Aspergillus species colonization and invasive disease in patients with AIDS.

Invasive aspergillosis is an uncommon infectious complication in patients with AIDS. Of the 972 patients with AIDS who were observed at our institution over a 10-year period, Aspergillus species were isolated from the respiratory sites of 45 patients before death. Invasive aspergillosis was documented at autopsy in four of these patients and was strongly suspected in an additional patient on whom an autopsy was not performed. A fifth case was documented at autopsy (no antemortem respiratory sample was obtained from this patient). Traditional risk factors for the development of invasive disease (neutropenia, hematologic malignancy, and/or corticosteroid use) were present in all of our patients with invasive aspergillosis. A review of the literature revealed reports of an additional 13 cases of invasive aspergillosis in patients with AIDS. Therapy with amphotericin B should be considered for neutropenic patients with AIDS who have pneumonia of uncertain etiology and from whom Aspergillus species have been isolated from a respiratory specimen.     

Invasive pulmonary aspergillosis with spontaneous resolution and the diagnostic utility of PCR from tissue specimens

This case describes a 61-year-old apparently immunocompetent female with invasive pulmonary aspergillosis (IPA) and eosinophilia who demonstrated spontaneous clinical and radiological recovery. The patient had a history of asthma and had been corticosteroid dependent until 2 months prior to her presentation. This report explores the role of PCR in confirming the diagnosis of invasive aspergillosis in circumstances where only histological data are available and highlights the fact that invasive infections with Aspergillus spp. can occur without profound immunological deficiency. The case also documents the resolution of IPA without specific therapy.     

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.     

Acute invasive pulmonary aspergillosis,shortly after occupational exposure to polluted muddy water,in a previously healthy subject

Invasive pulmonary aspergillosis (IPA) predominantly occurs in severely neutropenic immunocompromised subjects. The occurrence of acute IPA after brief but massive exposure to Aspergillus conidia in previously healthy subjects has been documented, although only six such cases have been reported. The diagnosis was delayed in all six of the affected patients, five of whom died. We report the case of a 50-year-old HIV-negative male, a water pipeline maintenance worker, who presented with acute-onset dyspnea and fever one day after working for 2 h in a deep pit containing polluted, muddy water. Over a one-month period, his general condition deteriorated markedly, despite antibiotic therapy. Imaging showed bilateral diffuse nodules with cavitation, some of which were surrounded by ground-glass opacity suggestive of a halo sign (a hallmark of IPA). Cultures (of sputum/bronchial aspirate samples) and serology were positive for Aspergillus fumigatus. After being started on itraconazole, the patient improved. We conclude that massive exposure to Aspergillus conidia can lead to acute IPA in immunocompetent subjects.     

Invasive pulmonary aspergillosis in patients with neoplastic diseases

Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in granulocytopenic patients. The purpose of this article is to review the current understanding of the microbiology, hospital epidemiology, clinical manifestations, diagnosis, prevention, and treatment of invasive pulmonary aspergillosis. Aspergillus conidia (spores) are inhaled from environmental sources into the paranasal sinuses and lower respiratory tract. Persistent fever, pulmonary infiltrates, and pleuritic pain in granulocytopenic patients receiving antibacterial antibiotics is a common manifestation of invasive pulmonary aspergillosis. Computerized tomographic scans of the chest often reveal characteristic peripheral nodules that also may progress to characteristic cavitary lesions. Hemoptysis may develop due either to hemorrhagic infarction during granulocytopenia or to the rupture of mycotic aneurysms during recovery from granulocytopenia. Aspergillus organisms may extend locally from the lung to involve other thoracic structures, including the heart and chest wall, and may disseminate to extrapulmonary sites, such as the brain, where focal neurological deficits ensue. Early diagnosis of invasive pulmonary aspergillosis may be difficult. Isolation of Aspergillus organisms from respiratory secretions of a persistently febrile granulocytopenic patient is usually indicative of invasive pulmonary aspergillosis and should not be dismissed as a contaminant or saprophyte. Amphotericin B is the treatment of choice; however, high dosages (1.0 to 1.5 mg/kg/day) are often necessary. Aspergillosis may develop in granulocytopenic patients who are already receiving empirical amphotericin B in lower doses (0.5 to 0.6 mg/kg/day). It is hoped that further investigation directed toward an understanding of pathogenesis, improving diagnostic methodology, and developing new therapeutic and preventive strategies will improve the outcome of this life-threatening infection.     

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.     

Significance of isolation of Aspergillus from the respiratory tract in diagnosis of invasive pulmonary aspergillosis. Results from a three-year prospective study

The isolation of Aspergillus species from respiratory secretions has been regarded as being of limited usefulness in the antemortem diagnosis of invasive pulmonary aspergillosis. One hundred and eight consecutive patients were evaluated in whom Aspergillus species were isolated from respiratory secretions. Invasive aspergillosis was not demonstrated in non-immunosuppressed patients or in patients with solid tumors in the absence of neutropenia. Lung tissue was examined in 17 patients with leukemia and/or neutropenia; all had invasive aspergillosis. Tissue examination was not performed in 20 neutropenic patients; of 17 not receiving antifungal therapy, 16 died. Multivariate statistical analysis showed that neutropenia and absence of cigarette smoking were significant predictors of invasive aspergillosis in patients with respiratory tract cultures yielding Aspergillus. All cases of invasive aspergillosis were associated with A. fumigatus or A. flavus. The isolation of A. fumigatus or A. flavus from the respiratory tract of a patient with leukemia and/or neutropenia is highly predictive of invasive infection. Empiric amphotericin B therapy, without the necessity for tissue diagnosis, should be considered in this patient subgroup.     

Allergic bronchopulmonary aspergillosis masquerading as invasive pulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a noninvasive complex hypersensitivity reaction that occurs in immunocompetent patients with asthma. Aspergillus can invade and disseminate, but this more commonly occurs in severely immunocompromised patients receiving high-dose corticosteroids. We report the case of a 13-year-old immunocompetent male patient with moderate persistent asthma who appeared to have invasive pulmonary aspergillosis on radiographic studies. With further evaluation and workup, it was determined that the patient did not have invasive pulmonary aspergillosis, but that he met the diagnostic criteria for ABPA. Although initially there was a deceptive invasive appearance, proper identification of ABPA facilitated selection of corticosteroid treatment that resulted in prompt clearing of the concerning infiltrates.     

Aspergillosis complicating neoplastic disease

From 1964 to June 1971, 93 cases of aspergillosis were encountered at Memorial Sloan-Kettering Cancer Center. The 29 cases diagnosed in 1969–1970 and the 15 cases diagnosed in the first half of 1971 represented, respectively, a doubling and a quadrupling since 1964–1965. The incidence of aspergillosis in patients with leukemia was seven times greater than in patients with Hodgkin's disease or lymphoma (p < 0.0005). By the first half of 1971, 41 per cent of the patients who died with acute leukemia had evidence of aspergillosis. Fourteen patients with solid tumors resembled patients with leukemia or lymphoma in that they had at least two of the following in common: corticosteroid treatment, cytotoxic therapy and leukopenia (less than 4,000 cells/mm³). Pulmonary involvement was present in 90 of 93 cases, disseminated disease in 23. The commonest clinical pattern was unremitting fever and development of pulmonary infiltrates despite broad-spectrurh antibiotic therapy. In an increasing number of cases aspergillosis followed Pseudomonas aeruginosa infections. When present, serum aspergillus precipitins correlated well with invasive disease, but a negative test result was far less reliable. In one case of acute myelogenous leukemia the patient recovered from pulmonary aspergillosis after surgical excision of the lesion and remission of her leukemia.The incidence of aspergillosis is increasing and should be considered in the setting of progressive pulmonary infiltrates in leukemic and other heavily immunosuppressed patients who respond poorly to antibacterial therapy. Earlier diagnosis may lead to more effective therapy.     

Invasive aspergillosis in patients with AIDS.

Invasive aspergillosis is a rare complication of AIDS. We discuss the cases of 18 patients with AIDS and invasive aspergillosis who were identified at our institution and 19 patients who are described in the literature. Twenty-one patients were either homosexual or bisexual, eight were intravenous drug users, three were hemophiliacs, two attributed their disease to a heterosexual contact, and one was a transfusion recipient; risk factors for AIDS were unknown for two patients. Twenty-eight of the 37 patients had pulmonary aspergillosis; for 18 of these 28, the lung was the sole site of disease. Aspergillosis involved the brain in 12 cases, the heart in five cases, and the kidney, sinuses, or skin in six other cases. Eleven patients had multiple sites of disease, and eight patients had extrapulmonary disease alone. Possible risk factors for aspergillosis included leukopenia (7 patients, of whom 5 were also neutropenic) and use of corticosteroids (8 patients), alcohol (6 patients), broad-spectrum antibiotics (5 patients), and antineoplastic agents (4 patients); 14 patients had no identifiable risk. Death was the usual outcome, despite treatment of patients with amphotericin B. In cases of AIDS and invasive aspergillosis, early diagnosis may lead to improved outcome.     

Invasive pulmonary aspergillosis

BACKGROUND: Invasive pulmonary aspergillosis usually occurs in immunocompromised patients. Mild abnormality of host defence is usually present in the chronic necrotising form of the disease. Acute aspergillus pneumonia usually affects patients who are seriously immunocompromised. OBJECTIVES: The purpose of the study was to highlight the possibility of occurrence of invasive pulmonary aspergillosis also in patients with mild abnormality of host defence. METHODS: In a retrospective study 6 patients were analysed. The inclusion criterion was evidence of Aspergillus sp. invasion in lung tissue. Lung tissue was obtained by biopsy or post mortem examination. RESULTS: There were 4 patients with acute aspergillus pneumonia. Two of them were severely immunocompromised - one with dermatomyositis, who was treated with high doses of corticosteroids and methotrexate, and the other with undiscovered miliary tuberculosis, who was treated for myelodysplastic syndrome instead with low doses of corticosteroids. The other 2 had mild immunosuppression: one was suffering from sarcoidosis and was treated with low doses of corticosteroids, the other had dilated cardiomyopathy, renal insufficiency and diabetes mellitus. The two patients with chronic necrotising pulmonary aspergillosis had mild abnormality of host defence: one had reactivation of tuberculosis and diabetes mellitus, the other had inactive tuberculosis and aspergilloma. CONCLUSIONS: Invasive pulmonary aspergillosis must be considered also in patients with mild immunosuppression and pulmonary infiltrates which do not respond to conventional treatment with antibiotic chemotherapy. The key to the diagnosis of invasive pulmonary aspergillosis is the histopathological demonstration of fungal invasion in lung tissue.     

The clinical spectrum of pulmonary aspergillosis

Aspergillus is a ubiquitous fungus that causes a variety of clinical syndromes in the lung, ranging from aspergilloma in patients with lung cavities, to chronic necrotizing aspergillosis in those who are mildly immunocompromised or have chronic lung disease. Invasive pulmonary aspergillosis (IPA) is a severe and commonly fatal disease that is seen in immunocompromised patients, while allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to Aspergillus antigens that mainly affects patients with asthma. In light of the increasing risk factors leading to IPA, such as organ transplantation and immunosuppressive therapy, and recent advances in the diagnosis and treatment of Aspergillus-related lung diseases, it is essential for clinicians to be familiar with the clinical presentation, diagnostic methods, and approach to management of the spectrum of pulmonary aspergillosis.     

重症慢性呼吸道疾病合并侵袭性肺曲霉病的临床特点

目的 总结重症慢性呼吸道疾病(CRD)合并侵袭性肺曲霉病(IPA)的临床特点,为早期诊断和治疗提供依据.方法 分析2004年10月至2007年2月在北京朝阳医院呼吸科重症监护室(RICU)住院的149例痰或BALF分离出曲霉的CRD患者资料.以SPSS 10.0统计软件进行数据处理,所有计量资料以均数±标准差表示,计数资料以例数表示.计量资料采用t检验,计数资料采用X2检验.结果 149例CRD患者中共收集16例IPA病例(COPD 11例,COPD合并支气管哮喘4例,支气管扩张症1例),其中3例确诊,10例临床诊断,3例拟诊.12例在人RICU前使用过大量糖皮质激素,15例使用广谱抗生素.15例临床表现为严重气道痉挛,9例行无创通气失败,14例因严重呼吸衰竭而需有创机械通气.12例X线胸片可见明显渗出影.外周血白细胞及中性粒细胞比例在疾病后期迅速增高;早期气管镜检查可见气道黏膜充血、水肿、糜烂,气道痉挛,痰液黏稠,后期气道黏膜可出现伪膜;早期真菌病原学检查阳性率低(2/12),后期阳性率高(10/12);早期治疗的患者存活率高(4/4),晚期治疗效果差(11/12),由呼吸衰竭迅速进展为多脏器衰竭是最主要的死亡原因.结论 CRD合并IPA并不少见,预后差.根据临床特点进行早期诊断及经验性治疗可改善患者的预后.     

Usefulness of the MSG/IFICG/EORTC diagnostic criteria of invasive pulmonary aspergillosis in the clinical management of patients with acute leukaemia developing pulmonary infiltrates

Invasive pulmonary aspergillosis (IPA) is a frequently fatal complication in patients with acute leukaemia. Because diagnosis is still difficult, non-invasive diagnostic criteria were recently proposed by MSG/IFICG/EORTC for study purposes. We have analysed their usefulness in the clinical management of acute leukaemic patients with pulmonary infiltrates. Twenty-seven infiltrates developed during 174 chemotherapy cycles given to 50 consecutive patients. According to diagnostic criteria, IPA was diagnosed in 42% of patients and 77.8% of pulmonary infiltrates. AML diagnosis and the first induction cycle were significant risk factors. “Proven” IPA was rare, occurring in one patient (2%). The diagnosis of “probable” IPA was made in seven patients (14%) and was strongly supported by the significant association of characteristic radiological lesions (“major” clinical criterion) with the positivity of one microbiological criterion (P = 0.026). Conversely, “possible” IPA was frequent (26%) because its pertinent diagnostic criteria were fulfilled in 48.1% of pulmonary infiltrates. However, in 84.6% of cases, the diagnosis of “possible IPA” aspecifically derived from the association of two conditions, a new pulmonary infiltrate with symptoms of lower respiratory tract infection (“minor clinical criterion”), together with the definition of “susceptible” host, which applied to 100% of our leukaemic patients. We conclude that, according to MSG/IFICG/EORTC criteria, a high number of pulmonary infiltrates would be diagnosed as IPA, but only a diagnosis of “proven/probable” IPA should be considered reliable in the clinical management of suspected IPA.     

Invasive pulmonary aspergillosis in solid organ transplant recipients

To discuss diagnosis, risk factors, clinical and radiologic manifestations of invasive pulmonary aspergillosis (IPA) that is accepted as an important mortality factor in organ transplant recipients. We retrospectively evaluated seven IPA cases who were diagnosed among 207 patients that had undergone organ transplantation surgery in our center between 1998-2001. Of seven patients, four was renal and three was liver recipients. Diagnosis was made histopathologically (three post-mortem, one transbronchial lung biopsy) in four patients while culture positivity (sputum and tracheal aspiration material) with clinical and radiological evaluation was the diagnostic criteria for three patients. The most common respiratory symptoms were fever, productive cough and dyspnea. The most common fiberoptic bronchoscopic findings were mucosal fragility, hemorrhage. In one patient plaque formation was found. One liver recipients had been on hemodialysis because of renal insufficiency (serum creatine was 2.6 mg/dL). All liver and kidney recipients had allograft failure. One liver and two kidney recipients had neutropenia, two liver and one kidney recipients had thrombocytopenia. Six patients had received amphotericin-B and/or itraconazole therapy. Four of the five exitus were receiving antifungal treatment. Three of them were lost in a short time while only one non-survivor had received itraconazole for three weeks. The most frequent CT findings were patchy infiltrations and nodule formation with or without cavitation. Five patients were lost in two months (mortality, 71.4 %), two survivors are under follow up. These findings showed, IPA should be thought in the differential diagnosis of pulmonary infections after organ transplantation.     

艾滋病肺部合并症六例分析

目的　提高对艾滋病肺合并症的认识。方法　对１９９２ 年３ 月～１９９７ 年８ 月间诊断的６例艾滋病患者进行分析。结果　并发卡氏肺囊虫性肺炎（ Ｐ Ｃ Ｐ）５ 例（ 其中１ 例为艾滋病首发表现） ,其临床表现为发热（５／５） ,呼吸困难（４／５） 和低氧血症（５／５） ,平均动脉血氧分压为５８ ｍｍ Ｈｇ（１ ｍｍ Ｈｇ ＝０１３３ ｋ Ｐａ ） ,胸部 Ｘ 片显示,两肺弥漫间质或肺泡性浸润。另有支气管真菌感染、肺结核和淋巴结结核各１ 例（ 痰抗酸杆菌阳性、结核菌素试验阴性） 。结论　艾滋病容易发生各种肺合并症,尤以 Ｐ Ｃ Ｐ多见。对既往身体健康的青壮年,如突然发生肺炎和呼吸衰竭应警惕 Ｐ Ｃ Ｐ 发生。对特定情况下发生的肺机会性感染应警惕艾滋病,并及时检查血抗人类免疫缺陷病毒（ Ｈ Ｉ Ｖ） 抗体。     

Diagnostic yield of bronchoscopy in histologically proven invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA) is a life-threatening infectious complication in neutropenic patients after high-dose chemotherapy or hematopoietic stem cell transplantation. Its diagnosis is mainly based on clinical symptoms, and radiological signs on thoracic CT scan. The value of bronchoscopy is controversial. We analyzed the diagnostic yield of bronchoscopy in 23 consecutive patients with histologically proven invasive pulmonary aspergillosis. In seven patients (30%) bronchoscopically obtained specimens were diagnostic for pulmonary fungal infection. Typical hyphae were detected by cytology in six patients and fungal cultures were positive in four cases. Patients with a positive bronchoscopic result presented more often with multiple changes on thoracic CT scan (71%; 5/7), but had received a lower median cumulative dose of amphotericine B (300 mg; 168-3010 mg) compared to patients with non-diagnostic bronchoscopy (25% multiple lesions (4/16); amphotericine dose 1100 mg, 260-2860 mg). The diagnostic yield of bronchoscopy was not associated with clinical symptoms or duration of neutropenia. Bronchoscopy allows the diagnosis of IPA in about one third of patients. Fungal cultures and cytological examination of intrabronchial specimens obtained during bronchoscopy have a high specificity, but its sensitivity is low. It is advisable to perform diagnostic bronchoscopy before starting antifungal therapy. Better diagnostic tools are urgently needed.     

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: 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.     

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.