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•哮喘变应原免疫治疗现状与思考上海交通大学医学院苏州九龙医院倪殿涛过敏性疾病作为一个全球性问题WAOWhiteBookonAllergy2011-2012•Asteadyincreaseintheprevalenceofallergicdiseasesgloballyhasoccurredwithabout30-40%oftheworldpopulationnowbeingaffectedbyoneormoreallergicconditionsTypesofallergiesAllergenAnysubstanceoftenaproteinthatinducesanallergyCommonallergens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”CommoncoldorallergyAsthma•DerivedfromtheGreekrootασθμαινω•Originallydidnotdefineadisease,butwasemployedtodescriberespiratorysymptomsofavarietyofpulmonaryconditions•Bythebeginningofthe20thcentury,asthmawasseentobeauniqueillnesscharacterizedby'spasmodicafflictionsofthebronchialtubes'.•Today,asthmaisseenasachronicinflammatorydiseasewhichisnotyetfullyunderstoodinitspathophysiology•Therapyisstillonthepathtobecomingoptimal.BergmannKC.Asthma.ChemImmunolAllergy.2014;100:69-80.盲人摸象2014GINA哮喘表型Allergicasthma:usuallyrespondwelltoinhaledcorticosteroid(ICS)treatmentNon-allergicasthma:oftenrespondlesswelltoICS.Late-allergicasthma:someadults,particularlywomen,patientwithasthmaforthefirsttimeinadultlife.Thesepatientstendtobenon-allergic,andoftenrequirehigherdosesofICSorarerelativelyrefractorytocorticosteroidtreatmentAsthmawithfixedairflowlimitation:somepatientswithlong-standingasthmadevelopfixedairflowlimitationthatisthoughttobeduetoairwaywallremodeling.Asthmawithobesity:someobesepatientswithasthmahaveprominentrespiratorysymptomsandlittleeosinophilicairwayinflammation.GINAGuidelinesforAsthma2014Terminologyofallergicphenomena•'idiosyncrasy'-'antipathy'-'Hypersensitivity'-'Anaphylaxis'-'allergy•A.F.CocaandR.A.Cookeintroducedtheterm'atopy'：'hypersensitiveness'occurredspontaneously•'atopy'gainedanewsense,sinceIgEisacharacteristic-Clinicallysimilardiseasessuchasasthma,rhinoconjunctivitisoreczemacanbefoundintheabsenceofIgE,andarethencalled'intrinsic'variantsofthesamediseaseChemImmunolAllergy.2014;100:46-52.CoombsandGell’sClassificationofHypersensitivityDoesintrinsicasthmaexist?•Tentofortypercentofasthmaticsareintrinsic•Analysisofbronchialmucosalexpressionofpro-eosinophilicandpro-atopicmarkers[IL-3,-4,-5,-13,GM-CSF,RANTES,MCP-3,IgEandhighaffinityIgEreceptor(FcepsilonRI)]•ThereweremoresimilaritiesthandifferencesinimmunopathologybetweenatopicandnonatopicHumbertM.Doesintrinsicasthmaexist?RevMalRespir.2000Feb;17(1Pt2):245-54..Allergicvsnonallergicasthma:whatmakesthedifference?•Nonallergic：Greaterage,femalesex,sinusalpolyposis,andFEV1below80%ofthepredictedvalue•Allergic：historyofhayfever,seasonalexacerbationofasthma,andasthmadurationAllergy.2002Jul;57(7):607-13.Asthmaphenotypes:nonallergic(intrinsic)asthma.•Thedefinition：subjectswithasthmaandwithwhomallergicsensitizationcannotbedemonstrated–negativeskinpricktestorinvitrospecific-IgEtesttoapanelofseasonalandperennialallergens•Nonallergicasthmaoccursin10%to33%ofindividualswithasthmaandhasalateronsetthanallergicasthma,withafemalepredominance.•NonallergicasthmaappearstobemoreseverethanallergicasthmainmanycasesandmaybelessresponsivetostandardtherapyPetersSP.Asthmaphenotypes:nonallergic(intrinsic)asthma.JAllergyClinImmunolPract.2014Nov-Dec;2(6):650-2..Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.•Controversieshaveemergedinrelationtothisconcept•NotfindingspecificallergensensitizationinanasthmaticpatientneitherexcludesanallergiccomponentnortheessentialrolethatimmunoglobulinEmayplayinasthma•Theatopicstatusisoneamongmanyotherquestions•Omalizumab,theonlymonoclonalanti-immunoglobulinEantibodycommercializedforasthma,shouldbetriedinpatientswithuncontrolledsevereasthmaindependentoftheiratopicstatusVenneraMdelC1,PicadoC1.Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.IntJGenMed.2014Jul8;7:365-71.哪些哮喘患者需要行AIT？•过敏的概念•总tIgESentietalAllergy2011;66(6):798•1911Noon1thSCIT•1950s1thSCITControlStudy;•1980s1thDBPCSLIT;•2000s1thsublingualTablet•2011sInnovatingforpatientbenefit100yeasofantigenspecificimmunotherpyAllergenspecificimmunotherapySelf-amplificationmechanismsofmastcellactivation:anewlookinallergy.•Thecurrentdefinitionofallergy,agroupofIgEmediateddiseasesappearsdifficulttocoverallallergicreactions•SinceevenIgEdependentallergicreactionsarecarriedoutthroughactivationofmastcellsandbasophils,andallallergensmentionedabovecanactivatethesecells•wehypothesizethatallergicreactionsaremastcellandbasophilmediatedinflammatoryprocessasitistheactivatedmastcellsandbasophilsthatinitiatethepathologicalprocessoftheimmediateallergicreactions•whereasIgEonlyservesasoneoftheactivatorsofthesecells.HeS,ZhangH,ZengX,YangP.CurrMolMed.2012Dec;12(10):1329-39.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？AIT适应症--中国专家共识AIT禁忌症-中国专家共识哮喘患者AIT现状结论Sublingualimmunotherapy•Included5,131patientsfrom63studieswereanalyzedthatsublingualimmunotherapy–improvessymptomsofasthma–reducestheuseofasthmamedications–improvesthequalityoflifeLinetal.Sublingualimmunotherapyforthetreatmentofallergicrhinoconjunctivitisandasthma:asystematicreview.JAMA2013;309:12