Risk of impaired nutritional status and flare occurrence in IBD outpatients

ContentslistsavailableatScienceDirect

Digestive

and

Liver

Disease

j o ur n a l ho me p a g e :w w w . e l s e v i e r . c o m / l o c a t e / d l d

Alimentary

Tract

Risk

of

impaired

nutritional

status

and

flare

occurrence

in

IBD

outpatients

Corinne

E.G.M.

Spooren

_,

_Dion

_S.J.

_Wintjens

_,

_Marin

_J.

_de

_Jong

_,

Andrea

E.

van

der

Meulen-de

Jong

_,

_Mariëlle

_J.

_{Romberg-Camps}

_,

_Marco

_C.

_Becx

_,

Jeroen

P.

Maljaars

_,

_Ad

_A.

_van

_Bodegraven

_,

_Nofel

_Mahmmod

_,

_Tineke

_Markus

_,

Wim

M.

Hameeteman

_,

_Ad

_A.M.

_Masclee

_,

_Bjorn

_Winkens

_,

_Daisy

_M.A.E.

_Jonkers

_,

Marie

J.

Pierik

a_{DepartmentofInternalMedicine,DivisionofGastroenterologyandHepatology,MaastrichtUniversityMedicalCentre+,Maastricht,TheNetherlands} b_{SchoolforNutritionandTranslationalResearchinMetabolism(NUTRIM),MaastrichtUniversityMedicalCentre+,Maastricht,TheNetherlands} c_{DepartmentofGastroenterologyandHepatology,LeidenUniversityMedicalCentre,Leiden,TheNetherlands}

d_{DepartmentofGastroenterology,Geriatrics,InternalandIntensiveCareMedicine(Co-MIK),ZuyderlandMedicalCentre,Sittard-Geleen-Heerlen,The}

Netherlands

e_{DepartmentofGastroenterologyandHepatology,St.AntoniusHospital,Nieuwegein,TheNetherlands} f_{CCUVN,DutchIBDPatientsOrganization,Woerden,Netherlands}

g_{DepartmentofMethodologyandStatistics,MaastrichtUniversity,Maastricht,TheNetherlands}

a

r

t

i

c

l

e

i

n

f

o

Received25February2019 Accepted23May2019 Availableonline15June2019 Keywords: Crohn’sdisease Nutritionalstatus Telemedicine Ulcerativecolitis

a

b

s

t

r

a

c

t

Background:Inflammatoryboweldisease(IBD)patientsareatriskofanimpairednutritionalstatus.The impactthereofontheIBDrelapseriskisclinicallyrelevant,thoughsparselyinvestigated.

Aim:Theaimwastoexploretheassociationbetweenanimpairednutritionalstatusriskandthe occur-renceofdiseaseflaresinIBDoutpatientsparticipatinginalongitudinaltelemedicinestudy.

Methods:IBDoutpatientswererecruitedfromthemyIBDcoachstudycohort,withoneyearclinical follow-up.ThroughmyIBDcoach,atelemedicinetool,patientsreportedondiseaseactivityandriskofimpaired nutritionalstatus(i.e.ShortNutritionalAssessmentQuestionnaire>1and/orBMI<18.5kg/m2_)everyone

tothreemonths.Datawasanalysedbygeneralizedestimatingequationmodelling.

Results:Intotal,417patientswereincluded.Duringfollow-up,49patients(11.8%)flaredafterinitial clinicalremissionand53patients(12.7%)showedanincreasedriskofimpairednutritionalstatus.The riskofimpairednutritionalstatuswasassociatedwithflareoccurrence(OR2.61(95%CI1.02–6.69)). Conclusions:TheriskofanimpairednutritionalstatuswasassociatedwithsubsequentflaresinIBD outpatients.ThisemphasizestheimportanceofmonitoringdiseaseactivityinIBDpatientsatriskof impairednutritionalstatus.

©2019EditriceGastroenterologicaItalianaS.r.l.PublishedbyElsevierLtd.Allrightsreserved.

1. Introduction

Inflammatoryboweldisease(IBD)isachronicinflammatory dis-easeofthegastrointestinaltract,withCrohn’s disease(CD)and ulcerativecolitis(UC)asmainsubtypes.Thediseasecourseis char-acterizedbyawidevariationindurationandfrequencyofrelapsing andquiescentperiodsbetweenpatients.Severalfactorshavebeen associated withrelapse risk,such asa highfrequency of flares

∗ Corresponding author at: Division of Gastroenterology and Hepatology, MaastrichtUniversityMedicalCentre+,POBox5800,6202AZ,Maastricht,The Netherlands.

E-mailaddress:c.spooren@maastrichtuniversity.nl(C.E.G.M.Spooren).

withinthe firstyear ofdiagnosis[1,2], poormedication adher-ence[3],and activesmokinginCD patients[4].However,these donotsufficientlypredictthediseasecourse.Identificationof fur-therfactorscontributingtothedevelopmentofrelapsesistherefore warranted.

IBDpatientsareatriskofanimpairednutritionalstatusdueto diseaserelatedchangesinabsorptionand/orrequirements,often incombinationwithanunbalanceddietaryintake[5].Reported prevalencesrangefrom16to75%inIBDpatients[6–8].The varia-tionmaybeduetoheterogeneityinstudymethodsanddefinitions usedfordefininganimpairednutritionalstatus,in many publi-cationsoften referred toas malnutrition.Definingmalnutrition remainschallenging.Therefore,theAmericanSocietyofParenteral andEnteralNutrition(ASPEN)recommendsdiagnostic characteris-https://doi.org/10.1016/j.dld.2019.05.024

ticstoidentifymalnutritioninadults,bywhichtwoofthefollowing six criteria need to be fulfilled: i.e. low energy intake, weight loss,lossofmusclemass,lossofsubcutaneousfat,fluid accumu-lation,and handgripstrength [9]. However,validated screening toolstoidentifypatientsatriskofmalnutrition,suchastheShort NutritionalAssessmentQuestionnaire(SNAQ)andthe Malnutri-tionUniversalScreeningTool(MUST),aremoreoftenused,since thesearelesstimeconsuming[10].

Animpairednutritionalstatusmayimpactdiseasecourse. Mal-nutrition,definedbytheSubjectiveGlobalAssessment,whichisa nutritionalassessmentinstrument,hasbeenfoundtoberelated toa diminishedqualityoflifeinhospitalizedpatientswithIBD [11].Inaddition,radiologicallyassessedlossofmusclemasswas foundtobeassociatedwithanincreasedriskofintestinalresection andpostoperativecomplicationsinIBDpatients[12–15]. Further-more,higherdiseaseactivitywasassociatedwithalowerskeletal muscleindexamongUCpatients[13].Inpreviouscross-sectional andlongitudinalstudies,activediseasewasreportedtoaffectbody compositioninbothCDandUCpatients[16–18].However,both CDandUCpatientswithquiescentdiseasecanalsosufferfroman alteredbodycomposition(i.e.fatmassandfatfreemass)[19,20]. Furthermore,ina prior study,thenutritionalstatus ofrecently diagnosedIBDpatientswasshowntobeaffectednegativelyina priorstudy[21].Itcanthusbehypothesizedthatanimpaired nutri-tionalstatuscouldbeariskfactorforthedevelopmentofdisease activity.Therefore,asanexplorativestudy,weaimedtoanalyse whethertheriskofanimpairednutritionalstatuswasassociated withflareoccurrenceinquiescentIBDoutpatientsinalongitudinal, observationalstudy.

2. Materialsandmethods

2.1. Studydesign

Forthepresentlongitudinalstudy,availabledatafromthe myIB-Dcoachstudywasusedinanexplorativeanalysis.MyIBDcoachisa telemedicinetool,accessibleonasecuredwebpagethrough com-puter,tabletorsmartphone,forthemonitoringofIBDpatientsat home[22]. InthemyIBDcoachtrial,theeffectofdisease moni-toringwithmyIBDcoachonhealthcareutilizationandqualityof carewasinvestigated.AllconsecutiveIBDpatientsbetween18–75 years,withsufficientknowledgeoftheDutchlanguageandinternet access,fromtwotertiaryreferralcentresandtwonon-academic hospitalsintheNetherlands wereeligiblefor inclusion for this trialandrandomizedinthemyIBDcoachorstandardcaregroup. AllpatientshadanestablisheddiagnosisofCDorUC,fulfillingthe internationaldiagnosticcriteria[23].

Everysinglemonth,patientsinthetelemedicinearmcompleted monitoringmodules,comprisingquestionsondiseaseactivity,use ofmedication,smokingstatus,weight,andmalnutritionriskbased ontheSNAQ.Ifapatientachievedremission(i.e.lowclinicalactivity forthreeconsecutivemonths),patientswereallowedtocomplete themonitoringmoduleonceeverythreemonths.Thestudydesign isdescribedindetailelsewhere[24].

ThemyIBDcoachstudywasapprovedbytheMedicalResearch Ethics Committee of the Maastricht University Medical Cen-tre+ (NL47697.068.14) and registered at ClinicalTrials.gov (NCT02173002) and the study protocol conformed to the pro-visionsof thedeclarationof Helsinki. Allpatientsgave written informedconsentpriortoparticipation[22,24].

PatientswhowererandomizedtothemyIBDcoachintervention groupwereincludedin thepresentstudy.Baseline characteris-tics(e.g.height,diseasephenotype,duration,andmedicationuse) wereextractedfrompatientfilesusingstandardizedregistration forms.Duringthe12monthsoffollow-up,informationonweight

(todetermineBMI),diseaseactivitybyasymptom-basedpatient reported outcome measure (the MonitorIBD At Home (MIAH) questionnaire[25]),andriskformalnutrition(bytheSNAQ)was obtainedeveryonetothreemonths.

InlinewiththemyIBDcoachtrial,diseaseactivity(flares)were definedasclinicalsymptomsindicativeofdiseaseactivity(i.e. pos-itive score on theMonitor IBD At Home (MIAH) questionnaire [25,26]orincreasedsymptomsduringoutpatientvisits)in com-binationwitheithera concurrentfaecalcalprotectin>250_␮g/g, ordiseaseactivityonendoscopy,magneticresonanceimaging,or computedtomography.Indailyclinicalpractice,incaseofclinically severe symptoms suggestive of IBD disease activity, the treat-ingphysicianoccasionallyjudgedthesesymptomstobeevident enoughtoadjusttherapy.Therefore,tocaptureallflares,also symp-tomsindicativeofdiseaseactivityresultingindoseescalationor initiationofanewdrugweredefinedasdiseaseactivity[22]. Oth-erwisepatientswereconsideredtobeinremission.

TheSNAQwasdevelopedasanon-invasivescreeningtoolto assess malnutrition in both in- and outpatient settings [27,28] and comprisesof three questions,i.e. unintentionalweightloss overapredefinedtimeperiod(dependingonweightloss:2or3 points),experienceofdecreased appetiteduringthelastmonth (1point),and/oruseofsupplementaldrinksortubefeeding dur-ingthelastmonth(1point).Forthepresentstudy,theriskofan impairednutritionalstatuswasdefinedasaSNAQ≥2pointsand/or BMI<18.5kg/m2_{.Bothparametersweredeterminedeveryoneto} threemonths.

2.2. Statisticalanalysis

Numericalvariableswerepresentedasmeanswith correspond-ingstandarddeviation(SD)andcategoricalvariablesasnumbers withpercentages.Baselinecharacteristicswerecomparedbetween groups(patientswhorelapseversuspatientswhodonotrelapse) bythe independentsamplest-test fornumerical variables, and Chi-squaretest orFisher’sexact testwhenappropriate, for cat-egorical variables. Generalizedestimating equations model was usedtoidentifyanassociationbetweentheriskofimpaired nutri-tionalstatusandthedevelopmentofflaresinthefollowingthree months.Thismethodaccountsforrepeatedmeasureswithinthe samepatient,withanunstructuredcovariancepattern.

Ateachtime-pointofmeasurement,flarestatus(yes/no),aswell astheriskofimpairednutritionalstatus(yes/no)wasrecorded. In patientswithquiescent disease,thefirstthree monthswere excludedfromtheanalysestopreventpotentialcarryovereffects ofhistologicalinflammationinclinicalinactivepatientsattimeof inclusion.Whenactivediseasewaspresentatinclusionorduring followup,thefollowingsixmonthswereexcludedfromthe analy-sesasawashoutperiod,andtostartthefollow-upfromaremissive stateonwards.

Forthegeneralizedestimatingequationsmodel,allpositive val-uesontheriskofanimpairednutritionalstatusinthethreemonths precedingaflarewereregardedaspossiblepredictors.

Table1

Patientcharacteristics,stratifiedbyoccurrenceofdiseaseflares.

Relapsers(n=49) Non-relapsers(n=368) p-Value

Crohn’sdiseasen(%) 26(53.1) 222(60.3) 0.331

Male,n(%) 15(30.6) 158(42.9) 0.100

BMI(kg/m2_{),mean(SD) 25.37(4.3) 25.14(4.0) 0.705}

Montrealatdiagnosisa

Age(CD&UC) 0.600

A1,<17years,n(%) 8(16.3) 60(16.3) A2,17–40years,n(%) 26(53.1) 219(59.5) A3,>40years,n(%) 15(30.6) 89(24.2) Diseaselocation(CD) 0.741 L1,ileal,n(%) 7(26.9) 73(32.9) L2,colonic,n(%) 6(23.1) 55(24.8) L3,ileocolonic,n(%) 13(50.0) 94(42.3) Diseasebehaviour(CD) 0.958 B1,non-stricturingnon-penetrating,n(%) 16(61.5) 134(60.6) B2,stricturing,n(%) 7(26.9) 57(25.8) B3,penetrating,n(%) 3(11.5) 30(13.6)

Diseaseextent(UC) 0.768

E1,proctitis,n(%) 2(8.7) 19(12.8)

E2,left-sided,n(%) 10(43.5) 69(46.3)

E3,pancolitis,n(%) 11(47.8) 61(40.9)

Ageatinclusion(years),mean(SD) 46.08(15.2) 43.95(13.7) 0.313

Diseasedurationatinclusion(years),mean(SD) 13.45(10.9) 13.39(10.4) 0.971

Activediseaseatinclusion,n(%) 4(8.2) 28(7.6) 0.908

Medicationuseatinclusion 0.434

Nomedication/5-ASA,n(%) 15(30.6) 142(39.3)

Immunomodulators,n(%) 16(32.7) 93(25.8)

Biologics,n(%) 18(36.7) 126(34.9)

Currentsmokingatinclusion,n(%) 1(2.0) 65(17.7) 0.005b

n,numberofpatients/SD,standarddeviation/BMI,bodymassindex/5-ASA,5-aminosalicylicacid.

a_{AccordingtotheMontrealclassification[45].} b_{p-Valuebelow0.05.}

3. Results

Intotal, 465IBD patientswere allocatedtotheintervention groupinthemyIBDcoachtrial[22].Patientswhowerenoteligible, i.e.neverstartedusingtheapplication,neverachievedaperiodof remissionorwerelosttofollow-upforotherreasonswereexcluded fromfurtheranalyses.Finally,417patientswereincludedinthe presentstudy.

Baselinecharacteristicsatinclusion,stratified byflarestatus duringfollowup,arepresentedinTable1.Duringfollow-up,49 (11.8%)individualpatients(CD=26,UC=23)experiencedaflare afterinitialremission.Lessactivesmokerswerefoundamongthose that relapsedduringfollow-up compared tothe‘non-relapsers’ (p=0.005).Nootherdifferencesinbaselinecharacteristicswere foundbetweenthesegroups.

Atinclusion, six (1.4%) patients had a BMI<18.5kg/m2_{, 216} (51.8%)patientshadaBMIof18.5–25kg/m2_{,147(35.3%)patients} had a BMI of 25–30kg/m2_{, and 48 (11.5%) patients had a} BMI>30kg/m2_{.Intotal,53(12.7%)individualIBDpatientswereat} riskofanimpairednutritionalstatusbasedonapositiveSNAQscore (n=45),BMI<18.5kg/m2_{(n=5),orboth(n=3)duringfollow-up.}

Inthegeneralizedestimatingequationsanalyses,theriskofan impairednutritionalstatuswasfoundtobeassociatedwiththe occurrenceofaflareinthefollowingthreemonths(OR2.61(95% CI1.02–6.69,p=0.046)).Furthermore,inthismodelfemalesex(OR 2.12(95%CI1.08–4.15,p=0.029))wasalsoidentifiedasariskfactor forthedevelopmentofaflare,whileactivesmokingshoweda neg-ativeassociation(OR0.14(95%CI0.02-0.97,p=0.047))(Table2). Inthegeneralizedestimatingequationsmodel,medicationuseat timeofinclusionwasnotincorporatedasconfounderduetothe smallnumberofrelapsingpatientsduringfollowup.When medica-tionuseattimeofinclusionwasaddedtothemodel,acomparable increasedriskwasfound(OR2.48(95%CI0.96–6.41,p=0.061)), thoughnotsignificant.

Table2

Multivariable generalized estimating equations model: association between impairednutritionalstatusriskinIBDanddiseaseflares.

OR 95%-CI p-value

Impairednutritionalstatus 2.61 1.02-6.69 0.046b

UCphenotype 1.43 0.78–2.65 0.251

Sex,female 2.12 1.08–4.15 0.029b

Activesmokera _{0.14 0.02–0.97 0.047}b

Diseasedurationa _{1.01 0.98–1.04 0.642}

OR,Oddsratio/95%-CI,95%-Confidenceinterval.

a_Atinclusion. b_{p-Valuebelow0.05.}

4. Discussion

Inthislongitudinalstudyindailypractice,theriskofanimpaired nutritionalstatus,definedbyapositiveSNAQorBMI<18.5kg/m2_, wasfoundtobeassociatedwiththeoccurrenceofaflare.

[31–34].Amicestudyontheeffectsoffastingshowed,forexample, thatchangesinimmuneresponseoccurratherearlyafter induc-ingnutritionaldeficiencies[32].After48h,activatedTcellsfrom fastedmiceshoweddecreased ability tosecreteIL-2 and IFN-y whencomparedwithcontrolfedmice.Aviciouscirclemaydevelop inwhichanimpairednutritionalstatusandintestinalinflammation affecteachother.Furthermore,malnutritionisfoundtoaffectthe microbiotacompositionandactivity,andtherebymayalsoimpact diseasecourse[35].Toourknowledge,thecurrentstudyisthefirst tospecificallyanalysetheassociationofimpairednutritional sta-tusriskonsubsequentflareoccurrence.Futurestudiesshouldalso addresspotentialunderlyingmechanisms.

Inthepresentstudy,theSNAQincombinationwithBMIwas usedasscreeningmethodforriskofanimpairednutritionalstatus, sincetheSNAQalonemayleadtounderreportinginanoutpatient setting[36].TheSNAQandMUSTbothcontainquestionson unin-tentionalweightlossandfoodintake.IncontrasttotheSNAQ,alow BMI(18.5–20or<18.5kg/m2_{)istakenintoaccountintheMUST} questionnaire.TheMUSTmayhoweverleadtooverreportingof patientsat riskintheoutpatient setting[36].Therefore, inline withoneofthediagnosticcriteriaformalnutritionbytheEuropean SocietyforClinicalNutritionandMetabolism(ESPEN)[10],onlya BMI<18.5kg/m2_{wasaddedtotheSNAQtocaptureallpatientsat} riskofimpairednutritionalstatusinthecurrentstudy.Fifty-three patientswereatriskofanimpairednutritionalstatusduring fol-lowup,ofwhichthemajorityofthepatients(n=45)hadapositive SNAQincombinationwithaBMI>18.5kg/m2_{,fivepatientshada} BMI<18.5kg/m2_{andanegativeSNAQ,andthreepatientshadboth} apositiveSNAQscoreandaBMI<18.5kg/m2_.

Theoveralldistributionofourpatientsoverthedifferentweight categories(accordingtotheWorldHealthOrganizationdefinitions) [37]werecomparable withpercentagesofoverweightand obe-sityina representative healthypopulationin South-Limburg, a provinceintheNetherlands[38].ThemajorityoftheIBDpatients inthepresentstudyhadanormalBMI(51.8%)whileasignificant proportionwasoverweight (35.3%)or obese(11.5%). Duetoan unfavourablefat-muscleratio,whichisnotnecessarilyreflectedby BMI,itcannotbeexcludedthatpatientswithaBMI18.5–25kg/m2 dohaveadecreasedmusclemassandaretherebyatriskofimpaired nutritionalstatus.

Acommonlyusedmodelforanalysingthebodycompositionis thetwo-compartmentmodelinwhichbodyweightissubdivided infatmassandfatfreemass.Skeletalmusclemassrepresentsa largeproportionofthefatfreemass.Priorstudiesreportedthat changesinfatfreemass,arenotalwayscapturedbymalnutrition screeningquestionnairesinIBDpatients[20,39].Thisunderlines thenecessityinfuturestudiestocombineamalnutritionscreening questionnairewithasimple,non-invasivebodycomposition anal-ysis,andalso,toincorporatechangesinfatfreemassfortimely identificationofpatientsatrisk.Atechniquewhichcanbe con-sideredisthehandgripstrength,asparameterofmusclestrength [40].

Inthepresentstudy,flaredevelopmentwasalsofoundtobe positivelyassociatedwithfemalesexandnegativelywithsmoking statusattimeofinclusion.InCDforexample,smokingisfound toincrease theriskofa flare,whereas inUCsmokingcessation is[41].Ourfindingmaybeaffectedbyanalysisofthetotal IBD population.SeparateanalysesforCDandUCwerenotperformed duetothelimitedsamplesize,butshouldbetakenintoaccountin futurestudies.

Amajorstrengthofthepresentstudyisthelongitudinaldesign ofthestudyinarelativelylarge,unselectedoutpatientstudy popu-lation.Thestudypopulationwasfoundtoberepresentativeforthe generalIBDpopulationintheSouthLimburgarea[22,42]. Further-more,bytheuseoftelemedicine,diseaseactivity,andmalnutrition screeningriskweremeasuredrepeatedlyandstandardized.

How-ever,somelimitationsofthisstudyshouldbeaddressed.Forthe present explorative study,available data fromthe myIBDcoach studywasused.Therefore,nosample sizecalculationhasbeen performed,andwewerenotabletocorrectforallpotential con-foundersforflaredevelopment,suchaspriorsurgery,timesince last flare,andprior smokingstatus. Thepresent studyshows a significantassociation betweenimpaired nutritional status risk and flareoccurrences in theentire IBD cohort. Separate analy-sesforCDandUCwerenotperformedduetoasmallnumberof patients.However,theseanalysesareofinterestsincefactors influ-encingflareoccurrencemaydifferbetweenthesephenotypes,and shouldbeincludedin futurestudies.Furthermore,ongoing his-tologicalinflammationattimeofinclusionandduringfollowup cannotbecompletelyexcluded,sincediseaseactivitywas moni-toredbyclinicalparameters.However,topreventcarryovereffects ofhistologicalinflammation,thefirstthreemonthsfrompatients withquiescentdiseasewereexcludedfromtheanalyses.Finally,it shouldbetakenintoaccountthatflarescanbeaffectedbyenteral nutrition,particularlyinCD[43].However,inthepresentstudy, useofenteralnutritionwaslimitedandwasnotfoundtoimpact ourfindings(datanotshown).

Theaimofthepresentexplorativestudywastoinvestigatean associationbetweentheriskofanimpairednutritionalstatusand flareoccurrence.Inclinicalpractice,ithasalreadybeenshownthat earlytreatmentofmalnourishedinpatientsforanydiseaseor oper-ation,basedonscreening,leadstoashorterlengthofhospitalstay andiscost-effective[44].Sincethisisthefirstlongitudinalstudy analysingtheassociation of impairednutritional status risk on flareoccurrences,ourresultsshouldbeconfirmedinothercohorts. Largerlongitudinalstudiesontheimpactofanimpairednutritional statusrisk,incorporatingbodycompositionanalysisandmuscle strength,andtakingconfoundersandseparateanalysisforCDand UCintoaccount,areofspecialinteresttoconfirmtheactualeffect ondiseaseactivity.Additionally,studiesontimelydietaryand/or physiotherapyinterventions,aimingtoimprovenutritionalstatus andtreatmentoutcomearewarranted.

Inconclusion,inthepresentlongitudinalobservationalstudy, wefoundanassociationbetweenthepresenceoftheriskofan impairednutritionalstatusandIBDflareoccurrence.This empha-sizestheimportanceofmonitoringdiseaseactivityinIBDpatients atriskofanimpairednutritionalstatus.

Conflictofinterest

Nonedeclared.

Funding

Forthepresent study,datafromthemyIBDcoachstudy was used. The myIBDcoach trial was supported by an academic incentive fund of the Maastricht University Medical Centre+ (31962340B).MyIBDcoachwasdevelopedbySananetBVusingan unrestrictedgrantfromFerring.

Acknowledgements

J. Haans, M. Cilissen, H. Tomlow, E. Keulen, J. Wilbrink, L. Colautti-Duijsens,M.Verwey,N.Peek,H.Slingerland,R. Veenen-daal,N.Ipenburg,M.vanKouwen,M.SomersK.Achterberg,E.Smit, M.Spruit.

References

[2]HoieO,WoltersF,RiisL,AamodtG,SolbergC,BernklevT,etal.Ulcerativecolitis: patientcharacteristicsmaypredict10-yrdiseaserecurrenceina European-widepopulation-basedcohort.AmJGastroenterol2007;102:1692–701. [3]FeaginsLA,IqbalR,SpechlerSJ.Case-controlstudyoffactorsthattrigger

inflam-matoryboweldiseaseflares.WorldJGastroenterol2014;20:4329–34. [4]DuttaAK,ChackoA.Influenceofenvironmentalfactorsontheonsetandcourse

ofinflammatoryboweldisease.WorldJGastroenterol2016;22:1088–100. [5]HartmanC,EliakimR,ShamirR.Nutritionalstatusandnutritionaltherapyin

inflammatoryboweldiseases.WorldJGastroenterol2009;15:2570–8. [6]ScaldaferriF,PizzoferratoM,LopetusoLR,MuscaT,IngravalleF,SicignanoLL,

etal.NutritionandIBD:malnutritionand/orSarcopenia?Apracticalguide. GastroenterolResPract2017;2017:8646495.

[7]CasanovaMJ,ChaparroM,MolinaB,MerinoO,BataneroR,Duenas-SadornilC, etal.Prevalenceofmalnutritionandnutritionalcharacteristicsofpatientswith inflammatoryboweldisease.JCrohnsColitis2017;11:1430–9.

[8]MijacDD,JankovicGL,JorgaJ,KrsticMN.Nutritionalstatusinpatientswith activeinflammatoryboweldisease:prevalenceofmalnutritionandmethods forroutinenutritionalassessment.EurJInternMed2010;21:315–9. [9]WhiteJV,GuenterP,JensenG,MaloneA,SchofieldM,Academy

Malnutri-tionWorkG,etal.Consensusstatement:academyofnutritionanddietetics andAmericanSocietyforparenteralandenteralnutrition:characteristics rec-ommendedfortheidentificationanddocumentationofadultmalnutrition (undernutrition).JPENJParenterEnteralNutr2012;36:275–83.

[10]CederholmT,BarazzoniR, AustinP,BallmerP,BioloG,BischoffSC,etal. ESPENguidelinesondefinitionsandterminologyofclinicalnutrition.ClinNutr 2017;36:49–64.

[11]NormanK,KirchnerH,LochsH,PirlichM.Malnutritionaffectsqualityoflifein gastroenterologypatients.WorldJGastroenterol2006;12:3380–5.

[12]BambaS,SasakiM,TakaokaA,TakahashiK,ImaedaH,NishidaA,etal. Sar-copeniaisapredictivefactorforintestinalresectioninadmittedpatientswith Crohn’sdisease.PLoSOne2017;12:e0180036.

[13]ZhangT,DingC,XieT,YangJ,DaiX,LvT,etal.Skeletalmuscledepletion corre-lateswithdiseaseactivityinulcerativecolitisandisreversedaftercolectomy. ClinNutr2017;36:1586–92.

[14]PedersenM,CromwellJ,NauP.Sarcopeniaisapredictorofsurgicalmorbidity ininflammatoryboweldisease.InflammBowelDis2017;23:1867–72. [15]ZhangT,CaoL,CaoT,YangJ,GongJ,ZhuW,etal.Prevalenceof

Sarcope-niaanditsimpactonpostoperativeoutcomeinpatientswithCrohn’sdisease undergoingbowelresection.JPENJParenterEnteralNutr2017;41:592–600. [16]RochaR,SantanaGO,AlmeidaN,LyraAC.Analysisoffatandmusclemassin

patientswithinflammatoryboweldiseaseduringremissionandactivephase. BrJNutr2009;101:676–9.

[17]BenjaminJ,MakhariaG,AhujaV,JoshiYK.BodycompositioninIndianpatients withCrohn’sdiseaseduringactiveandremissionphase.TropGastroenterol 2011;32:285–91.

[18]RipoliJ,MiszputenSJ,AmbroginiJrO,CarvalhoL.Nutritionalfollow-upof patientswithulcerativecolitisduringperiodsofintestinalinflammatory activ-ityandremission.ArqGastroenterol2010;47:49–55.

[19]GeerlingBJ,Badart-SmookA,StockbruggerRW,BrummerRJ.Comprehensive nutritionalstatusinpatientswithlong-standingCrohndiseasecurrentlyin remission.AmJClinNutr1998;67:919–26.

[20]ValentiniL,SchaperL,BuningC,HengstermannS,KoernickeT,TillingerW,etal. MalnutritionandimpairedmusclestrengthinpatientswithCrohn’sdisease andulcerativecolitisinremission.Nutrition2008;24:694–702.

[21]GeerlingBJ,Badart-SmookA,StockbruggerRW,BrummerRJ.Comprehensive nutritionalstatusinrecentlydiagnosedpatientswithinflammatorybowel dis-easecomparedwithpopulationcontrols.EurJClinNutr2000;54:514–21. [22]deJongMJ,vanderMeulen-deJongAE,Romberg-CampsMJ,BecxMC,

Mal-jaarsJP,CilissenM,etal.Telemedicineformanagementofinflammatorybowel disease(myIBDcoach):apragmatic,multicentre,randomisedcontrolledtrial. Lancet2017;390:959–68.

[23]Lennard-JonesJE.Classificationofinflammatoryboweldisease.ScandJ Gas-troenterolSuppl1989;170:2–6,discussion16-9.

[24]deJongM,vanderMeulen-deJongA,Romberg-CampsM,DegensJ,BecxM, MarkusT,etal.Developmentandfeasibilitystudyofatelemedicinetoolforall patientswithIBD:MyIBDcoach.InflammBowelDis2017;23:485–93.

[25]DeJongM,VandenHeuvelT,Romberg-CampsM,WinkensB,MarkusT,Masclee A,etal.Developmentofapatientreporteddiseaseactivityscoretoscreenfor mucosalinflammationininflammatoryboweldisease.JCrohnsColitis2015;9. S192-3.

[26]deJongMJ,RoosenD,DegensJ,vandenHeuvelTRA,RombergM,Hameeteman W,etal.Developmentandvalidationofapatient-reportedscoretoscreenfor mucosalinflammationininflammatoryboweldisease.JCrohnsColitis2018. [27]KruizengaHM,SeidellJC,deVetHC,WierdsmaNJ,vanBokhorst-devander

SchuerenMA.Developmentandvalidationofahospitalscreeningtoolfor mal-nutrition:theshortnutritionalassessmentquestionnaire(SNAQ).ClinNutr 2005;24:75–82.

[28]NeelemaatF,KruizengaHM,deVetHC,SeidellJC,ButtermanM,van Bokhorst-devanderSchuerenMA.Screeningmalnutritioninhospitaloutpatients.Can theSNAQmalnutritionscreeningtoolalsobeappliedtothispopulation?Clin Nutr2008;27:439–46.

[29]CushingKC,KordbachehH,GeeMS,KambadakoneA,AnanthakrishnanAN. Sarcopeniaisanovelpredictoroftheneedforrescuetherapyinhospitalized ulcerativecolitispatients.JCrohnsColitis2018.

[30]HoltDQ,VarmaP,StraussBJG,RajaduraiAS,MooreGT.Lowmusclemassat initiationofanti-TNFtherapyforinflammatoryboweldiseaseisassociatedwith earlytreatmentfailure:aretrospectiveanalysis.EurJClinNutr2017;71:773–7. [31]GerrietsVA,DanzakiK,KishtonRJ,EisnerW,NicholsAG,SaucilloDC,etal. LeptindirectlypromotesT-cellglycolyticmetabolism todriveeffector T-cell differentiation in a mouse model of autoimmunity. Eur J Immunol 2016;46:1970–83.

[32]SaucilloDC,GerrietsVA,ShengJ,RathmellJC,MaciverNJ.Leptin metaboli-callylicensesTcellsforactivationtolinknutritionandimmunity.JImmunol 2014;192:136–44.

[33]Cohen S, Danzaki K, MacIver NJ. Nutritional effects on T-cell immunometabolism.EurJImmunol2017;47:225–35.

[34]vanderHulstRR,vonMeyenfeldtMF,vanKreelBK,ThunnissenFB,Brummer RJ,ArendsJW,etal.Gutpermeability,intestinalmorphology,andnutritional depletion.Nutrition1998;14:1–6.

[35]JonkersDM.Microbialperturbationsandmodulationinconditions associ-atedwithmalnutritionandmalabsorption.BestPractResClinGastroenterol 2016;30:161–72.

[36]LeistraE,LangiusJA,EversAM,vanBokhorst-devanderSchuerenMA,Visser M,deVetHC,etal.ValidityofnutritionalscreeningwithMUSTandSNAQin hospitaloutpatients.EurJClinNutr2013;67:738–42.

[37]Physicalstatus:theuseandinterpretationofanthropometry.ReportofaWHO ExpertCommittee.WorldHealthOrganTechRepSer1995;854:1–452. [38]Ministerie van Volksgezondheid Welzijn en Sport. Gezondheidsmonitor

Volwassenen enOuderen; 2018 https://www.volksgezondheidenzorg.info/ onderwerp/gezondheidsmonitor-volwassenen-en-ouderen/regionaal. [39]CsontosAA,MolnarA,PiriZ,PalfiE,MihellerP.Malnutritionriskquestionnaire

combinedwithbodycompositionmeasurementinmalnutritionscreeningin inflammatoryboweldisease.RevEspEnfermDig2017;109:26–32.

[40]LuZL,WangTR,QiaoYQ,ZhengQ,SunY,LuJT,etal.Handgripstrengthindex predictsnutritionalstatusasacomplementtobodymassindexinCrohn’s disease.JCrohnsColitis2016;10:1395–400.

[41]CosnesJ.Smokinganddiet:impactondiseasecourse?DigDis2016;34:72–7. [42]vandenHeuvelTR,JonkersDM,JeuringSF,Romberg-CampsMJ,Oostenbrug LE,ZeegersMP,etal.Cohortprofile:theinflammatoryboweldiseasesouth limburgcohort(IBDSL).IntJEpidemiol2017;46:e7.

[43]LevineA,SigallBonehR,WineE.Evolvingroleofdietinthepathogenesisand treatmentofinflammatoryboweldiseases.Gut2018;67:1726–38.

[44]KruizengaHM,VanTulderMW,SeidellJC,ThijsA,AderHJ,VanBokhorst-de vanderSchuerenMA.Effectivenessandcost-effectivenessofearlyscreening andtreatmentofmalnourishedpatients.AmJClinNutr2005;82:1082–9. [45]SatsangiJ,SilverbergMS,VermeireS,ColombelJF.TheMontrealclassificationof