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WAOWhiteBookonAllergy2011-2012Asteadyincreaseintheprevalenceofallergicdiseasesgloballyhasoccurredwithabout30-40%oftheworldpopulationnowbeingaffectedbyoneormoreallergicconditionsTypesofallergiesAllergen

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”CommoncoldorallergyAsthmaDerivedfromtheGreekrootασθμαινωOriginallydidnotdefineadisease,butwasemployedtodescriberespiratorysymptomsofavarietyofpulmonaryconditionsBythebeginningofthe20thcentury,

asthma

wasseentobeauniqueillnesscharacterizedby'spasmodicafflictionsofthebronchialtubes'.Today,

asthma

isseenasachronicinflammatorydiseasewhichisnotyetfullyunderstoodinitspathophysiologyTherapyisstillonthepathtobecomingoptimal.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'-'allergyA.F.CocaandR.A.Cookeintroducedtheterm'atopy'：'hypersensitiveness'occurredspontaneously'atopy'gainedanewsense,sinceIgEisacharacteristic-Clinicallysimilardiseasessuchasasthma,rhinoconjunctivitisoreczemacanbefoundintheabsenceofIgE,andarethencalled'intrinsic'variantsofthesamediseaseChemImmunolAllergy.2014;100:46-52.CoombsandGell’sClassificationofHypersensitivityDoes"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..Allergicvsnonallergicasthma:

whatmakesthedifference?Nonallergic：Greaterage,femalesex,sinusalpolyposis,andFEV1below80%ofthepredictedvalueAllergic：historyofhayfever,seasonalexacerbationofasthma,andasthmadurationAllergy.2002Jul;57(7):607-13.Asthmaphenotypes:nonallergic(intrinsic)asthma.Thedefinition：subjectswithasthmaandwithwhomallergicsensitizationcannotbedemonstratednegativeskinpricktestorinvitrospecific-IgEtesttoapanelofseasonalandperennialallergensNonallergicasthmaoccursin10%to33%ofindividualswithasthmaandhasalateronsetthanallergicasthma,withafemalepredominance.NonallergicasthmaappearstobemoreseverethanallergicasthmainmanycasesandmaybelessresponsivetostandardtherapyPetersSP.Asthmaphenotypes:nonallergic(intrinsic)asthma.JAllergyClinImmunolPract.

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

VenneraMdelC1,

PicadoC1.Noveldiagnosticapproachesandbiologicaltherapeuticsforintrinsicasthma.IntJGenMed.

2014

Jul8;7:365-71.哪些哮喘患者需要行AIT？过敏的概念总tIgESentietalAllergy2011;66(6):7981911Noon1thSCIT1950s1thSCITControlStudy;1980s1thDBPCSLIT;2000s1thsublingualTablet2011sInnovatingforpatientbenefit100yeasofantigenspecificimmunotherpyAllergenspecificimmunotherapySelf-amplificationmechanismsofmastcellactivation:

anewlookinallergy.Thecurrentdefinitionofallergy,agroupofIgEmediateddiseasesappearsdifficulttocoverallallergicreactionsSinceevenIgEdependentallergicreactionsarecarriedoutthroughactivationofmastcellsandbasophils,andallallergensmentionedabovecanactivatethesecellswehypothesizethatallergicreactionsaremastcellandbasophilmediatedinflammatoryprocessasitistheactivatedmastcellsandbasophilsthatinitiatethepathologicalprocessoftheimmediateallergicreactionswhereas

IgEonlyservesasoneoftheactivatorsofthesecells.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