COPD患者继发侵袭性肺曲菌病的危险因素研究

目的探讨COPD患者继发侵袭性肺曲菌病（IPA）的危险因素。方法将37例COPD继发IPA患者（病例组）及74例未继发IPA的COPD患者（对照组）的临床指标纳入单因素和多因素分析。结果 COPD继发IPA与下列4个因素密切相关：机械通气（OR值为5.625,95%CI为1.601-19.765）,侵入性操作（OR值为4.876,95%CI为1.922-12.37）,低蛋白血症（OR值为3.618,95%CI为1.580-8.264）,使用激素（OR值为2.558,95%CI为1.086-6.026）。结论 COPD继发IPA是多个因素相互影响的结果,其中机械通气、侵入性操作、低蛋白血症、使用激素等4个因素是独立危险因素。     

Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients

BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis. Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy. From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests. We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the 215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the diagnosis was definite and in 14 it was suspected. In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans. On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days. In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days. INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.     

The accuracy of serum galactomannan assay in diagnosing invasive pulmonary aspergillosis

Galactomannan (GM) antigen is an aspergillus specific antigen that is released during the growth phase of invasive aspergillosis. We aimed to find the optimum cutoff and accuracy of serum Galactomannan assay in immunocompromised patients. Immunocompromised patients diagnosed with invasive pulmonary aspergillosis (IPA) based on the European Organization for Research and Treatment of Cancer/Invasive Mycosis Study Group (EORTC/MSG) with three levels of certainty proven, probable and possible, referred for GM antigen measurement at Immunology, Asthma and Allergy Research Institute (IAARI) from 2006 to 2009 and if they met the criteria were enrolled in this study. Totally 49 patients with IPA were enrolled in our study. According to EORTC/MSG, patients categorized into three levels of certainty: They were diagnosed as 'proven' invasive pulmonary aspergillosis 16(32.7%), 'probable' 18(36.7%) and 'possible' 15(30.6%). The most common host risk factor was solid tumors 17(34.7%). The accuracy of Galactomannan assay increased from 0.5 to 2 cutoffs. The optimum sensitivity and specificity obtained at the index cutoff of ≥1.5 for diagnosis of "proven" IPA; which were respectively, 69.2% and 72.2%. Other cutoffs had high variance between sensitivity and specificity for diagnosis of IPA. The calculated cutoff gained by receiver operating characteristic (ROC) analysis for detecting proven IPA was 1.5. Intermediate accuracy of serum GM test in conjunct with clinical findings would help early IPA detection among immunocompromised patients.     

Subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report

Subacute invasive pulmonary aspergillosis (IPA) represents a form of chronic pulmonary aspergillosis which affects immunocompetent individuals or mildly immunocompromised persons with underlying pulmonary disease. Pneumothorax can be a rare complication of subacute IPA due to a leakage of air from an air-filled lung cavitation into the pleural space. Herein, we report rare and unusual case of pneumothorax in a patient with pulmonary cavity infection. A 40-year-old woman was admitted to thoracic surgery due to complete pneumothorax of the left lung. She was active smoker with untreated chronic obstructive pulmonary disease (COPD). After thoracic drainage multiple cavity forms in the both lungs were noticed. Galactomannan antigen was positive in bronchoalveolar lavage as well as culture of Aspergillus fumigatus. Antifungal treatment by voriconazole was started and continued during 6 months with a favorable outcome. This case highlights that subacute IPA is a diagnose that should be considered in patients with end-stage COPD, low body mass index, or patient who developed pneumothorax. The results of our case show that voriconazole is a safe and effective treatment as primary or salvage therapy in subacute forms of IPA, irrespective of the immunological status of the patients.     

Remember mycobacterial disease in hairy cell leukaemia (HCL).

Primary intestinal invasive aspergillosis is rarely reported in leukaemic patients. We describe a case of jejunal invasive aspergillosis in the setting of aplasia following chemotherapy for acute myeloid leukaemia. The diagnosis was confirmed by biopsy obtained during surgery and our polymerase chain reaction (PCR) test confirmed Aspergillus flavus as the fungus responsible. This patient had high levels of circulating galactomannan, an antigen secreted by Aspergillus sp., in serum. The ELISA test for galactomannan has been developed to improve the diagnosis of invasive aspergillosis but presents a 5-15% false positive rate. We suggest that some false positive results might be due to non-respiratory invasive aspergillosis, the usual localization of invasive aspergillosis. Our PCR test was also positive in serum. In case of positive results in serum with antigen and/or PCR tests without respiratory symptoms, the intestinal localizations should be investigated.     

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.     

侵袭性肺曲霉菌病8例临床分析

目的总结侵袭性肺曲霉菌病(IPA)的临床特点,以利早期诊断。方法回顾性分析2006年4月至2006年12月解放军总医院呼吸科确诊的8例IPA患者的临床资料。结果本组病例全部经病理诊断为IPA。6/8的患者出现发热症状;1/2的患者具有"新月征"、"气环征"的CT表现;7/8的患者有病灶内空洞或空腔形成;1/2患者痰培养曲霉菌阳性,1/4的患者在病理诊断前痰培养阳性;本组入院前初次诊断正确率为0;本组1例系统性曲霉菌病患者死亡,7例经治疗好转出院。结论IPA的临床症状缺乏特异性,早期具有典型CT表现者较少,痰培养曲霉菌阳性率低,这些原因容易造成早期误诊。因此应关注有基础疾病的患者,对于新发肺部阴影者警惕IPA的可能,对可以耐受经皮肺穿刺或气管镜者,通过尽早病理检查等措施可提高早期诊断率。     

Invasive pulmonary aspergillosis associated with influenza B

Invasive pulmonary aspergillosis (IPA) usually occurs in immunocompromised patients. However, rarely, this infection can occur in normal hosts. This review of the literature identified 13 cases of IPA associated with influenza, of which 12 had influenza A and the type of influenza was not mentioned in the other case. Reported here is a case of IPA, which was associated with influenza B, in a 63-year-old immunocompetent woman. Her lungs showed gross invasion and she was treated with itraconazole and amphotericin B. She required mechanical ventilation for about 5 months but recovered completely. This is the first reported case of IPA associated with influenza B.     

Aspergillosis in the acquired immunodeficiency syndrome

The role of Aspergillus species as a pathogen in acquired immunodeficiency syndrome (AIDS) has not been clearly defined. From 1984 to 1989, more than 2,000 AIDS patients were seen at Beth Israel Medical Center, New York. Aspergillus was isolated in ten patients; seven had invasive disease and three had noninvasive disease. Invasive pulmonary aspergillosis (IPA) was diagnosed in six patients and invasive renal aspergillosis was found in one patient. Five were homosexual men and two were intravenous drug users. At presentation, all ten had fever, seven had cough, eight had dyspnea, and five had pleuritic chest pain. Chest roentgenograms revealed focal infiltrates in six patients, bilateral interstitial infiltrates in two patients, and bilateral pneumothoraces in one patient. Predisposing conditions included corticosteroid therapy in four, granulocytopenia (less than 1,000/cu m) in two, and broad-spectrum antibiotic therapy in five. Three of the four patients receiving corticosteroids received them as adjuvant therapy for Pneumocystis carinii pneumonia (PCP). Aspergillus was identified antemortem in eight patients, in bronchoalveolar lavage (BAL) fluid in six, in transbronchial biopsy specimen in three, in open lung biopsy specimen in one, and postmortem in one patient. Six of seven patients had at least one concomitant pulmonary process. Six underwent necropsy and findings showed IPA in three, disseminated aspergillosis in two, and PCP in one. Invasive aspergillosis, although significant, is uncommon in AIDS. When Aspergillus is isolated in the setting of corticosteroid therapy, antibiotics, or granulocytopenia, one must suspect invasive disease.     

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

Aspergillus spp. cultured in specimens from the airways of chronic obstructive pulmonary disease (COPD) patients are frequently considered as a contaminant. However, growing evidence suggests that severe COPD patients are at higher risk of developing invasive pulmonary aspergillosis (IPA), although IPA incidence in this population is poorly documented. Some data report that COPD is the underlying disease in 1% of patients with IPA. Definitive diagnosis of IPA in COPD patients is often difficult as tissue samples are rarely obtained before death. Diagnosis is therefore usually based on a combination of clinical features, radiological findings (mostly thoracic computed tomography scans), microbiological results and, sometimes, serological information. Of 56 patients with IPA reported in the literature, 43 (77%) were receiving corticosteroids on admission to hospital. Breathlessness was always a feature of disease and excess wheezing was present in 79% of patients. Fever (>38 degrees C) was present in only 38.5%. Chest pain and haemoptysis were uncommon. Six out of 33 (18%) patients had tracheobronchitis observed during bronchoscopy. The median delay between symptoms and diagnosis was 8.5 days. The mortality rate was high: 53 out of 56 (95%) patients died despite invasive ventilation and antifungal treatment in 43 (77%) of them. In chronic obstructive pulmonary disease patients, invasive pulmonary aspergillosis currently carries a very poor prognosis. Outcome could perhaps be improved by more rapid diagnosis and prompt therapy with voriconazole.     

56例肺曲霉病危险因素及临床特征分析

目的探讨侵袭性肺曲霉病(IPA)危险因素和临床特征,提高诊治水平。方法回顾性分析新疆医科大学第一附属医院2010年1月至2016年1月诊断为肺曲霉病患者的临床资料,分析IPA发生的高危因素、临床特点。结果 56例肺曲霉病患者中,24例为IPA,发生率42.86%。使用两种以上抗生素、慢阻肺、有创机械通气、多次痰培养曲霉阳性、重症肺炎为IPA高危因素,其中使用两种以上抗生素为独立危险因素。IPA患者易出现咯血,发热症状;肺部高分辨CT表现为多发、斑片样渗出、胸腔积液较多;IPA总体预后差。结论侵袭性肺曲霉病危险因素多,预后差,使用两种以上抗生素为IPA独立危险因素。     

Clinical applicability of the new EORTC/MSG classification for invasive pulmonary aspergillosis in patients with hematological malignancies and autopsy-confirmed invasive aspergillosis

Diagnosis of invasive pulmonary aspergillosis (IPA) is often difficult. Recently, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) has proposed new criteria for the classification of invasive fungal infections. We have studied the clinical applicability of this classification in 22 patients with hematological malignancies who had IPA at autopsy. While alive, according to the EORTC/MSG criteria, only 2 patients were classified as having proven IPA, 6 as probable, 13 as possible, and 1 was unclassifiable. Of the patients, 64% had no microbiological or major clinical criteria before death. Although the EORTC/MSG criteria are an important step forward in the standardization of definitions used for IPA in clinical research studies, most patients who die with extensive lung disease only reach a level of possible or probable IPA during life, further highlighting that these guidelines should not be used for clinical decision-making.     

Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemia

Respiratory failure is a severe complication of invasive pulmonary aspergillosis (IPA). Its pathogenesis is not well understood. We herein describe three cases of subacute respiratory failure that occurred during the recovery phase of neutropenia following induction chemotherapy for acute leukaemia with IPA. In each case, severe neutropenia (19-85 days), high-grade fever, severe anaemia, the use of granulocyte-colony-stimulating factor and increasing infusion volume were noted. As the neutrophil count was recovering, the shadows on the chest X-ray expanded with progressing hypoxia. We should pay attention to the respiratory failure during the recovery phase of neutropenia in patients with IPA.     

Toll样受体与侵袭性肺曲霉病研究进展

近年来,侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)的发病率呈上升趋势,严重威胁着免疫缺陷患者的生命.Toll样受体(Toll-like receptor,TLR)是一种病原体相关的分子模式识别受体.体内、体外实验均表明,TLR在IPA发病过程中发挥着重要作用,其中最为重要的是TLR2和TLR4.     

Cavitating invasive pulmonary aspergillosis visualized and diagnosed by ultrathin bronchoscopy

A definitive diagnosis of invasive pulmonary aspergillosis (IPA), which usually occurs in immunocompromised patients, is often difficult. We report two cases of cavitating IPA in a peripheral pulmonary region in patients who were receiving corticosteroids, in whom the cavity was successfully visualized and sampled during ultrathin bronchoscopy. Ultrathin bronchoscopy provides a new option for definitive diagnosis of cavitating IPA.     

Management of invasive pulmonary aspergillosis in hematology patients: a review of 87 consecutive cases at a single institution.

Eighty-seven patients with hematologic malignancies and invasive pulmonary aspergillosis (IPA) were identified between 1982 and 1995. Of these, 39 underwent lung resection on the basis of radiological detection of at least 1 lesion with imaging suggestive of aspergillosis (LISA). IPA was confirmed histologically in 35. The presence of LISA had 90% positive predictive value for IPA. The actuarial survival at 2 years was 36% for 37 patients treated surgically, 20% for 12 patients with unresected LISA but no cultures of Aspergillus species, and 5% for 21 patients diagnosed only by isolation of Aspergillus from respiratory secretions. Analysis by proportional hazard models showed a significant independent negative association between the radiological appearance of LISA and death from all causes. Relapsed hematologic disease was independently significantly associated with death. Age, sex, surgery, previous bone marrow transplantation, or Aspergillus isolation were not independent predictors of death. IPA presenting as LISA carries a relatively good prognosis, possibly explaining the better survival of patients undergoing surgery for such lesions.     

Surgical resection for successful treatment of invasive pulmonary aspergillosis: report of 3 cases

We present 3 patients, 2 with recent heart transplants, complicated with invasive pulmonary aspergillosis (IPA), treated successfully with surgical resection. These patients demonstrate the role of surgery in management of IPA, and 2 heart transplant patients are of particular interest as surgical treatment of IPA after solid organ transplantation is seldom reported.     

乙型肝炎病毒相关肝功能衰竭合并侵袭性肺曲霉菌病的临床特点与转归

目的 探讨HBV相关肝功能衰竭合并侵袭性肺曲霉菌病(IPA)的临床特征、危险因素、诊治及预后.方法 采用病例对照研究的方法,回顾性分析43例HBV相关肝功能衰竭合并IPA患者的临床特征、危险因素、诊治经过、预后及转归等,并选取同期住院的43例HBV相关肝功能衰竭合并单纯细菌感染患者以及43例未合并感染的HBV相关肝功能衰竭患者作为对照.计量资料采用方差分析,计数资料采用卡方检验,多因素分析采用Logistic回归分析.结果 合并感染的HBV相关肝功能衰竭患者PTA和PLT显著下降,MELD评分升高,尤以IPA组患者为著,合并IPA前后的对比结果亦是如此.IPA组患者1年内病死率为100.0%,明显高于单纯细菌感染组的65.10%,两者均高于未合并感染组的39.50%;Logistic回归分析结果显示,住院时间延长、使用大量抗菌药物、侵入性操作频繁等是HBV相关肝功能衰竭合并IPA的危险因素.结论 HBV相关肝功能衰竭患者合并IPA后病情迅速恶化、病死率高、预后差,提高对其早期表现的认知度,尽早诊断和进行强有力的抗真菌治疗,是提高HBV相关肝功能衰竭合并IPA患者生存率的有效方法.

Abstract：

Objective To investigate the clinical features, risk factors, diagnose, treatments and prognosis of patients with hepatitis B virus (HBV)-related liver failure complicated with invasive pulmonary aspergillosis (IPA). Methods A case-control study was performed to retrospectively analyze the clinical data of 43 patients with HBV-related liver failure complicated with IPA. A cohort of 43 patients with HBV-related liver failure complicated with bacterial infection only was analyzed at the same time and another cohort of 43 patients with HBV-related liver failure without any infections served as the control group. Results Compared with the control group, patients with infection had lower platelet counts and prothrombin activity, higher scores of model for end-stage liver disease (MELD), especially the patients with IPA (F=42.43,13.69,14, 22, all P＜0.01). And the similar results were observed in patients with IPA group before and after Aspergillus infection (F= 12.09,14.52,-16.74, all P＜0.01). Furthermore, the annual mortality was 100. 0% in patients with IPA,which was higher than that of patients complicated with bacterial infection only; and both groups were higher than control group of patients without infection. The statistic results showed that patients with longer length of stay, more antibiotics usage, and more invasive procedures were all risk factors of HBV-related liver failure complicated with IPA. Conclusions Conditions of patients with HBV-related liver failure deteriorate rapidly after complicated with IPA and patients have higher mortality and poorer prognosis.Therefore, it will be effective to enhance the recognition of the early clinical manifestations, and make diagnosis timely and treat with potent anti-fungal therapy to improve their survival.     

Chronic granulomatous disease in an adult recognized by an invasive aspergillosis

A 20-year-old man without any history of a pulmonary disease presented initially with a 1-day history of fever and tachypnea and developed an acute respiratory failure within 24 hours. Microbiological and histological examinations raised an invasive pulmonary aspergillosis (IPA). A chronic granulomatous disease was identified as the predisposing factor leading to this severe fungal infection. Chronic granulomatous disease is caused by a reduced ability of phagocytes to mount an oxidative burst due to a defect in the nicotinamide adenine dinucleotide phosphate oxidase. Although IPA occurs usually in severely immunocompromised patients, it should be kept in mind that there are an increasing number of cases developing IPA in the setting of apparent health or to date undiagnosed immunodeficiency that requires further diagnostics.     

COPD合并侵袭性肺曲霉病5例并文献复习

目的 分析重症COPD合并侵袭性肺曲霉病(IPA)患者临床特征,提高对COPD合并IPA的认识.方法 过从2015年6月至2016年3月西京医院呼吸与危重症科诊断的5例COPD合并IPA患者的资料进行回顾性分析及文献复习.结果 5例COPD合并IPA患者中确诊3例,临床诊断2例.在入住RICU前5例使用广谱抗生素,4例使用大量激素.5例均表现为气道显著痉挛,4例使用无创机械通气后有2例转为有创机械通气,2例自动出院.胸部CT早期无特殊表现,病情进展出现沿支气管周围渗出病变以及实变,病变多发.支气管镜下可见气道黏膜水肿、充血、溃烂、伪膜形成,痰液黏稠.病情进展迅速,病死率高.结论 COPD合并IPA容易误诊,病情进展快,病死率高,需充分认识其临床特点以提高诊断率及降低死亡风险.