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JResMedSci.2013Mar18(3):252254.

PMCID:PMC3732909

Diagnosticvalueofserumadenosinedeaminaselevelinpulmonarytuberculosis
ShahlaAfrasiabian,BehzadMohsenpour,KatayounHajiBagheri, 1NasehSigari, 2andKavehAftabi2
DepartmentofInfectiousDiseases,KurdistanUniversityofMedicalSciences,Sanandaj,Iran
1
DepartmentofRespiratoryDiseases,KurdistanUniversityofMedicalSciences,Sanandaj,Iran
2
MedicineCollege,KurdistanUniversityofMedicalSciences,Sanandaj,Iran
Addressforcorrespondence:Dr.KatayounHajiBagheri,DepartmentofInfectiousDiseases,Tohidhospital,KurdistanUniversityofMedicalSciences,
Sanandaj,Iran.Email:katayounhajibagheri@yahoo.com
Received2012Jun10Revised2012Aug22Accepted2012Nov17.
Copyright:JournalofResearchinMedicalSciences
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,whichpermits
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Abstract

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Background:

Insomestudies,thelevelofadenosinedeaminase(ADA)insputumandeffusionliquidswasusedforthediagnosis
oftuberculosis(TB).Butitisnotalwayspossibletoaccessthesematerials.Thegoalofthisstudyistoassessthe
diagnosticvalueofserumADAlevelsinpulmonaryTBpatients.
MaterialsandMethods:

Inthisstudy,40sputumsmearpositiveTBpatientswhowerehospitalizedand40nonTBpatientswhoreferred
forsurgerieswereselected.AserumsamplewascollectedandserumADAlevelwasmeasuredbyADAkit.
Results:

Theaverage(SD)ofserumADAinTBandnonTBpatientswere20.88(5.97)and10.69(2.98)U/L,
respectively(Pvalue<0.05).Thebestcutoffpointwas14U/L.Thecalculatedareaunderthereceiveroperating
characteristic(ROC)curvewas0.955(95%CI,0.9140.995)sensitivitywas92.7%(95%CI,84.7100)and
specificitywas88.1%(95%CI,78.397.8)(P<0.001).
Conclusion:

SerumADAlevelmaybeproposedasaproperindexforTBdiagnosis.
Keywords:Adenosinedeaminase,diagnosis,tuberculosis
INTRODUCTION

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Tuberculosis(TB)isoneofthemainreasonsofmortalityandmorbiditygloballyanditkillsabouttwomillion
peopleannually.[1,2]RecentstudiesshowedextensivedelayinTBdiagnosis.[3,4]Therearedifferentdiagnostic
methodsbuttheyhavesomedrawbacks.Topreparemycobacteriumculture,whichisthegoldenstandardforTB
diagnosis,itmaytake8weeks.FindingacidfastbacilliisthequickscreeningmethodforpulmonaryTBdiagnosis
nevertheless,itssensitivityislow.Thepolymerasechainreaction(PCR)testforTBdiagnosisisexpensiveandit
requiresskilledpersonnelandlotofequipments.Therefore,inrecentyears,therehasbeenagreatdemandfor
findingnewmicrobiological,genetic,immunological,andbiomedicaldiagnosticmethodstodiagnosisTBquickly
andaccurately.Measuringofadenosinedeaminase(ADA)activityisabiomedicalmethod.[5,6]ADAisan
enzymewhichcontributesinpurinmetabolism.[7]ADAisessentialforproliferationanddifferentiationof
lymphoidcells,especiallyTcells,andhelpsinthematurationofmonocytestomacrophages.ItseemsADAisan
indexforcellularimmunity[5]andpreviousstudieshaveproveditsvalueinTBdiagnosis,evenforassessingTB
effusions.[8,9]ActivityofthisenzymeincreasesinTBpatients.[9]Insomestudies,thelevelofADAinsputum
andserumwasusedfordiagnosisofTB,anditwasmonitoredduringTBtreatment.[10,11,12]However,previous
studiesusedeffusionfluidsandaverylimitednumberofstudiesusedpatientsserum.[5,6,7,8,9,10,12]Itisnot
alwayspossibletoaccesseffusionliquidseverywhereinpulmonaryandextrapulmonaryTBtherefore,itwould
behelpfultotakeadvantageofserumlevels.Thegoalofthisstudyistoassessthediagnosticvalueandcutoff
pointofserumADAlevelsinpulmonaryTBpatients.
MATERIALSANDMETHODS

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Itwasacrosssectionalstudy(2011),whichisconductedinTohidHospital(UniversityReferralHospital)in
SanandajinIran.Inourstudy,casegroupincluded40sputumsmearpositiveTBpatientswhowereadmittedin
infectiousdiseasewardofthehospital.InclusioncriteriaforTBpatientswere:Having2or3sputumpositive
smears,oronesputumpositivesmearandonepositivesputumculture,oronepositiveTBmicrobesmear
sputumandsuspectedchestradiography.[13]
Inaddition,40nonTBpatients,referredtoTohidHospitalinSannandajforsurgeries,wereselectedasthecontrol
group.Inclusioncriteriaforcontrolgroupwere:NothavinganyTBpatientintheirfamily,nothavinghistoryof
closecontactwithTBpatients,nothavinganyinfectiousdisease(accordingtotheinterviewandtheirrecords),not
havingfeveroranysymptomofillnessorofbeingtoxic,normalcellbloodcount,andnormalchestradiography.
AfterdiagnosisofTB(beforeinitiationoftreatment),bloodsamplesandpatientsapprovalofconsentform
(researchprojectnumber:1387/87)weretakenfromTBgroup(at7AM).Thensampleswerecentrifugedand
serumADAlevelsweremeasuredbyADAkitmanufacturedbyDiazymeLaboratoriesCompany.Inthefirststep,
adenosinewasaffectedbyADAanditbecomesdeammonizedandshiftedtoinosineandthenammoniacwas
released.Inthesecondreaction,becauseofglometat,releasedNH3hadbecomedehydrogenizedandwhenitgot
closetoallostericactivators,itcombinedwithNicotinamideadeninedinucleotidephosphateHydrogen(NADPH)
andreleasedNicotinamideadeninedinucleotidephosphate(NADP).Consequently,therewasadirectrelationship
betweenactivity(density)ofADAenzymeandspeedreductionofradiationabsorptionin340nanometer
wavelength(asNADPHchangedtoNADP+)itwasmeasuredbyDiazymeAdenosineDeaminaseAssayKitt
(DiazymeLaboratoryUSA).Then,datawereanalyzedusingStatisticalPackagefortheSocialSciences(SPSS)
11.5(Chicago,USA)softwareandROCcurvewasplotted.Inaddition,sensitivity,specificity,andconfidence
intervalof95%werecalculated.
RESULTS

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Fromall40TBpatientswhoparticipatedinthisstudy,16weremalesand24werefemales.From42participantsin
controlgroup,22weremalesand20werefemales.ThemostcommonagegroupforTBpatientswas50sandfor
controlgroup,itwas40s.Ageaveragewas59(13.5)inTBpatientsanditwas49(15.6)fornonTBpatients.
TheaverageofserumADAinTBpatientsgroupandcontrolgroupwas20.88(5.97)and10.69(2.98),
respectively.Thebestcutoffpointwas14U/Linwhichsensitivityandspecificitywere92.7%(95%CI,84.7100)
and88.1%(95%CI,78.397.8),respectively.Thepositiveandnegativepredicativevalueswere88.4%(95%CI,
7595.1)and92.5%(95%CI,79.698.4),respectively[Figure1].ThecalculatedareaundertheROCcurvewas
0.955(95%CI,0.9140.995)(P<0.001).
Figure1
Receiveroperatingcharacteristiccurveforserumadenosinedeaminasein
tuberculosisdiagnosis.Areaundercurvewas0.955

DISCUSSION

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Inthisstudy,serumADAlevelwasanappropriateindexfordiagnosingsmearpositiveTB.Highsensitivityand
specificitywereobservedinserumlevelof14U/L.Therefore,serumADAcouldbealsousedfordiagnosisof
pulmonaryTB.Moreover,inthisstudy,allTBpatientshadaserumlevelofmorethan22.5U/L.Hence,for
suspiciouscasesofTB,increasedlevelsofADAcouldfacilitatediagnosis.
DiagnosticvalueofserumADAinpulmonaryTBhasbeenassessedonlyinfewnumbersofstudies.Pairsetal.[7]
reportedanincreaseinADAlevelinTBpleuraleffusionotherstudieshavealsoconfirmedsuchanincreaseinTB
pericardialeffusions,peritoneum,andcentralnervoussystem(CNS).[11,14,15]Themainreasonfortheincreased
ADAlevelsinpleuraleffusionisthemovementofTlymphocytestowardthisarea.IncreaseinADAlevelisthe
resultofatropicalinflammatoryreactioncausedbymonocytesandmacrophages.[11,16]Whenalveolar
macrophagesareinfectedbymycobacterium,thisenzymecouldbefoundinserumduringactivepulmonary
disease.WhenTBinfectioniscontrolled,growthmarkersoflymphocytesdecreaseleucocyteswilldecreasein
serumADAlevelsconcurrentwiththedecreaseinlymphocytes.Becauseofthis,serumADAlevelcouldbe
utilizedasatreatmentresponseindex.[10,11,12]
InAgarwaletal.'sstudy,[17]ADAlevelwas15.3(0.23)inhealthypeople,19(0.68)innonpulmonaryTB
cases,and38.48(1.56)inpulmonaryTBpatients.InJhamariaetal.'sstudy,[6]theaverageofserumADAlevel
was19.9U/L(2.99)incontrolgroup,43.95U/L(2.48)insputumsmearpositivepeoplewithtypicalor
progressivedisease,and42.09U/L(1.46)and40.02U/L(2.58)innegativesputumpatientswithmildortypical
disease.Intheirstudy,inthecutoffpointof33U/L,sensitivityandspecificitywere98%and100%,respectively.
Itseemsthatasthediseaseprogresses,ADAlevelsincreasethissubjectwasnotconsideredinourstudy.In
anotherstudywithanADAlevelof26.2U/L,sensitivity,specificity,andpositivepredictivevaluewere95%,
83.3%,and79.2%,respectively.[18]

InGuptaetal.'sstudy,[19]sensitivity,specificity,positivepredictivevalue,andnegativepredictivevaluewere
92.8%,90%,92.8%,and90%,respectively,fordiagnosisofTBinpleuraleffusionwithanADAlevelofmore
than40.InCondeetal.'sstudy,[20]ADAlevelof14U/Lwaschosenascutoffpoint.Stevanovicetal.[12]
assessedserumsofextrapulmonaryTBpatientsandinacutoffpointof24,sensitivityandspecificitywere94.3%
and92.2%,respectivelyintheirstudy,serumADAleveldecreasedastreatmentstarted.InDilmacetal.'sstudy,
[21]serumADAlevelinpulmonaryTBpatientswasreportedas27.5(11)anditwas23.9(24)inChronic
ObstructivePulmonaryDisease(COPD)patients.InRasolinejad'sstudy,[22]serumADAlevelwas21.51in
pulmonaryTBpatientsand11.47inhealthypeopleincutoffpointof14.5U/L,sensitivityandspecificitywere
82%and80.6%,respectively.InLakshmietal.'sstudy,[23]averageADAlevelwas13.3U/Linnegativesmear
andnegativetuberculinpatients,33.52(15.22)insmearpositiveandpurifiedproteinderivative(PPD)positive
patients,and16.5(3.18)involunteerhealthypeople.SuchdifferencesmaybeduetoTBseverity,agegroups,
geneticdifferences,anddissimilaritiesincontrolgroups.Therefore,furtherstudiesforidentifyingnormalADA
levelsindifferentsocietiesmaybeuseful.
Fortunately,insomeautoimmunepatientslikerheumatoidarthritis,synovialADAlevelisnormalanditissimilar
tocontrolgroup.[24]Thus,inautoimmunediseasesthatinvolvelung,ADAlevelcouldbeusedforTB
differentiation.Insomestudies,ADA2wasalsoconsideredausefultoolfordiagnosis[16]itneedsfurtherstudies.
CONCLUSIONS

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Accordingtothisstudy,serumADAlevelisproposedasaproperindexforTBdiagnosisinacutoffpointof14,
itssensitivityandspecificityarecalculatedas92.7%and88.1%,respectively.
ACKNOWLEDGMENTS

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Thisstudywasfinanciallysupportedbyvicechancellorforresearchaffairs,KurdistanUniversityofMedical
Sciences(throughM.DthesisbelongstoDr.KavehAftabi).WethankMr.FardinGaribiandDr.EbrahimGhaderi
fortheirconsultantsinstatisticalanalysisandpaperpreparation.
Footnotes

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SourceofSupport:Nil
ConflictofInterest:Nonedeclared.

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