1、- FeNO用于哮喘患者的長(zhǎng)期管理呼出氣一氧化氮 (FeNO) 的產(chǎn)生NO 內(nèi)源性調(diào)節(jié)分子合成由一系列酶調(diào)節(jié) NO 合成酶 (NOS)由iNOS產(chǎn)生的NO主要由支氣管壁上皮細(xì)胞生成Th2(過(guò)敏性)引發(fā)的炎癥伴隨呼出氣NO的增高，通常和嗜酸粒細(xì)胞性炎癥相關(guān)Olin et al., Chest, 2006Smith et al., AJRCCM, 2004162200Figures in white = median and 95% C.I.Figures in orange = mean and S.D.ppb528618“Healthy”Untreated asthma部分哮喘病人為非EOS的

2、氣道炎癥, 用FeNO來(lái)診斷哮喘其敏感性及特異性不可能是100%健康人和未經(jīng)治療的哮喘患者FeNO值范圍哮喘與非哮喘患者FeNO測(cè)定結(jié)果任旭斌，劉春濤等 .中國(guó)呼吸與危重監(jiān)護(hù)雜志，2009.8（4），322-326哮喘組FeNO高于非哮喘組，P0.05 哮喘患者呼出氣一氧化氮(FeNO)含量顯著升高，并與氣道炎癥嚴(yán)重程度呈高度正相關(guān)FeNO與痰3%E細(xì)胞的相關(guān)性FeNO21 ppb與 3% 痰嗜酸性粒細(xì)胞密切相關(guān)在沒(méi)有用激素患者敏感性97%;特異性58%; 陽(yáng)性預(yù)測(cè)值86%，陰性預(yù)測(cè)值88% 在使用激素患者敏感性81%; 特異性25%;陽(yáng)性預(yù)測(cè)值74%;陰性預(yù)測(cè)值22J Investig Al

3、lergol Clin Immunol. 2015;25(2):107-11 哮喘急性加重與FeNO相關(guān)性Pijnenburg MW et al. Thorax. 2005 Mar;60(3):215-8.哮喘急性加重與FeNO相關(guān)性van der Valk RJP, Baraldi E, Stern G, Frey U, de Jongste JC. Daily exhaled nitric oxide measurements and asthma exacerbations in children. Allergy 2012; 67: 265271.FeNO與依從性的相關(guān)性Positiv

4、e correlation between adherence and reduction in FeNO levels*Adherence determined by calculating number of doses taken per day/doses prescribed x 100.Delgado-Corcoran et al. Pediatr Crit Care Med. 2004;5(1):48-52.FeNO, ppb100120Adherence,* %2003000100806040200-20Severe asthma (n=5)Moderate asthma (n

5、=17)n=41 visitsr=-0.76R2=0.56P=0.001非依從性組加強(qiáng)藥物干預(yù)后FeNO值下降更明顯Am J Respir Crit Care Med ,186:11021108,2012依從性組非依從性組47ppb21%79ppb26%Am J Respir Crit Care Med ,186, :11021108, 2012Non- Adherence group FeNO識(shí)別病人對(duì)激素的依從性病人自知FeNO水平對(duì)配合改善依從性的研究Clinical and Translational Allergy 2013, 3:37高FeNO水平的患者依從性明顯低于低、中FeNO

6、水平組的患者明確自己是處于高FeNO水平的患者配合改善依從性百分比明顯高于低、中FeNO水平的患者FeNO策略組顯著優(yōu)于對(duì)照組癥狀評(píng)分急性復(fù)發(fā)率The Journal of Allergy and Clinical Immunology, 639-648,2013FeNO以更少激素減少急性加重率Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma ：N Engl J Med 2005;352:2163-73FeNO 測(cè)定可以顯著減少I(mǎi)CS維持劑量，而不影響哮喘控制 哮喘其他控制指標(biāo)、肺功能、口

7、服激素或氣道炎癥水平（誘導(dǎo)痰嗜酸粒細(xì)胞計(jì)數(shù)）無(wú)差異。FeNO組Control組病人數(shù)（n）4648平均每日ICS用量(氟替卡松)370 g641 g 減少270g (P=0.003)急性發(fā)作頻率0.49 /人/年0.90 /人/年45.60%Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma ：N Engl J Med 2005;352:2163-73急性加重頻率-FeNO策略組優(yōu)于GINA策略組FeNO as a Marker of Airways Inflammation:The Pos

8、sible Implications in Childhood Asthma Management： Journal of Allergy Volume 2010 哮喘發(fā)作人數(shù)-FeNO策略組優(yōu)于GINA策略組FeNO as a Marker of Airways Inflammation:The Possible Implications in Childhood Asthma Management： Journal of Allergy Volume 2010 哮喘發(fā)作無(wú)哮喘發(fā)作抗炎藥物使用量FeNO組未顯著增加，而GINA策略組則顯著增加FeNO as a Marker of Airwa

9、ys Inflammation:The Possible Implications in Childhood Asthma Management： Journal of Allergy Volume 2010 FeNO StrategyControl StrategyStudyExacerbation RateTotal No. PatientsExacerbation RateTotal No. PatientsWeightRelative Rate (95% CI)Shaw 20070.33520.425122.1%0.79 (0.43, 1.44)Smith 20050.49460.94

10、88.1%0.54 (0.20, 1.46)Powell 20110.2881110.61510944.8%0.50 (0.33, 0.76)Combined0.312090.58208100.0%0.56 (0.42, 0.74)RR0.1 0.2 0.5 1.0 2 5 10Favors FeNO Favors Control惡化率降低47% Donohue, J.F. and N. Jain. Exhaled nitric oxide to predict corticosteroid responsiveness and reduce asthma exacerbation rates

11、. Respiratory Medicine, 2013. 107(7): p.943-952綜合3個(gè)研究，顯示與傳統(tǒng)臨床管理方法相比，F(xiàn)eNO指導(dǎo)的管理組哮喘急性發(fā)作率降低47%ICS劑量在FeNO管理組和對(duì)照組基本相同，或者傾向于FeNO策略組更低成人哮喘加重發(fā)生率的Meta分析FeNO較常規(guī)策略管理妊娠哮喘患者更有效降低急性發(fā)作率，減少吸入激素用量7550150Time, weeksExacerbations, nPowell et al. Lancet. 2011;378(9795):983-990.Control group (n=109)FeNO group051015202590

12、0800700600500VisitMean ICS dose, g/dControl group (n=109)FeNO group (n=111)123456P=0.043FeNO組急性發(fā)作率為28.8%，對(duì)照組急性加重率為 61.5% (P=0.011) NNT=6; 每6個(gè)基于FeNO策略治療的患者，有1名哮喘未急性發(fā)作與對(duì)照組(17%)相比，新生兒住院時(shí)間顯著減少(8%; P=0.046)更少的激素吸入量降低疾病的急性加重FeNO聯(lián)合ACQ更準(zhǔn)確判定哮喘控制2013ACQ評(píng)分一年后，F(xiàn)eNO策略組的控制水平與完全控制策略組相近激素用量FeNO策略組在三組中，無(wú)論ICS用量還是口服激素用量，都是最低的FeNO與FEV1聯(lián)合預(yù)判哮喘發(fā)作Role of Spirometry and Exhaled Nitric