慢性阻塞性肺疾病合并侵袭性肺曲霉病的危险因素及诊断进展

慢性阻塞性肺疾病（COPD）是常见的慢性呼吸系统疾病.侵袭性肺曲霉病（IPA）是肺曲霉病的一种类型,其危害最大,病死率最高.近年来,侵袭性肺曲霉病作为一种严重的机会性真菌感染,在COPD患者报道日益增多,除恶性肿瘤、器官移植外,COPD已成为IPA的第3位易患因素.据文献报道10％以上的COPD患者并发侵袭性肺曲霉病,5％以上合并IPA.另外有研究表明,全球约1％～2％ COPD患者死于IPA,而COPD合并IPA的病死率高达72％ ～ 95％.现将COPD合并IPA等风险因素研究及诊断进展综述如下.     

侵袭性肺曲霉病96例临床分析

近20年来,随着免疫抑制剂患者数量增加,侵袭性肺曲霉病发病呈增长趋势[1],为进一步提高对侵袭性肺曲霉菌病(invasive pulmonary spergillosis,IPA)的认识,对我院和同济医院呼吸内科2002～2006年诊断为侵袭性肺曲霉菌病的37例患者和近四年国内文献报道的侵袭肺曲霉菌病59例患者进行分析.     

无基础疾病及免疫缺陷的慢性坏死性肺曲霉病三例

曲霉(aspergillus)广泛存在于自然界,因机体的免疫状态、肺脏结构基础及孢子吸入量的不同,导致临床表现各异的肺曲霉病.临床上通常将肺曲霉病分为变应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA)、侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)和曲霉球 (aspergilloma,fungal ball)[1].慢性坏死性肺曲霉病(chronic necrotizing pulmonary aspergillosis,CNPA)又称为半侵袭性肺曲霉病(semi-invasive pulmonary aspergillosis),20世纪80年代由Gefter等[2 ]和Binder等[3]首先报道.目前认为是一种局限性侵袭性肺曲霉病,常发生于原有肺部基础疾病的患者,如尘肺、COPD、肺癌、肺结核、肺叶切除术后、肺囊性纤维 化或轻度免疫功能缺陷的患者,如长期服用糖皮质激素、糖尿病、嗜酒、高龄、营养不良及慢性肉芽肿[1.3].现报道3例无基础疾病及免疫功能缺陷的CNPA病例.     

关注非经典免疫抑制宿主的非典型肺曲霉病

肺曲霉病包括曲霉属真菌引起的侵袭性肺病和非侵袭性肺病,前者指侵袭性肺曲霉病（invasive pulmonary aspergillosis,IPA）及侵袭性气管支气管曲霉病,后者指曲霉真菌抗原和曲霉毒素引起的变态反应性支气管肺病及肺曲霉球。曲霉球多发生于肺结核、肺囊肿、肺脓肿、肺癌空洞及支气管扩张和肺囊性纤维化等结构破坏性肺病,曲霉菌呈局部定植寄生状态,多数患者无症状,少数患者可有反复少量咯血,偶尔发生大咯血,支气管动脉栓塞或手术切除曲霉球为有效治疗。变态反应性肺曲霉病,临床表现类似哮喘,对激素及口服伊曲康唑治疗反应良好。     

侵袭性肺曲霉病1例并文献复习

目的提高对侵袭性肺曲霉病的临床、胸部影像学、病原学和病理改变的认识。方法对1例经病理证实的侵袭性肺曲霉病患者的职业、临床表现、胸部X线、CT、气管镜和病理资料并结合文献进行回顾性分析。结果侵袭性肺曲霉病的临床表现缺乏特异性，典型的影像学检查显示胸膜下单发或多发结节状或斑片状阴影，并呈动态变化。GM试验用于诊断侵袭性肺曲霉病具快速灵敏的特点；侵袭性肺曲霉病的病理可见由大小规范，呈两分叉（Y形）的分隔菌丝引起的特征性的血管侵害，也可以表现为局限性肉芽肿或广泛化脓性肺炎。结论侵袭性肺曲霉病的临床表现和影像学改变非常复杂，在诊断中需要综合患者的各种临床资料（包括临床症状、放射学、血清学检查和病理）。     

原发性侵袭性肺曲霉病12例

侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)是一种严重的肺部感染,无特征性临床表现,过程凶险,病死率高,多发生于免疫缺陷或有免疫功能受损基础疾病的患者,即继发性侵袭性肺曲霉病.     

原发性侵袭性肺曲霉病12例

侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)是一种严重的肺部感染,无特征性临床表现,过程凶险,病死率高,多发生于免疫缺陷或有免疫功能受损基础疾病的患者,即继发性侵袭性肺曲霉病.     

变应性支气管肺曲霉病的诊断和治疗

曲霉可引起急性侵袭性肺曲霉病、慢性肺曲霉病和变应性支气管肺曲霉病(allergic bronchopulmonary aspergillosis,ABPA,也称过敏性支气管肺曲霉病),ABPA足机体对寄生于支气管内曲霉产生的变态反应性炎症[1].该病常在慢性哮喘或囊性纤维化(cystic fibrosis,CF)患者的基础上发生.     

侵袭性肺曲霉病的诊断与治疗

自从19世纪40年代，第1例侵袭性曲霉病（Invasive Aspergillosis）报道后，近年来，随着获得性免疫缺陷综合征（AIDS）以及恶性肿瘤患者的增多，骨髓和器官移植、肿瘤患者的放化疗及免疫抑制剂的应用，侵袭性曲霉病发病率急剧升高。1996年欧洲一项大样本的尸检结果显示，侵袭性曲霉病的发生率在12年内增加了近14倍。     

混合型肺曲霉病一例

<正>肺曲霉病主要分为三个类型:侵袭型肺曲霉病、变应性支气管肺曲霉病和慢性肺曲霉病[1,2]。文献报告[3～5]及临床工作中发现同一患者可同时存在不同的肺曲霉病类型,2014年牟向东等[3]提出混合型肺曲霉病的概念,有待临床进一步认识及探讨。现回顾分析广西壮族自治区人民医院2018-03收治的1例变应性支气管肺曲霉病与侵袭型肺曲霉病临床     

呼吸系统曲霉菌病重叠综合症的新进展

肺部曲霉菌病是少见病,但近年逐年增多,包括变应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)、曲菌球(aspergilloma)、慢性坏死性肺曲菌病(chronic necrotizing aspergillosis,CNA)、侵袭性肺曲菌病(invasive pulmonary aspergillosis,IPA)及全身播散性曲菌病等5型.其中ABPA、曲菌球甚至IPA可合并变应性曲霉菌性鼻窦炎(allergic Aspergillus sinusitis,AAS),可能与基础病及其治疗等因素有关.本文就近期文献报告的呼吸系统曲霉菌病重叠综合症作一综述.     

Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters

Between September 1993 and December 1993, during extensive hospital construction and indoor renovation, a nosocomial outbreak of invasive pulmonary aspergillosis occurred in acute leukemia patients treated in a regular ward that has only natural ventilation. The observed infection rate was 50%. Chemoprophylaxis with intravenous continuous low-dose amphotericin B was then instituted as a preventive measure. During the next 18 months invasive pulmonary aspergillosis developed in 43% of acute leukemia patients. After that period a new hematology ward was opened with an air filtration system through high-efficiency particulate air filtration (HEPA) filters, and a bone marrow transplantation program was started on the hematology service. During the following three years, none of the acute leukemia or bone marrow transplantation patients who were hospitalized exclusively in the hematology ward developed invasive pulmonary aspergillosis, although 29% of acute leukemia patients who were housed in a regular ward, because of shortage of space in the new facility, still contracted invasive pulmonary aspergillosis. Overall, 31 patients were diagnosed with invasive pulmonary aspergillosis during almost five years: 74% of patients recovered from invasive pulmonary aspergillosis, and 42% are long-term survivors; 26% of patients died of resistant leukemia with aspergillosis, but no one died of invasive pulmonary aspergillosis alone. In conclusion, during an on-going construction period, an extremely high incidence rate of invasive pulmonary aspergillosis in acute leukemia patients undergoing intensive chemotherapy was observed. Institution of low-dose intravenous amphotericin B prophylaxis marginally reduced the incidence rate of invasive pulmonary aspergillosis. Keeping patients in a special ward with air filtration through a HEPA system eliminated invasive pulmonary aspergillosis completely. Among patients who developed invasive pulmonary aspergillosis, early diagnosis and treatment are probably the explanation for the favorable outcome.     

Pulmonary fungal infections

PURPOSE OF REVIEW: Invasive fungal infections of the lung have historically been associated with an extremely high mortality. This review aims to disseminate the most recent advances in the diagnosis and management of fungal infections of the lung. RECENT FINDINGS: The number and diversity of immunosuppressed populations are growing rapidly. Transplant immunosuppression is becoming more aggressive early in the posttransplant period, potentially increasing the risk of invasive fungal infections. The galactomannan antigen test and the beta-D-glucan test have emerged as methods of serially monitoring at-risk patients for invasive aspergillosis. Their utility has been established in some neutropenic populations but not in solid organ transplant recipients. In-vitro studies, animal studies, and retrospective human studies support the use of combination antifungal therapy for invasive aspergillosis. Unfortunately no randomized clinical trials exist. SUMMARY: Invasive pulmonary aspergillosis will continue to be a major problem in immunocompromised patients in the future. Immense advances in the last 2-3 years are sure to improve outcome. Well-designed multicenter evaluations are still necessary, however, to optimize management as management options widen.     

Invasive pulmonary aspergillosis: identification of risk factors

Aspergillosis is the second most frequent fungal infection after candidiasis in teaching hospitals. Clinical manifestations of pulmonary aspergillosis range from asymptomatic colonization to disseminated disease. The aim of this study was to identify the risk factors associated with invasive pulmonary aspergillosis, in patients with positive pulmonary isolation of Aspergillus species. A review was undertaken of all clinical records with pulmonary isolation of Aspergillus species at Reina Sofia University Hospital from January 1995 to December 1998. Data collected were: age, gender, history of smoking, past medical history, such as chronic pulmonary disease, immunosuppression, granulocytopenia in the past 6 months and during the last admission, history of surgery including within the last year of the study period, number of hospital admissions and clinical evidence of invasive pulmonary aspergillosis. To investigate all the possible risk factors for invasive pulmonary aspergillosis, a multivariable logistic regression model was used. 132 patients with positive pulmonary isolation were identified, of which 42.4% had clinical evidence of invasive pulmonary aspergillosis. The independent factors significantly associated with invasive pulmonary aspergillosis were: granulocytopenia in the past 6 months, immunosuppression in the last admission and the number of hospital admissions within the past year. Patients with a history of granulocytopenia in the past 6 months and immunosuppression in the last admission are the high-risk group for invasive pulmonary aspergillosis. However, invasive pulmonary aspergillosis can also occur in mild granulocytopenic or even immunocompetent patients.     

Aspergilosis. Formas clínicas y tratamiento

Invasive aspergillosis, chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis are the clinical forms of aspergillosis. Although there is a great number of Aspergillus species, Aspergillus fumigatus-complex is the more frequent aetiological agent, regardless of clinical form or baseline condition. The increase in immunosuppressive agents and the higher use of corticosteroids in chronic obstructive pulmonary disease have led to aspergillosis becoming more prominent in recent years. Galactomannan detection and radiological diagnostic images complement the limitations of microbiology cultures in these patients. Voriconazole and liposomal amphotericin B are the gold standard in patients requiring therapy, and posaconazole, itraconazole, caspofungin and other echinocandins are effective alternatives. The prognosis depends of clinical forms and characteristics of the host, but it is particularly poor in the disseminated invasive forms.     

侵袭性肺曲霉菌病的临床诊治进展

侵袭性肺曲霉菌病是深部真菌感染性疾病，近年来发病率大大增加，死亡率极高，传统的诊断方法非常困难，治疗效果不佳。近年来，该病在诊断治疗上有很大的进展，本文就此进行综述。     

A case of non-invasive pulmonary aspergillosis that rapidly deteriorated]

The pulmonary diseases caused by the Aspergillus species include invasive forms, for example, invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and non-invasive pulmonary aspergillosis. Though these forms are defined pathologically by the presence of the Aspergillus species that invades the lung tissue, they are used as clinical entities. We report a case of non-invasive pulmonary aspergillosis which, from the clinical data, appeared likely to be misdiagnosed as the chronic invasive form. A 45 year-old man received chemoradiotherapy for lung cancer as well as undergoing an left upper lobectomy. Two weeks after the surgery the patient developed a cough, high fever and chest pain. Chest radiography and chest computed tomography showed a rapidly enlarging cavity with an internal mass and infiltration in the left lower lung field. A transbronchial biopsy specimen of the cavity wall showed fungal hyphae. Bronchial washing culture grew Aspergillus fumigatus. Itraconazole and amphotericin B were administered, but the patient's condition did not improve. A left lower lobectomy was performed. The histologic findings showed that the fungal hyphae were only on the surface of the cavity wall, and were surrounded by necrosis and widespread inflammatory cell infiltration. No fungal invasion of the viable lung tissue was seen. The area of infiltration revealed an organizing pneumonia without Aspergillus or other organisms. Our final diagnosis was non-invasive pulmonary aspergillosis. There has been no recurrence of the lung cancer or of the pulmonary aspergillosis in the three years since surgery. It is reported that non-invasive pulmonary aspergillosis passes through a period so active that it seems to be the invasive form for its entire clinical course. To avoid confusion in diagnosis, establishment of a comprehensive clinical classification of pulmonary aspergillosis will be needed.     

Discriminant scorecard for diagnosis of invasive pulmonary aspergillosis in patients with acute leukemia

Invasive pulmonary aspergillosis, a serious opportunistic infection in adult patients with acute leukemia, is difficult to diagnose antemortem. To identify patients with invasive pulmonary aspergillosis without reliance on invasive diagnostic procedures, a discriminant scorecard for invasive pulmonary aspergillosis based on clinical parameters was evaluated in a three-phase study. In phase I, the records of 62 patients, including 15 with invasive pulmonary aspergillosis, were reviewed. Eleven clinical parameters distinguished patients with invasive pulmonary aspergillosis from control subjects. These parameters were combined into a discriminant scorecard. In phase II, the discriminant scorecard was validated by a blinded, retrospective review of 94 consecutive admissions. The discriminant scorecard score was highly associated with the clinical outcome (p less than 0.0005). The sensitivity of the discriminant scorecard was calculated as a range from 62.9 to 92.8 percent and the specificity as a range from 87.5 to 98.3 percent. In phase III, the clinical utility of the discriminant scorecard was determined by its prospective application to 49 consecutive patient admissions. The discriminant scorecard identified patients with invasive pulmonary aspergillosis at an average of 4.1 days prior to clinical recognition of the disease and initiation of amphotericin B therapy. The discriminant scorecard outperformed a complex function based on multiple linear regressions, was easy to use, and did not require difficult calculations. Thus, for this patient population, the discriminant scorecard was an accurate, useful noninvasive screening test for invasive pulmonary aspergillosis. The scorecard allows more rapid clinical identification of patients with this infection and could lead to improved patient survival through earlier diagnostic and therapeutic intervention.     

Antigen detection in the diagnosis of invasive aspergillosis. Utility in controlled, blinded trials

Two blinded, controlled trials were done to evaluate the usefulness of fungal antigen detection for the diagnosis of invasive aspergillosis. Detection of Aspergillus fumigatus carbohydrate by radioimmunoassay was compared with antibody detection by an enzyme-linked immunosorbent assay and with diagnostic microbiologic and histopathologic procedures. In the first trial, antigenemia was detected in 4 of 6 leukemic patients with invasive pulmonary aspergillosis, but not in 8 acute leukemic controls or in 24 normal controls. Fungal antigenemia persisted for 8 to 75 days in 4 patients and seroconversion occurred at the onset of pulmonary infiltrates in 3. Antibody to A. fumigatus was detected in 2 of the 6 patients with aspergillosis, but also in 2 leukemic controls and 6 normal controls. Aspergillus species were identified in four of seven bronchoscopies done in 5 patients with invasive pulmonary aspergillosis. Prospective nasal cultures grew Aspergillus species in 4 of the 6 patients with invasive aspergillosis, but in only 1 patient was this information available before a histologic diagnosis was made. In a second trial, antigenemia was detected in 2 patients with invasive aspergillosis, and in 1 with possible invasive aspergillosis, but not in 9 controls. This study indicates that the radioimmunoassay for A. fumigatus antigen is a highly specific and moderately sensitive serodiagnostic test for invasive pulmonary aspergillosis. Prospective nasal cultures grew Aspergillus species in 4 of the 6 patients with invasive aspergillosis, but in only 1 patient was this information available before a histologic diagnosis was made. In a second trial, antigenemia was detected in 2 patients with invasive aspergillosis, and in 1 with possible invasive aspergillosis, but not in 9 controls. This study indicates that the radioimmunoassay for A. fumigatus antigen is a highly specific and moderately sensitive serodiagnostic test for invasive pulmonary aspergillosis.     

Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts

Invasive pulmonary aspergillosis occurs predominantly in individuals who are neutropenic or who have severe defects in cell-mediated immunity. The isolation of Aspergillus from respiratory secretions of normal hosts usually signifies tracheobronchial colonization, not disease. Recent experience with three nonimmunocompromised patients who had invasive pulmonary aspergillosis, each of whom had Aspergillus isolated from respiratory secretions early in his illness, led to a reassessment of the significance of the isolation of Aspergillus from tracheobronchial secretions. Two of 10 nonimmunocompromised, nonleukopenic individuals who had pulmonary infiltrates and whose sputum yielded Aspergillus had invasive pulmonary aspergillosis, whereas two of five individuals who had pulmonary infiltrates and whose bronchial washings grew Aspergillus had invasive disease. These findings indicate that invasive pulmonary aspergillosis should be considered when Aspergillus is isolated from the respiratory secretions of anyone who has pneumonia, regardless of host defense status.