Received:4May2016 | Accepted:4November2016 DOI: 10.1111/nmo.13003 ORIGINAL ARTICLE Gastrointestinal symptom severity in irritable bowel syndrome, inflammatory bowel disease and the general population A. D. Lee1,2,3,4,5 | B. M. Spiegel1,2,4,6,7 | R. D. Hays3,7,8 | G. Y. Melmed1 | R. Bolus4,6 | D. Khanna9 | P. P. Khanna9 | L. Chang6,10 1CenterforOutcomesResearchand Education,Cedars-SinaiMedicalCenter,Los Abstract Angeles,CA,USA Background: Irritablebowelsyndrome(IBS)andinflammatoryboweldisease(IBD) 2 DepartmentofMedicine,Divisionof patientsreportsimilargastrointestinal(GI)symptoms,yetcomparisonsofsymptom Gastroenterology,VAGreaterLosAngeles HealthcareSystem,LosAngeles,CA,USA severitybetweengroupsandwiththegeneralpopulation(GP)arelacking. 3RANDHealthProgram,SantaMonica,CA, Methods: WecomparedPatient-ReportedOutcomesMeasurementInformation USA System(PROMIS®)GIsymptomscalesmeasuringgastro-esophagealreflux(GER), 4UCLA/VACenterforOutcomesResearchand Education(CORE),LosAngeles,CA,USA disruptedswallowing,diarrhea,bowelincontinence,nausea/vomiting,constipa- 5DivisionofGastroenterology,Kaiser tion,bellypain,andgas/bloatingin:(i)USAGPsample,(ii)IBSpatients,and(iii) PermanenteLosAngelesMedicalCenter,Los IBD patients from tertiary care and community populations. Symptom severity Angeles,CA,USA scoreswerebasedonT-scoremetricwithmean50±10(standarddeviation)rela- 6DepartmentofMedicine,Divisionof DigestiveDiseases,DavidGeffenSchoolof tivetotheGP. MedicineatUCLA,LosAngeles,CA,USA Key Results: Of1643patientsenrolled,therewere253IBSpatients(68%F,mean 7DepartmentofMedicine,UCLADivisionof GeneralInternalMedicine,LosAngeles,CA, age45±15years),213IBDpatients(46%F,meanage41±14years),and1177GP USA subjects(57%F,meanage46±16years).IBSpatientsreportedgreaterseverityof 8 DepartmentofHealthServices,UCLA GER,disruptedswallowing,nausea/vomiting,bellypain,gas/bloating,andconsti- FieldingSchoolofPublicHealth,LosAngeles, CA,USA pationsymptomsthantheirIBDcounterparts(allP<.05).ComparedtotheGP,IBD 9DivisionofRheumatology,Universityof patientshadworsebellypain,gas/bloating,diarrhea,andbowelincontinence,but Michigan,AnnArbor,MI,USA lesssevereGERanddisruptedswallowing(allP<.05),andIBSpatientshadmore 10G.OppenheimerCenterofNeurobiologyof severe nausea/vomiting, belly pain, gas/bloating, and constipation (all P<.05). StressandResilience,DavidGeffenSchoolof MedicineatUCLA,LosAngeles,CA,USA Womenhadmoreseverebellypainandgas/bloatingthanmen,whereasmenhad moreseverebowelincontinence(allP<.05). Correspondence LinChang,G.OppenheimerCenterfor Conclusion & Inferences: IBSandIBDareassociatedwithmoresevereGIsymp- NeurobiologyofStressandResilience tomscomparedtotheGPexcludingesophagealsymptoms.UnlikeIBD,IBSisnot LosAngeles,CA,USA. Email: [email protected] characterizedbyobservableGIinflammationbutpatientsreportmoresevereupper andlowerGIsymptoms. KEYWORDS gender,inflammatoryboweldisease,irritablebowelsyndrome,symptomseverity Abbreviations: CD, Crohn’s disease; GER, gastro-esophageal reflux; GI, gastrointestinal; GP, general population; HRQOL, health-related quality of life; IBD, inflammatory bowel disease; IBS,irritablebowelsyndrome;PROMIS,Patient-ReportedOutcomesMeasurementInformationSystem;UC,ulcerativecolitis. Fundinginformation:ThisresearchwassupportedbyNIH/NIAMSU01AR057936A,theNationalInstitutesofHealththroughtheNIHRoadmapforMedicalResearchGrant(AR052177). DineshKhannawasalsosupportedby.NIAMSK24AR063120PujaKhannawassupportedbyRuthL.KirschsteinNationalResearchServiceAward(NRSA)InstitutionalResearchTrainingGrant NIAMS1T32AR053463andACRResearchandEducationFoundationClinicalInvestigatorFellowshipAward2009_11.RonD.HayswasalsosupportedbyNIH/NIAGrantsP30-AG028748 andP30-AG021684,andNCMHDGrant2P20MD000182.LinChangwasalsosupportedbyNIDDKP50DK64539. Neurogastroenterology & Motility 2016; 1–9 wileyonlinelibrary.com/journal/nmo © 2016 John Wiley & Sons Ltd | 1 2 | LEE ET AL. 1 | INTRODUCTION Key Points Irritablebowelsyndrome(IBS)andinflammatoryboweldisease(IBD) • Patientswithirritablebowelsyndrome(IBS)andinflam- aregastrointestinal(GI)disordersthatareassociatedwithabdominal matoryboweldisease(IBD)havesimilargastrointestinal pain,alterationinbowelhabits,relapsing-and-remittingcourses,and (GI)symptomsbutstudiescomparingsymptomseverity psychologicaldistress.1IncomparisontoIBSinwhichdiseasesever- between these groups and the general population are ityisusuallybasedonpatient-reportedsymptoms,currentresearchin lacking. IBDhasfocusedontheuseofserum,fecal,andcolonicmucosalin- • IBSpatientsexperienceworseupperandlowerGIsymp- flammatorybiomarkersassurrogatesfordiseaseseverity.2–4Relatively tomsthanIBDpatients.PatientswitheitherIBSorIBD less studied are patient-reported severity of GI symptoms between experienceworseepigastricandlowerGIsymptomsthan thesegroupsandthegeneralpopulation(GP). thegeneralpopulation,butcomparableorlessseverees- IBSisafunctionalboweldisorderinwhichabdominalpainisas- ophagealsymptoms. sociatedwithchangesinbowelhabitsanddisordereddefecation.It • Understanding the differences in symptom severity be- occursin10%–20%ofthegeneralpopulationandismorepredomi- tween patients will allow for improved symptom nantinwomenandthosewithunderlyingpsychologicalcomorbidities management. or co-existing functional disorders.5–7 The etiology of IBS is multi- factorial,butthepathogenesisisthoughttobeduetodysregulated brain–gut interactions in which peripheral and central sensitization patientgroupcomprisedofIBDandfunctionalGIdisorders,butre- can occur. Central sensitization at the spinal cord and brain level is gurgitationwasmorecommoninpatients.17Inthisstudy,wecompare associatedwithincreasedactivationinbrainregionsinvolvedinemo- differencesinupperandlowerGIsymptomseveritybetweenpatients tionalarousalandpainmodulation.8 withIBS,IBD,andtheGP,adjustingfordemographics.Wealsoas- Crohn’s disease (CD) and ulcerative colitis (UC) are chronic sess the effect of gender on GI symptom severity. We hypothesize immune-mediateddisordersclassifiedasIBDsthataffectlessthan1% that the IBS andIBD patient groupswill have greater symptom se- of the USA population.9 Increased prevalence is seen in genetically verityforbellypainandlowerGIsymptoms(e.g.,diarrhea,constipa- predisposed individuals and certain ethnic groups. These diseases tion,bowelincontinence)thantheGP,butthatIBSpatientswillhave arethoughtbecausedbychronicdysregulationofmucosalimmune greaterseverityofcertainGIsymptoms,includingbellypain,gasand function,andtherapiesdirectedagainstsuppressionormodulationof bloating,constipationthanIBDpatients,andtheGP.Inaddition,we inflammationaregenerallyeffective. Althoughtheextenttowhichthesediseaseprocesseshaveover- 10 lapping pathologies is controversial, traditional thinking attributes Belly pain 8 items theetiologyofpaininIBDtoobjectiveinflammatorychangeswithin thebowelandassociatedcomplications.Itiscommonlyassumedthat worsenedsymptomseveritycorrelateswithincreasedprevalenceof Gas and bloating 12 items inflammatorylesionsandcomplications,however,thissimplisticview ofpainpathogenesisdoesnotaccountforthefactthatpatientswith Diarrhea 5 items IBSoftenwillhavesimilarcomplaintswithoutobjectivediseasepa- thology. While IBS and IBD have both been associatedwith worse generalhealth-relatedqualityoflife(HRQOL),11itremainsunclearthe Constipation9 items extentthatspecificGIsymptomsaffectpatients.GIsymptomques- tionnairessuchastheGastrointestinalSymptomRatingScale(GSRS) Bowel 4 items andQualityofLifeinRefluxandDyspepsia(QOLRD),whichmeasure Incontinence thedegreeofGIsymptomdiscomfort,havebeendevelopedbuthave GI Symptoms Gastroesophageal onlybeenevaluatedinpatientswithrefluxdiseaseandIBSandmay 13 items Reflux notbeapplicabletoawiderrangeofGIdisordersandtheGP.12–15 The NIH Patient-Reported Outcomes Measurement Information Disrupted 7 items System(PROMIS®)GISymptomScalesassessgastro-esophagealre- swallowing flux(GER),disruptedswallowing,diarrhea,bowelincontinence,nausea 16 Nausea and andvomiting,constipation,GIpain,andgasandbloating (Figure1). 4 items vomiting ThePROMIS®GIinstrumentmeasuresdifferentfacetsofeachsymp- tomdomain,includingfrequency,amount,bothersomeness,andim- FIGURE 1 Gastrointestinalsubdomainsmeasuredbythe pact.Wepreviouslyfoundthattheprevalenceofheartburnwasnot PROMIS®GISymptomScale.Theeightsymptomdomainsandthe differentbetweenasampleoftheUSAgeneralpopulation(GP)anda numberofitemsintheGIPROMIS®questionnaireareshown LEE ET AL. | 3 hypothesize that women, in general, will report greater severity of individualswithawiderangeofdigestivedisorders.Unlikedisease- bellypainandgasandbloating,asdemonstratedinpreviousstudies.18 targeted measures for specific patient populations, the PROMIS® GI symptom scales were designed for symptom assessment in all individuals, whether within the GP or patient groups, who are ex- 2 | METHODS periencing a GI symptom. The GI symptom scales were developed following the criteria for qualitative and quantitative development 2.1 | Selection of participants of NIH PROMIS® measures with oversight of the NIH PROMIS® This study recruited adult patients from a variety of academic and SteeringCommittee.19–22Detailsoftheconstructionandevaluation community-basedgastroenterologyclinics.Inclusioncriteriaforthis ofthisinstrumenthavebeenpublished.14Factoranalysessupported cohortwereasfollows:(i)age18orolder,(ii)abletospeak,read,and thecreationoftheeightsymptomscales.Symptomseveritywascal- understandEnglish,(iii)haveaphysician-diagnosedGIdisorderinclud- culatedfromascaledscoreineachcategory,estimatedusingatwo- ingIBSorIBD(CDorUC),and(iv)abletoprovideinformedconsent. parametergradedresponsemodelwiththemeansetat50andthe