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。     

侵袭性肺曲霉病的诊断治疗进展

侵袭性肺曲霉病是肺曲霉病中最严重的类型,几乎总是继发于免疫受损或器官移植患者,病死率高,确诊和治疗比较困难。因此早期诊断、合理治疗及预防就显得尤为重要。近年一些新的检查方法具有早期诊断价值,不少新的抗真菌药物也具有高效低毒的特点,它们将非常有助于疾病的诊断和治疗。     

Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients

The efficacy of inhaled amphotericin B in prevention of invasive aspergillosis in patients with granulocytopenia (granulocytes less than 0.5 X 10(9)/l for greater than 10 days) was investigated over a 12-month period. Amphotericin B prophylaxis was administered twice daily for the period of granulocytopenia to 34 patients who were at risk during 144 episodes of granulocytopenia. The cohort at risk was compared with historical controls. In the 2 years prior to institution of prophylaxis, 14 patients (11.4% of those at risk) developed invasive aspergillosis. All cases occurred whilst the patients were nursed on the open wards. Aspergillosis did not develop in 25 granulocytopenic patients nursed in single rooms with HEPA filtration. Since institution of prophylaxis, there have been no cases of invasive aspergillosis. These data suggest that nebulized amphotericin B may be useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients, especially those nursed on the open wards, and warrants further investigation.     

Successful treatment of allergic bronchopulmonary aspergillosis with erythromycin and fluconazole]

A 30-year-old woman was admitted to our hospital because of productive cough, wheezing, and the disclosure of abnormal shadows on chest X-ray films. The patient was given a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) based on eight findings: asthma, eosinophilia, elevated serum IgE concentrations, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, lung infiltration, central bronchiectasis, and repeated culture of Aspergillus fumigatus in sputum. Because she refused steroids, we administered erythromycin. The volume of her sputum subsequently decreased, her symptoms were brought under control, and her serum IgE fell, but the lung infiltrates did not clear. Discontinuation of erythromycin resulted in exacerbation of the patient's asthmatic symptoms, with high fever, increased sputum volume and IgE levels, and worsening lung infiltrates. These symptoms responded well to oral prednisolone medication, but sputum culture was still positive for Aspergillus fumigatus. Following discontinuation of prednisolone, the patient was treated with erythromycin, to which oral fluconazole was added for 16 months. Subsequent sputum cultures were negative for Aspergillus fumigatus, and for 7 years thereafter the patient remained in remission. Erythromycin and anti-fungal drugs may be worth trying in cases of allergic bronchopulmonary aspergillosis.     

Locally invasive pulmonary aspergillosis in a healthy man successfully treated with oral fluconazole.

A 74-year-old healthy man with locally invasive form of pulmonary aspergillosis (PA) is reported. Chest X-ray film showed a segmental infiltration of right upper lobe (RUL) without cavitation, and the transbronchial lung biopsy specimen contained numerous hyphae of aspergillus species. Complication of bronchial asthma, or bronchiectasis were absent, and hyphae of aspergillus were present at only one segment of RUL. After 5 months of therapy with oral fluconazole, the PA had dramatically improved. Fluconazole was found to be effective for the locally invasive form of PA in a healthy man.     

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。     

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants

Abstract: Background. Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. Objective. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. Patients. The 2046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Methods. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. Results. We identified 33 cases of IA (28% disseminated) in 2046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1000 patient‐years (33 cases/6813 pt‐years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1000‐pt year vs. heart 0.4% (3/686) or 1.4 per 1000‐pt year vs. liver 0.7% (3/439) or 2.1 per 1000‐pt year vs. renal 0.4% (3/733) or 1.2 per 1000‐pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). Conclusions. The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.     

侵袭性曲霉菌感染的诊断治疗进展

侵袭性曲霉病（invasive aspergillosis,IA）主要发生在免疫受损人群,如急性白血病、骨髓干细胞移植、实体器官移植、恶性肿瘤化疗等患者。近年来的流行病学观察表明,IA患者的发病率有逐年增多趋势,在尸解病例中超过了念珠菌感染。本病的病死率很高,在56％～88．1％之间。早期诊断后应用抗真菌药物治疗可以显著改善患者预后。对于侵袭性曲霉菌感染,目前研究的焦点问题集中在早期诊断方法和有效治疗手段这两方面。由于IA的临床表现缺乏特殊性,其早期诊断十分困难,如何提高早期诊断水平一直是一个挑战。侵袭性曲霉菌感染的治疗手段有限,传统药物不良反应较多限制了其广泛应用,新型抗真菌药物的开发和应用一直是临床的迫切需要。     

侵袭性肺曲霉病诊治需要注意的几个问题

近20年来侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)作为器官移植受者、骨髓干细胞移植受者以及合并有慢性肺部疾病患者主要的并发症在临床上明显增多,也是患者致残和死亡的原因之一。该文就IPA诊治过程中需要注意的几个问题,如IPA的诊断标准、肺曲霉病的分类、半乳甘露聚糖抗原(galactomannan,GM)试验和1,3-β-D葡聚糖(G试验)检测对IPA诊断的价值、IPA的临床处理原则以及IPA的抗真菌药物治疗等问题作一讨论。     

Current approaches to diagnosis and treatment of invasive aspergillosis

Filamentous fungi (moulds) are ubiquitous soil inhabitants whose conidia are inhaled into the respiratory tract, where they may cause life-threatening infections. Among these infections is invasive aspergillosis, which is a major cause of morbidity and mortality in the severely immunocompromised. Risk factors for invasive aspergillosis include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. Invasive aspergillosis most commonly involves the sinopulmonary tract reflecting inhalation as the principal portal of entry. Chest computed tomography scans and new non-culture-based assays such as antigen detection and polymerase chain reaction may facilitate the early diagnosis of invasive aspergillosis, but have limitations. Reflecting an important unmet need, there has been a significant expansion in the antifungal armamentarium. The second-generation triazole, voriconazole, was superior to conventional amphotericin B as primary therapy for invasive aspergillosis, and is the new standard of care for this infection. There is significant interest in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B formulation as therapy for invasive aspergillosis. In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials.     

Effect of fluconazole prophylaxis on the incidence of invasive candida infections and bacteraemias in patients with acute leukaemia

Objectives: The efficacy of fluconazole prophylaxis to prevent invasive candida infections in patients with acute leukaemia receiving chemotherapy is not clear. Fluconazole prophylaxis might increase the number of bacteraemias and cause outbreaks of non‐albicans yeast infections. A retrospective single‐centre study was conducted to investigate the effect of fluconazole prophylaxis on the incidence and the species of invasive candida infections and on the number of bacteraemias. Methods: All 1089 adult acute leukaemia patients treated with chemotherapy in 1978–2004 at Helsinki University Central Hospital were included. Data of positive blood cultures, histological samples, and fungal cultures was collected from the patient charts and the microbiology laboratory database. Fluconazole prophylaxis was used in all patients from 2000 on. Results: Invasive candida infection was diagnosed in 74 out of 847 patients (8.7%) treated without fluconazole prophylaxis and in four out of 242 patients (1.6%) receiving the prophylaxis (P < 0.001). The incidence of non‐albicans infections did not increase in the fluconazole prophylaxis group. A larger proportion of patients developed bacteraemias in the prophylaxis group (65%) compared to the non‐prophylaxis group (52%) (P < 0.001). A trend towards more gram‐positive bacteraemias was seen in the prophylaxis group. Invasive candida infections were more common in patients with acute lymphoblastic leukaemia than those with acute myeloid leukaemia, 10.5% vs. 5.9% (P = 0.008). Conclusions: Fluconazole prophylaxis was effective in preventing invasive candida infections in patients with acute leukaemia without increasing non‐albicans infections. The risk of bacteraemias, however, increased     

Current role of minimally invasive approaches in the treatment of early gastric cancer

Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing approximately 50%of newly detected gastric cancer cases in Asian countries.Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis.Laparoscopic and robotic resections for early gastric cancer,including function-preserving resections,have propagated through advances in technology and surgeon experience.The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer.     

血清半乳甘露聚糖在重症患者肺部曲霉菌感染分级诊断中的作用

目的 探索血清半乳甘露聚糖(GM)在重症患者侵袭性肺部曲霉菌感染(IPA)诊断中的作用.方法 前瞻性研究,入选2007年2月-2008年7月北京协和医院加强医疗科中怀疑IPA的患者.每周2次送榆痰真菌培养及血清GM,记录培养及GM阳性的时间、GM的吸光度指数(ODI).按诊断标准刚顾性分为确诊、临床诊断、拟诊及非感染.分析GM在不同诊断级别中的阳性率及在指导分级诊断中的作用.进一步根据患者是否存在粒细胞缺乏及接受影响免疫功能的治疗情况,分为粒细胞缺乏组、非粒细胞缺乏但接受影响免疫功能治疗组及非粒细胞缺乏且未接受影响免疫功能治疗组,比较GM在不同宿主人群中的敏感性、特异性及ODI.结果 94例纳入本研究,最终确诊4例,临床诊断29例,拟诊34例,非IPA 27例.94例中30例GM阳性,总体阳性率31.9%.GM阳性率与诊断级别有明确的相关性.在确诊的4例中,GM阳性3例;临床诊断者阳性率65.5%(19/29);拟诊者阳性率17.6%(6/34),非IPA组阳性率7.4%(2/27)(P=0.001).针对确诊及临床诊断者,GM敏感性66.7%(22/33)、特异性92.6%(25/27)、阳性预计值91.7%(22/24)、阴性预计值69.4%(25/36).GM阳性时间早于真菌培养2～10(5.33±2.17)d.另外,宿主不同GM的阳性率、敏感性、ODI也存在差异.在粒细胞缺乏组、非粒细胞缺乏但接受影响免疫功能治疗组及非粒细胞缺乏且未接受影响免疫功能治疗组间,GM的阳性率分别为52.9%、41.7%、34.6%(P=0.015);敏感性分别为80.0%、70.0%、53.8%(P=0.011);ODI分别为1.365(0.582～6.736)、1.123(0.623～6.868)、0.554(0.522～0.823)(P=0.005).结论 GM在重症患者IPA的早期诊断中仍有指导意义,早于微生物学;其阳性率及敏感性的高低与诊断级别和宿主有关.在应用影响免疫功能的治疗的宿主中有更高的敏感性和ODI.