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.     

Chronic necrotizing pulmonary aspergillosis in the surgically treated lung]

A 76-year-old man was admitted because of bloody sputum persisting for 3 months. Right upper lobectomy had been performed for non-small cell lung cancer (well-differentiated adenocarcinoma, pT1NOMO) 6 years prior, and the patient had uncontrolled diabetes. Chest computed tomography on admission showed a 1-cm nodule (fungus ball) in a cavitary lesion and consolidation with an air bronchogram were present in the right lung. Aspergillus flavus was detected in the patient's sputum, and laboratory tests were positive for Aspergillus antigen and antibody. Chronic necrotizing pulmonary aspergillosis (CNPA) was diagnosed in the surgically treated lung.     

Superinfection of chronic necrotizing pulmonary aspergillosis by Mycobacterium tuberculosis.

A 63-year-old woman with chronic necrotizing pulmonary aspergillosis complicated by active pulmonary tuberculosis is reported. A small infiltrative shadow appeared, but no definite diagnosis was made. Six years later the shadow was found to have increased in size; chest CT revealed a fungus ball, while a transbronchial lung biopsy revealed aspergillus hyphae. The intrabronchial inoculation of amphotericin B proved ineffective, and a lobectomy was performed. Histopathologic findings showed necrotic granulomas containing aspergillus and some acid-fast bacilli. While the superinfection of healed tuberculous lesions by Mycobacteria or Aspergillus species is well documented, their coexistence is rare.     

Place of surgery in pulmonary aspergillosis and other pulmonary mycotic infections

Surgery is part of the therapeutic strategy of aspergillosis and mucormycosis. The aspergilloma is defined as a rounded mass, developing in a cavity by the proliferation of spores of Aspergillus. The most common complication was haemoptysis reported in 50-95% of cases. The pleuropulmonary lesions predisposing are: tuberculosis, residual pleural space, emphysema and lung destroyed by fibrosis or radiotherapy or bronchiectasis. The indications for surgery depend on symptoms, respiratory function, the parenchyma and the type of aspergilloma (simple or complex). In a patient with an intrapulmonary aspergilloma, lung resection preceded by embolization is recommended based on respiratory function. For intrapleural aspergilloma, thoracoplasty is recommended according to the patient's general condition. The invasive pulmonary aspergillosis (IPA) is characterized by an invasion of lung tissue and blood vessels by hyphae in immunocompromised patients. The death rate of patients who have an API after treatment for leukemia or lymphoma was 30 to 40%, after bone marrow transplantation 60%, after solid organ transplantation from 50 to 60% and after any other cause of immunocompromising from 70 to 85%. The main cause of these deaths is massive hemoptysis. Surgery (lobectomy) is indicated for the prevention of hemoptysis when the mass is in contact with the pulmonary artery or one of its branches, and if it increases in size with the disappearance of border security between the mass and the vessel wall. The patient will be operated in an emergency before the white blood cells do not exceed the threshold of 1000 cells/μl. A persistent residual mass after antifungal treatment may justify a lung resection (lobectomy or wedge) before a new aggressive therapy. Mucormycosis affects patients following immunocompromising states--haematologic malignancy, diabetes mellitus, transplantation, burns and malnutrition. The treatment of pulmonary mucormycosis combines surgical and medical approach.     

A case of pulmonary aspergillosis presenting the pulmonary arterial supply suggested with dynamic MRI]

A 67-year-old man with a past history of pulmonary tuberculosis had been referred to our department complaining of bloody sputum. The chest radiograph on admission showed a cavity in the left upper lung field. Chest CT showed a mass-like fungus ball in the cavity. Pulmonary aspergillosis was diagnosed from the sputum mycology, serum Aspergillus antigen and antibody. Even though 150 mg per day Funguard (micafungin sodium) was given intravenously for 4 weeks, the pulmonary aspergillosis did not improve. Dynamic MRI obtained 20 seconds after intravenous injection of contrast material revealed penetrating vessels in the wall of the cavity, and dilated and proliferative vessels surrounding the cavitary lesion. On the basis of the MRI findings which suggested the risk of massive hemoptysis, we performed left upper lobectomy. The histological specimen revealed dilated pulmonary arteries in the wall of the cavity, corresponding to the penetrating vessels on MRI. This is the first report of radiologic-pathologic correlation using dynamic MRI for pulmonary aspergillosis, to the best of our knowledge.     

慢性空洞性肺曲菌病临床表现

目的 探讨慢性空洞性肺曲菌病的临床症状、影像学特点、诊断和治疗方法.方法 对3例误诊为肺结核而长期抗结核治疗无效,甚至导致肺毁损,经手术切除病变肺叶或经支气管肺活检术,病理确诊为慢性空洞性肺曲菌病的临床资料进行总结.结果 慢性空洞性肺曲菌病常见的临床症状为慢性咳嗽、疲劳不适,严重者出现气短.影像学显示空洞出现在肺上叶,且进行性增大,有时为多发.组织学检查在空洞内可找到真菌菌丝,周围肺组织有慢性炎症和肺纤维化,伴有胸膜肥厚.结论 慢性空洞性肺曲菌病是慢性肺曲菌病的一种亚型,临床上少见,常见影像学特点是肺内空洞进行性增大,组织学检查在空洞内可找到真菌菌丝,治疗上需积极抗真菌,必要时可手术.     

A case of chronic necrotizing pulmonary aspergillosis diagnosed using percutaneous intracavitary endoscopy]

A 65-year-old man with pneumoconiosis visited our hospital for dyspnea on effort. Chest radiography and computed tomography on admission showed cavities with an air-fluid level, consolidation in the right lower lung, and right pleural effusion. The thoracic cavity and an infected cyst were drained, and antibiotics were administered. On detection of molds like Aspergillus species and of aspergillus antigen from the sputum, aspergillosis was suspected and amphotericin B was administered intravenously. Renal dysfunction caused by amphotericin B led to its withdrawal. Abnormal shadows in the chest radiographs and computed tomograms did not improve. To aid in diagnosis, percutaneous intracavitary endoscopy was performed. Yellow-white mural nodules resembling cauliflower were found on endoscopic examination, and a biopsy specimen of the nodules showed hyphae of Aspergillus. Aspergillus fumigatus was cultured from the intracavity fluid. Pulmonary aspergillosis was diagnosed and amphotericin B was administered via the drainage catheter in order to protect renal function. The abnormal shadows then disappeared and the subsequent clinical course was good. In this case, percutaneous intracavitary endoscopy was useful in diagnosing pulmonary aspergillosis.     

A case of pulmonary aspergillosis accompanied with eosinophilic pneumonia]

An infiltrative shadow was observed in the upper lobe of the left of a 60-year-old man lung during the course of paroxysmal tachycardia. Fever and coughing occurred one month later, and ground-glass opacities (GGOs) were found extensively in the lower left lung field. Although his condition strongly suggested allergic bronchopulmonary aspergillosis (ABPA) due to significantly increased eosinophil count in the peripheral blood and bronchoalveolar lavage fluid of the lower lobe of the left lung, anti-aspergillus antibody precipitation, and positive immediate intradermal test, the Rosenberg diagnostic criteria for ABPA were not satisfied. He was given a diagnosis of eosinophilic pneumonia, and GGO disappeared when itraconazole and prednisolone were administered. However, since the shadow in the upper lobe of the left lung later increased and percutaneous thoracocentesis revealed the presence of Aspergillus fumigatus, prednisolone treatment was discontinued and micafungin was administered. Nonetheless, the shadow spread into both lungs and regardless of treatment with amphotericin-B, the patient died. Although the present case is different from a typical ABPA, it indicates that allergic reaction can be induced by Aspergillus infection in the lung field, apart from the central airway. In addition, the development of an appropriate therapeutic strategy against both infection and allergy in such cases is essential.     

A case of ankylosing spondylitis associated with pulmonary aspergillosis and amyloidosis]

A 56-year-old man was admitted because of diarrhea, cough, weight loss, and disturbance of consciousness. He had been diagnosed as having ankylosing spondylitis at 18-years old. The spondylitis progressed until there was complete rigidity of the spine including the neck, hip and knee joints. Human leukocyte antigen (HLA) B27, which has been characteristic of ankylosing spondylitis, was also present in this case. A chest radiograph showed pleural thickness and a cavity in the right upper lobe; and a soft tissue mass and fluid level was found in the cavity. Aspergillus fumigatus was detected in the sputum and pulmonary aspergillosis was diagnosed. Biopsy of the colon revealed that a large interstitial amyloidosis. Despite the treatment of the patient's malnutrition and lung aspergillosis using amphotericin B, the clinical course was rapidly progressive and the patient died of respiratory failure due to lung aspergillosis. It is important to be aware of these rare complications, which are correlated with the prognosis in cases of ankylosing spondylitis.     

Importance of open lung biopsy in the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies

Invasive pulmonary aspergillosis is a serious infectious complication in immunocompromised patients. Recent reports indicate its favorable clinical outcomes by early diagnosis with chest computed tomography scan. We retrospectively analyzed our experiences with histopathological evaluation by open lung biopsy in 31 patients (32 cases) with hematologic malignancies, suspected of having invasive pulmonary aspergillosis clinically and radiologically. Although the initial computed tomography findings of all cases were highly indicative of invasive pulmonary aspergillosis by demonstrating nodules or masses with a halo sign (16 cases), segmental area of consolidation with ground-glass attenuation (7 cases), both nodules or masses with a halo sign and segmental area of consolidation with ground-glass attenuation (7 cases) and poorly defined centrilobular nodules (2 cases), we could histopathologically confirm invasive fungal infections only in 17 cases (53.1%) by open lung biopsy. There were 13 cases of invasive pulmonary aspergillosis, two cases of aspergilloma, and two cases of mucormycosis. No fungal hyphae were found in the other 15 cases: organizing pneumonia in seven cases, pulmonary hemorrhage in three cases, brochiolitis obliterans with organizing pneumonia in two cases, and CMV pneumonia, pulmonary tuberculosis, candida pneumonia in one case each, respectively. We could perform open lung biopsy without mortality and significant morbidity. In view of the low positive predictive value of chest computed tomography scan and the very low morbidity of open lung biopsy, this procedure is recommendable for the diagnosis of invasive pulmonary aspergillosis and determination of its treatment.     

Combination therapy of micafungin and itraconazole for a case of pulmonary aspergillosis]

The patient was a 73-year-old female who visited a physician with a chief complaint of fever, and was diagnosed with pneumonia. Ampicillin/sulbactam was administered, but ineffective, and the patient was referred to our hospital. In addition to severe inflammatory findings, cavity lesions were observed in the right upper lobe on plain chest X-ray and thoracic CT. Since Aspergillus fumigatus was cultured in bronchoalveolar lavage, a definite diagnosis of pulmonary aspergillosis was made. Intravenous administration of micafungin was initiated, but severe inflammatory findings persisted, and infiltrative shadows rapidly expanded. Oral itraconazole was concomitantly administered, and clinical symptoms and findings slowly improved. The plasma trough levels of micafungin, itraconazole, and hydroxyitraconazole were higher than the minimal inhibitory concentrations for the etiologic fungus, A. fumigatus, throughout the treatment period. No adverse events of the concomitant treatment were observed. Combination of the two antifungal agents may be effective for intractable pulmonary aspergillosis.     

Aspergillus spondylodiskitis in a patient with chronic obstructive pulmonary disease

Invasive aspergillosis is a well-known complication in immunocompromised patients. There are only a few reports of invasive aspergillosis in non-immunocompromised patients. We describe a 72-year-old female patient with clinical signs of spondylodiskitis occurring 4 months after what had appeared to be successful treatment of pulmonary aspergillosis. The patient used inhalation corticosteroids on a daily basis because of chronic obstructive pulmonary disease (COPD). Spondylodiskitis of the intervertebral disc Th11 and Th12 with involvement of both adjacent vertebral bodies was confirmed by magnetic resonance imaging. Histopathological examination revealed the presence of septate hyphae, indicative of Aspergillus species. Subsequently, evidence of Aspergillus spondylodiskitis was obtained by amplification of Aspergillus-DNA with a specific polymerase chain reaction method. Aspergillus spondylodiskitis after pulmonary aspergillosis is only very rarely encountered. Patients with COPD, managed with short-term courses of systemic corticosteroids or with high-dose corticosteroid inhalation therapies, are considered non-immunocompromised but might be at risk of developing invasive aspergillosis.     

A case of chronic necrotizing pulmonary aspergillosis]

A 70-year-old woman with diabetes mellitus who was following a therapeutic diet showed an infiltrative shadow in the right upper lung field on chest roentgenogram in April, 1986. She was diagnosed as having pneumonia and was treated for five months with several antibiotics, but the abnormal shadow on chest roentgenograms increased in size. Therefore, she was admitted to our hospital in October 1986. Although tubercle bacilli were not isolated from her sputum or from materials obtained by bronchoscopic examination, we made an initial diagnosis of pulmonary tuberculosis based on the findings of chest roentgenograms, tomographs and CT scanning. In spite of treatment with antituberculous drugs, the infiltrative shadow with cavity on chest roentgenograms continued to increase in size, and the patient developed occasional hemoptysis. Percutaneous needle biopsy was performed in February 1987 to establish a definite diagnosis, and the presence of Aspergillus fumigatus was confirmed by microscopic examination and culture. After treatment with miconazole and 5-FC for 3 to 4 months, the abnormal shadow on the chest roentgenogram gradually disappeared and was almost undetectable one year later. The clinical course of this patient was considered to be strongly indicative of chronic necrotizing pulmonary aspergillosis, which was described by Binder et al. in 1982.     

Fatal invasive pulmonary aspergillosis triggered by influenza B virus infection in an individual with idiopathic pulmonary fibrosis]

A 56-year-old man with idiopathic pulmonary fibrosis developed acute symptoms, including fever and cough. Chest X-ray and CT scan films revealed consolidations and ground glass opacities in the bilateral lungs suggestive of massive pneumonia and acute respiratory distress syndrome (ARDS). Microscopic examination by a transbronchial lung biopsy from the right middle lobe demonstrated numerous hyphae of aspergillus. Despite treatment with anti-fungal agents, respiratory failure rapidly progressed, and the patient died on the 21st hospital day. Postmortem examination of the lung showed multiple abscesses with hyphae of aspergillus invading into small pulmonary artery and alveoli, which were the characteristic findings of invasive pulmonary aspergillosis (IPA). In addition, diffuse alveolar damage was also present, associated with the typical features of UIP such as honeycombing in the bilateral lungs. The serum anti-influenza B virus antibody was high at 512-fold. Therefore, it was speculated that influenza B virus infection triggered superimposed aspergillus infection leading to fatal IPA associated with ARDS.     

Superinfection by Aspergillus fumigatus of a pulmonary lesion caused by Mycobacterium xenopi

A 36-year-old man had a pulmonary infection with a cavity in the right upper lobe caused by Mycobacterium xenopi. A superinfection by Aspergillus fumigatus occurred 1 year later. Both organisms were found in the resected lung specimen. The patient remained asymptomatic after surgery. The superinfection of healed tuberculous lesions by 'atypical' mycobacteria or Aspergillus species is well known but the co-existence of the 2 organisms is very rare.     

Abscess of residual lobe after pulmonary resection for lung cancer

Abscess of the residual lobe after lobectomy is a rare but potentially lethal complication. Between January 1975 and December 2006, 1,460 patients underwent elective pulmonary lobectomy for non-small-cell lung cancer at our institution. Abscess of the residual lung parenchyma occurred in 5 (0.3%) cases (4 bilobectomies and 1 lobectomy). Postoperative chest radiography showed incomplete expansion and consolidation of residual lung parenchyma. Flexible bronchoscopy revealed persistent bronchial occlusion from purulent secretions and/or bronchial collapse. Computed tomography in 3 patients demonstrated lung abscess foci. Surgical treatment included completion right pneumonectomy in 3 patients and a middle lobectomy in one. Complications after repeat thoracotomy comprised contralateral pneumonia and sepsis in 1 patient. Residual lobar abscess after lobectomy should be suspected in patients presenting with fever, leukocytosis, bronchial obstruction and lung consolidation despite antibiotic therapy, physiotherapy and bronchoscopy. Computed tomography is mandatory for early diagnosis. Surgical resection of the affected lobe is recommended.     

Case of pulmonary pseudallescheriasis responding successfully to treatment with voriconazole]

A 27-year-old man was admitted with hemoptysis in October 2005. Chest radiograph and CT showed multiple nodules forming a large mass in the left upper lobe. We suspected pulmonary aspergillosis because we detected filamentous fungi made of chains of cells in the bronchial washing fluid. On October 6, therapy with micafungin was initiated. Despite this intervention, the patient's clinical status worsened. On Octorber 11, we suspected pulmonary pseudallescheriasis because we detected colonis resembling white down in Sabouraud agar, thus mica-fungin was discontinued due to the lack of response and we began treatment with voriconazole. The patient's clinical status subsequently improved. We performed a left upper lobectomy, because residual the shadows were recognized on chest CT. Here we report a rare case of pulmonary pseudallescheriasis successfully treated with voriconazole and left upper lobectomy.     

Pulmonary vein thrombosis following bilobectomy

Acute thrombosis of the pulmonary vein following lobectomy or bilobectomy is a rare complication with no standard guideline for diagnosis or management. In this report, we present a case of right upper lobe vein thrombosis following a middle and lower lobectomy. Diagnosis was confirmed by ventilation-perfusion lung scan, pulmonary angiogram, and bronchoscopy. The patient was treated conservatively with no further complications and had a partial recovery of the circulation to the right upper lobe. A review of the literature is also presented along with the experimental data demonstrating the mechanisms of recovery.     

An autopsy case of Aspergillus pneumonia after inhalation of a great deal of dust in a mushroom factory]

A man in his forties with alcoholic liver injury was referred to our hospital because of progressive dyspnea and diffuse infiltrative shadows in both lung fields. Two weeks before admission he had carried a lot of rotten Enoki mushrooms in his factory, and then inhaled a great deal of airborne dust. Serological examination showed extremely elevated beta-D-glucan and positive Aspergillus antigen. Culture of dust collected from the floor of the factory proved to be positive for Aspergillus fumigatus. Aspergillus pneumonia was diagnosed and treatment with anti-fungal drugs was started. In spite of intensive treatment he died of respiratory failure. The autopsy disclosed multiple abscess formation containing hyphae of Aspergillus fumigatus and granulomatous reaction with multinuclear giant cells. However, there was no Aspergillus invasion in other organs. This was a rare case of invasive pulmonary aspergillosis that developed after inhalation of organic dust in a non-immunocompromised host.     

Allergic bronchopulmonary aspergillosis progressing to allergic granulomatosis and angiitis (Churg-Strauss syndrome)

A 50-yr-old woman had a right upper lobectomy that revealed the pathologic changes of eosinophilic pneumonia and mucoid impaction. In the mucus plug within the segmental bronchus, aspergillus was demonstrated by direct staining. A diagnosis of allergic bronchopulmonary aspergillosis was made. After a latent period of 17 yr, she presented with the clinicopathologic features of the Churg-Strauss Syndrome. The putative role of aspergillus in the etiology of this syndrome is discussed.