Slide1哮喘症状由尚未被控制的气道炎症所致炎症反应的双通道Slide2AdaptedfromNationalInstitutesofHealthGlobalInitiativeforAsthma:GlobalStrategyforAsthmaManagementandPrevention:APocketGuideforPhysiciansandNurses.PublicationNo.95-3659B.Bethesda,MD:NationalInstitutesofHealth,1998;BjermerLRespirMed2001;95:703-719.炎症反应在哮喘中的重要性哮喘本质上是一种炎症反应疾病炎症反应导致气管收缩及气道高反应性,从而产生症状对轻中度哮喘病人应首先进行控制炎症的治疗Slide3•抑制多种炎症介质–细胞因子–粘附分子–可诱导的酶•对炎性反应的多种作用AdaptedfromPeters-GoldenM,SampsonAPJAllergyClinImmunol2003;111(suppl1):S37-S48.炎症反应的双通道皮质激素的作用Slide4尽管使用了吸入激素,气道炎症仍持续存在ICS=inhaledcorticosteroids;OCS±ICS=receivedoralcorticosteroidswithorwithoutICSAdaptedfromLouisRetalAmJRespirCritCareMed2000;161:9-16.20,00010,0001,000100101Eosinophil103/gsputumControlgroup轻到中度哮喘ICSlow-dose(n=10)ICShigh-dose(n=15)OCS(n=10)OCS±ICS(n=7)重度哮喘p<0.01p<0.001p<0.001p<0.01n=74Slide5白三烯其它炎性介质Thisslideisanartisticrendition.AdaptedfromHolgateST,Peters-GoldenMJAllergyClinImmunol2003;111(1suppl):S1-S4;HolgateSTetalJAllergyClinImmunol2003;111(1suppl):S18-S36;HendersonWRJretalAmJRespirCritCareMed2002;165:108-116;Peters-GoldenM,SampsonAPJAllergyClinImmunol2003;111(1suppl):S37-S42;VarnerAE,LemanskeRFJr.InAsthmaandRhinitis.Oxford,UK:BlackwellScience,2000:1172-1185.无炎症反应炎症反应哮喘白三烯:在哮喘早期及疾病全程中的重要性Slide6炎症反应的双通道半胱氨酰白三烯受体的表达NeutrophilMonocyteMacrophageBasophilPluripotenthemopoieticstemcellTCellsEosinophilBLymphocyteCCR3CD4+CD8+CD19M-CSF,GM-CSF,IL-3LTC4,LTD4,LTE4LN5MastCellLTC4LTD4LTE4M-CSFGM-CSFIL-5IL-3GM-CSFLTC4LTD4LTE4CD14IL5RβRepresentstheCysLT1receptorAdaptedfromFigueroaDJetalAmJRespirCritCareMed2001;163:226-233;MelloretalProcNatlAcadSciUSA2001;98:7964-7969CysLT1RCD34+Slide7炎症反应的双通道半胱氨酰白三烯在炎性细胞受体上的作用嗜酸细胞肺巨噬细胞Smooth-musclecellB淋巴细胞CysLT=cysteinylleukotriene;PBMC=peripheralbloodmononuclearcellsAdaptedfromFigueroaDJetalAmJRespirCritCareMed2001;163:226-233.单核细胞Slide8AdaptedfromPeters-GoldenM,SampsonAPJAllergyClinImmunol2003;111(suppl1):S37-S48.炎症反应的双通道白三烯是强大的炎症介质其它介质受体其它介质光胱氨酰光胱氨酰白三烯受体白三烯受体光胱氨酰光胱氨酰白三烯白三烯Slide9AdaptedfromHayDWPetalTrendsPharmacolSci1995;16:304-309.炎症细胞(肥大细胞,嗜酸性细胞)感觉神经(C纤维)CysLTs水肿血管粘液转运减少嗜酸性细胞内流阳离子蛋白释放,上皮细胞损伤收缩和增生气道平滑肌粘液分泌增多气道上皮炎症反应的双通道半胱氨酰白三烯在哮喘中的核心作用Slide10p=NSbetweengroupsAdaptedfromO’ShaughnessyKMetalAmRevRespirDis1993;147:1472-1476.18.7201612840UrinaryLTE4excretion(ng/mmolcreatinine)18.4PlaceboFluticasonepropionate吸入丙酸氟替卡松对尿中白三烯量的影响1000µg虽然氟替卡松明显改善了过敏原诱导的支气管狭窄(p<0.02),但在降低尿LTE4浓度方面无显著效果治疗期14天,洗脱期21天后交叉,最后一天过敏原刺激N=10Slide11**p<0.05vs.baselineAdaptedfromDworskiRetalAmJRespirCritCareMed1994;149:953-959.0.30.20.10UrinaryLTE4(ng/mgcreatinine)Post-allergenchallengeBaselineControlPrednisone*口服强的松对尿中白三烯量的影响Slide12*p<0.02vs.normalindividuals;**p<0.05vs.normalindividualsAdaptedfromPavordIDetalAmJRespirCritCareMed1999;160:1905-1909.14121086420SputumCysLTlevels(ng/ml)Controls控制(n=10)6.4Allpatientswithasthma所有哮喘患者(n=26)9.4*Patientswi...