慢性肺曲霉病的診斷與管理

1、慢性肺曲霉病的診斷與管理,江西省人民醫(yī)院呼吸內(nèi)科 童波,目錄,慢性肺曲霉病的定義,慢性肺曲霉病的臨床表現(xiàn)類型,慢性肺曲霉病的診斷,慢性肺曲霉病的管理,總結(jié),目錄,慢性肺曲霉病的定義,慢性肺曲霉病的臨床表現(xiàn)類型,慢性肺曲霉病的診斷,慢性肺曲霉病的管理,總結(jié),Definitions of CPA,The most common form of CPA is CCPA. Untreated it may progress to chroni

2、c fibrosing pulmonary aspergillosis (CFPA). Less common manifestations of CPA include Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung

3、disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patien

4、ts.,D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eur Respir J 2015.,目錄,慢性肺曲霉病的定義,慢性肺曲霉病的臨床表現(xiàn)類型,慢性肺曲霉病的診斷,慢性肺曲霉病的管理,總結(jié),Present by David Denning,ECCMID 10th May 2015 in Barcelona,慢性曲霉菌病臨床表現(xiàn)分類Clinical phenotypes of chronic Asp

5、ergillus spp diseases,單發(fā)曲霉球Single/simple aspergilloma,慢性壞死性/亞急性肺曲霉菌病Chronic necrotizing pulmonaryaspergillosis (CNPA) or subacuteInvasive aspergillosis (SAI),慢性空腔性肺曲霉菌病Chronic cavitary pulmonaryaspergillosis (CCPA)

6、,慢性纖維化肺曲霉菌病Chronic fibrosingpulmonary aspergillosis (CFPA),曲霉菌肉芽腫Aspergillus nodule(s),CCPA是最常見的CPA類型CCPA不治療可進(jìn)展為CFPA曲霉結(jié)節(jié)與單純性曲霉腫較少見免疫功能受損患者常見SAIA,,CPA的分類與定義,CCPA-慢性空洞型肺曲霉病; CFPA-慢性纖維性肺曲霉病; SAIA-亞急性侵襲性曲霉病/慢性壞死性/半侵襲性

7、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 observation and very few

8、, 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

9、 with saccular bronchiectasis. Surgical resection by video-assisted thoracic surgery was performed because of recurrent haemoptysis and a requirement for anticoagulant therapy.,D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eu

10、r Respir J 2015.,CCPA, formerly called complex aspergilloma, usually shows multiple cavities, which may or may not contain an aspergilloma , in association with pulmonary and systemic symptoms and raised inflammatory mar

11、kers, 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

12、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

13、to 2007 (i.e. 1990s) showed “upper lobe fibrosis”, without a firm diagnosis.,A large cavity with pleural thickening is visible on the left in both images, with additional small cavities inferiorly in 2012, and contractio

14、n 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),Imaging showing chronic cavitary pulmonary aspergillosis s

15、howing 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 disting

16、uished from the thickened 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 of

17、ten an end result from untreated CCPA. Extensive fibrosis with fibrotic destruction of at least two lobes of lung complicating CCPA, leading to a major loss of lung function. Usually the fibrosis is solid in appearance,

18、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 aspergillomas may be present.,,,Imaging of ch

19、ronic fibrosing pulmonary aspergillosis complicating chronic cavitary pulmonary aspergillosis, which followed tuberculosis, with mild chronic obstructive pulmonary disease. Complete opacification of the left hemi-thorax

20、developed between February 1998, when a left 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

21、fungal hyphae.,One or more nodules (<3 cm), which do not usually cavitate, are an unusual form of CPA . They may mimic carcinoma of the lung, metastases, cryptococcal nodule, coccidioidomycosis or other rare pathogens

22、 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 necrosis is frequen

23、t. 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 ax

24、ial views within the lung window showing Aspergillus nodules, of variable size and borders, and a fungus ball filling a cavity with a wall of variable thickness in a patient with pre-existing bronchiectasis and cicatrici

25、al atelectasis of the middle lobe.,Aspergillus nodule(s),Subacute invasive aspergillosis (SAIA) was previously termed chronic necrotising or semi-invasive pulmonary aspergillosis. SAIA occurs in mildly immunocompromised

26、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,

27、prolonged corticosteroid administration or other modest immunocompromising agents, chronic obstructive lung disease, connective tissue disorders, radiation therapy, non-tuberculous mycobacterial (NTM) infection or HIV in

28、fection. Patients are more likely to have detectable Aspergillus antigen in blood, and will show hyphae invading lung parenchyma, if a biopsy is done.,The chest radiograph shows a large irregular right upper-lobe cavitar

29、y lesion that developed with multiple symptoms over 6 weeks during treatment with sorafenib. The patient presented with unresectable hepatocellular carcinoma.,The computed tomography scan shows a dual cavity with moderat

30、ely 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 diseas

31、e entity of chronic progressive pulmonary aspergillosis. New nomenclature, “chronicprogressive pulmonary aspergillosis (CPPA) ” for the clinical syndrome including both CNPA and CCPA is proposed. It is difficult to dist

32、inguish between these two entities based on the clinical course and characteristics and radiological findings.,respiratory investigation 54 (2016) 85–91.,目錄,慢性肺曲霉病的定義,慢性肺曲霉病的臨床表現(xiàn)類型,慢性肺曲霉病的診斷,慢性肺曲霉病的管理,總結(jié),CPA: diagnosis c

33、riteria and definitions,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162–174,Methods for diagnosing CPA,TTNA: Transthoracic needle aspiration; 1: Confirmatory studies are nee

34、ded; 2: In forms of CNPA with a semi-invasive nature, the antigen can sometimes be positive for GM .,Respiration 2014;88:162–174,Frequency of underlying condition in CPA,Chronic Pulmonary Aspergillosis: An Update on Dia

35、gnosis and Treatment. Respiration 2014;88:162–174,SAFS: Severe asthma with fungal sensitisation.1: Community-acquired pneumonia requiring hospitalisation.,慢性肺曲霉菌病-抗體檢測Aspergillus antibody diagnosis of CPA,Present by Da

36、vid Denning,ECCMID 10th May 2015 in Barcelona,,,,,,患者人群Population,目的Intention,干預(yù)手段Intervention,SoR,QoE,文獻(xiàn)Reference,備注Comment,,,,在非免疫抑制患者中伴有空腔/結(jié)節(jié)肺浸潤,Cavitary or nodularpulmonary infiltrate in Non-immunocompromised p

37、atients,診斷或排除慢性肺曲霉菌病,DiagnosisOrexclusionof CPA,曲霉抗體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;Baxt

38、er, 2012; VanToorenenbergen,2012,BTS,1970;Uffredi, 2003;Kitasato, 2009;Ohba, 2012;Baxter, 2012,Schonheyder1987; Nimomiya,1990;,Denning, 2003;Agarwal, 2012,IgG和曲霉沉淀素的標(biāo)準(zhǔn)建立尚未完成,,哮喘/變態(tài)反應(yīng)性肺曲霉菌?。ˋBPA）/囊性纖維化(CF),Asthma

39、/ABPA/CF,Aspergillus precipitins,曲霉沉淀素,曲霉抗體IgM,曲霉抗體IgA,曲霉抗體IgE,Brouwer, 1988;,多數(shù)室內(nèi)測試尚未應(yīng)用，主要原因是不確定的敏感性,曲霉肉芽腫的敏感性尚不確定,目錄,慢性肺曲霉病的定義,慢性肺曲霉病的臨床表現(xiàn)類型,慢性肺曲霉病的診斷,慢性肺曲霉病的管理,總結(jié),Proposed management of chronic pulmonary aspergillosis

40、 in Japan,respiratory investigation 54 (2016) 85–91.,Proposal for a global therapeutic strategy algorithm of CPA. ITCZ = Itraconazole;L-AMB = liposomal amphotericinB; POSA = posaconazole; SA = simple aspergilloma;

41、VRCZ = voriconazole.,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162–174,Responses (clinical improvement and/or complete response) to systemic antifungal treatments: main cl

42、inical studies,Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2014;88:162–174,[Values are n (%)],a: Micafugin; b: voriconazole.,續(xù)前表,case 1,case 1,case 2,case 2,case 3,曲霉結(jié)節(jié),總結(jié),人群中CPA有一