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1、Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,淺談免疫受損宿主的肺部感染,衛(wèi)生部北京醫(yī)院呼吸內(nèi)科 李燕明,青霉素的覺察是醫(yī)學史上,里程碑意義的大事,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數(shù)超過2023萬,TB等一些已被掌握的疾病“死灰復燃”,免疫受損宿主,imm

2、unocompromised host,ICH,腫瘤:發(fā)病率上升與治療進步,自身免疫性和其他免疫相關(guān)性疾病,器官移植突破和進展,HIVAIDS流行,感染是影響ICH病程和預后的最重要因素，肺是感染的主要靶器官。,Definition of immunocompromise,“A state in which the response of the host to a foreign antigen is not normal”,Immunocompromise can be congenital or acquired,Basic immunology,Nonspecific,Anatomic

3、al barriers:纖毛運動，酶，粘膜屏障等,Immunology responses:抗原遞呈作用，TLRs，j巨噬細胞和白細胞的吞噬作用，分泌性IgA等,Specific,a real challenge,Wide array of pathogens,High mortality,不同類型,ICH感染存在顯著差異,細胞免疫損害：細胞內(nèi)病原體為主，,奴卡菌、分支桿菌、軍團菌，以及真菌、病毒,體液免疫缺陷：Ig 缺乏或低下、補體削減、脾切除術(shù)后,其肺部感染病原體主要是肺炎鏈球菌、流感嗜血桿菌等。,不同類型,ICH感染存在顯著差異,WBC500,S.pneumoniae,200-500,S

4、.pneumoniae,TB,50-200,P.carinii,TB,50,P.carinii,CMV,MAC,ICH肺炎特點,起病方式差異大，可隱匿，也有急驟起病，呈爆發(fā)性經(jīng)過,發(fā)熱常為首發(fā)病癥,高熱常見；,咳嗽發(fā)生率不高，干咳為主,ICH 肺炎特點,激素/免疫抑制劑可干擾甚至掩蓋臨床表現(xiàn),肺部體征不明顯,X線表現(xiàn)與感染進展不同步,病變以多葉為主,粒缺者X-ray肺部炎癥可反響稍微，,ICH 肺炎特點,病情進展多快速：感染易播散，易引起重癥感染，病死率高,感染病原體種類多：幾乎涵蓋全部致病微生物，混合感染多見，病變組織炎癥反響少，病原體數(shù)量多,The diagnostic approach,

5、What is the type of immunodeficiency?,How profound is the immunosuppression?,A thorough physical examination,Non-invasive tests,Invasive tests,免疫機制受損的認定,原發(fā)性免疫防范機制缺損:兒童反復呼吸道感染常提示。青年期才消失病癥簡潔漏診，反復發(fā)作是其特點,繼發(fā)性免疫損害:多有明確根底疾病和或免疫抑制藥物治療史;,AIDS:中青年患者的“特別“感染都應檢測HIV。,Need to consider:,Bacteria,Legionella,Nocardi

6、a,Mycobacteria,Viruses,Fungi,P.carinii,BUT,in ICH“all bets are off”multiple pathologies do coexist,Case 1,92/M，前列腺癌骨轉(zhuǎn)移。去世前10天消失發(fā)熱，體溫3738，伴咳嗽、咯痰和呼吸困難，雙肺可聞及干濕性羅音。WBC 0.72109，N：91.4%，胸部X線提示雙下肺斑片影，診斷為雙下肺炎，賜予抗菌藥物治療。,Case 1-尸檢病理,霉菌性化膿性肺炎毛霉伴血管侵害血栓形成，肺梗死，真菌性肉芽腫性肺炎隱球菌，吸入性肺炎肺泡腔可見植物細胞和橫紋肌細胞，播撒性結(jié)核病，霉菌性腎膿腫，前列腺癌并

7、脊椎、肋骨、肝、腎上腺及淋巴結(jié)轉(zhuǎn)移。,Case 2,83/M，因類天皰瘡長期應用強的松5 mgd-1治療，無其它根底疾病。因發(fā)熱、腹痛、腹脹5天收入院，體溫達40，臨床考慮麻痹性腸梗阻，治療10天后死亡。,尸檢病理：胃十二指腸潰瘍伴霉菌感染，腐蝕小動脈引起消化道大出血，肝臟小灶性出血、壞死，邊緣見霉菌；病毒性肺炎繼發(fā)細菌感染，有包涵體并有透亮膜形成,Bacterial infection,常見HAP細菌，耐藥：綠膿、大腸、不動MRSA等,肺炎鏈球菌：疫苗,Noninvasive ventilation rather than traditional MV,軍團菌：更易形成空洞和胸腔積液,奴卡氏

8、菌：易發(fā)生于嚴峻ICH中肺、腦、皮膚或播散，肺部多形成空洞和/或膿胸，預后差。,Tuberculosis,粟粒性肺結(jié)核和播散性結(jié)核病多見,MDRTB,MAC-HIV/AIDS,我國，任何緣由的免疫抑制患者結(jié)核病均特別常見,ICH與非ICH肺結(jié)核比較,特點,ICH,Non-ICH,病灶分布,肺葉分布差異不明顯,多上葉尖后段下葉背段,形態(tài)學,多缺乏多形特點，常呈均一一致的片狀浸潤影,多形態(tài),肺內(nèi)播散,多見,少見,肺外播散,較多見,少見,空洞,少見,多見,胸腔積液,常見,少見,肺外結(jié)核,播散性結(jié)核,PPD,陽性率低,治療效果差,MDR,年發(fā)病率,5.57.9%,The Deadly Partners

9、hip,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*,PNEUMONIA,(%),DEATHS,(%),Adults,Children,Adults,Children,Solid Organ TX,14/25,7/18,2/25,3/18,Hematolog.Malignancy,

10、24/35,1/3,11/35,1/3,TOTAL,38/60(63%),8/21 (38%),13/60 (22%),4/21(19%),*Adapted from“Human Influenza”,KG Nicholson,Textbook of Influenza,1998,page229-review of literature thru 1998,PCP,1981.6月美國CDC:洛杉磯和紐約男性同性戀中消失特別高發(fā)的PCP,共同特點是患者T淋巴細胞削減和功能低下。至1983年從患者中分別出HIV，從而確定PCP是HIV/AIDS的重要相關(guān)感染,PCP-Patients at Ris

11、k,AIDS at CD4 200.,Congenital and acquired defects in cellular immunity.,Organ transplantation recipients.,Chemotherapy.,Corticosteroids.,Malnutrition.,Premature birth.,Symptoms of Disease-PCP,Triad of symptoms,Non-productive,dry cough,Breathless-ness(dyspnea),Fever,Fujii,T.et al.Journal of Infectio

12、n and Chemotherapy.2023;13:1-7,Diagnosis,Giemsa stain,Gomori methenamine Silver stain,AIDS和非AIDS的PCP比較,臨床表現(xiàn),非,AIDS,AIDS,呼吸困難,常見,常見,咳嗽,常見,常見,進展速度,快（,7-12d),漸進（,2-5w）,低氧血癥,嚴重,不嚴重,胸片,雙肺彌漫性間質(zhì)浸潤,不對稱或雙側(cè)間質(zhì)浸潤,治療反應,快（,3-5d）,慢（,5-9d）,復發(fā),少見,常見,對再次治療反應,好,肺損傷,治療副作用,通常較輕,常見，可嚴重,Empiric treatment,Difficult because

13、 of the broad differential diagnosis,Aggressive early diagnostic procedures should precede antimicrobial therapy,幾個問題,如何到達治療效果又避開不必要和盲目的聯(lián)合治療,ICH：發(fā)熱+肺浸潤：感染，非感染,如何把握ICH感染時的糖皮質(zhì)激素和免疫抑制劑的使用：短暫停用或減量,非感染因素引起多需加用或加大糖皮質(zhì)激素用量，鑒別特別重要,Imaging approach,The degree and type of immunosuppression may have an impact,N

14、ormal chest exam and CXR is possible10%,Diffuse perihilar infiltrates,PCP,CMV,Legionella,Pulmonary nodules,Fungi,Nocardia,mycobacteria,Cavitary lesions,TB,invasive pulmonary aspergillosis,CT-pulmonary infiltratets,infection and noninfectious:hemorrhage,drug-induced lung disease,pulmonary edema,pulmo

15、nary embolism,febrile pneumonitis:drug-induced,acute eosinophilic pneumonia,OP,pulmonary vasculitis,Differential diagnosis of pulmonary infiltrates in ICH,感染因素,Bacteria:綠膿，金葡,Fungi:曲霉，毛霉，PCP，念珠菌屬,Viruse:CMV,VZV,RSV influenza,Mycobacteria,非感染因素,Pulmonary edema,Progression of underlying disease,Radiat

16、ion toxicity,Drug-induced disease,DAH,BOOP,Secondary alveolar proteinosis,TRALI(Transfusion-related acute lung injury),34/M,AML,結(jié)節(jié)，實變，磨玻璃，胸水，,RSV,36/F,allogeneic bone marrow transplantation,磨玻璃和磨玻璃樣結(jié)節(jié),CMV,23/M,neutropenia following bone marrow transplantation,磨玻璃和實變,Candida albicans,47/F,allogeneic bone marrow transplantation,Halo sign+pleural effusion,IA,25/F,neutropenia(760/mm)following bone marrow transplantation,air-crescent,IA,32/M,non-Hodgkins lymphoma,實變，四周磨玻璃,mucormycosisna,39/M,non-Hodg