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1、浅谈免疫受损宿主的肺部感染,卫生部北京医院呼吸内科 李燕明,青霉素的发现是医学史上 里程碑意义的事件,The war against infectious diseases has been win-U.S.Surgeon General 1969,TODAY每年因感染性疾病死亡的人数超过2000万TB等一些已被控制的疾病“死灰复燃”,免疫受损宿主immunocompromised hostICH,肿瘤:发病率升高与治疗进步自身免疫性和其他免疫相关性疾病器官移植突破和发展HIVAIDS流行 感染是影响ICH病程和预后的最重要因素，肺是感染的主要靶器官。,Definition of immuno
2、compromise,“A state in which the response of the host to a foreign antigen is not normal”Immunocompromise can be congenital or acquired,Basic immunology,NonspecificAnatomical barriers:纤毛运动，酶，粘膜屏障等Immunology responses:抗原递呈作用，TLRs，j巨噬细胞和白细胞的吞噬作用，分泌性IgA等Specific,a real challenge,Wide array of pathogens
3、High mortality,不同类型ICH感染存在显著差异,细胞免疫损害：细胞内病原体为主，奴卡菌、分支杆菌、军团菌，以及真菌、病毒体液免疫缺陷：Ig 缺乏或低下、补体减少、脾切除术后其肺部感染病原体主要是肺炎链球菌、流感嗜血杆菌等。,不同类型ICH感染存在显著差异,WBC500mm3:绿脓杆菌、大肠杆菌、克雷白杆菌等G-杆菌，真菌亦较常见。屏障破坏致防御机制损害：葡萄球菌、绿脓杆菌和毗邻部位的定殖菌。,Solid-organ transplantation,Ventilator-associated pneumoniaNeutropeniaOpportunistic causes of p
4、neumoniaMycobacteriaViruses(eg,CMV)FungiP.carinii,Risks from treatment of hematologic malignancies,Neutropenia from chemotherapyBacterial infections(especially Pseudomonas)and AspergillusHodgkins disease/splenectomyStreptococcus pneumoniae,H.influenzae,Treatment of graft versus host diseaseFungal,my
5、cobacterial and viral,不同类型ICH感染存在显著差异血液病,骨随移植早期（1月）:主要为败血症，细菌，IFI中期（13月）:CMV肺炎最常见，其次PCP、细菌、其它真菌感染仍有发生后期（3月）delayed CMV,其它病毒，肺部感染仍以细菌性为主，肺炎链球菌、金黄色葡萄球菌等，结核未经化疗：粒细胞白血病容易发生化脓菌感染，而淋巴瘤易罹患结核和真菌感染。接受化疗后相关性大多不复存在。,HIV infection,Pneumococcal pneumonia and tuberculosis at any CD4 countThe risk of opportunistic
6、 infections causing pneumonia rises substantially when the CD4 lymphocyte count is below 200,Etiology of pneumonia in HIV,Stratified by CD4 count500S.pneumoniae200-500S.pneumoniae,TB50-200P.carinii,TB50P.carinii,CMV,MAC,ICH肺炎特点,起病方式差别大，可隐匿，也有急骤起病，呈暴发性经过发热常为首发症状,高热常见；咳嗽发生率不高，干咳为主,ICH 肺炎特点,激素/免疫抑制剂可干扰
7、甚至掩盖临床表现肺部体征不明显X线表现与感染发展不同步病变以多叶为主,粒缺者X-ray肺部炎症可反应轻微，,ICH 肺炎特点,病情进展多迅速：感染易播散，易引起重症感染，病死率高感染病原体种类多：几乎涵盖所有致病微生物，混合感染多见，病变组织炎症反应少，病原体数量多,The diagnostic approach,What is the type of immunodeficiency?How profound is the immunosuppression?A thorough physical examination Non-invasive testsInvasive tests,免疫
8、机制受损的认定,原发性免疫防御机制缺损:儿童反复呼吸道感染常提示。青年期才出现症状容易漏诊，反复发作是其特点继发性免疫损害:多有明确基础疾病和（或）免疫抑制药物治疗史;AIDS:中青年患者的“非常感染都应检测HIV。,Need to consider:,BacteriaLegionellaNocardiaMycobacteriaVirusesFungiP.carinii,BUT,in ICH“all bets are off”multiple pathologies do coexist,Case 1,92/M，前列腺癌骨转移。去世前10天出现发热，体温3738，伴咳嗽、咯痰和呼吸困难，双肺可
9、闻及干湿性罗音。WBC 0.72109，N：91.4%，胸部X线提示双下肺斑片影，诊断为双下肺炎，给予抗菌药物治疗。,Case 1-尸检病理,霉菌性化脓性肺炎（毛霉）伴血管侵犯血栓形成，肺梗死，真菌性肉芽肿性肺炎（隐球菌），吸入性肺炎（肺泡腔可见植物细胞和横纹肌细胞），播撒性结核病，霉菌性肾脓肿，前列腺癌并脊椎、肋骨、肝、肾上腺及淋巴结转移。,Case 2,83/M，因类天疱疮长期应用强的松5 mgd-1治疗，无其它基础疾病。因发热、腹痛、腹胀5天收入院，体温达40，临床考虑麻痹性肠梗阻，治疗10天后死亡。尸检病理：胃十二指肠溃疡伴霉菌感染，腐蚀小动脉引起消化道大出血，肝脏小灶性出血、坏死，边
10、缘见霉菌；病毒性肺炎继发细菌感染，有包涵体并有透明膜形成,Bacterial infection,常见HAP细菌，耐药：绿脓、大肠、不动MRSA等肺炎链球菌：疫苗Noninvasive ventilation rather than traditional MV军团菌：更易形成空洞和胸腔积液奴卡氏菌：易发生于严重ICH中（肺、脑、皮肤或播散），肺部多形成空洞和/或脓胸，预后差。,Tuberculosis,粟粒性肺结核和播散性结核病多见MDRTBMAC-HIV/AIDS,我国，任何原因的免疫抑制患者结核病均非常常见,ICH与非ICH肺结核比较,肺外结核 播散性结核 PPD阳性率低,治疗效果差 M
11、DR 年发病率5.57.9%,The Deadly Partnership,TB and HIV Today,Viral infection,CMV,VZV,RSV,parainfluenza,influenza,Pneumonia and Death during Influenza Infection of Adults and Children with Hematological Malignancy or Organ TX*,*Adapted from“Human Influenza”,KG Nicholson,Textbook of Influenza,1998,page229-r
12、eview of literature thru 1998,PCP,1981.6月美国CDC:洛杉矶和纽约男性同性恋中出现异常高发的PCP,共同特点是患者T淋巴细胞减少和功能低下。至1983年从患者中分离出HIV，从而确定PCP是HIV/AIDS的重要相关感染,PCP-Patients at Risk,AIDS at CD4 200.Congenital and acquired defects in cellular immunity.Organ transplantation recipients.Chemotherapy.Corticosteroids.Malnutrition.Prem
13、ature birth.,Symptoms of Disease-PCP,Triad of symptomsNon-productive,dry coughBreathless-ness(dyspnea)Fever,Fujii,T.et al.Journal of Infection and Chemotherapy.2007;13:1-7,Diagnosis,Giemsa stain,Gomori methenamine Silver stain,AIDS和非AIDS的PCP比较,Empiric treatment,Difficult because of the broad differe
14、ntial diagnosisAggressive early diagnostic procedures should precede antimicrobial therapy,几个问题,如何达到治疗效果又避免不必要和盲目的联合治疗ICH：发热+肺浸润：感染，非感染如何掌握ICH感染时的糖皮质激素和免疫抑制剂的使用：短暂停用或减量非感染因素引起多需加用或加大糖皮质激素用量，鉴别非常重要,Imaging approach,The degree and type of immunosuppression may have an impact Normal chest exam and CXR
15、is possible（10%）Diffuse perihilar infiltratesPCP,CMV,LegionellaPulmonary nodulesFungi,Nocardia,mycobacteriaCavitary lesionsTB,invasive pulmonary aspergillosis,CT-pulmonary infiltratets,infection and noninfectious:hemorrhage,drug-induced lung disease,pulmonary edema,pulmonary embolism febrile pneumon
16、itis:drug-induced,acute eosinophilic pneumonia,OP,pulmonary vasculitis,Differential diagnosis of pulmonary infiltrates in ICH,感染因素Bacteria:绿脓，金葡Fungi:曲霉，毛霉，PCP，念珠菌属Viruse:CMV,VZV,RSV influenzaMycobacteria,非感染因素Pulmonary edemaProgression of underlying diseaseRadiation toxicityDrug-induced diseaseDAHB
17、OOPSecondary alveolar proteinosisTRALI(Transfusion-related acute lung injury),34/M,AML,结节，实变，磨玻璃，胸水，RSV,36/F,allogeneic bone marrow transplantation 磨玻璃和磨玻璃样结节 CMV,23/M,neutropenia following bone marrow transplantation 磨玻璃和实变Candida albicans,47/F,allogeneic bone marrow transplantationHalo sign+pleural effusionIA,25/F,neutropenia(760/mm)following bone marrow transplantation air-crescentIA,32/M,non-Hodgkins lymphoma,实变，周围磨玻璃mucormycosisna,39/M,non-Hodgkins lymphoma,磨玻璃样结节cryptococcosis,29/M,AIDS,磨玻璃，囊样变，气胸PCP,miliary tuberculosis,谢谢,
