慢性坏死性肺曲霉病与肺曲霉球临床病理比较分析

目的 了解慢性坏死性肺曲霉病(CNPA)与肺曲霉球的临床表现、影像学和病理学特点.方法 回顾性分析2000至2004年浙江大学附属第一医院手术和病理证实的8例CNPA和26例肺曲霉球患者的临床表现、影像学和病理资料.结果 CNPA和肺曲霉球在发病年龄上差异无统计学意义,且都好发于陈旧性肺结核与肺脓肿患者.8例CNPA患者均有咳嗽、咳痰,7例咯血,5例伴全身中毒症状.26例肺曲霉球患者中,最常见的症状为咯血,有25例,咳嗽、咳痰17例,2例伴有全身中毒症状.影像学上,CNPA和肺曲霉球均可出现空气新月征,有提示性诊断意义,但前者空洞周围有浸润阴影、洞壁较厚和洞壁不规则等特征.病理学上,CNPA和肺曲霉球都可见锐角分支、有隔膜的曲霉菌丝,但前者的特点是肺组织内有曲霉菌丝侵袭、组织坏死和肉芽形成,曲霉菌只在空洞或扩张成囊的支气管内生长,不侵犯肺组织.结论 组织病理检查是鉴别CNPA和肺曲霉球的金标准,临床和影像学检查也有一定价值.     

Chronic necrotising pulmonary aspergillosis: a rare complication in a case of silicosis

Chronic necrotising pulmonary aspergillosis (CNPA) is a rare complication of silicosis whose diagnosis requires a high index of suspicion as it mimics tuberculosis. We report a case of a 52-year-old male with a long history of silica dust exposure and progressively increasing dyspnoea for the past eight years, productive cough, fever, weight loss for past three months and hemoptysis for preceding three weeks. Based on the clinical, radiological and microbiological evidence, he was diagnosed to be a case of CNPA with aspergilloma complicating silicosis.     

Calcium oxalate crystal deposition in a patient with Aspergilloma due to Aspergillus niger

Discrimination between aspergilloma and chronic necrotizing pulmonary aspergillosis (CNPA) based on radiological findings can difficult. We describe a patient with aspergilloma and organizing pneumonia that was possibly caused by Aspergillus niger infection and radiologically mimicked CNPA. A postmortem histological analysis showed diffuse alveolar damage that had originated in peri-cavitary lung parenchyma. Calcium oxalate or Aspergillus niger was located inside, but not outside the cavity in the right upper lobe. Calcium oxalate or other unknown hyphal bioactive components might provoke severe lung inflammation not only adjacent to the cavity, but also on the contralateral side.KEY WORDS : Calcium oxalate crystal deposition, aspergilloma, black deposits, Aspergillus niger     

Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients.

STUDY OBJECTIVE: To characterize clinical, radiographic, and CT findings of chronic necrotizing pulmonary aspergillosis (CNPA) in patients with pneumoconiosis. METHODS: We studied 10 patients with pneumoconiosis who were seen at Asahi Rosai Hospital and received a clinical diagnosis of CNPA during a 15-year period, and detailed the long-term clinical and radiologic courses of four cases. RESULTS: All patients were men, ranging in age from 48 to 77 years (mean, 60.1 years). Their occupational histories included pottery making (n = 9) and coal mining (n = 1). Chest radiographic findings by the International Labor Organization profusion grading system were greater than category 2. All patients were symptomatic, with a productive cough, hemoptysis, and dyspnea. Serum findings were positive for the Aspergillus antibody in seven patients. The radiologic findings consisted of parenchymal infiltrates and cavities mostly containing mycetoma, which generally involved the upper lobes. The disease progressed slowly; in one patient, broad destruction of the lung was observed after > 10 years without antifungal administration. Most of the patients experienced clinical and radiologic improvement after receiving antifungal therapy, by oral, inhaled, or intracavitary administration. CONCLUSIONS: Chronic persistent or progressive upper-lobe infiltrates and cavities in patients with pneumoconiosis should raise the possibility of CNPA. Early diagnosis and initiation of effective therapy are recommended to achieve a better outcome.     

慢性坏死性肺曲霉病的诊断与治疗

目的 探讨慢性坏死性肺曲霉病（CNPA）的诊断与治疗。方法本研究包括8例2000年至2004年间在浙江大学医学院附属第一医院经病理证实的慢性坏死性肺曲霉病住院病例，结合文献分析其临床表现、影像学、诊断和治疗方法。结果CNPA是少见的一种肺曲霉病。最常见的症状是咳嗽、咳痰（8／8）、咯血（7／8）和全身中毒症状（5／8）。“空气新月征”有提示性诊断意义，在本组共发现4例，实变阴影也较为多见（5／8）。CNPA的病理特点是肺组织内曲霉菌丝侵袭、组织坏死和肉芽形成。结论CNPA的临床表现无特异性，影像学检查在其诊断中起重要作用，其诊断需要病理依据支持。所有CNPA患者都需要系统抗真菌药物治疗，对于病程迁延和反复咯血者可以考虑手术切除。     

肺曲霉病外科治疗分析(附15例报告)

目的:探讨肺曲霉病的诊断、外科手术治疗原则、方法及效果。方法:回顾性分析我科2005年至2011年手术治疗的15例采用外科手术治疗的肺曲霉病患者的临床资料和随访结果。结果:15例患者术后证实均为曲霉病,术前诊断符合率为93.3%(14/15),影像学诊断符合率为73.3%(11/15),全组无手术死亡,随访4个月～6年无肺曲霉病复发和播散。结论:手术治疗肺曲霉病能消除症状,预防咯血复发,减少抗真菌药物对患者影响,可根治进而延长患者生命提高患者生活质量。因此,一旦确诊应积极手术治疗。     

Analysis of chronic necrotizing pulmonary aspergillosis (CNPA) cases complicated with non-tuberculous mycobacteriosis (NTM)

OBJECTIVE: To clarify the clinical feature of chronic necrotizing pulmonary aspergillosis (CNPA) complicated with non-tuberculous mycobacteriosis (NTM). SUBJECTS AND METHODS: Forty-one CNPA cases underlying NTM were analyzed according to their clinical backgrounds. RESULTS: Concerning the radiological type of prior NTM, CNPA cases were classified into two groups; 1) resembling pulmonary tuberculosis that usually shows cavitary lesion and 2) micronodule and bronchiectasis pattern, and more than half of cases (61.0%) were classified as the latter type. Average duration between prior NTM and CNPA was 1354 days. Isolation of Aspergillus spp. from sputum was 15 out of 41 (36.6%). Positive rates for Aspergillus galactomannan antigen and anti-aspergillus antibody were 58.5%, 46.3% respectively. With regard to subspecies of mycobacteria, M. avium was most frequent (82.9%). Since 6.8% of NTM cases develop CNPA within 10 years, careful observation of CNPA was required for the management of NTM.     

Chronic necrotizing pulmonary aspergillosis as a complication of pulmonary Mycobacterium avium complex disease

OBJECTIVE AND BACKGROUND: To investigate the characteristic clinical features of chronic necrotizing pulmonary aspergillosis (CNPA) as a complication of pulmonary Mycobacterium avium complex (MAC) disease. METHODS: Clinical analysis of nine cases without a history of old pulmonary tuberculosis in whom CNPA was found to be a complication during the follow-up period for MAC disease. RESULTS: The average duration from the diagnosis of pulmonary MAC disease to the diagnosis of CNPA was 36.0 months. Five patients received antituberculous therapy including clarithromycin for pulmonary MAC disease, but this treatment was ineffective in most. A positive culture for Aspergillus spp. from sputum and a bronchoscopic specimen and clinical evidence of a chronic infective process were recognized in all cases at the time of detection of CNPA. Serological fungal examinations for anti-Aspergillus IgG antibody were initially negative and became positive in all cases during the follow-up period of pulmonary MAC disease. The presence of CNPA surrounding the cavity previously caused by MAC was characterized by local thickening of the cavity with a fungus ball and the appearance of an infiltration shadow surrounding the cavity. In most of the cases, CNPA was at first treated with oral itriconazole and then with i.v. infusion of micafungin, but the clinical efficacy was generally poor. CONCLUSION: The results of this study showed that during the long follow-up period of patients with pulmonary MAC disease it is important to not only carry out serological examinations, but also perform radiological examinations using chest CT.     

Undiagnosed lung cancer complicated by intracavitary aspergillosis]

A 54-year-old man was treated with an antifungal agent (itraconazole) for post-tuberculous intracavitary aspergillosis. Though clinical and radiological findings indicated that the patient's symptoms had gone into remission, aspergillosis recurred 4 months after the cessation of antifungal chemotherapy, requiring that the patient undergo an operation. Intraoperative and pathological findings revealed a squamous cell carcinoma contiguous to the cavity containing the aspergilloma. Though a few cases of aspergilloma within cavitating pulmonary carcinomas have been reported in the literature, the case of lung cancer we report was thought to arise from preformed lung scars surrounding a post-tuberculous cavity that contained an aspergilloma. Although conclusive distinctions between neoplasms and fungal infections are difficult to make, careful observation of the radiographic features is necessary when treating patients with fungus ball-type aspergillosis.     

Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients

BACKGROUND: There is no recognized medical treatment for chronic pulmonary aspergillosis (CPA) apart from surgery in patients with simple aspergilloma. To evaluate the efficacy of voriconazole in this setting, we conducted a retrospective multicenter study over a 3-year period. METHODS: For inclusion in the study, patients had to have received voriconazole for treatment of confirmed or probable CPA with a follow-up of at least 6 months. Clinical, radiologic, and mycologic data were collected at baseline, every 2 to 3 months, and at the end of treatment or at the date point. RESULTS: Twenty-four patients were included in the study, among which 9 patients presented with chronic cavitary pulmonary aspergillosis and 15 presented with chronic necrotizing pulmonary aspergillosis (CNPA). Voriconazole was given as a first-line treatment to 13 patients. The median duration of treatment and follow-up were 6.5 and 10 months, respectively. Three patients had to stop treatment with voriconazole because of toxicity. Symptoms and imagery findings were improved in 16 of 24 patients and 17 of 24 patients, respectively, at the end of follow-up. Mycology, which was positive at baseline in 21 of 23 patients, was negative in 18 of 19 patients at the end of follow-up; serologic test results were also negative in 6 of 19 evaluable patients, all of whom had CNPA. Improved radioclinical findings and mycologic eradication were observed at the end of follow-up in 11 of 19 patients (58%). Patients in whom the disease was controlled had a significantly longer median duration of treatment than patients in whom it was uncontrolled (9 vs 6 months, respectively; p = 0.04). CONCLUSION: Voriconazole provides effective treatment of CPA with an acceptable level of toxicity.     

肺曲菌病的X线表现与病理对照分析

目的对照病理改变探索肺曲菌病X线影像形成的机制?方法对51例肺曲菌病的X线所见,与28例病理标本对照分析?结果过敏性及侵袭性各1例,寄生性49例?X线影象在寄生性中最具特点,在基础性病变形成的空洞/空腔中有大小不等,形态不一的菌块,形成游离于空洞内的球体,洞内球周为具有特征的半月征及晕征?是寄生性肺曲菌病的主要诊断依据?结论1.肺结核是寄生性肺曲菌病的最多见的基础病?2.支气管动脉造影证实:曲菌病咯血的病理基础是支气管动脉损害。     

Pseudo-tumoral aspergilloma

Aspergilloma is the most common form of pulmonary aspergillosis, generally developing pre-existing lung cavities. Fiberoptic bronchoscopy is required in case of hemoptysis. We report the case of a 74-year-old man with pulmonary aspergilloma where fiberoptic bronchoscopy visualized mycetoma and cavitation. Visualization and biopsy of the fungus ball during fiberoptic bronchoscopy is rare.     

Bronchopulmonary aspergillosis infections in the non-immunocompromised patient

The definition of broncho-pulmonary aspergillosis infections in non-immunocompromised patients remains vague and a wide range of clinical, radiological and pathological entities have been described with a variety of names, i.e. simple aspergilloma, complex aspergilloma, semi-invasive aspergillosis, chronic necrotizing pulmonary aspergillosis, chronic cavitary and fibrosing pulmonary and pleural aspergillosis, pseudomembranous tracheobronchitis caused by Aspergillus, and invasive aspergillosis. However, these disease entities share common characteristics suggesting that they belong to the same group of pulmonary aspergillosis infectious disorders: 1- a specific diathesis responsible for the deterioration in local or systemic defenses against infection (alcohol, tobacco abuse, or diabetes); 2- an underlying bronchopulmonary disease responsible or not for the presence of a residual pleural or bronchopulmonary cavity (active tuberculosis or tuberculosis sequelae, bronchial dilatation, sarcoidosis, COPD); 3- generally, the prolonged use of low-dose oral or inhaled corticosteroids and 4- little or no vascular invasion, a granulomatous reaction and a low tendency for metastasis. There are no established treatment guidelines for broncho-pulmonary aspergillosis infection in non-immunocompromised patients, except for invasive aspergillosis. Bronchial artery embolization may stop hemoptysis in certain cases. Surgery is generally impossible because of impaired respiratory function or the severity of the comorbidity and when it is possible morbidity and mortality are very high. Numerous clinical cases and short retrospective series have reported the effect over time of the various antifungal agents available. Oral triazoles, i.e. itraconazole, and in particular voriconazole, appear to provide suitable treatment for broncho-pulmonary aspergillosis infections in non-immunocompromised patients.     

Two cases of pulmonary aspergillosis successfully treated with combinated micafungin and itraconazole therapy

We report 2 cases of pulmonary aspergillosis treated successfully by combining micafungin and traconazole. Case 1: A 51-year-old man with hemoptysis and dyspnea on effort treated for pulmonary tuberculosis and aspergillosis was found on chest CT on admission to have a fungus ball in the left upper lobe and increasing consolidation around the cavity of both lung fields. Bronchoscopy proved positive for aspergillus PCR in bronchial lavage. He was diagnosed with chronic necrotizing pulmonary aspergillosis, based on clinical and radiological findings and the positive reaction for aspergillus PCR. He was treated with micafungin alone at first, this proved ineffective, so itraconazole was added, resulting in improvement. Case 2: A 24-year-old woman with stabilized Hodgkin's disease (mixed). She had suffered from a cough and back pain, and chest CT showed increasing consolidation inside and around a giant bulla. She was diagnosed with chronic necrotizing pulmonary aspergillosis, based on isolation for Aspergillus sp. in sputum culture and a positive reaction for Aspergillus antigen in bronchial lavage and Aspergillus antibody in serum. She was treated with the combined micafungin and itraconazole, which rapidly improved symptoms and radiological findings. Pulmonary aspergillosis therapy is often difficult, because delivery of the drug to the infection site is limited and drug tolerance is poor. We found that combination micafungin and itraconazole therapy is tolerable and effective in these cases.     

Noninvasive Aspergillus pulmonary disease

Noninvasive Aspergillus pulmonary disease may be the result of a host response to Aspergillus antigens or colonization of the lung with Aspergillus species. The prototype example of each of these phenomena are allergic bronchopulmonary aspergillosis and aspergilloma. Allergic bronchopulmonary aspergillosis is a form of asthma associated with a Type I, III, and IV allergic response to Aspergillus antigens. It presents clinically as asthma but is also associated with bronchiectasis, airway destruction, and permanent lung injury if inadequately treated. Treatment consists of anti-inflammatory agents such as corticosteroids. Antifungal agents may also be useful to lower the fungal antigen load. Aspergillomas grow in areas of devitalized lung. They may manifest as asymptomatic radiographic abnormalities. The concern is that they may lead to hemoptysis that can be life threatening. Definitive treatment is surgical resection, but this is often prohibited because these patients often have inadequate lung function to tolerate thoracic surgery. Other treatment options include azoles and percutaneous instillation of antifungals.     

肺结核并发肺曲菌球47例外科治疗

目的　探讨肺曲菌球与肺结核的关系及其诊断和治疗;方法 对13年经外科手术治疗的47例肺结核合并曲菌球病人进行回顾性分析;结果 男性31例,占66.0%,病程>5年27例。咯血症状突出,41例,占87.2%。47例肺结核合并曲菌球中,术前明确诊断32例,占68.1%,漏误诊率31.8%。45例治愈,占95.7%,死亡2例,占4.2%。术后并发症10例,分别为胸腔感染、支气管胸膜瘘、肺炎、肺不张、支气管哮喘、呼吸衰竭和失血性休克。结论 肺曲菌球病见于肺结核空洞患者,在长期规律抗结核治疗后仍反复咯血,漏诊率较高,手术治疗为首选,效果较好。     

Endobronchial aspergilloma – Presenting as solitary pulmonary nodule

As compared to aspergilloma which is usually developed after complication of tuberculosis in India, endobronchial aspergilloma is a rare disease entity. We report a rare case of endobronchial aspergilloma which is presented radiologically as a solitary pulmonary nodule. A 24-year-old male presented to the Department of Tuberculosis and Chest Diseases with moderate to severe hemoptysis for the last three months. Chest X-ray (PA view) showed ill-defined homogenous shadow in the right upper zone. CECT Thorax review showed intrabronchial mass in the posterior segment of the right upper lobe. CT-guided FNAC was performed, which reveals Aspergillus hyphae mixed with sputum and necrotic material, without any evidence of malignancy. Fibreoptic bronchoscopy was done, it reveals a ball-like region, occluding partially, the lumen of the posterior segment of right upper lobe with hyperemia. The ball was movable. Biopsy was performed and it revealed a partially eroded lining of metaplastic squamous epithelium, overline of chronically inflamed granulation tissue and scar intermingled with fungal hyphae. Serological test for Aspergillus precipitin was positive. The ball was removed using forceps and basket. Endobronchial aspergilloma may be present as solitary pulmonary nodule on chest X-ray. Bronchoscopic and endobronchial biopsies are invaluable in the diagnosis of endobronchial aspergilloma.     

Pleural perforation of an aspergilloma cavity occurring in a patient with interstitial lung disease

An aspergilloma is a fungus ball resulting from colonization of pre-existing pulmonary cavities, which usually represents a non-invasive form of aspergillosis. Spontaneous rupture of the cavity containing the fungi into the pleural space is an unusual complication that has been reported occasionally in patients with leukemia and invasive aspergillosis. We report on this unusual complication occurring in a patient with underlying interstitial lung disease, in whom the aspergilloma cavity abruptly ruptured into the pleural space with subsequent hydropneumothorax and pleural spillage of the fungi.     

慢性阻塞性肺疾病合并侵袭性肺曲霉病病例报告并文献回顾

目的:结合文献总结慢性阻塞性肺疾病(COPD)合并侵袭性肺曲霉病(IPA)患者的临床特征,提高早期诊治水平。方法:对1例经支气管镜肺活检确诊的重度COPD合并IPA患者的临床资料进行分析,并回顾复习有关文献。结果:COPD合并IPA患者严重呼吸困难多见。本例患者胸部CT可见中央型支气管扩张、小结节影、不典型渗出影,血清半乳甘露聚糖抗原检测(GM试验)及1.3-β-D葡聚糖检测(G试验)阳性。经支气管镜肺活检病理学检查见曲菌丝及炎症细胞浸润。结论:COPD合并IPA诊断困难,病死率高,综合分析临床表现、影像学、微生物学及血清学检查结果是提高诊断率、改善预后的有效手段。若临床情况允许,应尽早进行支气管镜等有创检查确定诊断。     

Results of surgical treatment for pulmonary aspergilloma with 26 cases in six years: a single center experience

Surgery for pulmonary aspergilloma is reputed to be risky. We analyzed our results of the surgical treatment for pulmonary aspergilloma. Between 2003 and 2009, 26 patients underwent thoracotomy for treatment of pulmonary aspergilloma in our center. Results were evaluated retrospectively. There were 5 female and 21 male patients, with a mean age of 44 ± 11.6 years (28-70). The patients were divided into two groups, group A (simple aspergilloma; n= 8) and group B (complex aspergilloma; n= 18). Major underlying diseases were tuberculosis (61.5%). The most common indication for operation was hemoptysis (57.6%). Of our patients, 23% were complaining of massive hemoptysis or recurrent hemoptysis. Other patients were complaining of mild symptoms and some of them were totally asymptomatic. We performed 15 (57.6%) lobectomies (3 with associated segmentectomies), 8 (30.6%) segmentectomies/wedge resections, 2 (7.6%) pneumonectomies, and 1 (3.8%) cavernoplasty. Postoperative complications occurred in 15 (57.6%) patients. Complications occurred in 72.2% patients of complex aspergilloma, whereas 25% occurred in simple aspergilloma (p= 0.03). Major complications included prolonged air leak, empyema, air space. One patient who underwent lobectomies for complex aspergilloma developed bronchopleural fistula and died of respiratory failure on the 20th postoperative day. Operative mortality was 3.8%. The average postoperative hospital stay was 12.9 days. The mean follow-up period was average 44 months. The actuarial survival at 3 years was 90% and 100% for complex aspergilloma and simple aspergilloma, respectively (p> 0.05). There was two recurrence of disease (8%). But no recurrence of hemoptysis. Low morbidity rate may have been due to the selection of patients with localized pulmonary disease in this study. Surgical resection of asymptomatic or symptomatic pulmonary aspergilloma is effective in preventing recurrence or massive hemoptysis for patients whose condition is fit for pulmonary resection with reasonable mortality, morbidity and survival rates.