哮喘变应原免疫治疗现状与思考苏州九龙医院倪殿涛

哮喘变应原免疫治疗现状与思考苏州九龙医院倪殿涛Typesofallergies2021/4/272Allergen

Any

substance

often

a

protein

that

induces

an

allergy

Commonallergens过敏原种类很多“除了水、葡萄糖和盐之外都可以成为过敏原”2021/4/273Commoncoldorallergy2021/4/274AsthmaDerivedfromtheGreekrootασθμαινωOriginallydidnotdefineadisease,butwasemployedtodescriberespiratorysymptomsofavarietyofpulmonaryconditionsBythebeginningofthe20thcentury,

asthma

wasseentobeauniqueillnesscharacterizedby'spasmodicafflictionsofthebronchialtubes'.Today,

asthma

isseenasachronicinflammatorydiseasewhichisnotyetfullyunderstoodinitspathophysiologyTherapyisstillonthepathtobecomingoptimal.BergmannKC.Asthma.ChemImmunolAllergy.2014;100:69-80.2021/4/275盲人摸象2021/4/2762014GINA哮喘表型Allergicasthma:usuallyrespondwelltoinhaledcorticosteroid(ICS)treatmentNon-allergicasthma:oftenrespondlesswelltoICS.Late-allergicasthma:someadults,particularlywomen,patientwithasthmaforthefirsttimeinadultlife.Thesepatientstendtobenon-allergic,andoftenrequirehigherdosesofICSorarerelativelyrefractorytocorticosteroidtreatmentAsthmawithfixedairflowlimitation:somepatientswithlong-standingasthmadevelopfixedairflowlimitationthatisthoughttobeduetoairwaywallremodeling.Asthmawithobesity:someobesepatientswithasthmahaveprominentrespiratorysymptomsandlittleeosinophilicairwayinflammation.GINAGuidelinesforAsthma20142021/4/277Terminologyofallergicphenomena'idiosyncrasy'-'antipathy'-'Hypersensitivity'-'Anaphylaxis'-'allergyA.F.CocaandR.A.Cookeintroducedtheterm'atopy'：'hypersensitiveness'occurredspontaneously'atopy'gainedanewsense,sinceIgEisacharacteristic-Clinicallysimilardiseasessuchasasthma,rhinoconjunctivitisoreczemacanbefoundintheabsenceofIgE,andarethencalled'intrinsic'variantsofthesamediseaseChemImmunolAllergy.2014;100:46-52.2021/4/278CoombsandGell’sClassificationofHypersensitivity2021/4/279Does"intrinsic"asthmaexist?Tentofortypercentofasthmaticsare"intrinsic"Analysisofbronchialmucosalexpressionof"pro-eosinophilic"and"pro-atopic"markers[IL-3,-4,-5,-13,GM-CSF,RANTES,MCP-3,IgEandhighaffinityIgEreceptor(FcepsilonRI)]ThereweremoresimilaritiesthandifferencesinimmunopathologybetweenatopicandnonatopicHumbertM.Does"intrinsic"asthmaexist?RevMalRespir.2000Feb;17(1Pt2):245-54..2021/4/2710Allergicvsnonallergicasthma:

whatmakesthedifference?Nonallergic：Greaterage,femalesex,sinusalpolyposis,andFEV1below80%ofthepredictedvalueAllergic：historyofhayfever,seasonalexacerbationofasthma,andasthmadurationAllergy.2002Jul;57(7):607-13.2021/4/2711Asthmaphenotypes:nonallergic(intrinsic)asthma.Thedefinition：subjectswithasthmaandwithwhomallergicsensitizationcannotbedemonstratednegativeskinpricktestorinvitrospecific-IgEtesttoapanelofseasonalandperennialallergensNonallergicasthmaoccursin10%to33%ofindividualswithasthmaandhasalateronsetthanallergicasthma,withafemalepredominance.NonallergicasthmaappearstobemoreseverethanallergicasthmainmanycasesandmaybelessresponsivetostandardtherapyPetersSP.Asthmaphenotypes:nonallergic(intrinsic)asthma.JAllergyClinImmunolPract.

2014Nov-Dec;2(6):650-2..2021/4/2712Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.ControversieshaveemergedinrelationtothisconceptNotfindingspecificallergensensitizationinanasthmaticpatientneitherexcludesanallergiccomponentnortheessentialrolethatimmunoglobulinEmayplayinasthmaTheatopicstatusisoneamongmanyotherquestionsOmalizumab,theonlymonoclonalanti-immunoglobulinEantibodycommercializedforasthma,shouldbetriedinpatientswithuncontrolledsevereasthmaindependentoftheiratopicstatus

VenneraMdelC1,

PicadoC1.Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.IntJGenMed.

2014

Jul8;7:365-71.2021/4/2713哪些哮喘患者需要行AIT？过敏的概念总tIgE2021/4/2714SentietalAllergy2011;66(6):7981911Noon1thSCIT1950s1thSCITControlStudy;1980s1thDBPCSLIT;2000s1thsublingualTablet2011sInnovatingforpatientbenefit100yeasofantigenspecificimmunotherpy2021/4/2715Allergenspecificimmunotherapy2021/4/2716Self-amplificationmechanismsofmastcellactivation:

anewlookinallergy.Thecurrentdefinitionofallergy,agroupofIgEmediateddiseasesappearsdifficulttocoverallallergicreactionsSinceevenIgEdependentallergicreactionsarecarriedoutthroughactivationofmastcellsandbasophils,andallallergensmentionedabovecanactivatethesecellswehypothesizethatallergicreactionsaremastcellandbasophilmediatedinflammatoryprocessasitistheactivatedmastcellsandbasophilsthatinitiatethepathologicalprocessoftheimmediateallergicreactionswhereas

IgEonlyservesasoneoftheactivatorsofthesecells.HeS,ZhangH,ZengX,YangP.CurrMolMed.2012Dec;12(10):1329-39.2021/4/27172021/4/2718过敏性疾病实验室诊断的理想程序皮试、斑贴试验↓（阳性）过敏原、半抗原或小分子物质↓嗜碱性粒细胞/肥大细胞激发试验 ↓（阳性）（阴性基本排除急性过敏）

特异性IgE、IgG检测

（阴性）

（阳性）

（阳性）

类过敏反应IgE依赖性IgG依赖性

↓

（目前定义为过敏）（目前定义为食物不耐受）

避免接触类过敏原

↓↓（IgG阳性）

脱敏疗法的适应症低敏食物、食物脱敏？2021/4/2719AIT适应症--中国专家共识2021/4/2720AIT禁忌症-中国专家共识2021/4/2721哮喘患者AIT现状2021/4/27222021/4/2723结论2021/4/27242021/4/2725SublingualimmunotherapyIncluded5,131patientsfrom63studieswereanalyzedthatsublingualimmunotherapyimprovessymptomsofasthmareducestheuseofasthmamedicationsimprovesthequalityoflifeLinetal.Sublingualimmunotherapyforthetreatmentofallergicrhinoconjunctivitisandasthma:asystematicreview.JAMA2013;309:1278-882021/4/27262021/4/27272021/4/2728AIT的安全性2021/4/2729哮喘AIT困惑与思考2021/4/2730过敏原识别过敏原的特异性诊断查找过敏原是与其他学科的基本区别2021/4/2731IgE介导变态反应的诊断AllergicrhinitisanditsimpactonasthmaAllergy,2008,s1-153.2021/4/2732体内试验-皮肤试验皮内试验I型速发性变态反应点刺试验I型速发性变态反应斑贴试验IV型迟发型变态反应2021/4/2733常用过敏原点刺液种类螨属：户尘螨、粉尘螨、热螨、仓储螨宠物毛发皮屑：猫毛、狗毛树木花粉：桤木、榛属、杨属、榆科、柳属、悬铃木杂草花粉：蒿草、豚草、葎草、鸡足草、酥油草、毒麦、梯牧草、牧场草作物花粉：向日葵、玉米真菌：链格孢、毛壳菌、芽枝霉、镰刀菌、青霉、扩展青霉、点青霉蟑螂：德国小蠊、美洲大蠊2021/4/2734体外试验-sIgE检测严重皮炎不能作皮试者皮试假阳性的划痕症患者皮肤反应差的老年人及3岁以下儿童用药的影响严重过敏状态发作者对作皮试时产生的不适恐惧者对过敏严重度评估拟行特异性免疫治疗者2021/4/2735我国过敏原体外诊断种类RAST-放射过敏原吸附试验FEIA-固相荧光酶免疫技术（CAP）免疫印迹技术（AS）ELISA-酶联免疫吸附试验免疫捕获法（酶联免疫吸附试验中之一种）过敏原芯片：固相／液相免疫化学发光法过敏原诱发组胺释放试验：期望能解决IgE不能解决的问题2021/4/2736五种免疫球蛋白的血浆浓度

（mg/dL）IgG1200（40000）IgM150（5000）IgA300（10000）IgD3（100）IgE0.03（1）血中IgE含量甚微，仅为血中IgG的四万分之一特异性IgE含量则更甚微2021/4/2737一般的免疫学方法测不到sIgE放射过敏原吸附试验(RAST)

荧光免疫标记分析法ELISA（酶联免疫吸附测定）蛋白芯片检测荧光酶免法（ImmunoCAPSweden）是检测的金标准2021/4/2738总IgE的意义总IgE没有正常值，只定上限端值，儿童50KU/L成人60KU/L新生儿的总IgE很低，随年龄增长升高，10-15岁达顶峰，以后又逐步下降，男性高于女性理想的情况下，总IgE应该是0或极低2021/4/2739