospectivelyenrolledinthestudy.Allsubjectswhoagreedtoparticipateinourinvestigationunderwentcarefulhistorytakingphysicalandclinicalexamination,uppergastrointestinalendoscopytoassessthepresenceornotofoesophagealmucosalinjury,routinebiochemistry,andupperabdominalultrasound.Themedicalhistoryincludedinformationontreatmentwithacidsuppressivemedication（inparticularprotonpumpinhibitors（PPIs））andsymptomaticresponsetoPPItherapy.Patientsreporting

50%symptomimprovementwereconsideredresponderstoPPItherapy.Patientstreatedwithantisecretorydrugswereaskedtodiscontinueacidsuppressivetherapyatleast30daysbeforetheendoscopicexamination.Duringthewashoutperiod,patientswereallowedtouseanoralantacidoralginateonanas-neededbasisforthereliefofheartburn.Basedontheresultsofupperendoscopy,patientswerethensubdividedintothreemajorgroups–Barrett’soesophagus,erosiveoesophagitisandNERD–incaseswherethetypicalsymptomsofGORDwerepresent,andwherevisibleoesophagealmucosalinjurywasabsent.PatientswithBarrett’soesophagusanderosiveoesophagitiswerenotincludedinthepresentstudy.Within1–5days（median3days）fromtheupperendoscopy,patientswithNERDunderwentambulatorycombinedimpedance-pHmonitoring.Exclusioncriteriawere:

historyofthoracic,oesophagealorgastricsurgery;

primaryorsecondarysevereoesophagealmotilitydisorders（eg,achalasia,scleroderma,diabetesmellitus,autonomicorperipheralneuropathy,myopathy）;

underlyingpsychiatricillness;

useofnon-steroidalanti-inflammatorydrugs（NSAIDs）andaspirin;

presenceofpepticstrictureandduodenalorgastriculceronupperendoscopy,evidenceoferosiveoesophagitisatprevious（2–5years）endoscopy,presenceofdyspepticsymptomsasmajorsymptoms.Inwomenofchildbearingage,pregnancywasexcludedbyurineanalysis.Duringuppergastrointestinalendoscopy,biopsiesweretakenfromtheantrumandthecorpusforassessingthepresenceofHelicobacterpylori.Patientswereaskedtodiscontinueanymedicationthatwouldinfluenceoesophagealmotorfunctionatleast1weekbeforeadministeringthequestionnairesandperformingtestsofoesophagealfunction.

Allparticipantsgavewritteninformedconsentbeforeenteringthestudy.

Symptomquestionnaire

Beforethe24hpH-impedancestudy,eachpatientcompletedafunctionaldyspepsiaquestionnaireasreportedandvalidatedpreviously.13Thisquestionnaireincludedquestionsonthepresenceandintensity（range,0–3;

where0=absent,1=mild,2=moderate,and3=severe,interferingwithdailyactivities）ofepigastricpain,bloating,postprandialfullness,earlysatiety,nausea,vomiting,excessivebelchingandepigastricburning.Also,typicalGORDsymptoms（ie,heartburnandregurgitation）wereevaluatedusingthesamequestionnaire（0=absent,1=mild,2=moderate,and3=severe）.Asecondinvestigatorcompletedastructuredinterviewwiththepatientincludingacarefulmedicalhistory（includingheightandweight）,currentmedication,tobaccouseandalcoholconsumption.

OesophagealmultichannelintraluminalimpedanceandpHmonitoring

Oesophagealimpedance-pHmonitoringwasperformedusinganambulatorymultichannelintraluminalimpedanceandpH（MII-pH）monitoringsystem（Sleuth;

SandhillScientific,HighlandRanch,Colorado,USA）.ThesystemincludedaportabledataloggerandacatheterwithoneantimonypHelectrodeandeightimpedanceelectrodesat2,4,6,8,10,14,16and18cmfromthetipofthecatheter.Eachpairofadjacentelectrodesrepresentedanimpedance-measuringsegment（2cmlength）correspondingtoonerecordingchannel.ThesiximpedanceandonepHsignalswererecordedat50Hzona128MB