1、慢性肺曲霉病的诊断与管理,江西省人民医院呼吸内科 童波,目录,慢性肺曲霉病的定义,慢性肺曲霉病的临床表现类型,慢性肺曲霉病的诊断,慢性肺曲霉病的管理,总结,目录,慢性肺曲霉病的定义,慢性肺曲霉病的临床表现类型,慢性肺曲霉病的诊断,慢性肺曲霉病的管理,总结,Definitions of CPA,The most common form of CPA is CCPA. Untreated it may progress to chronic fibrosing pulmonary aspergillosis (CFPA). Less common manifestations of CPA inc
2、lude Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (3 month
3、s) usually found in moderately immunocompromised patients.,D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eur Respir J 2015.,目录,慢性肺曲霉病的定义,慢性肺曲霉病的临床表现类型,慢性肺曲霉病的诊断,慢性肺曲霉病的管理,总结,Present by David Denning,ECCMID 10th May 2015 in Barcelona,慢性曲霉菌病临床表现分类Clinical phenotypes of chronic Aspergillus spp diseases,单发曲霉
4、球Single/simple aspergilloma,慢性坏死性/亚急性肺曲霉菌病Chronic necrotizing pulmonaryaspergillosis (CNPA) or subacuteInvasive aspergillosis (SAI),慢性空腔性肺曲霉菌病Chronic cavitary pulmonaryaspergillosis (CCPA),慢性纤维化肺曲霉菌病Chronic fibrosingpulmonary aspergillosis (CFPA),曲霉菌肉芽肿Aspergillus nodule(s),CCPA是最常见的CPA类型CCPA不治疗可进展为
5、CFPA曲霉结节与单纯性曲霉肿较少见免疫功能受损患者常见SAIA,CPA的分类与定义,CCPA-慢性空洞型肺曲霉病; CFPA-慢性纤维性肺曲霉病; SAIA-亚急性侵袭性曲霉病/慢性坏死性/半侵袭性曲霉病,D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eur Respir J 2015.,Single (simple) pulmonary aspergilloma is a single fungal ball in a single pulmonary cavity. There is no progression over months of obse
6、rvation and very few, if any pulmonary or systemic symptoms and serological or microbiological evidence implicating Aspergillus spp.,Simple aspergilloma that developed within a post-tuberculous cicatricial atelectasis of the left upper lobe with saccular bronchiectasis. Surgical resection by video-a
7、ssisted thoracic surgery was performed because of recurrent haemoptysis and a requirement for anticoagulant therapy.,D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eur Respir J 2015.,CCPA, formerly called complex aspergilloma, usually shows multiple cavities, which may or may not contain an aspergilloma ,
8、 in association with pulmonary and systemic symptoms and raised inflammatory markers, over at least 3 months of observation. Untreated, over years, these cavities enlarge and coalesce, developing pericavitary infiltrates or perforating into the pleura, and an aspergilloma may appear or disappear. Th
9、us serological or microbiological evidence implicating Aspergillus spp. is required for diagnosis.,Chronic cavitary pulmonary aspergillosis showing marked progression between a) 2007 and b) 2012. Chest radiographs prior to 2007 (i.e. 1990s) showed “upper lobe fibrosis”, without a firm diagnosis.,A l
10、arge cavity with pleural thickening is visible on the left in both images, with additional small cavities inferiorly in 2012, and contraction of the left upper lobe. The right side shows interval development of a large cavity, with some pleural thickening. Neither cavity contains a fungal ball.,a),b
11、),Imaging showing chronic cavitary pulmonary aspergillosis showing an axial view with a) lung and b) mediastinal windows at the level of the right upper lobe. Multiple cavities are visible with a fungus ball lying within the largest one. The wall of the cavities cannot be distinguished from the thic
12、kened pleura or the neighbouring alveolar consolidation. The extra pleural fat is hyperattenuated (white arrows). *: the dilated oesophagus should not be confused with a cavity.,a),b),*,*,CFPA is often an end result from untreated CCPA. Extensive fibrosis with fibrotic destruction of at least two lo
13、bes of lung complicating CCPA, leading to a major loss of lung function. Usually the fibrosis is solid in appearance, but large or small cavities with surrounding fibrosis may be seen. Serological or microbiological evidence implicating Aspergillus spp. is required for diagnosis. One or more aspergi
14、llomas may be present.,Imaging of chronic fibrosing pulmonary aspergillosis complicating chronic cavitary pulmonary aspergillosis, which followed tuberculosis, with mild chronic obstructive pulmonary disease. Complete opacification of the left hemi-thorax developed between February 1998, when a left
15、 upper lobe cavity with a fluid level was present, and May 1999. Multiple left lung autopsy percutaneous biopsies showed evidence of chronic inflammation, but no granulomas or fungal hyphae.,One or more nodules (3 cm), which do not usually cavitate, are an unusual form of CPA . They may mimic carcin
16、oma of the lung, metastases, cryptococcal nodule, coccidioidomycosis or other rare pathogens and can only be definitively diagnosed on histology. Nodules in patients with rheumatoid arthritis may be pure rheumatoid nodules or contain Aspergillus. Tissue invasion is not demonstrated, although necrosi
17、s is frequent. Sometimes lesions larger than 3 cm in diameter are seen and may have a necrotic centre. These are not well described in the literature and are best described as “mass lesions caused by Aspergillus spp.”.,Successive axial views within the lung window showing Aspergillus nodules, of var
18、iable size and borders, and a fungus ball filling a cavity with a wall of variable thickness in a patient with pre-existing bronchiectasis and cicatricial atelectasis of the middle lobe.,Aspergillus nodule(s),Subacute invasive aspergillosis (SAIA) was previously termed chronic necrotising or semi-in
19、vasive pulmonary aspergillosis. SAIA occurs in mildly immunocompromised or very debilitated patients and has similar clinical and radiological features to CCPA but is more rapid in progression. SAIA typically occurs in patients with diabetes mellitus, malnutrition, alcoholism, advanced age, prolonge
20、d corticosteroid administration or other modest immunocompromising agents, chronic obstructive lung disease, connective tissue disorders, radiation therapy, non-tuberculous mycobacterial (NTM) infection or HIV infection. Patients are more likely to have detectable Aspergillus antigen in blood, and w
21、ill show hyphae invading lung parenchyma, if a biopsy is done.,The chest radiograph shows a large irregular right upper-lobe cavitary lesion that developed with multiple symptoms over 6 weeks during treatment with sorafenib. The patient presented with unresectable hepatocellular carcinoma.,The compu
22、ted tomography scan shows a dual cavity with moderately thick walls, an external irregular edge and some material within the cavity on an almost normal lung background.,a patient with hepatocellular carcinoma being treated with the sorafenib.,a),b),The new clinical disease entity of chronic progress
23、ive pulmonary aspergillosis. New nomenclature, “chronicprogressive pulmonary aspergillosis (CPPA) ” for the clinical syndrome including both CNPA and CCPA is proposed. It is difficult to distinguish between these two entities based on the clinical course and characteristics and radiological findings
24、.,respiratory investigation 54 (2016) 8591.,目录,慢性肺曲霉病的定义,慢性肺曲霉病的临床表现类型,慢性肺曲霉病的诊断,慢性肺曲霉病的管理,总结,CPA: diagnosis criteria and definitions,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162174,Methods for diagnosing CPA,TTNA: Transthoracic needle aspiration; 1:
25、 Confirmatory studies are needed; 2: In forms of CNPA with a semi-invasive nature, the antigen can sometimes be positive for GM .,Respiration 2014;88:162174,Frequency of underlying condition in CPA,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162174,SAFS
26、: Severe asthma with fungal sensitisation.1: Community-acquired pneumonia requiring hospitalisation.,慢性肺曲霉菌病-抗体检测Aspergillus antibody diagnosis of CPA,Present by David Denning,ECCMID 10th May 2015 in Barcelona,患者人群Population,目的Intention,干预手段Intervention,SoR,QoE,文献Reference,备注Comment,在非免疫抑制患者中伴有空腔/结节
27、肺浸润,Cavitary or nodularpulmonary infiltrate in Non-immunocompromised patients,诊断或排除慢性肺曲霉菌病,DiagnosisOrexclusionof CPA,曲霉抗体IgG,Aspergillus IgG antibody,Aspergillus IgM antibody,Aspergillus IgA antibody,Aspergillus IgE antibody,A,A,D,D,B,II,II,III,III,II,Guitard, 2012;Baxter, 2012; VanToorenenbergen,2
28、012,BTS,1970;Uffredi, 2003;Kitasato, 2009;Ohba, 2012;Baxter, 2012,Schonheyder1987; Nimomiya,1990;,Denning, 2003;Agarwal, 2012,IgG和曲霉沉淀素的标准建立尚未完成,哮喘/变态反应性肺曲霉菌病（ABPA）/囊性纤维化(CF),Asthma/ABPA/CF,Aspergillus precipitins,曲霉沉淀素,曲霉抗体IgM,曲霉抗体IgA,曲霉抗体IgE,Brouwer, 1988;,多数室内测试尚未应用，主要原因是不确定的敏感性,曲霉肉芽肿的敏感性尚不确定,目录,
29、慢性肺曲霉病的定义,慢性肺曲霉病的临床表现类型,慢性肺曲霉病的诊断,慢性肺曲霉病的管理,总结,Proposed management of chronic pulmonary aspergillosis in Japan,respiratory investigation 54 (2016) 8591.,Proposal for a global therapeutic strategy algorithm of CPA. ITCZ = Itraconazole;L-AMB = liposomal amphotericinB; POSA = posaconazole; SA = simple
30、aspergilloma; VRCZ = voriconazole.,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162174,Responses (clinical improvement and/or complete response) to systemic antifungal treatments: main clinical studies,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162174,Values are n (%),a: Micafugin; b: voriconazole.,续前表,case 1,case 1,case 2,case 2,case 3,曲霉结节,总结,人群中CPA有一定的发病率要重视CPA的识别、诊断与管理,谢 谢 指导,2016年09月21日科室学习,
