如何早期发现难治性哮喘人群中的嗜酸性肉芽肿性血管炎

HowtoEarlyFindEGPAinSevereAsthmatics如何早期发现难治性哮喘人群中的嗜酸性肉芽肿性血管炎LadderTreatmentofAsthma：

GlobalGuidelinein2015GINA2015,Box3-5,Step2(5/8)*Forchildren6-11years,theophyllineisnotrecommended,andpreferredStep3ismediumdoseICS**ForpatientsprescribedBDP/formoterolorBUD/formoterolmaintenanceandrelievertherapy#Tiotropiumbysoft-mistinhalerisindicatedasadd-ontreatmentforpatientswithahistoryofexacerbations;itisnotindicatedinchildren<18years.PREFERRED

CONTROLLER

CHOICEOther

controller

optionsRELIEVERSTEP1STEP2STEP3STEP4STEP5LowdoseICSConsiderlowdoseICSLeukotrienereceptorantagonists(LTRA)Lowdosetheophylline*Med/highdoseICSLowdoseICS+LTRA(or+theoph*)As-neededshort-actingbeta2-agonist(SABA)As-neededSABAor

lowdoseICS/formoterol**Lowdose

ICS/LABA*Med/high

ICS/LABAReferforadd-ontreatmente.g.anti-IgEAddtiotropium#HighdoseICS

+LTRA

(or+theoph*)Addtiotropium#Addlow

doseOCSSevereasthmaMildMild--ModerateRefractorAsthma17.4%AlladultasthmaSevereasthma3-5%EurRespirJ2014;43:343–3731.Untreatedrefractorasthma

2.

SevereandrefractorasthmawithoutremovedmutiplefactorsBadobedienceFailingtomasterinhalationtechniqueEnvironmentalfactors:allergens,smokingIncorrectdiagnosisSeriouscomplicationsSevereandRefractorAsthma

重症难治性哮喘

Severeasthma：ThedrugtherapywasrequiredforLevel-4and5asthmaaccordingtoGINAGuideinthepastyear(ThelargedoseofICScombinedLABAorleukotrienemodifier/theophyline),orthesystemiccorticosteroidtreatmentlastedat≥50%ofthetimetopreventfromthe“uncontrollable”asthma;orthe“uncontrollable”asthmastilloccurredevenifinabovetreatment.

ASpecialCase：asthma？Female，40yearsold，6yearsasthmaduration，withtreatmentofSeretideanddisconnectedoralprednisonebutrepeatedattacks;Intermittentfeverandlimbsweaknessfor6months;Physicalexamination：rhonchusofdoublelung;Muscleforcegrade4overdoubleupperlimbwristjoints;Muscleforcegrade2ofwristextensor、wristflexorandinterdigitmuscle.AccessoryExaminationsPeripheralBlood：EOS58%BoneMarrowExamination:

Eosinophilia,otherswasnormal.InducedSputum：Neu50%，Eos37%，Mac12.5%，Lym0.5%。BronchoalveolarLavage：Neu58%,MQ9%,EOS32.5%,Lym0.5%TotalIgE:

1484

kU/LElectromyography：Multipleperipheralnerveweredamagedseverely.(考虑多发性周围神经重度损害)ChestCTandparanasalsinusCTChestCT1、Multipleinflammationofbilaterallungs,especiallyintonguesectionofleftupperpulmonary.2、Smallnodulesshadowoffrontsectionandupperrightlungandbacksectionofrightlowerlobe(inflammatorygranuloma).ParanasalsinusCT：leftmaxillarysinusinflammationandbilateralethmoidsinusinflammationBronchialmucosabiopsyandTBLBClinicalvasculitisperformance(infraredthermalimaging)

FinalDiagnosis:EGPA最后诊断：EGPATreatmentofHigh-doseglucocorticoidsandimmunosuppressorBeforeAfter张清玲，戴冽etal.2016InspiredbyacaseFemale，44yearsoldparoxysmalcoughandpolypneafor20months，recurrenceformorethan1monthJuly2013April2014

Beforeheartinvolvement

April2014（EOS

1%）

AfterheartinvolvementJuly2014（EOS

48%）hypoxemiaThethirdadimission：chestdistress、polypnea、severelyrestrictedlungfunction、elevatedmyocardialenzymes、abnormalelectrocardiogram、hypoxemiaANCA(-)Finaldiagnosis:EGPA（heartandlunginvolved，

ANCA

-）

EosinophilicGranulomatosisWithPolyangiitis，EGPAChurg-Strausssyndrome，renamedasEGPAin2012attheinternationalChapelHillconsensusconference.EGPA,arareautoimmunedisease,ispotentiallylife-threateningsystemicnecrotizingvasculitideswhichmainlyaffectssmall-to-medium-sizedvesselsandcausesdifferentdegreesoforgandysfunctionincludinglung,heart,skinanddigestivetracts.ThecauseisuncertainbutitissignificantlyrelatedwithallergyandallergicdiseaseandalmostallEGPApatientshadasthma.ThoughttodiagnoseasEGPA

EGPA诊断思路?

DiagnosiscriteriaofEGPAfromtheAmericanCollegeofRheumatologyin1990

1990年美国风湿病协会EGPA的诊断标准

(1)Asthma；

(2)BloodEosinophilia(≥10％or≥1.5×109／L；

(3)Singleormultipleneuropathy；

(4)MigratoryinfiltratesOflung；

(5)Nasosinusitis；

(6)Eosnophilsinfiltrationextra-vascularDiagnoseasEGPAaslongasmeetingfourofsixaboveToDiagnoseasEGPAEarly

如何早期诊断EGPA(1)Severeasthma;(2)Bloodeosinophilia(≥10％or≥1.5×109／L);(3)RecurrentmigratoryinfiltratesOflung(especiallyininfiltratesaroundairwaysofthebronchialtreedistribution)Suggestion：Tofindwhetherthereislunginfiltratesandeosnophilsinfiltrationsurroundingorinpulmonaryvascularbylungbiopsy.Study：SevereAsthmaVSEGPA（onlylunginvolvement）VSEGPA(mutiplesystemsinvolved)

重症哮喘vsEGPA（仅肺受累）vsEGPA（多系统受累）RetrospectiveanalysisofclinicalcharacteristicsamongsevereasthmaandEGPApatients(2013.8-2016.9)Severeasthma（48cases）EGPA（onlylunginvolvement）（32cases）EGPA（mutiplesystemsinvolved）（31cases）Gender,age,BMI,familyhistory,nasosinusitisInducedsputum、lungfunction、FeNO、imagingtests、biopsyHematologicalexaminations（bloodEOS、ESR、TIGE、ANCA）SevereasthmaIntrapulmonaryEGPASystemicEGPAPN483231--Sex,no.M/F22/2616/1618/13NSAgeatdiagnosis(years)46.4±16.045.7±10.345.1±14.2NSBMI(kg/m2)22.7(5.6)22.9(3.5)22.2(3.7)NSAtopy,no.(%)28(58.3)16(50.0)13(41.9)NSHistoryofsmoking,no.(%)10.0(20.8)3(9.4)4(12.9)NSSinusitis,no.(%)42(87.5)28(87.5)18(58.1)<0.05#&DurationofasthmaatEGPAdiagnosis(years)6.0(10.0)4.0(6.0)1.0(4.0)<0.05#&

Results(1)---ClinicalCharacteristics(临床特征）*SevereasthmaVSIntrapulmonaryEGPA#SevereasthmaVSSystemicEGPA&IntrapulmonaryEGPAVSSystemicEGPAComparedwithsevereasthma，amongintrapulmonaryEGPApatientssinusitisratealsowashighanddurationwasshorter.

Results(2)

---Hematologicalexaminations（1）（血液学检查)Severeasthma(N=48)IntrapulmonaryEGPA(N=32)SystemicEGPA(N=31)PCRP(mg/L)-------0.7(1.9)(N=21)4.6(15.3)(N=20)<0.05&ESR(mm/h)11.0(16.0)19.5(34.2)(N=22)24.5(52.0)(N=24)<0.05*#CEA3.1(4.4)4.2(6.7)2.4(1.9)<0.05&P-ANCA（+）no.(%)--------1.0(4.0)1.0(4.0)NSIGG(g/L)10.7(4.0)(N=22)11.1(3.1)(N=21)12.0(5.1)(N=16)NSIGA(g/L)1.6(1.2)2.0(1.0)2.0(1.3)NSIGM(g/L)1.3±0.51.2±0.51.2±0.5NSSerumtotalIgE,(KU/L)167.5(340.0)432.0(990.0)1020(1931.0)(N=25)<0.05*#&*SevereasthmaVSIntrapulmonaryEGPA#SevereasthmaVSSystemicEGPA&IntrapulmonaryEGPAVSSystemicEGPAAmongintrapulmonaryEGPApatients,ESR,CEAandTIgEwereobviouslyhigh.

Results(2)

---Hematologicalexaminations(2)AmongintrapulmonaryEGPApatients,bloodEos%andTIgEweresignificantlyhigh.Results(2)

---Hematologicalexaminations(3)

AmongintrapulmonaryEGPApatients,ESRweresignificantlyhigh.

Results(3)

---LungFunction(肺功能检查)Severeasthma(N=48)IntrapulmonaryEGPA(N=32)SystemicEGPA(N=31)PFEV1%Pred(%)66.7(29.1)(N=48)64.1(23.0)(N=31)71.0(30.6)(N=25)NSFVC%Pred(%)90.4±14.882.4±16.088.2±18.6NSFEV1/FVC(%)60.1±14.262.3±17.866.0±14.4NSMEFF%Pred(%)21.7(19.7)28.7(18.0)35.0(36.6)NSDLCOSB%Pred(%)84.2±15.890.0±17.070.2±20.7<0.05#&DCLOVA%Pred(%)100.6(24.5)107.8(24.9)91.9(21.9)<0.05*&TLC%Pred(%)114.5(25.5)(N=36)101.5(26.1)(N=24)101.4(26.1)(N=14)<0.05*#RV%Pred(%)156.8(85.2)129.5(94.5)131.0(69.1)NSRV/TLC(%)45.4(12.8)106.6(99.5)125.0(43.7)<0.05*#Z5%Pred(%)1.4(0.8)(N=36)1.6(0.9)(N=17)1.2(1.1)(N=14)NSR5%Pred(%)1.2(0.6)1.5(0.8)1.2(1.1)NSR20%Pred(%)1.2±0.61.3±0.61.2±0.7NSX5%Pred(%)2.4(5.6)1.8(14.5)0.05(13.6)NS*SevereasthmaVSIntrapulmonaryEGPA#SevereasthmaVSSystemicEGPA&IntrapulmonaryEGPAVSSystemicEGPAComparedwithsevereasthma，amongintrapulmonaryEGPApatients,thediffusingfunctionwasbetterbutairtrappingwasmoreobvious.Results(4)

---Eos%andNeu%ofInducedSputumAmongintrapulmonaryEGPApatients,Eos%ofinducedsputumweresignificantlyhighbutNeu%wassimilaramong3groups.Results(5)

---FeNOTherewasnodifferenceamong3groups.Results(6)

---Eos%andNeu%ofBA