1、SKL Respir Dis IntrapulmoaryEGPASubtypeIdentificationBasedonClinicalParameterClustering基于临床参数聚类分析识别出的基于临床参数聚类分析识别出的嗜酸性肉芽肿性血管炎亚型嗜酸性肉芽肿性血管炎亚型-肺内型肺内型 EGPASKL Respir Dis Eosinophilic Granulomatosis With PolyangiitisEosinophilic Granulomatosis With Polyangiitis，EGPA(CSS)EGPA(CSS)Churg-Strausssyndrome，ren
2、amedasEGPAin2012attheinternationalChapelHillconsensusconference.EGPA,arareautoimmunedisease,ispotentiallylife-threateningsystemicnecrotizingvasculitideswhichmainlyaffectssmall-to-medium-sizedvesselsandcausesdifferentdegreesoforgandysfunctionincludinglung,heart,skinanddigestivesystems.SKL Respir Disn
3、 (1)(1)哮喘哮喘（或喘息发作）；或喘息发作）；n (2)(2)嗜酸粒细胞增多嗜酸粒细胞增多(10(10或绝对值或绝对值11.5 510109 9L L；n (3)(3)单发或多发神经病变；单发或多发神经病变；n (4)(4)非固定性肺浸润非固定性肺浸润；n (5)(5)鼻窦炎；鼻窦炎；n (6)(6)血管外嗜酸粒细胞浸润。血管外嗜酸粒细胞浸润。6 6条标准中符合条标准中符合4 4条可以诊断条可以诊断TheAmericanCollegeofRheumatology1990criteriafordiagnosisofEGPA:1.Asthma2.Eosinophilsgreaterthan1
4、0%ofadifferentialwhitebloodcellcount3.Presenceofmononeuropathyorpolyneuropathy4.4.Non-fixed pulmonary infiltratesNon-fixed pulmonary infiltrates5.Presenceofparanasalsinusabnormalities6.HistologicalevidenceofextravasculareosinophilsDiagnosiscanbesetupifatleastfourofthesesixcriteriaarepositiveEGPA(CSS
5、)EGPA(CSS)的诊断标准的诊断标准(1990(1990年美国风湿病协会年美国风湿病协会)SKL Respir DisEosinophilicGranulomatosisWithPolyangiitisEosinophilicGranulomatosisWithPolyangiitis(EGPA,Multi-organinvolved)(EGPA,Multi-organinvolved)40 female,asthma 6 yearsSinusitis/polyposis 3 yearsFrequently exacerbation with Seretide and oral predn
6、isonePeripheral neuropathy 1 yearBlood EOS:60%Induced Sputum：Eos 37%BALF EOS 32.5%FEV1-3.0(65%pred)VC 5.3(97%)Brochus reversibility positiveTBLB:infiltration of eosinophilsTIgE:1484 kU/L ischemicnecrosisSKL Respir Dis EGPA issue raised by a case presentaionFemale，44 years oldDiagnosed as Asthma for
7、20 monthsFrequently exacerbationJuly 2013April 2014SKL Respir DisNo heart failure present 2014,April（Blood EOS 1%）Female,40ys,Asthmaduration:20monthsSpirometry:Severeobstruction(Normalaftertreatment)SaO2:84%EKG:ST-TChangedANCA(-)Heart failure present (prednison 20mg qd)2014,July（Blood EOS 48%）Severe
8、 asthmaSKL Respir DisFinal Diagnosis:EGPA(Lung and Heart Involved,ANCA:Negative）TBLB:Eosinophils infiltration in the lung and in/surround the vesselsSKL Respir DisNo heart failure present 2014,April（Blood EOS 1%）Female,40ys,Asthmaduration:20monthsSpirometry:Severeobstruction(Normalaftertreatment)SaO
9、2:84%EKG:ST-TChangedANCA(-)Heart failure present (prednison 20mg qd)2014,July（Blood EOS 48%）EGPA (Lung involved )EGPA(Multi-organs involved)SKL Respir Disn (1)(1)哮喘哮喘（或喘息发作）；或喘息发作）；n (2)(2)嗜酸粒细胞增多嗜酸粒细胞增多(10(10或绝对值或绝对值11.5 510109 9L L；n (3)(3)单发或多发神经病变；单发或多发神经病变；n (4)(4)非固定性肺浸润非固定性肺浸润；n (5)(5)鼻窦炎；鼻窦炎
10、n (6)(6)血管外嗜酸粒细胞浸润。血管外嗜酸粒细胞浸润。哮喘合并外周血哮喘合并外周血嗜酸粒细胞增多嗜酸粒细胞增多10，尽早做，尽早做TBLBTheAmericanCollegeofRheumatology1990criteriafordiagnosisofEGPA:1.Asthma2.Eosinophilsgreaterthan10%ofadifferentialwhitebloodcellcount3.Presenceofmononeuropathyorpolyneuropathy4.4.Non-fixed pulmonary infiltratesNon-fixed pulmonar
11、y infiltrates5.Presenceofparanasalsinusabnormalities6.HistologicalevidenceofextravasculareosinophilsBiopsyconsiderredinasthmawithbloodeosinophils1010%)EGPA(CSS)EGPA(CSS)的诊断标准的诊断标准(1990(1990年美国风湿病协会年美国风湿病协会)早期诊断早期诊断(EGPA early diagnosis)SKL Respir Dis:How to identifed EGPA earlier(only lung damaged)i
12、n severe asthma population?如何发现重症难治性哮喘人群的EGPA？nDifficulttotreatasthma难治性哮喘难治性哮喘(17.4%)Asthma所有成人哮喘所有成人哮喘nSevereasthma3.6%(EGPA？,%)Issues RasiedSKL Respir Dis2 year studySevereAsthmaVSIntrapulmoaryEGPAVSSystemicEGPA重重症哮喘症哮喘 vs EGPA（肺内型）（肺内型）vs EGPA（全身型）（全身型）Retrospectiveanalysisofclinicalcharacterist
13、icsamongsevereasthmaandEGPApatients(2013.8-2016.9)Severeasthma（48cases）IntrapulmoaryEGPA（32cases）SystemicEGPA(multi-organsinvolved)（31 cases）Gender,age,BMI,family history,nasosinusitisInduced sputum、lung function、FeNO、imaging tests、biopsyHematological examinations（blood EOS、ESR、TIGE、ANCA）SKL Respir
14、Disn (1)(1)哮喘哮喘（或喘息发作）；或喘息发作）；n (2)(2)嗜酸粒细胞增多嗜酸粒细胞增多(10(10或绝对值或绝对值11.5 510109 9L L；n (3)(3)单发或多发神经病变；单发或多发神经病变；n (4)(4)非固定性非固定性肺浸润；肺浸润；n (5)(5)鼻窦炎；鼻窦炎；n (6)(6)血管外嗜酸粒细胞浸润。血管外嗜酸粒细胞浸润。TheAmericanCollegeofRheumatology1990criteriafordiagnosisofEGPA:1.Asthma2.Eosinophilsgreaterthan10%ofadifferentialwhiteb
15、loodcellcount3.Presenceofmononeuropathyorpolyneuropathy4.Non-fixed pulmonaryinfiltrates5.Presenceofparanasalsinusabnormalities6.HistologicalevidenceofextravasculareosinophilsEGPA(CSS)EGPA(CSS)的诊断标准的诊断标准(1990(1990年美国风湿病协会年美国风湿病协会)IntrapulmoaryEGPA：Diagnosissetupif5abovecriteriaarepositiveSystemicEGPA
16、Diagnosissetup:1.asthmapatients,2.Presenceofparanasalsinusabnormalities3.BloodEosinophilsgreaterthan10%4.ExtrapulmonaryorgansdamagedSKL Respir DisSevere asthma Intrapulmonary EGPA Systemic EGPAPN483231-Sex,no.M/F22/2616/1618/13NSAge at diagnosis(years)46.416.045.710.345.114.2NSBMI(kg/m2)22.7(5.6)22.
17、9(3.5)22.2(3.7)NSAtopy,no.(%)28(58.3)16(50.0)13(41.9)NSHistory of smoking,no.(%)10.0(20.8)3(9.4)4(12.9)NSSinusitis,no.(%)42(87.5)*28(87.5)*18(58.1)0.05Duration of asthma6.0(10.0)*4.0(6.0)*1.0(4.0)0.05 Results(1)-Clinical Characteristics (临床特征）临床特征）*P0.05,comparedwithSystemicEGPAPercentage of sinusit
18、is and duration in Percentage of sinusitis and duration in intrapulmonaryEGPAis higher than that in is higher than that in systemicEGPASKL Respir Dis Results(2)Hematologicalexaminations（血液学检查（血液学检查)Severe asthma(N=48)Intrapulmonary EGPA(N=32)Systemic EGPA(N=31)PCRP(mg/L)-0.7(1.9)*4.6(15.3)0.05ESR(mm
19、/h)11.0(16.0)19.5(34.2)#24.5(52.0)#0.05CEA3.1(4.4)4.2(6.7)*2.4(1.9)0.05P-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)1.30.51.20.51.20.5NSESR is higher in both EGPA groupsCRP is higher in Systemic EGPA compared with
20、Intrapulmonary EGPACRP is higher in Systemic EGPA compared with Intrapulmonary EGPAOnly 4%positive in EGPA groups Only 4%positive in EGPA groups*P0.05,comparedwithSystemicEGPA#P0.05,comparedwithSevereAsthmaSKL Respir Dis Results(2):HematologicalexaminationsBlood Eos%and TIgE were significantly highe
21、r is EGPA groupsSKL Respir Dis Results(3)-Lung Function(肺功能检查肺功能检查)Severe asthma(N=48)IntrapulmonaryEGPA(N=32)Systemic EGPA(N=31)PFEV1%Pred(%)66.7(29.1)(N=48)64.1(23.0)(N=31)71.0(30.6)(N=25)NSFVC%Pred(%)90.414.882.416.088.218.6NSFEV1/FVC(%)60.114.262.317.866.014.4NSMEFF%Pred(%)21.7(19.7)28.7(18.0)35
22、0(36.6)NSDLCO SB%Pred(%)84.215.8*90.017.0*70.220.70.05DCLO VA%Pred(%)100.6(24.5)#107.8(24.9)91.9(21.9)0.05TLC%Pred(%)114.5(25.5)101.5(26.1)101.4(26.1)0.05RV%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)0.05Z5%Pred(%)1.4(0.8)(N=36)1.6(0.9)(N=17)1.2(1.1)(N=14)N
23、SR5%Pred(%)1.2(0.6)1.5(0.8)1.2(1.1)NSR20%Pred(%)1.20.61.30.61.20.7NSX5%Pred(%)2.4(5.6)1.8(14.5)0.05(13.6)NSThe diffusing function is lower in systemic EGPA compared with IntrapulmonaryEGPARV/TLC(%)is higher in systemic EGPA compared with Intrapulmonary EGPA*P0.05,comparedwithSystemicEGPA#P0.05,compa
24、redwithIntrapulmonaryEGPAP0.05,comparedwithSevere asthmaSKL Respir DisResults(4)-Eos%and Neu%of Induced SputumCompared witn severe asthma,Eos%of induced sputum in intrapulmonary EGPA patients were significantly high.The Neu%was similar among 3 groups.SKL Respir DisResults(5)-FeNOThere was no differe
25、nce among 3 groups.SKL Respir Dis Results(6):CT CharacteristicsSimilar chest CT scan changing between intrapulmonary EGPA and systemic EGPA(maculas shadow,multiple small lymph node of mediastinum,enlarged lymph node of mediastinum and and bronchiolitis)SKL Respir DisResults(7)-Lung Biopsy Characteri
26、sticsSimilar biopsy presentation patients(Eosinophils infiltration surrounding or in the vessel and Eosinophils infiltration in the lung)between intrapulmonary EGPA and systemic EGPASKL Respir DisResults(8)ScreeplotofprincipalcomponentanalysisClinicalprofiledatawereprocessedwithPCA,andthe8largestpri
27、ncipalcomponentsextractedexplained73.437%oftheinformationcontainedintheoriginaldata,suggestingthatthese8componentsaloneexplainedmostofthevariabilityamonggroups.SKL Respir Dis8components(factorloading)SKL Respir Dis Results(8)-Clustering Analysis(聚类分析聚类分析)Group1Group22subgroupswereidentified:Subgroup
28、1:SevereasthmaSubgroup2:IntrapulmonaryEGPAandSystemicEGPASKL Respir DisConclusionThereisapopulationinasthmapopulationspresentingonlyinlungdamagesimilartoEGPA(CSS)patients.Thispopulationpresentdifferentclinicalcharacteristicsfromsevereasthmatics.IntrapulmoaryEGPASubtypewereidentifiedbasedonclinicalpa
29、rameterclustering.SKL Respir DisConsensus of EGPA in China2016 June EGPA patients featured involvement of respiratory system only has similar clinical presentations as EGPA patients featured involvement of multiple systems which is different from difficult-to-treat asthma.Its necessary to diagnose e
30、arly for EGPA from difficult-to-treat asthma.It will be helpful for a better prognosisSo we gathered specialists of respirology and rheumatology to hold a conference on May 22nd,2016 in Shenzhen,china.The first protocol will be produce on Sept.2016.Acknowledgementn nNHLINHLI，Imperial College London
31、Imperial College London Kian.F.ChungKian.F.Chungn nStateLaboratoryofRespiratoryStateLaboratoryofRespiratoryDiseases,GuangzhouMedicalCollege,Diseases,GuangzhouMedicalCollege,Nanshan Zhong Nanshan Zhong Rongchang Chen Rongchang Chen Jingping Zheng Jingping Zheng Shiyue LiShiyue Li JingLiJingLiBaoqingSunBaoqingSunJiaxingXieJiaxingXieZhengdaoLai,MinzhiQiuZhengdaoLai,MinzhiQiuZhiqiangWang,PeikaiHuangZhiqiangWang,PeikaiHuangAsthmaandallergyteamAsthmaandallergyteamThank you!v中山大学附属第三医院：古洁若教授中山大学附属第三医院：古洁若教授v中山大学孙逸仙纪念医院：戴冽教授中山大学孙逸仙纪念医院：戴冽教授v复旦大学附属中山医院：姜林娣教授复旦大学附属中山医院：姜林娣教授
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