鼻炎ppt課件.ppt

過敏性鼻炎 哮喘同一氣道的疾病白三烯在過敏性鼻炎 哮喘中的作用 Thispresentationincludespreliminaryresultsofanongoingclinicalprogram AdaptedfromNationalInstitutesofHealthGlobalInitiativeforAsthma GlobalStrategyforAsthmaManagementandPrevention APocketGuideforPhysiciansandNurses PublicationNo 95 3659B Bethesda MD NationalInstitutesofHealth 1998 BousquetJetalJAllergyClinImmunolSuppl2001 108 5 S148 S149 Slide1 SGA2001 W 6472 SS 哮喘及過敏性鼻炎兩者均是炎癥性疾病 哮喘Achronicinflammatorydisorderinwhichexposuretovariousstimuliresultsinairwayobstructionandairflowlimitation過敏性鼻炎AnIgE mediatedinflammatorydisorderinwhichexposureofthenasalmembranestoallergensleadstonasalsymptoms 過敏性鼻炎 EpidemiologicLinksBetweenAllergicRhinitisandAsthma過敏性鼻炎同哮喘有相似的發(fā)病情況 Studyofworldwideprevalenceofatopicdiseasesin463 801children13 14yearsofage Childrenself reportedsymptomsover12monthsusingquestionnaires AdaptedfromtheInternationalStudyofAsthmaandAllergiesinChildhood ISAAC SteeringCommittee Lancet1998 351 1225 1232 Slide2 SGA2001 W 6472 SS 哮喘 EpidemiologicLinksBetweenAllergicRhinitisandAsthma過敏性鼻炎是哮喘的危險因素 過敏性鼻炎能增加哮喘的危險約 3倍 Slide3 SGA2001 W 6472 SS 23 yearfollow upofcollegefreshmenundergoingallergytesting databasedon738individuals 69 male withaverageageof40years AdaptedfromSettipaneRJetalAllergyProc1994 15 21 25 121086420 ofpatientswhodevelopedasthma 10 5 Allergicrhinitisatbaseline n 162 3 6 Noallergicrhinitisatbaseline n 528 p 0 002 EpidemiologicLinksBetweenAllergicRhinitisandAsthma大部分的哮喘患者同時患有鼻炎 近80 的哮喘病人有過敏性鼻炎 Slide4 SGA2001 W 6472 SS AdaptedfromTheWorkshopExpertPanel ManagementofAllergicRhinitisanditsImpactonAsthma ARIA PocketGuide APocketGuideforPhysiciansandNurses 2001 BousquetJandtheARIAWorkshopGroupJAllergyClinImmunol2001 108 5 S147 S334 SibbaldB RinkEThorax1991 46 895 901 LeynaertBetalAmJRespirCritCareMed2000 162 1391 1396 Asthmaalone Allergicrhinitisalone Allergicrhinitis asthma 0 9 EpidemiologicLinksBetweenAllergicRhinitisandAsthma治療過敏性鼻炎能相對減輕治療哮喘的資源利用 Slide7 SGA2001 W 6472 SS Retrospectivecohortstudyofcostsoveraperiodofuptooneyearincurredbypatients12to60yearsofagewithbothallergicrhinitisandasthma AdaptedfromCrystal PetersJetalJAllergyClinImmunol2002 109 1 57 62 2 52 01 51 00 50 ofpatients 未接受過敏性鼻炎治療的病人 n 1357 接受過敏性鼻炎治療的病人 n 3587 2 3 p 0 01 住院率降低61 SharedPathophysiologyofAllergicRhinitisandAsthma過敏性鼻炎同哮喘有共同的促發(fā)因子 非甾體類解熱鎮(zhèn)痛藥 e g aspirin 室內(nèi)過敏源House dustmiteAnimaldanderInsects e g cockroachallergen Tobaccosmoke室外過敏源PollensMolds Slide9 SGA2001 W 6472 SS AdaptedfromNationalInstitutesofHealthGlobalInitiativeforAsthma GlobalStrategyforAsthmaManagementandPrevention APocketGuideforPhysiciansandNurses PublicationNo 95 3659B Bethesda MD NationalInstitutesofHealth 1998 WorkshopExpertPanelManagementofAllergicRhinitisanditsImpactonAsthma ARIA PocketGuide APocketGuideforPhysiciansandNurses 2001 SharedPathophysiologyofAllergicRhinitisandAsthma過敏性鼻炎同哮喘有共同的免疫病理途徑 CysLTs cysteinylleukotrienes PGs prostaglandins PAF plateletactivatingfactorBasedonandmodifiedfromCasaleTB AminBVClinRevAllergyImmunol2001 21 1 27 49 KayABNEnglJMed2001 344 30 37 Slide10 SGA2001 W 6472 SS Membrane bound IgE Acuteallergicreactionincludingearly phaseresponse Chronicallergicreactionincludinglate phaseresponse Mastcell Tcells Allergen Cytokines PreformedmediatorsHistamine NewlyformedmediatorsCysLTs PGs PAF Eosinophils SharedPathophysiologyofAllergicRhinitisandAsthma過敏性鼻炎和哮喘有相似的速發(fā)相 遲發(fā)相反應 AdaptedfromVarnerAE LemanskeRFJr In AsthmaandRhinitis 2nded Oxford BlackwellScience 2000 1172 1185 TogiasAJAllergyClinImmunol2000 105 6pt2 S599 S604 Slide11 SGA2001 W 6472 SS AsthmaAllergicrhinitis Symptomscore Timepostchallenge hr 1 Antigenchallenge 3 4 8 12 24 Immediate early phase Latephase FEV1 change Time hr 1 10 24 0 2 3 4 5 6 7 8 9 0 50 100 SharedPathophysiologyofAllergicRhinitisandAsthma以嗜酸性細胞為主的炎癥是過敏性鼻炎和哮喘的共同特點 Eos eosinophils neut neutrophils MC mastcells Ly lymphocytes MP macrophagesAdaptedfromBousquetJetalJAllergyClinImmunolSuppl2001 108 5 S148 S149 Slide12 SGA2001 W 6472 SS 嗜酸性細胞侵潤 AllergicRhinitis Asthma AdaptedfromTogiasAAllergy1999 54 suppl57 94 105 Slide13 SGA2001 W 6472 SS Aspirationofinflammatorysecretionsfromtheupperairwayintothelowerairway Shiftfromnasaltomouthbreathing Nasobronchialreflex Systemicmediationofnasalandlower airwayinflammation SharedPathophysiologyofAllergicRhinitisandAsthma過敏性鼻炎 哮喘 內(nèi)在的相互作用機制 氣道高反應的發(fā)生率 ClinicalLinksBetweenAllergicRhinitisandAsthma過敏性鼻炎的患者在花粉季節(jié)會有更多的氣道高反應 Slide15 SGA2001 W 6472 SS Studyofbronchialhyperreactivityinpatients meanage20years withhayfever challengeswereperformedinthefallofoneyearandapproximatelysixmonthslater Provocativedose 1mgcausesa20 fallinFEV1AdaptedfromMadoniniEetalJAllergyClinImmunol1987 79 358 363 6050403020100 ofpatients 非花粉季節(jié) 花粉季節(jié) n 27 11 48 p 0 02 ClinicalLinksBetweenAllergicRhinitisandAsthma鼻腔的抗原激發(fā)會增加氣道高反應 ChangefrombaselineinPC20afternasalprovocation Slide16 SGA2001 W 6472 SS Randomizedcrossovertwo dayinvestigationoftherelationshipbetweenallergicrhinitisandlowerairwaydysfunctioninpatientswithallergicrhinitisandasthma meanage31 4years LowerPC20values provocativedoseofmethacholinecausing20 fallinFEV1 indicategreaterhyperresponsiveness p 0 011 p 0 0009AdaptedfromCorrenJetalJAllergyClinImmunol1992 89 611 618 0800Baseline 320 GeometricmeanPC20 methacholine mg ml Placebo n 10 Allergen n 10 1200Postchallenge 1600Postchallenge Time ClinicalLinksBetweenAllergicRhinitisandAsthma哮喘病人有鼻腔炎癥 鼻粘膜中的嗜酸性細胞計數(shù) Slide17 SGA2001 W 6472 SS Studyofwhethernasalmucosalinflammationexistsinasthmaregardlessofthepresenceofallergicrhinitisinatopicsubjects20to66yearsofage BarsrepresentmedianvaluesAdaptedfromGagaMetalClinExpAllergy2000 20 663 669 181614121086420 Eosinophils fieldofnasalbiopsy Rhinitis Norhinitis Control n 9 n 8 n 10 p 0 001 p 0 001 Asthmatic ClinicalLinksBetweenAllergicRhinitisandAsthma鼻腔及支氣管粘膜的炎癥變化互相關聯(lián) Slide18 SGA2001 W 6472 SS Studyofwhethernasalmucosalinflammationexistsinasthmaregardlessofthepresenceofallergicrhinitisinatopicsubjects20to66yearsofage AdaptedfromGagaMetalClinExpAllergy2000 20 663 669 4035302520151050 Asthmaticnasalmucosaeosinophils 0 r 0 851 p 0 001 Asthmaticbronchialmucosaeosinophils 5 10 15 20 25 30 n 17 ClinicalLinksBetweenAllergicRhinitisandAsthma支氣管的抗原激發(fā)能增加氣道及鼻腔的炎癥指標 Slide19 SGA2001 W 6472 SS Evaluationofallergicinflammationintheupperandlowerairwaysafterbronchialchallengeinnonasthmaticallergicrhinitispatientsvs controls agerange18 31years T0 beforechallenge T24 24hourspostchallenge p 0 05 p 0 01 p 0 001AdaptedfromBraunstahlG JetalAmJRespirCritCareMed2000 161 2051 2057 T0 100806040200 Eosinophils no cells mm2 Controlpatients n 8 Allergicpatients n 8 T24 T24 T0 160012008004000 Unchallengedleftlung Allergen challengedrightmiddlelobe Nasaltissue laminapropria Bronchialtissue subepitheliallayer TheAllergicRhinitisanditsImpactonAsthma ARIA InitiativeARIA建議共同治療同時兼顧上 下氣道 過敏性鼻炎的患者需被評估是否有哮喘哮喘的患者需被評估是否有過敏性鼻炎共同治療的策略是在安全有效的基礎上同時兼顧上 下氣道 Slide25 SGA2001 W 6472 SS AdaptedfromBousquetJetalJAllergyClinImmunolSuppl2001 108 5 S148 S149 ClinicalLinksBetweenAllergicRhinitisandAsthma抗白三烯的治療能改善哮喘及過敏性鼻炎的終點指標 Slide22 SGA2001 W 6472 SS Multicenter 12 weekdouble blind randomizedtrialinpatients15to81yearswithseasonalallergicrhinitis Multicenter randomized 12 weekdouble blindtrialofmontelukastvs placeboinpatients15yearsandolderwithasthma p 0 001montelukastvs placeboAdaptedfromReissTFetalArchInternMed1998 158 1213 1220 MalmstromKetal Posterpresentationatthe57thAAAAIAnnualMeeting March16 21 2001 3 151050 0 6 9 12 15 Placebo n 273 Asthma Mean SEFEV1 0 0 1 0 2 0 3 0 4 0 5 Montelukast10mgoncedailyatbedtime n 348 AllergicRhinitis DaytimeNasalSymptomScore Montelukast10mgoncedaily n 408 Changefrombaselinescore LSmean MorningFEV1mean changefrombaseline Weeks 白三烯的合成途徑 5 LO 5lipoxygenase FLAP 5 lipoxygenase activatingprotein 5 HPETE 5 hydroperoxyeicosatetraenoicacid CysLT1 cysteinylleukotrieneantagonistsAdaptedfromHolgateSTetalJAllergyClinImmunol1996 98 1 1 13 SmithLJArchInternMed1996 156 2181 2189 ArachidonicAcid CysLT1receptorantagonists 5 HPETE LTB4 LTC4LTD4LTE4 LTA4 FLAP 5 LO 5 LOandFLAPinhibitors 半胱胺酰白三烯在鼻腔及呼吸道組織中的作用 AdaptedfromHayDWPChest1997 111 Suppl2 35S 45S LemanskeRFJAMA1997 278 22 1855 1873 HayDWPetalTrendsPharmacolSci1995 16 304 309 Airwayepithelium Increasedmucussecretion Decreasedmucustransport Cationicproteins epithelialcelldamage SensoryCfibers Smoothmuscle lungsonly Contractionandproliferation Inflammatorycells e g mastcells eosinophils Bloodvessel Edema Cysteinylleukotrienes Eosinophilrecruitment Increasedreleaseoftachykinins 半胱胺酰白三烯在速發(fā)相 遲發(fā)相的反應階段 PAF platelet activatingfactorAdaptedfromTogiasAJAllergyClinImmunol2000 105 6pt2 S599 S604 RachelevskyGJPediatr1997 131 348 355 RouadiP NaclerioR SRS AtoLeukotrienes TheDawningofaNewTreatment SHolgaate SDahlen eds Oxford England BlackwellScience 1997 CreticosPSetalNEnglJMed1984 31 1626 1630 Symptomscore Antigenchallenge 1 3 4 8 12 TimePostchallenge hours EarlyphaseCysteinylleukotrienes prostaglandins thromboxanes histamine heparin proteases PAF LatephaseCysteinylleukotrienes cytokines 24 半胱胺酰白三烯鼻腔的抗原刺激中被發(fā)現(xiàn) vs baseline vs previouspollendoseandbaselineAdaptedfromCreticosPSetalNEnglJMed1984 31 1626 1630 p 0 01 6543210 TotalCys LT ng ml Pre 10 n 17 Ragweedpollengrains challengedose Diluentchallenge 100 1000 5000 p 0 03 p 0 004 p 0 02 AdaptedfromVolovitzBetalJAllergyClinImmunol1988 82 3pt1 414 418 LTC4concentrations n 16 MeanLTC4 ng ml Before During After 121086420 Ragweedseason Meansymptomscore Before During After 121086420 Ragweedseason Symptoms n 16 半胱胺酰白三烯的濃度隨癥狀的嚴重程度而增加 p 0 001 p 0 05 1 87 0 43 5 52 0 7 4 45 1 04 6 8 1 6 10 61 1 5 7 8 2 1 半胱胺酰白三烯刺激增加鼻腔氣道的阻力 p 0 05vs baselineNAR nasalairwayresistanceAdaptedfromOkudaMetalAnnAllergy1988 60 537 540 changeinNAR Challenge Hour 150125100 1 21357911 LTD4wasapproximately5000timesmorepotentthanhistamineinmediatingnasalresponses n 7 半胱胺酰白三烯刺激增加