1、慢性肺曲霉病的诊断与管理目录目录慢性肺曲霉病的定义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临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的诊断慢性肺曲霉病的管理慢性肺曲霉病的管理总结总结目录目录慢性肺曲霉病的定义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临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的诊断慢性肺曲霉病的管理慢性肺曲霉病的管理总结总结Definitions of CPA The most common form of CPA is.Untreated it may progress to chronic fibrosing pulmonary asper
2、gillosis().Less common manifestations of CPA include and.All these entities are found in non-immunocompromised patients with prior or current lung disease.(formerly called chronic necrotising pulmonary aspergillosis)is a more rapidly progressive infection(3 months)usually found in moderately immunoc
3、ompromised patients.D.DENNING ET AL.ESCMID/ERS GUIDELINES.Eur Respir J 2015.目录目录慢性肺曲霉病的定义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临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的诊断慢性肺曲霉病的管理慢性肺曲霉病的管理总结总结Present byPresent by David Denning ECCMID 10ECCMID 10thth May 2015 in Barcelona May 2015 in Barcelona慢性曲霉菌病临床表现分类Clinical phenotypes of
4、chronic Clinical phenotypes of chronic Aspergillus spp diseasesAspergillus spp diseases单发曲霉球Single/simple aspergillomaSingle/simple aspergilloma慢性坏死性/亚急性肺曲霉菌病Chronic necrotizing pulmonaryChronic necrotizing pulmonaryaspergillosis(CNPA)or subacuteaspergillosis(CNPA)or subacuteInvasive aspergillosis(S
5、AI)Invasive aspergillosis(SAI)慢性空腔性肺曲霉菌病Chronic cavitary pulmonaryChronic cavitary pulmonaryaspergillosis(CCPA)aspergillosis(CCPA)慢性纤维化肺曲霉菌病Chronic fibrosingChronic fibrosingpulmonary aspergillosis(CFPA)pulmonary aspergillosis(CFPA)曲霉菌肉芽肿Aspergillus nodule(s)Aspergillus nodule(s)CCPA是最常见的CPA类型CCPA不治
6、疗可进展为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SAIACPA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 分 类定 义单纯性曲霉肿非免疫功能受损的患者存在含有真菌球的单一肺部空洞，且血清学或微生物学证据提示曲霉属(Aspergillus spp.)感染，无症状或仅有轻微症状，在至少3个月的观察期内未出现影像学进展CCPA存在1个或多个含有1个曲霉球或不规则腔内结构的肺部空洞(薄壁或厚壁)，且血清学或微生物学证据提示曲霉属感染，有明显的肺部和/或系统症状，在至少3个月的观察期内出现明显的影像学
7、进展(新空洞、空洞外周浸润增加、或纤维化增加)CFPACCPA并发出现的至少2个肺叶出现严重的纤维化破坏并导致大部分肺功能丧失。单个存在空洞的肺叶出现严重纤维化破坏仅代表影响该肺叶的CCPA。通常纤维化表现为肺部实变，但也可表现为周围出现纤维化的较大空洞曲霉结节一种少见的CPA类型，出现1个或多个形成或不形成空洞的结节。可与结核球、肺癌、球孢子菌病以及其他疾病相似，只有通过组织学检查才能确诊。尽管常出现坏死，但不会出现组织浸润。SAIA/CNPA在1-3个月内出现的侵袭性曲霉病，常发生在存在轻度免疫功能受损的患者之中，存在多种影像学特征，包括空洞形成、结节、“脓肿形成”的进展性实变等。受累肺部
8、组织活检可见菌丝，微生物学检查结果与侵袭性曲霉病一致，特别是血液(或呼吸道液体)曲霉半乳甘露聚糖抗原阳性D.DENNING ET AL.ESCMID/ERS GUIDELINES.Eur Respir J 2015.Single(simple)pulmonary aspergillomaSingle(simple)pulmonary aspergilloma is a single fungal ball in a single pulmonary cavity.There is no progression over months of observation and very few,if
9、 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.Surgical resection by video-assisted thoracic surgery was performed because of
10、recurrent haemoptysis and a requirement for anticoagulant therapy.D.DENNING ET AL.ESCMID/ERS GUIDELINES.Eur Respir J 2015.CCPACCPA,formerly called complex aspergilloma,usually shows multiple cavities,which may or may not contain an aspergilloma,in association with pulmonary and systemic symptoms and
11、 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.Thus serological or microbiological evidence implicating Aspergil
12、lus spp.is required for diagnosis.Chronic cavitary pulmonary aspergillosis showing marked progression between and.Chest radiographs prior 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 additiona
13、l 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)Imaging showing showing an axial view with a)lung and b)mediastinal windows at the level of th
14、e 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 dilated oesophagus shoul
15、d not be confused with a cavity.a)b)*CFPACFPA 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 in appearance,but large or small cavities with
16、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 cavitary pulmonary aspergillosis,which followed,with mild
17、chronic obstructive pulmonary disease.Complete opacification of the left hemi-thorax 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
18、 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 and can only be definitively diagnosed on histology.Nodules in patients with rheumatoid art
19、hritis 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 may have a necrotic centre.These are not well described in the literature and are best described as“.”.Successive
20、 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 variable thickness in a patient with pre-existing bronchiectasis and cicatricial atelectasis of the middle lobe.Aspergillus noduleAspergillus nodule(s s)Suba
21、cute invasive aspergillosis(SAIA)Subacute invasive aspergillosis(SAIA)was previously termed chronic necrotising or semi-invasive pulmonary aspergillosis.SAIA occurs in mildly immunocompromised or very debilitated patients and has similar clinical and radiological features to CCPA but is more rapid i
22、n progression.SAIA typically occurs in patients with diabetes mellitus,malnutrition,alcoholism,advanced age,prolonged corticosteroid administration or other modest immunocompromising agents,chronic obstructive lung disease,connective tissue disorders,radiation therapy,non-tuberculous mycobacterial(N
23、TM)infection or HIV infection.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 cavitary lesion that developed with multiple symptoms during treatmen
24、t with sorafenib.The patient presented with unresectable hepatocellular carcinoma.The computed tomography scan shows a dual cavity with moderately thick walls,and some material within the cavity on an almost normal lung background.a patient with hepatocellular carcinoma being treated with the sorafe
25、nib.a)b)The new clinical disease entity of chronic progressive pulmonary aspergillosis.New nomenclature,“”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 fin
26、dings.respiratory investigation 54(2016)8591.目录目录慢性肺曲霉病的定义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临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的诊断慢性肺曲霉病的管理慢性肺曲霉病的管理总结总结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,p
27、roductive 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
28、 or 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
29、infection,leukaemia and chronic granulomatous disease)Chronic Pulmonary Aspergillosis:An Update on Diagnosis and Treatment.Respiration 2014;88:162174Methods for diagnosing CPAClinical examination for risk factors:Alcoholism,tobacco abuse,diabetes,corticosteroid use,COPD or undernourishment,ICU patie
30、nts,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 of GM in BAL1Biopsy sample(perfibroscopic or
31、 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,the antigen can sometimes be positive for GM.Respi
32、ration 2014;88:162174Frequency of underlying condition in CPAChronic Pulmonary Aspergillosis:An Update on Diagnosis and Treatment.Respiration 2014;88:162174SAFS: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
33、 Aspergillus antibody diagnosis of CPAof CPAPresent byPresent by David Denning ECCMID 10ECCMID 10thth May 2015 in Barcelona May 2015 in Barcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment在非免疫抑制患者中伴有空腔/结节肺浸润Cavitary or nodularpulmonary infiltrate in Non-immunocompromised pati
34、ents诊断或排除慢性肺曲霉菌病DiagnosisOrexclusionof CPA曲霉抗体IgGAspergillus IgG antibodyAspergillus IgM antibodyAspergillus IgA antibodyAspergillus IgE antibodyA AA AD DD DB BII IIII IIIII IIIIII IIIII IIGuitard,2012;Baxter,2012;VanToorenenbergen,2012BTS,1970;Uffredi,2003;Kitasato,2009;Ohba,2012;Baxter,2012Schonhe
35、yder1987;Nimomiya,1990;Denning,2003;Agarwal,2012IgG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/CFAspergillus precipitins曲霉沉淀素曲霉抗体IgM曲霉抗体IgA曲霉抗体IgEBrouwer,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目录慢性肺曲霉病的定义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临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的诊断慢性肺曲霉病的管理慢性肺曲霉病的管理总结总结Propo
36、sed management of chronic pulmonary aspergillosis in respiratory investigation 54(2016)8591.Proposal for a therapeutic strategy algorithm of CPA.ITCZ=Itraconazole;L-AMB=liposomal amphotericinB;POSA=posaconazole;SA=simple aspergilloma;VRCZ=voriconazole.Chronic Pulmonary Aspergillosis:An Update on Dia
37、gnosis and Treatment.Respiration 2014;88:162174Responses(clinical improvement and/or complete response)to systemic antifungal treatments:main clinical studiesChronic Pulmonary Aspergillosis:An Update on Diagnosis and Treatment.Respiration 2014;88:162174Values are n(%)a:Micafugin;b:voriconazole.续前表case 1case 1case 2case 2case 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
