慢性肺曲霉病的診斷與管理課件

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Definitions of CPAThe most common form of CPA is CCPA. Untreated it may progress to chronic fibrosin

2、g 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 disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pu

3、lmonary aspergillosis) is a more rapidly progressive infection (3 months) usually found in moderately immunocompromised patients. D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eur Respir J 2019.Definitions of CPAThe most com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Present

4、 by David Denning ECCMID 10th May 2019 in Barcelona慢性曲霉菌病臨床表現(xiàn)分類Clinical phenotypes of chronic Aspergillus 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 pulmonaryaspergillosi

5、s (CCPA)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SAIAPresent by David Denning ECCMICPA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/半侵襲性曲霉病 分 類定 義單純性曲霉腫非免疫功能受損的患者存在含有真菌球的單一肺部空洞，且血清學(xué)或微生物學(xué)證據(jù)提示曲

6、霉屬(Aspergillus spp.)感染，無癥狀或僅有輕微癥狀，在至少3個月的觀察期內(nèi)未出現(xiàn)影像學(xué)進展CCPA存在1個或多個含有1個曲霉球或不規(guī)則腔內(nèi)結(jié)構(gòu)的肺部空洞(薄壁或厚壁)，且血清學(xué)或微生物學(xué)證據(jù)提示曲霉屬感染，有明顯的肺部和/或系統(tǒng)癥狀，在至少3個月的觀察期內(nèi)出現(xiàn)明顯的影像學(xué)進展(新空洞、空洞外周浸潤增加、或纖維化增加)CFPACCPA并發(fā)出現(xiàn)的至少2個肺葉出現(xiàn)嚴重的纖維化破壞并導(dǎo)致大部分肺功能喪失。單個存在空洞的肺葉出現(xiàn)嚴重纖維化破壞僅代表影響該肺葉的CCPA。通常纖維化表現(xiàn)為肺部實變，但也可表現(xiàn)為周圍出現(xiàn)纖維化的較大空洞曲霉結(jié)節(jié)一種少見的CPA類型，出現(xiàn)1個或多個形成或不形成空

7、洞的結(jié)節(jié)。可與結(jié)核球、肺癌、球孢子菌病以及其他疾病相似，只有通過組織學(xué)檢查才能確診。盡管常出現(xiàn)壞死，但不會出現(xiàn)組織浸潤。SAIA/CNPA在1-3個月內(nèi)出現(xiàn)的侵襲性曲霉病，常發(fā)生在存在輕度免疫功能受損的患者之中，存在多種影像學(xué)特征，包括空洞形成、結(jié)節(jié)、“膿腫形成”的進展性實變等。受累肺部組織活檢可見菌絲，微生物學(xué)檢查結(jié)果與侵襲性曲霉病一致，特別是血液(或呼吸道液體)曲霉半乳甘露聚糖抗原陽性D. DENNING ET AL. ESCMID/ERS GUIDELINES. Eur Respir J 2019.CPA的分類與定義CCPA-慢性空洞型肺曲霉病; CFPA-Single (simple)

8、 pulmonary aspergilloma is a single fungal ball in a single pulmonary cavity. There is no progression over months of observation and very few, if any pulmonary or systemic symptoms and serological or microbiological evidence implicating Aspergillus spp.Simple aspergilloma that developed within a pos

9、t-tuberculous cicatricial atelectasis of the left upper lobe 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. Eur Respir J 2019.Singl

10、e (simple) pulmonary aspeCCPA, 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 markers, over at least 3 months of observation. Untreated, over years, thes

11、e cavities enlarge and coalesce, developing pericavitary infiltrates or perforating into the pleura, and an aspergilloma may appear or disappear. Thus serological or microbiological evidence implicating Aspergillus spp. is required for diagnosis.Chronic cavitary pulmonary aspergillosis showing marke

12、d progression between a) 2019 and b) 2019. Chest radiographs prior to 2019 (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 2019, and contraction of the left

13、 upper lobe. The right side shows interval development of a large cavity, with some pleural thickening. Neither cavity contains a fungal ball.a)b)CCPA, formerly called complex Imaging showing chronic cavitary pulmonary aspergillosis showing an axial view with a) lung and b) mediastinal windows at th

14、e 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 thickened pleura or the neighbouring alveolar consolidation. The extra pleural fat is hyperattenuated (white arrows). *: the dilat

15、ed oesophagus should not be confused with a cavity.a)b)*Imaging showing chronic cavitaCFPA is often 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

16、 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 aspergillomas may be present.Imaging of chronic fibrosing pulmonary aspergillosis complicating chronic cavita

17、ry pulmonary aspergillosis, which followed tuberculosis, with mild chronic obstructive pulmonary disease. Complete opacification of the left hemi-thorax developed between February 2019, when a left upper lobe cavity with a fluid level was present, and May 2019. Multiple left lung autopsy percutaneou

18、s biopsies showed evidence of chronic inflammation, but no granulomas or fungal hyphae.CFPA is often an end result frOne 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 ot

19、her 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 necrosis is frequent. Sometimes lesions larger than 3 cm in diameter are seen and

20、 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 variable size and borders, and a fungus ball filling a cavity with a wall of v

21、ariable thickness in a patient with pre-existing bronchiectasis and cicatricial atelectasis of the middle lobe.Aspergillus nodule(s)One or more nodules (3 cm), wSubacute invasive aspergillosis (SAIA) was previously termed chronic necrotising or semi-invasive pulmonary aspergillosis. SAIA occurs in m

22、ildly 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, prolonged corticosteroid administration or other modest

23、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 will show hyphae invading lung parenchyma, if a b

24、iopsy 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 computed tomography scan shows a dual cavity with moder

25、ately 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)Subacute invasive aspergillosiThe new clinical disease entity of chronic progressive pulmonary aspergill

26、osis. 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.respiratory investigat

27、ion 54 (2019) 8591.The new clinical disease entit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CPA: diagnosis criteria and definitions1Chronic pulmonary or general symptoms including at least 1 of the following (for a minimum of 3 months in duration): weight loss, product

28、ive cough or haemoptysis2A progressive formation and expansion of single or multiple pulmonary cavitations surrounded by a wall and possible pleural thickening on radio-imaging 3A positive result for a serum Aspergillus spp. precipitins test or an isolation of Aspergillus spp. from the pulmonary or

29、pleural cavity4Increased biological inflammatory syndrome markers (C-reactive protein, plasma viscosity or erythrocyte sedimentation rate)5The exclusion of all other causes that could imitate the symptoms (bronchial carcinoma, TB and atypical mycobacteria)6No overt immunocompromising conditions (HIV

30、 infection, leukaemia and chronic granulomatous disease)Chronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2019;88:162174CPA: diagnosis criteria and deMethods for diagnosing CPAClinical examination for risk factors: Alcoholism, tobacco abuse, diabetes, corticosteroid

31、use, COPD or undernourishment, ICU patients, patients with cirrhosisChest X-ray and CT: Important for a presumptive diagnosis Radiological appearance described as simple or complex aspergillomaSerological testingSputum, bronchoscopy or bronchoscopy with BAL: Direct examination and culture Detection

32、of GM in BAL1Biopsy sample (perfibroscopic or percutaneous TTNA biopsy): With histological analysis or microbiological cultureVideo-assisted thoracoscopyDetection of GM in serum2TTNA: Transthoracic needle aspiration; 1: Confirmatory studies are needed; 2: In forms of CNPA with a semi-invasive nature

33、, the antigen can sometimes be positive for GM .Respiration 2019;88:162174Methods for diagnosing CPAClinFrequency of underlying condition in CPAChronic Pulmonary Aspergillosis: An Update on Diagnosis and Treatment. Respiration 2019;88:162174SAFS: Severe asthma with fungal sensitisation.1: Community-

34、acquired pneumonia requiring hospitalisation.Frequency of underlying condit慢性肺曲霉菌病-抗體檢測Aspergillus antibody diagnosis of CPAPresent by David Denning ECCMID 10th May 2019 in Barcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻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 inf

35、iltrate in Non-immunocompromised patients診斷或排除慢性肺曲霉菌病DiagnosisOrexclusionof CPA曲霉抗體IgGAspergillus IgG antibodyAspergillus IgM antibodyAspergillus IgA antibodyAspergillus IgE antibodyAADDBIIIIIIIIIIIIGuitard, 2019;Baxter, 2019; VanToorenenbergen,2019BTS,1970;Uffredi, 2019;Kitasato, 2009;Ohba, 2019;Baxter, 2019Schonheyder1987; Nimomiya,1990;Denning, 2019;Agarwal,