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PubMed1995

Renal aspergillosis and AIDS.

Primary renal aspergillosis is an extremely rare entity. Only 19 cases have been reported, 3 of them in patients with AIDS. We report one new case of renal aspergillosis in a patient with AIDS. His disease pattern was multiple bilateral renal abscesses with a normal excretory pathway. The treatment established was percutaneous drainage and systemic antifungal drugs. He had a bad evolution and died 14 weeks after diagnosis. In the previously reported cases of aspergillosis in patients with AIDS, the manifestation was unilateral renal abscess.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Pulmonary aspergillosis in mice: treatment with a new triazole SCH39304.

The triazole SCH39304 was compared with amphotericin B and fluconazole for the treatment of pulmonary aspergillosis in corticoid-immunosuppressed mice intranasally challenged with 5 x 10(6) conidia of Aspergillus fumigatus. In vitro, the minimum inhibitory concentration (MIC) for fluconazole was greater than 80 micrograms/ml, for SCH39304 40 micrograms/ml, and for amphotericin B 0.29 micrograms/ml. Beginning 1 day after challenge, groups of 10 mice were treated orally, twice daily, for 15 days with Noble agar (control), SCH39304, fluconazole, or amphotericin B at various doses. For lung tissue counts of A. fumigatus, mice were similarly challenged and treated only for 5 days with SCH39304, fluconazole, or amphotericin B. Only SCH39304 significantly reduced the number of A. fumigatus in the lung. SCH39304 at doses of 5 mg/kg or higher significantly prolonged the survival of mice, as did amphotericin B at 3 mg/kg. Fluconazole did not significantly prolong survival at doses of 15 or 30 mg/kg. SCH39304 appears to be as effective as amphotericin B in murine pulmonary aspergillosis and warrants further evaluation for aspergillosis in humans.

Amphotericin B↗
PubMed1991

Ulcerative tracheobronchitis after lung transplantation. A new form of invasive aspergillosis.

Invasive aspergillosis is frequently a fatal disease in the setting of immunosuppression, including organ transplant recipients. The fungus usually affects lung parenchyma and may disseminate from there. We have recently noted tracheobronchitis in six patients with heart-lung and lung transplants, three of whom had deep mucosal ulceration and histologic evidence of invasive aspergillosis. This apparently new form of invasive disease is initially limited to the anastomosis site and large airways. Ulceration, necrosis, cartilage invasion, and formation of a pseudomembrane are the pathologic features. In two patients subsequent disseminated aspergillosis occurred with a fatal outcome. In the two single-lung recipients, disease was limited to the transplanted side emphasizing the importance of abnormal local defense mechanisms in the airways of lung transplant recipients. Routine bronchoscopic examination of the airways is important in early detection of this complication. Oral therapy with the new, antifungal agent itraconazole was successful in five of the six patients, with fatal relapse in one. A classification of the various forms of saprophytic, allergic, and invasive forms of aspergillus tracheobronchitis, to include this new entity, is proposed.

Adult↗
PubMed1982

Bronchopleural fistula complicating invasive pulmonary aspergillosis.

Pleural involvement has been notably absent in reviews of invasive pulmonary aspergillosis. This report describes the development of a bronchopleural fistula complicating invasive aspergillosis in a patient receiving chemotherapy for leukemia. The fungal hydropneumothorax occurred despite early diagnosis of the pulmonary infection and prompt treatment with amphotericin B. Closed pleural drainage and continued antifungal medication resulted in ultimate cure of the infection. The presumed pathophysiologic aspects of this event are discussed and the literature on pleural aspergillosis is reviewed.

Adult↗
PubMed1985

Pulmonary cavitation and massive hemoptysis in invasive pulmonary aspergillosis. Influence of bone marrow recovery in patients with acute leukemia.

The influence of bone marrow recovery on the clinical and radiographic course of invasive pulmonary aspergillosis in patients with acute leukemia has not been well characterized. We studied 26 patients with acute leukemia and invasive pulmonary aspergillosis, comparing those who recovered from chemotherapy-induced granulocytopenia (Group 1, 15 patients) with those who did not (Group 2, 11 patients). Radiographic evidence of pulmonary cavitation was not seen in any Group 2 patient, but developed in 11 of 15 (73%) Group 1 patients (p less than 0.005). In these patients, cavitation always occurred after marrow recovery, an average of 2.0 days (range: 0 to 6 days) after the granulocyte count exceeded 500/mm3. Eight patients in Group 1 and 2 in Group 2 experienced a total of 38 episodes of hemoptysis. Four of the 26 patients, all in Group 1, developed massive hemoptysis (greater than 150 ml of blood per episode), leading to 1 death. In 3 of these 4 patients, cavitation preceded the episode of massive hemoptysis. At the time of massive bleeding, the granulocyte count was greater than 500/mm3, the platelet count greater than 38,000/mm3, and the other coagulation parameters were normal in all 4 patients. Our findings demonstrate that in patients with acute leukemia undergoing chemotherapy, bone marrow recovery markedly influences the clinical and radiographic course of invasive pulmonary aspergillosis. Development of a granulocyte count greater than 500/mm3 is associated with pulmonary cavitation, and on occasion with massive hemoptysis.

Acute Disease↗
PubMed1979

Acute disseminated aspergillosis during the neonatal period. Report of an instance in a 14-day-old infant.

We describe an infant who died with extensive lesions of disseminated aspergillosis on the 18th day of postnatal life. Aspergillus fumigatus was recovered from blood cultures. Initial clinical manifestations were suggestive of hepatitis, and steroids and antibiotics were used in the treatment. This therapy may have fostered the onset of an opportunistic mycosis. Advanced multisystemic aspergillotic lesions were seen at autopsy, especially prominent in lungs and gastrointestinal tract. The extent and magnitude of the lesions observed suggest inception of the disease very early in life, although no case of human aspergillosis has been known to be congenital. Neonatal aspergillosis is poorly characterized. Only four previously reported cases came to our notice in which the disease could be diagnosed in the first month of life. The ubiquitous nature of pathogenic Aspergillus, joined to aggresive treatments designed to achieve increased survivals in neonatology, could potentially result in greater numbers of cases of this and other uncommon mycoses.

Aspergillosis↗
PubMed1988

Invasive pulmonary aspergillosis of horses: an association with acute enteritis.

Invasive pulmonary aspergillosis was identified in 19 horses. In 16 cases mycotic lesions were associated with enterocolitis; 14 cases appeared to result from Salmonella infection. Pulmonary lesions included multifocal areas of acute necrosis, leukocytoclastic vasculitis, and thrombosis with fibrinosuppurative inflammation surrounding mycelial masses. Thromboemboli with fungi were in the brain and kidneys of three cases. Factors which appeared to predispose to pulmonary aspergillosis included corticosteroid therapy, disseminated neoplasms, hepatitis, pleuritis, and peritonitis. This study suggests that immunocompromise and invasion of Aspergillus sp. from damaged intestine are more important in causing equine pulmonary aspergillosis than inhalation of spores.

Acute Disease↗
PubMed2002

Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenic patients.

Invasive pulmonary aspergillosis is a major cause of morbidity and mortality in neutropenic patients. Microbiological and serological tests are of limited value. The diagnosis should be considered in neutropenic patients with fever not responding to antibiotics, and typical findings on thoracic computed tomography scan. Whenever possible, diagnosis should be confirmed by tissue examination. Newer techniques, such as polymerase chain reaction may change the current diagnostic approach. Therapeutic strategies consist of prophylaxis in risk groups and the early application of antifungal agents in suspected or probable disease. Amphotericin B as desoxycholate or lipid formulation is the current standard medication in invasive infection, although it has major side effects. Its role is challenged by the new azole derivates, such as itraconazole and voriconazole, and the new echinocandins. Additional therapies with cytokines, such as granulocyte macrophage colony stimulating factor and interferon-gamma, and with granulocyte transfusions are under evaluation. In selected cases lung resection is of proven diagnostic and therapeutic value. This paper analyses the current understanding of the pathogenesis and epidemiology of invasive aspergillosis and reviews the actual diagnostic and therapeutic strategies for invasive pulmonary aspergillosis in neutropenic patients.

Amphotericin B↗
PubMed2003

Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus, causing severe asthma that may progress to bronchiectasis. Sputum neutrophilia can occur in association with sputum eosinophilia and correlates with the degree of bronchiectasis. The mechanisms of sputum neutrophilia in ABPA are not known. The aim of this study was to investigate the role of the chemokine interleukin (IL)-8 in sputum neutrophilia in ABPA. Induced sputum was obtained from subjects with ABPA (n=29), and compared to nonsensitised asthma (n=9) and healthy controls (n=21). Semiquantitative polymerase chain reaction was used to assess IL-8 gene expression in induced sputum and IL-8 protein was measured by enzyme-linked immunosorbent assay. Sputum IL-8 protein was significantly higher in ABPA compared to asthma and controls. IL-8 messenger ribonucleic acid/glyceraldehyde-3-phosphate dehydrogenase ratio was elevated in ABPA compared to asthma and controls. Sputum IL-8 correlated with sputum neutrophils, matrix metalloproteinase-9 levels and forced expiratory volume in one second. Interleukin-8 gene expression and protein release were increased in allergic bronchopulmonary aspergillosis and correlated with airway neutrophilia and airway obstruction. The interleukin-8-mediated neutrophil influx in allergic bronchopulmonary aspergillosis may induce lung damage via release of matrix metalloproteinase-9, potentially leading to bronchiectasis.

Adult↗
PubMed1995

Aspergillus culture filtrates and sputum sols from patients with pulmonary aspergillosis cause damage to human respiratory ciliated epithelium in vitro.

Aspergillus species frequently colonize lower respiratory tracts and lungs with localized underlying conditions (healed tuberculous cavity, cystic fibrosis, bronchiectasis, etc.) even in subjects without systemic predisposing factors. We investigated the in vitro effects of culture filtrates of Aspergillus species and sputum sols from patients with pulmonary aspergillosis on ciliary beat frequency (CBF) and epithelial integrity of human respiratory ciliated epithelium. Culture filtrates of 25 clinically isolated fungi (16 Aspergillus fumigatus, three Aspergillus niger, one Aspergillus flavus, three Candida albicans, and two Cryptococcus neoformans) were obtained by culturing the fungi in Medium-199 at 37 degrees C for 7 days, and five sputum sols were obtained from patients with pulmonary aspergillosis infected by A. fumigatus. During 6 h experiments using a photometric technique, 14 out of 16 A. fumigatus culture filtrates caused progressive and significant reduction in CBF associated with marked epithelial disruption, whilst the culture filtrates of A. niger and A. flavus caused minor epithelial damage without slowing of CBF, and Medium-199 alone (Control) showed neither epithelial damage nor slowing of CBF. All of the sputum sols also caused significant slowing of CBF as well as epithelial disruption. Culture filtrates of C. albicans and Cr. neoformans had no effects on human respiratory epithelium. We conclude that Aspergillus species, especially A. fumigatus release a factor (or factors) which causes damage to respiratory epithelium and slows CBF, and that these factors may contribute to the colonization of the lower respiratory tracts by the Aspergillus species and may possibly contribute to the further proliferation and spread of the lesions in pulmonary aspergillosis.

Adult↗
PubMed1998

Chest radiographic staging in allergic bronchopulmonary aspergillosis: relationship with immunological findings.

The question of whether a chest radiographic severity staging system could be correlated with standard blood/serum diagnostic indices in allergic bronchopulmonary aspergillosis (ABPA) was addressed in 41 patients. Asthma and positive Aspergillus fumigatus (AF) serology were considered essential diagnostic inclusion criteria. Eosinophil count, serum immunoglobulin (Ig)E and immediate skin hypersensitivity were also tested to grade patients as "definite" or "likely" ABPA. Definite cases had all five of these factors present, whereas likely cases had three or more. Chest radiographs were examined by experienced radiologists blinded to the clinical data. The six-stage radiographic score (0-5) was based on the severity and duration of changes seen: stage 0: normal; stage 1: transient hyperinflation; stage 2: transient minor changes; stage 3: transient major changes; stage 4: permanent minor changes; and stage 5: permanent major changes. Significant positive correlations (p<0.05) were observed between peak AF titres (expressed as an index), peak eosinophil count and radiographic severity stage. When considered as subgroups, these correlations approached, but did not reach, significance for the group with "likely" ABPA (n=28), but in the group with definite ABPA (n=13), there was a high correlation between radiographic score and peak AF index (r=0.59), as well as peak eosinophil count (r=0.62). This study suggests that the peak Aspergillus fumigatus index and eosinophil counts correlate best with the severity of radiographic stages in allergic bronchopulmonary aspergillosis. This chest radiographic staging system may be useful in the clinical assessment and management of patients with allergic bronchopulmonary aspergillosis, particularly in those patients with more severe radiographic stages.

Antibodies, Fungal↗
PubMed1976

Central nervous system aspergillosis in two young adults.

Unusual and unique features were present in the cases of two patients with central nervous system aspergillosis: One had a previously unreported complication of aspergillosis, extracranial internal carotid artery thrombosis documented by angiography, and in the other patient, cerebral granulomas developed from Aspergillus fumigatus in association with intravenous narcotic abuse. The latter etiologic mechanism was suggested once before. Neither of these patients showed other underlying disease. A detailed neuropathologic examination correlated the salient clinical findings with formation of aspergillosis cerebral granulomata, basilar meningitis, and arterial occlusion. Diagnostic and therapeutic methods in this disease are limited.

Adult↗
PubMed2001

Disseminated aspergillosis inciting intestinal ischaemia and obstruction.

Invasive aspergillosis is an opportunistic infection that characteristically affects the immunocompromised host, resulting in a high degree of morbidity and mortality. Although the portal of entry is usually pulmonary, there are rare reports of invasive aspergillosis localized to the gastrointestinal tract. In addition, haematological spread may develop, with life threatening disseminated infection involving the vital organs and the gastrointestinal tract. Although disseminated infection is well recognized, the CT findings of gastrointestinal disease have not been reported to our knowledge. We describe the CT findings in a patient with invasive aspergillosis involving the gastrointestinal tract, which resulted in intestinal ischaemia complicated by small bowel obstruction.

Aged↗
PubMed1982

Aspergillosis of the nose and paranasal sinuses.

Aspergillosis is becoming an increasingly recognized pathogen in the sinonasal tract. The courses of two patients, one seemingly healthy and one with a terminal malignancy, are reviewed. These patients illustrate the clinical course, difficulties in diagnosis, and management of patients with aspergillosis of the sinonasal tract. Aspergillus is a common endogenous contaminant of the upper respiratory tract; however, bacterial sinusitis may trigger its growth and proliferation. Aspergillus fumigatus is the most common species implicated in paranasal sinus disease in the United States. The maxillary antrum is the most commonly involved site in the paranasal sinuses. Originally, aspergillosis was described in healthy patients, but it has become increasingly recognized in the immunocompromised and the chronically debilitated. Paranasal sinus Aspergillus infections are classified as non-invasive and fulminant. The treatment is primarily surgical. Antifungal chemotherapeutic agents are used in the treatment of central nervous system involvement and in the fulminant form of the disease.

Adult↗
PubMed2004

Predicting outcome after lung resection for invasive pulmonary aspergillosis in patients with neutropenia.

STUDY OBJECTIVES: To investigate the factors that predict survival after lung resection for invasive pulmonary aspergillosis (IPA) in patients with neutropenia, in order to assist the selection of patients who are most likely to have a successful outcome. DESIGN: Retrospective single-center study. SETTING: University hospital hemato-oncologic isolation unit and division of thoracic surgery. PATIENTS: Forty-one patients with hematologic disease and suspected IPA who underwent lung resection. INTERVENTIONS: Lobectomy (n = 23), wedge resection (n = 16), and enucleation (n = 2). RESULTS: Mortality within 30 days was 10% (4 of 41 patients). Major perioperative complications occurred in 10%. One death was possibly related to surgery (pleural aspergillosis). Of the patients with proven aspergillosis, 87.1% were cleared of infection, but fungal relapse occurred in 10%. Overall survival was 65% at 6 months, 58% at 12 months, and 40% at 5 years after surgery. Baseline characteristics and intraoperative data did not differ significantly between survivors and nonsurvivors at 6 months or 12 months after surgery. Perioperative complications did not significantly influence the outcome. Multivariate analysis of 12-month survival revealed that the variables, progression, or recurrence of the underlying hematologic disease (relative risk [RR], 4.64; 95% confidence interval [CI], 3.51 to 5.77; p < 0.0001), fungal relapse (RR, 5.06; 95% CI, 3.83 to 6.28; p < 0.0001), and to a minor extent the type of the underlying hematologic disease (p < 0.018) were the most important predictors of patient survival. CONCLUSIONS: Lung resection for IPA is feasible with an acceptable operative risk. While at 10%, the perioperative mortality is considerable; the nonsurgical mortality is reported to be between 30% and 90%. Fungal infection is cleared in > 80% of patients. Mid- to long-term survival can be achieved if the underlying hematologic disease is under control. It is not yet possible to define a group of patients with IPA who are most likely to benefit from lung resection.

Adolescent↗
PubMed1977

Allergic bronchopulmonary aspergillosis in three patients with normal chest x-ray films.

Three patients with allergic bronchopulmonary aspergillosis had normal chest x-ray films at the time of dianosis. None had a history of pneumonitis or abnormal chest x-ray films in the past. On the basis of clinical and immunologic data that indicated the presence of allergic bronchopulmonary aspergillosis, bronchograms were obtained, which revealed evidence of proximal bronchiectasis in each patient. These early changes in bronchial architecture were not evident on the plain x-ray films of the chest but were revealed by bronchographic study. The diagnosis of allergic bronchopulmonary aspergillosis may be made even in the presence of normal chest x-ray films.

Antibodies, Fungal↗
PubMed1979

Disseminated aspergillosis, Cushing's syndrome, and oat cell carcinoma of the lung.

Disseminated aspergillosis is a known complication of neoplastic disease; however, it is usually associated with neoplasms of the hematopoietic or lymphoreticular systems or with immunosuppressed states. We describe the previously unreported association of disseminated aspergillosis and Cushing's syndrome secondary to a corticotropin-secreting oat cell carcinoma of the lung, and we review the current literature on disseminated aspergillosis complicating neoplastic disease.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed2006

Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000.

OBJECTIVE: Invasive aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients. The incidence of invasive aspergillosis has increased significantly in recent decades in parallel with the increasing number and improved survival of immunocompromised patients. IA in adults has been well characterized; however, only a few small studies of IA in children have been reported. Therefore, the objective of this study was to describe the incidence and outcomes of children with IA. METHODS: We performed a retrospective cohort study using the 2000 Kids Inpatient Database, a national database of hospital inpatient stays during 2000. IA was defined as aspergillosis that occurred in a child with malignancy (solid tumor, leukemia, or lymphoma), hematologic/immunologic deficiency, or transplant (bone marrow or solid organ). Discharge weighting was applied to the data to obtain nationally representative estimates of disease. RESULTS: During 2000, there were an estimated 666 pediatric cases of IA among 152,231 immunocompromised children, yielding an annual incidence of 437/100,000 (0.4%) among hospitalized immunocompromised children. Children with malignancy accounted for the majority (74%) of cases of IA. The highest incidence of IA was seen in children who had undergone allogeneic bone marrow transplantation (4.5%) and those with acute myelogenous leukemia (4%). The overall in-hospital mortality of immunocompromised children with IA was 18%. Children with malignancy and IA were at higher risk for death than children with malignancy and without IA. Pediatric patients with IA had a significantly longer median length of hospital stay (16 days) than immunocompromised children without IA (3 days). The median total hospital charges for patients with IA were $49309 compared with immunocompromised children without IA ($9035). CONCLUSIONS: The impact of IA on increases in mortality, length of hospital stay, and the burden of cost in the hospital setting underscores the need for improved means of diagnosis, prevention, and treatment of IA in immunocompromised children.

Adolescent↗