一氧化氮呼气测定的临床意义和应用.ppt

一氧化氮呼气测定的临床意义和应用,仅供医疗专业人士参考审批编号：415.126,022有效期：2015.9.22-2016.9.21,EurRespirJ2006;28:264267,炎症是慢性气道疾病的核心,气道疾病共同点：症状气流受限气道高反应,正常的支气管,有炎症的支气管,我们需要气道炎症的生物标记物帮助诊断监测,潜在病理学问题嗜酸细胞或者非嗜酸细胞?气道高反应性?,气道炎症疾病面临的问题,临床诊断是咳嗽？哮喘?COPD？其他气道炎症疾病？,对治疗的反应性对ICS治疗反应好吗？(开始治疗/增加剂量/减少剂量)?对白三烯受体拮抗剂反应好吗？,A,B,C,D,SimpsonetalRespirology2006;11:54-61,A.NeutrophilicB.EosinophilicC.MixedcellularityD.Paucigranular,气道炎症类型,气道炎症评估,传统评估方式：症状病史肺功能,炎症评估有创：支气管粘膜活检支气管肺泡灌洗无创：诱导痰激发试验FeNO,内容,一、FeNO预测哮喘患者对ICS的反应性二、FeNO在慢性咳嗽诊断的作用,FeNO-Th2驱动的炎症标记物方便快捷预测患者对ICS的反应性,气道过敏性炎症Th2驱动,嗜酸性细胞：靠近管腔，基底膜，和破坏相关肥大细胞：靠近肺部的神经，和AHR相关,AllergyAsthmaImmunolRes.2010Apr;2(2):87-101,NatMed.2012May4;18(5):716-25,FeNO显示嗜酸性细胞哮喘患者对激素的反应更佳,Berryetal.Thorax.2007;62(12):1043-1049.,Noneosinophilicasthma(n=11),Week,MeanFeNO,ppb,0,0,8,8,Placebo,P=0.14,Eosinophilicasthma(n=12),0,0,8,8,P=0.72,MeanmethacholinePC20,mg/mL,Placebo,Mometasone400g/d,90,0,10,20,30,40,50,60,70,80,0,0,Week,8,8,P=0.003,Placebo,P=0.01,0,0,8,8,Placebo,Mometasone400g/d,Mometasone400g/d,Mometasone400g/d,90,0,10,20,30,40,50,60,70,80,0,0.5,1,1.5,2,2.5,0,0.5,1,1.5,2,2.5,FeNO协助判断对激素治疗的反应性*,FeNO的预测准确性显著高于传统方式,FigurereprintedfromSmithetalwithpermissionoftheAmericanThoracicSociety.Copyright2011AmericanThoracicSociety.*Steroidresponse(fluticasone500g/dfor4weeks)definedasFEV1increaseof12%orincreaseinmeanmorningpeakflow(overprevious7days)of15%.PositivebronchodilatorresponsedefinedasFEV1increaseof12%frombaseline15minutesafteralbuterolinhalation.Smithetal.AmJRespirCritCareMed.2005;172(4):453-459.,FeNO,FEV1bronchodilatorresponse,Sensitivity,0,0.25,0.50,0.75,1.00,1.00,0.75,0.50,0.25,0,N=52patientswithundiagnosedrespiratorysymptoms,1-Specificity,FeNO易于早期发现ICS的依从性差,MeanFeNOlevelsweresignificantlyreducedinpatientswithgoodICSadherence*FEV1levelswerenotsubstantiallydifferentamongadherencegroups,SD,standarddeviation.*Adherencedeterminedbycalculatingnumberofdosestakenperday/dosesprescribedx100.Good,moderate,andpooradherencedefinedas75%adherence,50%to75%adherence,or40%increasefrompreviousstableFeNOlevel.Chroniccoughand/orwheezeand/orshortnessofbreathfor6weeks.Forexample,rhinosinusitis,bronchiectasis,primaryciliarydyskinesia,anxiety-hyperventilation,cardiacdisease,GERD,orvocalcorddysfunction.Dweiketal.AmJRespirCritCareMed.2011;184(5):602-615.3,SmithAD,CowanJO,FilsellS,etal.Diagnosingasthma.Comparisonsbetweenexhalednitricoxidemeasurementsandconventionaltests.AmjRespirCritCareMed2004;169:473-84,SmithAD,CowanJO,BrassettKP,etal.Exhalednitricoxide.Apredictorofsteroidresponse.AmJRespirCritCareMed2005;172:453e9,NPV92%,PPV82%,47,Cutpointforsteroidresponsiveness,ppb,Figureingreen=optimumcutpoint,16,0,200,NosteroidresponsivenessNPVs85-95%,SteroidresponsivenessPPVs75-85%,Olinetal.,Chest,2006Smithetal.,AJRCCM,2005Pijnenburgetal.,Thorax,2005,FeNO值47ppb的病人对激素的治疗反应性高,IncreasedFENOpredictssteroidresponsivenessinpatientswithnon-specificrespiratorysymptoms,PC20AMP(doublingdoseshift),Compositesymptomscore,FEV1(percentchange),BaselineFENO(ppb),47,Peakflow(percentchange),Smithetal.AJRCCM,2005,FeNO47病人ICS治疗后症状、肺功能及AHR均显著改善,N=52,已经使用ICS治疗的病人，如果还没有得到控制，增加ICS剂量对患者是否获益?,FeNO仍然可以预测增加ICS剂量对患者是否获益,PerezdeLlanoetal.,ERJ,2010,FeNO测定,已经使用ICS治疗的病人,PerezdeLlanoetal.,ERJ,2010,经过ICS治疗的哮喘患者FeNO26ppb为嗜酸性气道炎症的可能性加大，NPV=85%,FeNO差异：慢性咳嗽是否有嗜酸性气道炎症,PachecoA,etal.Gastroesophagealreflux,airwayeosinophilicinflammationandchroniccough.Respirology.2011;16:9949.,40.5ppb,FeNO:变应性咳嗽和CVA、EB的差别,Respirology.2008May;13(3):359-64,FeNO对EB有很高的阴性预测值,OhMJetal.Exhalednitricoxidemeasurementisusefulfortheexclusionofnonasthmaticeosinophilicbronchitisinpatientswithchroniccough.Chest.2008Nov;134(5):990-5.,FeNO预测慢性咳嗽对ICS的反应性,Hahn,P.Y.,T.Y.Morgenthaler,andK.G.Lim,Useofexhalednitricoxideinpredictingresponsetoinhaledcorticosteroidsforchroniccough.MayoClinProc,2007.82(11):p.1350-5.,FeNO可以在不明原因的慢咳患者中对经验性使用激素提供指导,Hsu,J.Y.,C.Y.Wang,Y.W.Cheng,andM.C.Chou,Optimalvalueoffractionalexhalednitricoxideininhaledcorticosteroidtreatmentforpatientswithchroniccoughofunknowncause.JChinMedAssoc,2013.76(1):p.15-9.,FeNO30ppb分组,FeNO在慢性咳嗽中的诊治应用,FeNO替代诱导痰在慢性咳嗽诊治中的应用,小结,FeNO可以作为慢性咳嗽病人有效的筛查手段FeNO较高，病人被诊断为CVA或EB的可能性大，病人从ICS治疗中获益可能性大，避免激素的经验性使用FeNO测定方便快捷对于无法开展诱