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Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,43,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,Klik for at redigere i masteren,Klik for at redigere teksttypografierne i masteren,Andet niveau,Tredje niveau,Fjerde niveau,Femte niveau,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,FeNO指导临床治疗支气管哮喘及慢性咳嗽思考,FeNO指导临床治疗支气管哮喘及慢性咳嗽思考,1,案 例,(,一,),案 例(一),2,第一次就诊时间,:08-14,李,XX,女,53,岁,主诉,:,反复咳嗽气喘,2,年,加重,1,周,.,现病史,:,2,年来间断咳嗽气喘,在春季及秋季显著,遇烟雾及油漆汽车尾气等会加重,有时夜间,发作,有明显喉鸣音,初曾在当地社区医院予服氨茶碱,咳喘宁可缓解,未重视,.,第一次就诊时间:08-14,3,1,年前因夜间咳喘症状加重曾在军区总医院查体两肺哮鸣音,,,全胸片阴性,,,查肺功能,+,支气管舒张试验,,,提示轻度阻塞性肺通气功能障碍,,,支气管舒张试阳性,,,诊断考虑支气管哮喘,,,予信必可都保,(,布地奈德福莫特罗粉吸入剂规格,:160/4.5ug)2,吸,BID,,应用。使用不规则,。1,月后自行停药到今,。1,周前进食海鲜后咳喘症状加重,同时皮肤荨麻疹,复来就诊,.,不发热,无咯血,无头痛,无腹痛,无肢体关节疼痛,,,畏风,不发热,食欲一般,,,睡眠不安,,,二便调。舌质淡红,,,苔薄白,,,脉浮紧,。,1年前因夜间咳喘症状加重曾在军区总医院查体两肺哮鸣,4,查体,:,轻度喘促貌,,,四肢及胸部皮肤散在潮红之荨麻疹,,,搔痒,,,有抓痕,。,唇无紫绀,,,两肺可闻及散在哮鸣音,,,心率,82,次,/,分,,,律齐,。,诊断 中医,:,哮病,(,风痰证,),西医,:,支气管哮喘急性发作,因患者不同意住院,予查血常规,查,FENO;,先临时处理,:,予呼吸科门诊综合治疗室吸氧并予以雾化,布地奈德雾化液,.3mg,特布他林雾化液,5mg,雾吸,st,异丙托溴铵,500ug,雾化治疗后喘促改善,血常规提示,EOS 7%;FENO:223PPB.,患者不服中药,.,同时路远不同意每天来门诊持续雾化,。,查体:轻度喘促貌,四肢及胸部皮肤散在潮红之荨麻疹,搔痒,有抓,5,予信必可都保,(,布地奈德福莫特罗粉吸入剂规格,:160/4.5ug)2,吸,BID,,嘱必要时临时加吸,。,枸地氯雷他定,8.8mg,口服,QN.,服用,1,周,;,嘱症情加重及时住院治疗,上述药物吸入持续,3,月,。,避免接触各种吸入性或食入性可疑过敏原,。,予信必可都保(布地奈德福莫特罗粉吸入剂规格:160/4.5u,6,11-09,复诊,.,症情明显改善,,,询问,3,月期间,,,均规律使用吸入剂,(,常在普通门诊取药或外院取药,),皮疹在此次发病,1,周内消退,,,平时吸入剂偶有加吸到一天,5,次到,6,次,(,含正常的,4,次,),,发病,1,月后基本无白天症状,,2,月来,,,仅夜间偶有胸闷气短,偶有喉鸣,.,平时无鼻塞流涕等,.,自认为完全控制,。,本次就诊目的想停吸入用药物,。,查体,:,两肺呼吸音稍粗,,,未闻啰音,。,予复查,FENO,、,血常规,结果,:198PPB,,,血常规:,EOS 6.9%,。,治疗选择,:,信必可都保,(,布地奈德福莫特罗粉吸入剂规格,:160/4.5ug)2,吸,BID?,11-09 复诊.,7,案例,(,二,),案例(二),8,第一次就诊时间,:08-30,黄,XX,女,45,岁,.,主诉,:,反复咳嗽,6,月,.,现病史,:,6,月来,,,反复咳嗽,,,咽痒,,,咽干,,,常在接触冷空气,(,空调风,),油烟,,,灰尘后咳嗽加剧,无痰,,,无咯血,,,同时近,3,月来有夜间咳嗽,偶有喉鸣音,,,气短,,,胸闷。外院查胸部,CT,阴性,,,按支气管炎输液抗生素,1,周,,,咳嗽未缓解,。,平时在车间工作,,,灰尘亦大,,,尽管戴口罩但仍不能控制咳嗽,。,回家后稍安,,,夜间咳嗽更剧,,,常不能入睡,。,不发热,,,无盗汗,,,食纳一般,,,平时畏风,,,舌体胖大,,,边有齿印,,,舌尖红,,,苔薄白,,,脉细弦,。,查体,:,一般情况可,咽充血(,+),,扁桃体不肿大,两肺呼吸音稍粗,未闻干湿性啰音,.,心率,78,次,/,分,律齐,。,第一次就诊时间:08-30,9,予查血常规:,EOS 6% ;FENO :68,PPB.,螨过敏原试验,.,粉尘螨,(+),屋尘螨,(+),;查肺功能示小气道功能减退,支气管舒张试验阳性,。,诊断 中医,:,咳嗽病,(,风痰脾虚证,),西医:咳嗽变异性哮喘,予信必可都保,(,布地奈德福莫特罗粉吸入剂规格,:160/4.5ug)1,吸,BID,嘱必要时临时加吸,.,地氯雷他定,5 mg,口服,QN.,服用半月,.(,患者不同意脱敏治疗,),予查血常规:EOS 6% ;FENO :68 PPB.螨过,10,中药方治标以祛风化痰解痉止咳,治本以益气固卫调运脾胃,;,半月后复诊调整中药,.,避免接触各种吸入性或食入性可疑过敏原,.,症情加重及时住院治疗,.3,月后复查,FENO.,患者辞工回家治疗,坚持每半月复诊一次,中药调整,症状在第一周后控制,1,月后夜间症状明显不著,信必可都保上述剂量再吸,2,月,准备复查,FENO,后决定是否停吸,,2,月来中药以改治本为主。,中药方治标以祛风化痰解痉止咳,治本以益气固卫调运脾胃,11,11-01,复诊,.,患者无咳嗽,偶有气短,胸闷,无咽痒。,查体:咽充血(,),,扁桃体不肿大,双肺呼吸清,予复查,FENO:20 PPB,;,血常规:,EOS 4.6%,因患者无法坚持服中药,需要停服中药。,治疗选择:信必可都保是否需继续应用?可否单独予孟鲁司特钠口服?。,11-01复诊.,12,案例,(,三,),案例(三),13,第一次就诊时间,:10-18,唐,XX,,男,,33,岁,主诉,:,反复咳嗽气短,3,月,加重,1,周,。,现病史,:,3,月来间断咳嗽,干咳嗽,与季节变化无关,,进食后易咳嗽,气短,偶有嗳气,反酸,白天和直立位时易干咳,睡觉后一般不咳嗽,,遇烟雾及油漆汽车尾气等刺激性偶有加重,有时夜间发作,似曾有过喉鸣音,曾外院查全胸片阴性,肺功能,+,支气管舒张试验,提示肺功能正常,支气管舒张试验阴性,.,先后在外院予服阿莫西林,抗过敏药物西替利嗪、孟鲁司特钠及中成药咳喘宁等偶有缓解但经常反复。病程中不发热,无咽痛,无胸痛,无腹痛,无睡眠欠佳,食欲可,二便调。口干,舌体胖大,边有齿印,舌尖红,苔垢腻,脉细弦。,第一次就诊时间:10-18,14,查体,:,咽充血,(+),扁桃体不肿大,双肺呼吸音粗,未闻明显干湿性啰音,心率,76,次,/,分,律齐,未闻杂音,。,予查血常规,全胸片,FENO,螨过敏原,。,血常规结果,CRP 、,白细胞总数,,,各项分类,,,均正常,;,全胸片阴性,,,螨过敏原,(-),FENO 21 PPB。,考虑上述检查结果阴性或偏低原因与服用过抗过敏药及白三烯受体拮抗剂可能有关,由于无法做支气管激发试验,仍不能排除咳嗽变异性哮喘,胃食道反流性咳嗽可能性亦存在。,查体:咽充血(+),扁桃体不肿大,双肺呼吸音粗,未闻明显干湿,15,诊断初步考虑:咳嗽变异性哮喘?胃食道反流性咳嗽?,诊断 中医,:,咳嗽病,(,脾胃不和,肺胃气逆,),西医,:,慢性咳嗽查因:,1、,咳嗽变异性哮喘?,2、,胃食道反流性咳嗽?,征得患者同意,予信必可都保,(,布地奈德福莫特罗粉吸入剂规格,:160/4.5ug)1,吸,BID,嘱必要时临时加吸,。,予兰索拉唑,15mgBID,口服;,枸橼酸莫沙必利,5mgTID,口服。建议胃镜检查。必要时测食道,24,小时,PH,值。因不服中药,未开。半月后复诊。有病情加重随时急诊。,治疗选择:应该不应该开信,必可都保?,诊断初步考虑:咳嗽变异性哮喘?胃食道反流性咳嗽?,16,第二次复诊时间,:11-01,服药及吸药期间咳嗽确有明显改善,但停服兰索拉唑、,枸橼酸莫沙必利后反酸著,且咳嗽加重,。,我院消化科胃镜检查:提示慢性胃窦炎,,HP(+),,反流性食管炎。停信必可都保,继续予服兰索拉唑、,枸橼酸莫沙必利,并加服孟鲁司特钠。半月后复诊。,第二次复诊时间:11-01,17,FeNO,判断气道炎症患者,ICS,反应性,FeNO判断气道炎症患者ICS反应性,18,气道炎症是多种呼吸道疾病的核心,inflammation,19,哮喘,COPD,慢性咳嗽,气道炎症是多种呼吸道疾病的核心 inflammation1,A,B,C,D,Simpson et al Respirology 2006; 11: 54-61,气道炎症类型,A,.,嗜中性粒细胞型,B,.,嗜酸性粒细胞型,C,.,混合型,D.,寡粒细胞型,ABC D Simpson et al Respirolo,20,呼出气一氧化氮,(NO),的产生,NO,内源性调节分子,合成由一系列酶调节,NO,合成酶,(NOS),由,iNOS,产生的,NO,主要由支气管壁上皮细胞生成,Th2(,过敏性,),引发的炎症伴随呼出气,NO,的增高,通常和嗜酸性炎症相关,呼出气一氧化氮 (NO) 的产生NO 内源性调节分子,Guo FH, De Raeve HR, Rice TW, Stuehr DJ, Thunnissen FB, Erzurum SC. Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. Proc Natl Acad Sci U S A 1995;92:7809-13.,Northern Blot,人类气道中的,iNOS,表达,吸入激素和,SABA,治疗,3,周后,Guo FH, De Raeve HR, Rice TW,22,激素对,iNOS,的影响,Figures reproduced from Thorax, Redington et al, 56,351-357, 2001 with permission from BMJ Publishing Group Ltd.,Redington et al. Thorax. 2001;56:351-357.,Control,Asthma,(- steroid),Asthma,(+ steroid),激素对iNOS的影响Figures reproduced f,FeNO,与嗜酸性粒细胞性气道炎症相关性高,Berry MA et al.,Clin Exp Allergy,. 2005;35(9):1175-1179.,100,Sputum eosinophil count (%),*,Male,Female,0.1,0.3,1,3,10,30,Exhaled NO concentration (ppb),100,30,10,3,1,0.3,0.1,P,.001,R,= 0.52,气道内嗜酸性细胞炎症是,FeNO,增高的主要原因,FeNO 与嗜酸性粒细胞性气道炎症相关性高Berry MA,24,FeNO,较比其它指标能更快反应,ICS,的有效性,Dweik et al. Am J Respir Crit Care Med. 2011;184(5):602-615.,Courtesy,of Prof. J. de Jongste, NL,FeNO,FEV1,“,FeNO,在,预测激素的反应,性上优于,肺量测定,舒张试验,峰流速变化以及气道,激发试验”,FeNO较比其它指标能更快反应ICS的有效性Dweik et,47,“,Normal,”,Cut point for steroid responsiveness,ppb,Figure in green = optimum cut point,16,0,200,No steroid responsiveness,NPVs 85-95%,Steroid responsiveness,PPVs 75-85%,Olin et al., Chest, 2006,Smith et al., AJRCCM, 2005,Pijnenburg et al., Thorax, 2005,较高,FeNO,水平的病人对激素的治疗反应性高,47“Normal”Cut point for steroi,26,PC,20,AMP (doubling dose shift),Composite symptom score,FEV,1,(percent change),Baseline FE,NO,(ppb),47,47,Peak flow (percent change),Smith et al. AJRCCM, 2005,N=52,较高,FeNO,水平,病人,ICS,治疗后症状、肺功能及,AHR,均显著改善,PC20 AMP (doubling dose shift),FeNO,预测慢咳患者激素反应性的研究,Mayo Clin Proc. 2007,;,82,(,11,):,1350-1355,FeNO预测慢咳患者激素反应性的研究Mayo Clin Pr,28,FeNO,高的慢咳患者激素反应性好,Use of Exhaled Nitric Oxide in Predicting Response to Inhaled Corticosteroids for Chronic Cough,。,Mayo Clin Proc. 2007,;,82,(,11,):,1350-1355,FeNO高的慢咳患者激素反应性好Use of Exhaled,FeNO,中、高水平的咳嗽患者,症状缓解更为明显,中、高,FeNO,水平的慢性咳嗽患者在经过激素治疗后,其,症状缓解患者,的数目和,FeNO,水平下降明显优于低,FeNO,水平,患者,Koshela and Purokuvi Cough 2013,9:15,FeNO中、高水平的咳嗽患者,症状缓解更为明显中、高FeNO,仅以,FeNO,水平决定慢咳患者是否使用激素治疗可取得良好效果,.,J Chin Med Assoc, 2013. 76(1): p. 15-9.,FeNO=30,FeNO30,仅以FeNO水平决定慢咳患者是否使用激素治疗可取得良好效果.,呼出气一氧化氮测定在慢性咳嗽诊治中的应用价值初探,抗炎治疗,4,周,后咳嗽缓解患者的基线,FENO,值明显高于未缓解患者,(63,42)ppb vs (28,13)ppb (t=3.91,,,P=38.8 ppb,Oh,等, 2008,=31.7 ppb,Hahn,等, 2007,=38 ppb,张永明,林江涛,2011,=40 ppb,=31 ppb,=36 ppb,万玉峰等,2012,34.1 ppb,Jeng-Yuan Hsu,等, 2013,=33.9 ppb,FeNO在慢性咳嗽中的诊治应用FeNO值判断CVA判断E,FeNO,水平越高的患者判断其从激素治疗中获益的准确率越高,Am J Respir Crit Care Med. Vol 180.pp 846-852,2009,FeNO水平越高的患者判断其从激素治疗中获益的准确率越高Am,34,哮喘患者,FeNO,水平与进一步激素治疗小气道功能改善的研究,.,Yoon, et al.,Korean J Pediatr. 2012;55(9):330-336,哮喘患者FeNO水平与进一步激素治疗小气道功能改善的研究.,35,哮喘管理目标:达到并维持哮喘控制,Fractional exhaled nitric oxide and forced expiratory flow between 25% and 75% of vital capacity in children with controlled asthma. JY. Yoon, et al.,Korean J Pediatr. 2012;55(9):330-336,6,周后观察结果,临床控制好的病人(但,FeNO,还处与中、高水平,)是否,还能从加大激素治疗中获益?,哮喘管理目标:达到并维持哮喘控制Fractional exh,36,结果:小气道功能改善, FeNO,进一步,下降,Fractional exhaled nitric oxide and forced expiratory flow between 25% and 75% of vital capacity in children with controlled asthma. JY. Yoon, et al.,Korean J Pediatr. 2012;55(9):330-336,结果:小气道功能改善, FeNO进一步下降Fractiona,37,Advances in the clinical applications of exhaled nitric oxide measurements,.,FeNO,水平判断激素治疗获益的荟萃分析,Journal of Breath Research,2012,6(4):047102-047102,Advances in the clinical appli,38,Taylor J Breath Res 2012,低,FeNO,值的患者,对激素治疗有反应的可能性低,FeNO,水平判断激素治疗获益的荟萃分析,-,很高的阴性排除价值,Taylor J Breath Res 2012低FeNO值,39,2011,年,ATS:FeNO,临床指南,在,慢性气道炎症疾病,中,,使用,FeNO,检测,鉴别气道炎症类型,(,嗜酸粒细胞性气道炎症诊断,中使用,FeNO,),确定该个体对,皮质类固醇治疗产生反应的可能性,(,可能因气道炎症而出现慢性呼吸道症状的个体中使用,FeNO,检测,确定其对皮质类胆固醇治疗反应的可能性,),2011年ATS:FeNO临床指南在慢性气道炎症疾病中,使用,40,对,ICS,治疗反应性,不太可能,对,ICS,治疗反应性,很有可能,2011,美国胸科学会(,ATS,),FeNO,指南,*Increasing defined as 40% increase from previous stable FeNO level.,Chronic cough and/or wheeze and/or shortness of breath for 6 weeks.,For example,rhinosinusitis, bronchiectasis, primary ciliary dyskinesia, anxiety-hyperventilation, cardiac disease, GERD, or vocal cord dysfunction.,Dweik et al.,Am J Respir Crit Care Med.,2011;184(5):602-615.,3, Smith AD, Cowan JO, Filsell S, et al. Diagnosing asthma. Comparisons between exhaled nitric oxide measurements and conventional tests. Am j Respir Crit Care Med 2004;169:473-8,4, Smith AD, Cowan JO, Brassett KP, et al. Exhaled nitric oxide. A predictor of steroid response. Am J Respir Crit Care Med 2005;172:453e9,EMD/000585/00,NPV,92,% ,PPV,82% ,低,FeNO,水平,中度,/,增加的,FeNO,水平,*,高,FeNO,水平,成人,25 ppb,儿童,25-50 ppb,儿童,20-35 ppb,成人,50 ppb,儿童,35 ppb,不太可能是嗜酸性细胞炎症,极可能是嗜酸性细胞炎症,对ICS治疗反应性对ICS治疗反应性2011美国胸科学会(,小结,-,FeNO,水平作为患者激素治疗获益的敏感指标,FeNO,值低,对于初诊病人:,排除嗜酸性气道炎症,提示患者从,ICS,治疗中获益可能性低,经过,ICS,治疗的病人:,如果病人,FeNO,值处于低水平,病人从增加激素剂量的治疗中获益可能性低,FeNO,值高,对于初诊病人:,极可能是嗜酸性气道炎症,提示患者从,ICS,治疗中获益可能性大,经过,ICS,治疗的病人:,如果病人依然处于高水平,提示患者继续增加激素剂量的治疗中获益可能性大,*,排除长期,ICS,治疗,,FeNO,处于中高水平,但稳定的病人,小结- FeNO水平作为患者激素治疗获益的敏感指标FeNO值,对前,三,个案例的治疗方案的个人看法,:,案,1:,继续使用吸入糖皮质激素,;,案,2:,由于,FENO,处于低等状态,:,增强吸入激素疗收益应小,选用顺尔宁,.,案,3:,当初宜直接选用顺尔宁,FeNO指导临床治疗支气管哮喘及慢性咳嗽思考课件,感 谢 聆 听!,感 谢 聆 听!,44,
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