1、在临床实践中学习和认识肺曲霉病的临床多样性讨论1根据肺部CT，您最可能(单选)给出的影像学诊断是1、双肺炎症2、间质性肺疾病3、病毒性肺炎4、外源性过敏性肺泡炎(EAA)5、嗜酸细胞性肺炎(EP)6、隐源性机化性肺炎(COP)7、肺血管炎8、肺曲霉病1月5日（发病8天）1月12日（发病15天）n痰培养及血培养(二次)均未见致病菌生长n痰涂片查菌：G、G球菌口咽部正常菌群n痰查抗酸杆菌：阴性、需要重复n支原体抗体:1:80(+)-不能确定、治疗中复查n军团菌抗体:阴性治疗中复查n结明试验（）：-不能除外假阳性可能治疗方案 莫西沙星（拜复乐）400mg Qd 静滴哌拉西林/他唑巴坦(特治星)4.5
2、 Q8h 静滴覆盖不能绝对除外耐药的G-细菌双鼻导管吸氧(2Lmin)同时给予安噻吗、安溴索等对症治疗 讨论2根据肺部CT，您最可能(单选)给出的影像学诊断是1、支扩并感染2、金葡菌肺炎3、肺结核病4、军团菌病5、肺曲霉病支扩并感染金葡菌肺炎肺结核病军团菌病肺炎(空腔罕见)肺曲霉病讨论3结合临床，您最可能(单选)给出的影像学诊断是1、支扩并感染2、金葡菌肺炎3、肺结核病4、军团菌病5、肺曲霉病n既往健康n起病以气短、干咳为首发症状，一周后出现发热，大量粘液痰，后期出现棕色痰n双肺多发病灶，呈进行性加重伴空洞形成n经验性系统抗感染治疗无效气短、干咳、支气管痉挛变应原？发热、坏死性肺炎侵袭性病原体
3、即可作为 变应原又可作为 侵袭性病原体？真菌/曲霉？讨论4关于患者最后诊断，您的意见是痰涂片标本Aspergillus fumigatusAspergillus nigerKOH-calcofluor mount showing septate Aspergillus hyphaeImmune dysfunctionFrequency of aspergillosisImmune hyperactivityFrequency of aspergillosisAcute IASubacute IAAspergillomaChronic pulmonaryABPASevere asthma wit
4、h fungal sensitisationAllergic sinusitisDegree of immunocompromiseRisk of acquisition(and pace of progression)Normal immunity,high inoculumHIV infectionChronic leukaemiaShort course glucocorticoidsAcute respiratory infection,ie influenzaTemporary neutropeniaLong term glucocorticoids etcSolid organ t
5、ransplant+rejection+CMVAIDSLeukemia and profound neutropeniaAllogeneic stem cell transplant+GVHDRelapsed/uncontrolled leukemia5%10%15%20%25%Medical ICU,COPD+sepsis起病-急性、亚急性、慢性发热-无发热、低热、中等度热、高热咳嗽和咳痰-刺激性干咳、白粘痰、黄粘痰、黄褐色粘痰咯血-无、小量、大量支气管痉挛 -严重-免疫功能正常或增高宿主 -轻中度-免疫功能一般低下 -无支气管痉挛-免疫功能严重低下呼吸衰竭 -无-免疫缺陷、严重-免疫正常和
6、增高Exposure of the lung by Aspergillus 免疫缺陷 -严重 severe immuno-compromised侵袭性曲霉病 /可以是社区获得 Invasive aspergillosis /community acquired infection 免疫缺陷 -轻中度严重mild to moderate immunocompromised慢性空腔性 肺曲霉病 +/-曲菌球Chronic cavitary pulmonary aspergillosis+/-fungal ball ABPAEAABronchial asthma with aspergillus s
7、ensitizationSimple(single)aspergillomaPatient RKHaempotysis,nil else Positive Aspergillus antibodies in bloodLobectomySimple(single)aspergillomaPatient NMPositive Aspergillus antibodies in bloodLobectomyAugust 2006 May 2009Community acquired New cough pneumonia requiring ICU care 4 years laterBilate
8、ral pulmonary cavities in the upper lungs surrounded by circumferential pleural thickening and containing aspergillomasExposure of the lung by Aspergillus 免疫缺陷 -严重 severe immuno-compromised侵袭性曲霉病 /可以是社区获得 Invasive aspergillosis /community acquired infection 免疫缺陷 -轻中度严重mild to moderate immunocompromi
9、sed慢性空腔性 肺曲霉病 +/-曲菌球Chronic cavitary pulmonary aspergillosis+/-fungal ball ABPAEAABronchial asthma with aspergillus sensitization Common HRCT Patterns:Centrilobular Nodules 小叶中心性结节Ground-Glass 磨玻璃影Consolidation 实变Air Trapping 气体陷闭Fibrosis 纤维化Patel RA et al.Journal of Computer Assisted Tomography;24(
10、6):965-970Tubular Opacities(Mucoid Impaction)AtelectasisLucency(air trapping)Gotway MB et al.Journal of Computer Assisted Tomography;26(2):159-173Exposure of the lung by Aspergillus 免疫缺陷 -严重 severe immuno-compromised侵袭性曲霉病 /可以是社区获得 Invasive aspergillosis /community acquired infection 免疫缺陷 -轻中度严重mild
11、 to moderate immunocompromised慢性空腔性 肺曲霉病 +/-曲菌球Chronic cavitary pulmonary aspergillosis+/-fungal ball ABPAEAABronchial asthma with aspergillus sensitization气道侵袭性病变 (airway invasive disease)气腔侵袭性病变 (airspace invasive disease血管侵袭性病变 (angioinvasive disease)Tait,Thorax 1993;48:1285Wheezing 4 days before
12、 death,immunocompromisedPseudomembranous Aspergillus tracheobronchitis with IPA in COPDBulpa Eur Resp J 2007;30:782Invasive bronchiolar aspergillosis in a patient undergone bone marrow transplantation.-Thin-section CT shows peripheral branching structures associated with focal areas of consolidation
13、 -can also be seen in Bronchopneumonia aspergillosis,(a)Conventional CT scan through the upper lungs shows a segmental area of consolidation in the right upper lobe with visible air bronchogram.(b)Photograph of the corresponding autopsy specimen shows segmental consolidation(c)High-power photomicrog
14、raph of a small area of consolidation shows tissue necrosis.Scattered Aspergillus organisms can be identified in the necrotic tissue(arrows).白血病并发侵袭性曲菌病AIDS病人急性侵袭性曲菌异体BMT病人急性侵袭性曲菌病细菌性肺炎 单一形态(时相均一)叶段分布 腺泡结节 空气支气管征 坏死(液-气平)收缩不明显曲霉菌肺炎 多发病灶/多种征象 肿块伴晕影 大片坏死 空气新月征 组织中小气泡影Pulmonary InfarctInvasive pulmonar
15、y aspergillosisIPAIPA occurs in 7%of acute leukaemia patients,10-15%allogeneic BMT patientsHerbrecht,Denning et al,NEJM 2002;347:408-15.Halo signPresentationDuring TreatmentKo JP et al.Journal of Thoracic Imaging;17(1):70-73内眼炎皮肤损害急性侵袭性曲霉病的肺外表现Exposure of the lung by Aspergillus 免疫缺陷 -严重 severe immu
16、no-compromised侵袭性曲霉病 /可以是社区获得 Invasive aspergillosis /community acquired infection 免疫缺陷 -轻中度严重mild to moderate immunocompromised慢性空腔性 肺曲霉病 +/-曲菌球Chronic cavitary pulmonary aspergillosis+/-fungal ball ABPAEAABronchial asthma with aspergillus sensitization双侧慢性浸润伴钙化提示既往结核病(箭).上叶浸润明显进展双侧肺实质实变慢性(半侵袭性)肺曲菌
17、病Chronic semi-invasive pulmonary aspergillosis慢性半侵袭性曲菌病曲菌病所致慢性肉芽肿性病变左上叶圆形实变伴有空腔慢性半侵袭性（坏死性）肺曲菌病Chronic invasive pulmonary aspergillosisGotway MB et al.Journal of Computer Assisted Tomography;26(2):159-173肺曲霉病所致空洞慢性半侵袭性（坏死性）肺曲菌病Chronic invasive pulmonary aspergillosisExposure of the lung by Aspergillu
18、s Acute IAChronic cavitary pulmonary aspergillosis+/-fungal ballChronic fibrosing pulmonary aspergillosis+/-fungal ball AllergyABPAEAAOVERLAP syndrome12344Eur Respir Rev 2011;20:121,156174No diseaseCultures/AntigenSigns andsymptoms Cultures/histopathologySequelaeProphylaxisPreemptiveEmpiricalCrude M
19、ortality60-90%Disease burdenTreatmentMorbidity/MortalityBeta-glucan/GM/PCR test?Fever-drivenDiagnostic-driven急性侵袭性/变应性/重叠综合症 -出现呼吸衰竭和/或迁徙病灶/危及生命 -可以综合考虑予以经验性治疗亚急性/慢性曲霉病应力争目标治疗 -鉴别诊断包括：结核病、奴卡菌病 -完全不同的治疗方案.7-10 daysNodular Lesion with Halo Sign(N=143)Nodular Lesion without Halo Sign(N=143)Greene R,et
20、al.ECCMID.2003.52.4%62.3%40.9%29.1%41.5%15.8%All treatedVoriconazoleAmphotericin BCure%Aspergillosis:obtaining a diagnosisFine Fine needle needle biopsybiopsySputumSputumBroncho-Broncho-alveolar alveolar lavagelavageSurgical Surgical biopsybiopsyCT scanCT scanGalacto-Galacto-mannan,mannan,glucan,glu
21、can,PCRPCRGalactoGalactomannan,mannan,glucan,glucan,PCRPCRWalsh TJ,et al.Clin Infect Dis 2008;46:32760.Maertens J et al.Bone Marrow Transplantation 2011;46:70918Bohme A et al.Ann Hematol 2009;88:97110Thursky KA,et al.Intern Med J 2008;38:496520.Airways/nasal exposure to airborne Aspergillus Acute(3
22、months)Aspergilloma（Saprophytic Aspergillosis）Chronic cavitary(necrotizing)pulmonary -semi-invasive Chronic fibrosing pulmonary aspergillosis Chronic invasive sinusitis Maxillary(sinus)aspergilloma Allergic Allergic bronchopulmonary(ABPA)急性起病、反复发作 Extrinsic allergic alveolitis(EAA)急性亚急性慢性 Asthma wit
23、h fungal sensitisation 反复发作 Allergic Aspergillus sinusitis Immune statusImmune dysfunctionFrequency of aspergillosisImmune hyperactivityFrequency of aspergillosisAcute IASubacute IAAspergillomaChronic pulmonaryABPASevere asthma with fungal sensitisationAllergic sinusitis不同个体表现不同Immune dysfunctionFrequency of aspergillosisImmune hyperactivityFrequency of aspergillosisInvasive aspergillosisChronic pulmonaryAllergic aspergillosis.同一个体随着免疫状态不同而呈现不同表现
