1、季节性流感、新甲型H1N1流感与禽流感的临床特征与对策,Dept of Respiratory&Critical Care Medicine PEKING UNIVERSITY PEOPLES HOSPITAL,内容,概述临床特征应对策略,一、概述,甲流感病毒类型：季节性流感（SI）、新甲型流感（NI）和禽流感（AI）基因特点：基因漂移和转变均可能衍生为新型流感大流行SI&NI感染受体：-2,6-糖苷唾液酸AI感染受体：-2,3-糖苷唾液酸,influenza V,Host cell with Virus attachment,NI和AI（H5）现状,H5:大陆首例2005.10.27，40例
2、,病死率65%(26/40);WHO1997HK,2003年后高发,病死率58.5%(330/564)H1:,WHO SI-NI-AI-BI现状,WHO SI-NI现状,二、临床特征,上呼吸道鼻、咽、喉下呼吸道肺炎，包括SARI（严重急性呼吸感染综合症）细支气管炎严重肺病和全身表现ARDSMODS 严重性：AINISI,南京医科大学鼓楼医院蔡后荣教授提供,H5N1infection,诊断,流行病学暴露史临床ILI症状危重症病例肺炎/ALI/ARDS/MODS实验室诊断RT-PCR/病毒分离/双份血清,三、应对策略,治疗：对症：药物、氧疗（鼻面罩、无创、有创、ECMO）抗病毒：神经氨酸酶抑制剂、
3、阿比多尔等特异性治疗：恢复期血浆/免疫血浆辅助：激素？他汀类药物等感控：做好个人防护预防：疫苗接种,抗病毒治疗,神经氨酸酶抑制剂M2通道阻滞剂广谱抗病毒,抗RNA病毒,Moscona A.Neuraminidase Inhibitors for Influenza.NEJM 2005;353:1363-73.,神经氨酸酶抑制剂,奥司他韦扎那米韦（10mg BID 吸入；600mg bid静脉；由于是乳糖悬液，不能给予呼吸机雾化治疗）帕拉米韦（peramivir，iv 600mg/d x 5-10)Laninamivir(20mg/40mg 长效）,达菲治疗可降低抗生素治疗下呼吸道感染的比率,J
4、efferson T,et al.Neuraminidase inhibitors for preventing and treating influenza in healthy adults:systematic review and meta-analysis.BMJ 2009;339:b5106,抗病毒治疗,M2通道阻滞剂：抑制病毒在胞内包装成病毒颗粒金刚烷胺金刚乙胺,广谱抗病毒,利巴韦林,机制磷酸化产物为病毒合成酶的竞争性抑制剂抑制肌苷单磷酸脱氢酶流感病毒RNA聚合酶mRNA鸟苷转移酶抑制病毒RNA和蛋白质合成广谱抗RNA病毒，其主要作用于抗HCV感染，对流感病毒等作用均有限,阿比多
5、尔（arbidol）,抗病毒机制主要是增加流感病毒HA构象转换的稳定性抑制病毒外壳HA与与宿主细胞膜的融合作用阻断流感病毒的复制穿入细胞核直接抑制病毒RNA和DNA的合成调节免疫和诱导干扰素表达，增加抗病毒效果广谱抗病毒：流感病毒、呼吸道合胞病毒、鼻病毒、柯萨奇病毒、腺病毒，其抗RNA病毒的作用较抗DNA病毒的作用更有效剂量：200mg/d,5-10d,Arbidol:a broad-spectrum antiviral compound that blocks viral fusion.,Boriskin YS,et al.Curr Med Chem 2008;15(10):997-1005
6、.,恢复期血浆/免疫血浆治疗,我国2例接受免疫血浆，2接受恢复期血浆，均存活,This was a 31 years old man with H5 infection.He developed to ARDS also,and was administrated with invasive mechanical ventilation,but his clinical situation was still unstable.On day 13 and 14 after onset of illness,he was administrated with 3 units of convale
7、scent plasma.,Ann Intern Med.2006;145:599-609.,与对照组相比，恢复期血浆治疗对1919H1N1死亡率影响,早期和晚期恢复期血浆治疗对1919H1N1死亡率的影响,Ann Intern Med.2006;145:599-609.,辅助治疗探求新方法,激素辅助治疗的利与弊,我国重症和危重症H1患者的管理,25篇文献406例，男208（51.2%），孕妇44（10.8%）年龄:3M-72Y治疗达菲401（98.8%）：75mgBid x 5；150mg Bid x 10激素306（75.4%）：40-500mg/d,3-10d or moreIVIG,小
8、儿病例,1g/kg.d x 2恢复期血浆8（2%），7例治愈机械通气：无创41（10.1%），有创79（19.5%）ECMO：5例，2例存活Outcome:治愈363（89.4%），病死43（10.6%）,我国H5病例的临床管理,37 cases，F 21(56.8%），pregnant 4（10.8%）Age:2Y-62YManagement Oseltamivir 17（45.9%）：75mgBid x 5Corticosteroids 36（97.3%）：20-1000mg/d,3-10d or moreIVIG 21（56.8%）3-25g/d,1-44dConvalescent/va
9、ccinated plasma 4（10.8%），all recoveredMechanical ventilation：NIPPV 18（48.6%），IPPV 29(78.4%)Outcome:recovered 13（35.1%），died 24（64.9%）,Am J Respir Crit Care Med Vol 183.pp 12001206,2011,40%,83例2009H1N1感染所致ARDS患者激素使用状况,Am J Respir Crit Care Med Vol 183.pp 12001206,2011,83例2009H1N1感染所致ARDS患者激素使用状况,Am J
10、 Respir Crit Care Med Vol 183.pp 12001206,2011,结论,no evidence of a beneficial effect of corticosteroids in patients with ARDS secondary to influenza pneumonia,but suggests that very early(3d)corticosteroid therapy may be harmful.,28家医院ICU in South Korea from 2009.09-2010.02A total of 245 patients,10
11、7(44%)received adjuvant steroid treatment90-day mortality rate of patients given steroids(58%,62 of 107)was significantly higher than that of those not given steroids(27%,37 of 138)(P,0.001).,Am J Respir Crit Care Med Vol 183.pp 12071214,2011,结论,Adjuvant corticosteroids were significantly associated
12、 with higher mortality in critically ill patients with pH1N1 infection.,免疫调节剂,他汀类 HMG-CoA（羟甲基戊二酰辅酶A）inhibitors-HDL cholesterol and prevent cardiovascular and cerebrovascular disease-anti-inflammatory(pleiotropic)effects贝特类 PPAR agonists(过氧化物酶体增生物激活受体)-regulate lipid metabolism,fatty acid oxidation-a
13、nti-inflammatory and immunomodulatory effects格列酮类 PPAR agonists-increase sensitivity to insulin-anti-inflammatory and immunomodulatory effects,炎性分子间的相互作用,Ac-CoA,HMG-CoA,Mevalonate甲羟戊酸,Farnesyl-PP,Statin,SREBP-2,Cholesterol,LDLR,LDL-C,Normolipidemic effect(liver),Pleiotropic effects(vascular wall),TG
14、,HDL-C,IL6 iNOS,TNF-MCP-1,L-FABP,ApoA1,PPAR,PPAR,15d-PGJ2,COX-2,MARK,PKC,Geranylated proteinsRhoA,Cdc42,Rac,Geranylgeranyl-PP二牛龙牛儿基-胰多肽,HMG-CoA 羟甲基戊二酰辅酶APPAR 过氧化物酶体增生物激活受体MARK 微管亲和性调节激酶FABP 脂肪酸结合蛋白,固醇调节元件结合蛋白,38,实验性急性肺损伤以及Statins&PPAR激动剂的作用,HO-1:heme oxygenase-1 血红素加氧酶-1,39,流感免疫发病机制以及Statins&PPAR激动剂
15、的作用,La Gruta NL,et al.Immunol Cell Biol 2007;85:85-92.,STATINs临床应用,Brett SJ,et al.Pre-admission statin use and in-hospital severity of 2009 pandemic influenza A(H1N1)disease.PloS ONE 2011;6(4):e18120Frost FJ,et al.Influenza and COPD mortality protection as pleitropic,dose-dependent effects of statin
16、s.Chest 2007;131:1006-12.Kwong JC,et al.Influenza morbidity and mortality in elderly patients receiving statins:a cohort study.PloS ONE 2009;4(11):e8087,肺炎时短期Statins治疗对死亡率的影响,1995-2006：9073例肺炎，年龄4090Y，1398例statin治疗,Douglas I,et al.BMJ 2011;342:d1642,烷胺类药物,对新H1N1耐药，国外H5N1耐药国内H5N1尚有效,预防,WHO SI-NI现状,预防
17、Vaccine Strains for the 201112 Influenza Season,201112 U.S.季节流感疫苗病毒株与2010-11相同A/California/7/2009(H1N1)-like antigensA/Perth/16/2009(H3N2)-like antigensB/Brisbane/60/2008-like antigens新A(H1N1)疫苗病毒株来源于2009流感大流行病毒株,6M-8Y流感疫苗剂量,儿童是否接种过1次以上疫苗,第二次加强疫苗至少在4W以后接种,接种1次疫苗,是,不是,展望,有效抗病毒药物的使用有限，尤其是缺乏静脉抗病毒药物和早期干预治疗特异性抗病毒药物的种类有限危重症病例的抢救仍以对症支持为主免疫疫苗接种仍然是避免大规模流行的有效预防手段,THANK YOU FOR YOUR ATTENTION,
