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PubMed1983

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.

Acute Disease↗
PubMed1993

Treatment of aspergillosis with itraconazole.

OBJECTIVE: To review the role of itraconazole as oral therapy for the major infections caused by Aspergillus spp.: allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis. DATA SOURCES: A MEDLINE search of articles published in the English language between 1986 and 1993 was used to identify relevant citations, including review articles. In addition, a search of the published abstracts of the past two Interscience Conferences on Antimicrobial Agents and Chemotherapy (ICAAC) was performed. STUDY SELECTION: Clinical trials that evaluated itraconazole therapy in either allergic bronchopulmonary aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed. Trials were evaluated based upon entry criteria for the diagnosis of each type of aspergillosis, risk factors for the development of aspergillosis (neutropenia, transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and dose and duration of itraconazole therapy. DATA SYNTHESIS: Overall, the clinical trials of itraconazole therapy for aspergillosis are limited and of variable quality. In the treatment of allergic bronchopulmonary aspergillosis, itraconazole has been reported to prompt a reduction in corticosteroid dosage in selected patients. There have been no controlled trials of itraconazole as treatment for aspergilloma, but data from several open-label trials suggest that this agent may be of clinical benefit in aspergilloma, primarily as an alternative to surgery. The use of itraconazole for invasive aspergillosis has been evaluated in several trials, most often in patients who were intolerant to amphotericin B treatment. Response to oral itraconazole has generally been promising. CONCLUSIONS: Although itraconazole offers promise for oral therapy against infections caused by Aspergillus spp., it should not presently be regarded as primary therapy for any of these diseases. Amphotericin B, in doses ranging from 1 to 1.5 mg/kg to a total dose of 1.5-4.0 g, should remain the treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole use should be restricted to patients who experience severe toxicity with amphotericin B therapy. Corticosteroids continue to be first-line therapy for allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved for those patients who would benefit from a reduction in corticosteroid dose.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Risk factors for invasive aspergillosis in liver transplant recipients.

Aspergillosis is a potential, severe, and usually early complication of liver transplantation. New promising strategies, such as detecting Aspergillus antigenemia, have been used for the diagnosis of aspergillosis in immunosuppressed patients, but the impact in solid organ transplantation is not well known. A case-control study in 260 adults who underwent liver transplantation from January 1994 to June 2000 was performed. A case was defined as any liver transplant recipient with a proven or probable diagnosis of invasive aspergillosis. Controls were defined as a liver transplant recipient without aspergillosis infection with a survival longer than two months after transplantation. Clinical and analytical variables, including Aspergillus antigenemia, were compared. A special analysis was performed in patients in whom late aspergillosis developed (after day 100 posttransplantation). Among 260 patients, invasive aspergillosis developed in 15 (5.6%). Median time from transplantation to aspergillosis in 13 patients with sufficient data for analysis was 126 days (range, 22 to 1117). Seven (54%) developed the infection after day 100 posttransplantation. Thirty-eight patients were used as controls. Antigenemia was available in nine of 13 cases and in 33 of 38 controls. By multivariate analysis, retransplantation (OR, 29.9 [95% CI, 2.1 to 425.1]), dialysis requirements after transplantation (OR, 24.5 [95% CI, 1.25 to 354]), and the presence of Aspergillus antigenemia in serum at any time point after transplantation (OR, 50.0 [95% CI, 3.56 to 650]) were independently associated to aspergillosis. In the subgroup of patients that developed late aspergillosis, cytomegalovirus infection (OR, 6.7 [95% CI, 1.0 to 42.5]) was the only independent factor associated. Hepatic and renal dysfunction predispose to Aspergillus infection in liver transplant recipients. Cytomegalovirus infection and increased immunosuppression favor invasive aspergillosis during the late posttransplantation period. Aspergillus antigenemia seems to be a good predictor of invasive aspergillosis.

Adult↗
PubMed1997

Invasive aspergillosis in human immunodeficiency virus-infected children.

BACKGROUND: Aspergillosis is an uncommon yet serious opportunistic infection in patients with AIDS. It has been extensively reported in HIV-infected adult patients. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of aspergillosis in a large HIV-infected pediatric population. METHODS: We reviewed the records of all 473 HIV-infected children followed in the Pediatric Branch of the National Cancer Institute for 9 years from 1987 through 1995 for the presence of Aspergillus infection. RESULTS: Seven (1.5%) patients developed invasive aspergillosis during the study period. All patients had low CD4 counts reflecting severe immunosuppression. Sustained neutropenia (> 7 days) or corticosteroid therapy as a predisposing factor for invasive aspergillosis was encountered in only two patients (28%). Invasive pulmonary aspergillosis developed in five patients and cutaneous aspergillosis in two. The most common presenting features in patients with pulmonary aspergillosis were fever, cough and dyspnea. Patients with cutaneous aspergillosis were diagnosed during life and successfully treated with amphotericin B and surgery, whereas diagnosis of pulmonary aspergillosis was made clinically in only one patient. CONCLUSIONS: Aspergillosis is an uncommon but highly lethal opportunistic infection in HIV-infected children. Invasive pulmonary aspergillosis should be considered in the differential diagnosis in febrile, HIV-infected children with persistent pulmonary infiltrates.

AIDS-Related Opportunistic Infections↗
PubMed2000

Pulmonary aspergillosis in an unselected autopsy series.

The present study was performed to analyze the relationship between underlying diseases and the morphologic form of aspergillosis. This retrospective analysis of 3284 autopsies yielded 18 cases of aspergillosis. The specific diagnosis of aspergillosis was rendered by a monoclonal antibody versus Aspergillus spp. Patients with hematological disorders, such as acute leukemia and aplastic anemia, made up about 35% of all patients dying of invasive aspergillosis. Diseases of the airways and the pulmonary parenchyma constituted the second most pathogenetic factor for the development of aspergillosis. The morphologic form of aspergillosis was closely related to the underlying diseases. Non- and semi-invasive forms of aspergillosis--saprophytic infection and chronic necrotizing aspergillosis--were observed only in patients with an isolated underlying pulmonary disease devoid of any other precipitating factor. In contrast, seven patients, five of whom suffered from hematological diseases, had no underlying lung disease and developed aspergillus pneumonia. The remaining 5 patients with aspergillus pneumonia showed a combination of underlying extrapulmonary disease and pulmonary alterations that preceded aspergillosis. The local distribution of fungal infection showed a characteristic distribution pattern with a predominance of the upper lung lobes. Hematogeneous spread beyond the lungs occurred exclusively in cases with aspergillus pneumonia. We conclude that the different forms of aspergillosis are closely related to the nature of the underlying disease.

Adult↗
PubMed2007

Allergic bronchopulmonary aspergillosis: an Indian perspective.

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis is an immunologically mediated lung disease that is caused by hypersensitivity to antigens of the genus Aspergillus. This review summarizes the clinical presentation, radiologic profile, lung functions and immunologic studies on allergic bronchopulmonary aspergillosis from India. Data regarding Aspergillus sensitization in asthmatics are presented. The association of allergic bronchopulmonary aspergillosis with allergic Aspergillus sinusitis and aspergilloma is also highlighted. RECENT FINDINGS: Allergic bronchopulmonary aspergillosis is now an emerging disease in India. Sensitization to Aspergillus antigens is not uncommon in our patients with asthma. Although asthma commenced in these subjects in their early 20s, allergic bronchopulmonary aspergillosis was recognized more than a decade later. Allergic bronchopulmonary aspergillosis can also occur in patients without clinical asthma. Radiology is crucial to the diagnosis of allergic bronchopulmonary aspergillosis. The remarkable radiological similarity to pulmonary tuberculosis has important clinical implications in our country as patients with allergic bronchopulmonary aspergillosis often receive antituberculous therapy for a long time. Although oral corticosteroids still remain the cornerstone for management, itraconazole has emerged as an adjunct therapy in appropriate situations. Concomitant occurrence of allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis is now being increasingly recognized. SUMMARY: All asthmatic subjects with a positive skin prick test to Aspergillus antigens must be evaluated for allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis should be excluded.

Adrenal Cortex Hormones↗
PubMed1972

Use of the immunodiffusion test in the serodiagnosis of aspergillosis.

The diagnostic value of an immunodiffusion (ID) test with standardized precipitinogens derived from five Aspergillus species was determined with sera from 60 proven and 12 suspected cases of aspergillosis. The data demonstrated that the greatest number of aspergillosis cases were detected by the concurrent use of A. fumigatus and A. niger precipitinogens. With these precipitinogens, the ID test permitted the serodiagnosis of aspergillosis in 82% of the 60 proven cases and in 83% of the 12 suspected cases. The presence of one or more precipitins was indicative of aspergilloma, of allergic bronchopulmonary aspergillosis, or of invasive aspergillosis. Precipitins were detected in 93% of the sera from patients with aspergilloma, in 50% of the sera from patients with allergic bronchopulmonary aspergillosis, and in 88% of the sera from patients with invasive aspergillosis. Although the presence of one or two precipitin bands could indicate any form of aspergillosis, the presence of three or four was strong evidence of either aspergilloma or invasive aspergillosis. The ID test was found to be 100% specific in an evaluation of its effectiveness with 65 sera from individuals with other systemic mycotic infections, bacterial or neoplastic diseases, and from apparently normal humans. In diagnosed cases of aspergillosis, the examination of serial serum specimens provided information about the clinical course of the disease. A reduction in the number of precipitin bands and significant titer changes were noted as the patients responded to therapy.

Animals↗
PubMed1995

Use of the Pastorex aspergillus antigen latex agglutination test for the diagnosis of invasive aspergillosis.

AIMS: To evaluate the Pastorex aspergillus antigen latex agglutination test for the diagnosis of invasive aspergillosis in patients undergoing liver or bone marrow transplantation. METHODS: Serum samples were taken at least twice weekly post-transplant and tested for Aspergillus antigen. Latex agglutination test results were compared with microbiological examination of respiratory, urine and bile specimens. Serum samples from liver transplant patients were also tested for antibodies to Aspergillus fumigatus by counter immunoelectrophoresis. RESULTS: Eight of the 91 patients studied developed invasive aspergillosis. Positive latex agglutination tests were obtained in eight of 187 (4.3%) serum samples from four of these eight patients. The other four patients with invasive aspergillosis gave consistently negative latex agglutination tests. A positive latex agglutination test was the first indication of invasive aspergillosis in two patients; these patients were already on amphotericin B. Positive latex agglutination tests were the only evidence of invasive aspergillosis in one patient who subsequently died of the infection. False positive latex agglutination tests were obtained in five of 83 (6%) patients with no evidence of invasive aspergillosis and misleading positive cultures seen in nine of 83 (10.8%). No antibodies were detected in three of four liver transplant patients with invasive aspergillosis. Conversely, antibodies were detected in 63 of 262 (24%) serum samples from 43 liver transplant patients with no evidence of invasive aspergillosis; one of these patients had an antibody titre of 1:2 on four separate occasions. CONCLUSIONS: The Pastorex aspergillus antigen latex agglutination test, when used alone, lacks sensitivity and specificity for the early diagnosis of invasive aspergillosis. A diagnosis was made in all patients with invasive aspergillosis when both culture and antigen tests were performed although using these criteria a false positive diagnosis would have been made in 13 of 83 (15.6%) patients. Microbiological and serial serological investigations for antigen should both be performed and the results considered in conjunction with radiological and clinical evidence.

Aspergillosis↗
PubMed2004

Craniocerebral aspergillosis of sinonasal origin in immunocompetent patients: clinical spectrum and outcome in 25 cases.

OBJECTIVE: Craniocerebral aspergillosis of sinonasal origin has been reported mainly in immunocompromised patients with high mortality, and it has been described very infrequently in immunocompetent hosts. This retrospective study focuses on clinical outcome in relation to anatomic locations of invasive aspergillosis of sinonasal origin in immunocompetent patients with emphasis on our preliminary experience with use of preoperative orally administered itraconazole. METHODS: Medical records of patients treated in two tertiary care hospitals from 1991 to 2003 were reviewed retrospectively. All patients had radiological evidence of disease in the paranasal sinuses with or without intracranial extension. The study cohort was divided into three types on the basis of area of involvement revealed by computed tomographic or magnetic resonance imaging scans of brain. All patients underwent surgical intervention and treatment with antifungal therapy. Preoperative orally administered itraconazole therapy was used in four patients on the basis of neuroradiological features. Clinical outcome was assessed with the Glasgow Outcome Scale, and univariate analysis of prognostic factors was performed with 95% confidence interval (P = 0.05). RESULTS: Mean patient age was 36.5 years (range, 14-74 yr) with a male preponderance (male-to-female ratio, 23:2). Nasal stuffiness (n = 13), headaches (n = 10), proptosis (n = 9), and nasal discharges (n = 7) were major presenting clinical features. Radiological data were obtained by computed tomographic (n = 25) and magnetic resonance imaging (n = 20) scans of the brain, and diagnoses were established by histopathological analysis (n = 20) or/and fungal cultures (n = 15). Preoperative orally administered itraconazole was given in four patients with intracerebral aspergillosis. Overall mortality was 28% and was highest in patients with Type 1 aspergillosis (66.7%). Type 3 aspergillosis and use of preoperative itraconazole remained statistically significant prognostic factors. CONCLUSION: Craniocerebral aspergillosis in immunocompetent hosts has three patterns of presentation that seem to correlate with clinical outcomes. Intracerebral aspergillosis (Type 1) is associated with the worst clinical outcome. Patients with orbital and cranial base aspergillosis (Type 3) had good recovery. Intracranial extradural aspergillosis (Type 2) remained intermediate on the Glasgow Outcome Scale. Preoperative orally administered itraconazole therapy may improve clinical outcome in patients with intracerebral aspergillosis. Prospective clinical studies are required to make firm clinical therapeutic recommendations.

Adolescent↗
PubMed1997

Pulmonary aspergillosis in acquired immune deficiency syndrome: autopsy study of an emerging pulmonary complication of human immunodeficiency virus infection.

Pulmonary aspergillosis has recently been described as an emerging infection in patients with acquired immune deficiency syndrome (AIDS), but the pathological changes have not been well documented. In this autopsy study, 17 cases of AIDS-related pulmonary aspergillosis were identified from the files of two institutions. With the exception of hypersensitivity reactions, the entire spectrum of pulmonary aspergillosis was represented. Thirteen patients exhibited acute invasive aspergillosis, and seven patients had evidence of subacute or chronic invasive infection, four of whom also had areas of acute invasion. One patient had necrotizing bronchial aspergillosis as well as acute invasive infection, and one individual had saprophytic colonization of a cavity caused by previous Pneumocystis carinii pneumonia (PCP) without evidence of invasive aspergillosis. The same conditions known to predispose immunocompromised individuals without human immunodeficiency virus (HIV) infection to invasive pulmonary aspergillosis were also identified in these patients with AIDS and included neutropenia, steroid therapy, and underlying lung disease. Additional pulmonary conditions were identified in all but one case and consisted mainly of infection or some form of chronic lung disease. In particular, half of the cases were associated with pulmonary fibrosis related to prior PCP. All cases occurred in or after 1990, confirming the perception of the recent emergence of aspergillosis in AIDS. As suggested by this study, one reason for this may be that patients with AIDS are now living long enough to develop one or more of the predisposing conditions for pulmonary aspergillosis.

AIDS-Related Opportunistic Infections↗
PubMed1994

Computed tomography (CT) in the diagnosis of sinus aspergillosis.

19 patients with radiodense sinus concretions found on standard radiography underwent a preoperative computed tomographic examination of the sinus maxillaris and the sinus concretions. 13 patients (68.4%) with the occurrence of radiodense concretions presented postoperative histologically and microbiologically diagnosed sinus aspergillosis infection. In 13 patients, the sinus concretions had a density higher than 2000 HU (Hounsfield unit) and 6 patients had concretions with a density lower than 2000 HU. 12 (92.3%) of 13 patients with concretions having a density greater than 2000 HU had a postoperatively diagnosed sinus aspergillosis infection. The incidence of diagnosed sinus aspergillosis increased from 68.4% by standard radiography to 92.3% by computed tomographic examination on the supposition that the concretions have a density higher than 2000 HU. The computer tomography (CT)-density of sinus concretions in patients with diagnosed sinus aspergillosis was 2826.7 +/- 362.8 HU. The concretions of patients without sinus aspergillosis had a lower density (788.1 +/- 916.8 HU; p < 0.001). CT-density of root filling material presented nearly the same number in patients with aspergillosis infection (2789.3 +/- 287.5 HU) and in patients without sinus aspergillosis infection (2635.0 +/- 367.8 HU). In patients with diagnosed sinus aspergillosis, a significant correlation between the density of sinus concretions and the density of adjoined dental root filling material was found. Our study demonstrates that an additional preoperative paranasal sinus CT inclusive densitometry of the sinus concretions present is more sensitive than standard radiography for predicting the diagnosis of sinus aspergillosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed2002

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.

Adolescent↗
PubMed2000

Central nervous system aspergillosis in patients with human immunodeficiency virus infection. Report of 6 cases and review.

Central nervous system (CNS) aspergillosis is a relatively uncommon complication of human immunodeficiency virus (HIV) infection. We describe 6 patients with the acquired immunodeficiency syndrome (AIDS) who developed CNS aspergillosis, and we review a total of 33 cases of CNS aspergillosis among HIV-infected individuals that were diagnosed by histology and/or culture. All patients were diagnosed with advanced HIV infection. Major risk factors for the disease included neutropenia and corticosteroid use. The most common presenting symptoms were nonspecific neurologic manifestations including headache, cranial or somatic nerve weakness or paresthesia, altered mental status, and seizures. The most common sites of additional Aspergillus involvement were the lungs, sinuses, ears, and orbits, while in one-fourth of the cases CNS was the only site of Aspergillus infection. The final diagnosis of CNS aspergillosis was made on autopsy in more than half the cases, and medical treatment of CNS aspergillosis was unsuccessful in all cases. CNS aspergillosis should be included in the differential diagnosis of HIV-infected patients who present with nonspecific neurologic symptoms and signs. If we take into account the much higher prevalence of invasive aspergillosis of the lungs, the findings in the present report suggest that CNS aspergillosis in HIV-infected individuals occurs more often as a result of direct extension from the sinuses, orbits, and ears than through hematogenous spread from the lungs. Physicians should be aware that the CNS might be the only site of Aspergillus involvement and include CNS aspergillosis in the differential diagnosis of HIV-infected patients presenting with focal neurologic signs and symptoms, especially when the head CT reveals hypodense lesions.

Adult↗
PubMed1977

Studies in chronic allergic bronchopulmonary aspergillosis. 4. Comparison with a group of asthmatics.

A comparison is made of lung function tests and radiographic findings in 20 asthmatic patients with allergic bronchopulmonary aspergillosis paired in terms of sex, age, and duration of asthma with 20 other asthmatics in whom the diagnosis of aspergillosis was excluded in order to see if the aspergillosis causes more lung damage. One hundred per cent of the patients with aspergillosis and 75% of the patients with asthma alone showed a significantly reduced forced expiratory volume in one second (FEV1) before bronchodilator. All the patients in the two groups had a significantly reduced maximal expiratory flow at 50% vital capacity breathing air (V50air) but the severity of the reduction was statistically greater in the aspergillosis group. Reversibility in FEV1 of 15% and more was found in 50% of patients with asthma alone as against 31% of patients with aspergillosis. The degree of reversibility of FEV1 was also statistically greater in patients with asthma alone. Improvement of less than 20% of V50 after helium-oxygen breathing was found in 33% of the patients with asthma alone and in 75% of the patients with aspergillosis. Patients with aspergillosis also showed significantly (0-001 less than P less than 0-01) more reduced gas transfer factor. Radiological features of overinflation were as common in the two groups. Tubular and ring shadows were found in 95% and 60% respectively of patients with aspergillosis as against 45% and 15% of patients with asthma alone.

Adult↗
PubMed1995

Pathogenesis of pulmonary aspergillosis. Granulocytopenia versus cyclosporine and methylprednisolone-induced immunosuppression.

Patients with chemotherapy-induced granulocytopenia for neoplastic diseases and those receiving cyclosporin A plus corticosteroids for prevention and treatment of organ transplant rejection are two immunologically distinct patient populations with high risks for development of invasive pulmonary aspergillosis. In order to compare the pathogenesis of aspergillosis in these two high-risk populations and to further characterize the role of cyclosporin A in development of pulmonary aspergillosis, we studied the patterns of infection and inflammation in two clinically applicable rabbit models of invasive pulmonary aspergillosis. There were striking differences in the patterns of infection and inflammation of invasive pulmonary aspergillosis according to the type of underlying immune defect. Among rabbits challenged with the same intratracheal inoculum, there was a 100% mortality for invasive pulmonary aspergillosis in profoundly granulocytopenic rabbits in comparison with a 100% mortality for invasive pulmonary aspergillosis in profoundly granulocytopenic rabbits in comparison with a 100% survival in rabbits immunosuppressed with cyclosporin A plus methylprednisolone (CsA+MP). Lesions of pulmonary aspergillosis in granulocytopenic rabbits consisted predominantly of coagulative necrosis, intraalveolar hemorrhage, and scant mononuclear inflammatory infiltrate. By comparison, pulmonary foci in rabbits immunosuppressed by CsA+MP consisted mainly of neutrophilic and monocytic infiltrates, inflammatory necrosis, and scant intraalveolar hemorrhage. There was extensive infiltration by hyphae with angioinvasion in granulocytopenic rabbits, whereas conidia in various stages of germination predominated in CsA+MP treated animals in which there was a paucity of hyphae or angioinvasion. Extrapulmonary disease predominated in granulocytopenic rabbits. Methylprednisolone was the major immunosuppressive drug in rabbits treated with CsA+MP. Cyclosporin A alone did not increase the progression of pulmonary aspergillosis and did so only when used chronically with methylprednisolone.

Agranulocytosis↗
PubMed2000

Aspergillosis of central nervous system: a study of 21 patients seen in a university hospital in south India.

AIM: To study the pattern of central nervous system aspergillosis in a tropical country. MATERIAL AND METHODS: Case records of patients with CNS aspergillosis seen by the authors in a university hospital in south India were reviewed. RESULTS: Of the 21 patients seen during the study period, 16 (76%) patients had intracranial invasion by contiguous spread from paranasal sinuses and one had from ear. Predisposing risk factors were present in two (12.5%) patients with sinocranial aspergillosis and in both patients with disseminated form. Skull bases syndromes were the presenting features in 13 patients, six patients presented with features of intracranial space occupying lesion and two patients had stroke like presentation. CT scans showed intracranial extradural contrast enhancing mass lesions in the anterior, middle or posterior cranial fossa in addition to mass lesions in the paranasal sinuses in 13 patients with sinocranial aspergillosis and in seven orbital lesions. Intracerebral contrast enhancing mass lesion was the CT finding in both the patients with solitary cerebral aspergillus granuloma and in the patient with otocranial aspergillus granuloma. Well-formed granuloma with dense fibrosis was the histological feature in patients with sinocranial and otocranial aspergillosis. Angioinvasion was the pathological feature in both the patients with disseminated form of aspergillosis. Surgical treatment was sub-radical in our series. Survival rates were not good even after surgical and antifungal chemotherapy. CONCLUSIONS: This study suggests that in this part of the world sinocranial aspergillosis is the most common form of histologically verified CNS aspergillosis. Associated predisposing factors and immune status of the host determine the clinical syndrome and type of pathology in patients with CNS aspergillosis.

Aspergillosis↗
PubMed1996

Aspergillosis: a disease with many faces.

Aspergillus causes a variety of pulmonary diseases. For the most part, they can be divided into three groups: mycetoma, invasive aspergillosis, and allergic forms of aspergillosis. The mycetoma form of aspergillosis has no effective treatment other than surgery, which is reserved for the severely symptomatic patient, usually with massive hemoptysis. Invasive aspergillosis is a dangerous pulmonary infection seen in patients who are generally severely immunocompromised. It is treated with amphotericin B and success in treatment of this form of aspergillosis is limited. Two of the allergic forms of Aspergillus infection, allergic bronchopulmonary aspergillosis and bronchocentric granulomatosis, are treated with steroids. The third allergic type of reaction, hypersensitivity lung, is best treated by removal of the patient from exposure to the antigen. Although these are the characteristic forms of aspergillosis, there is occasional overlap of the different types of aspergillosis.

Adult↗
PubMed2004

Azoles for allergic bronchopulmonary aspergillosis associated with asthma.

BACKGROUND: Allergic bronchopulmonary aspergillosis is hypersensitivity to the fungus Aspergillus fumigatus that complicates patients with asthma and cystic fibrosis. The mainstay of treatment for allergic bronchopulmonary aspergillosis remains oral corticosteroids, though this does not completely prevent exacerbations and may not prevent the decline in lung function. OBJECTIVES: The purpose of this review was to determine the efficacy of azoles in the treatment of allergic bronchopulmonary aspergillosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register using the terms: (allergic bronchopulmonary aspergillosis OR aspergillosis OR allergic pulmonary aspergillosis OR allergic fungal and disease OR allergic mycotic and disease) AND (azole OR triazole OR itraconazole OR ketoconazole). Date of last search January 2003. SELECTION CRITERIA: All controlled trials that assessed the effect of azole antifungal agents compared to placebo or other standard therapy for allergic bronchopulmonary aspergillosis were reviewed. Patients with cystic fibrosis were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twelve trials were identified, but only three were prospective, randomised and controlled. A total of 94 participants were included. One demonstrated a reduction in immunological markers of disease activity and symptom scores using ketoconazole 400 mg daily for 12 months. There was no significant improvement in lung function. The other two examined the use of itraconazole for 16 weeks. In one there was a reduction in sputum eosinophils by 35% compared to 19% with placebo (p < 0.01). In the same trial, the number of exacerbations requiring oral corticosteroids was 0.4 per patient with itraconazole compared with 1.3 per patient with placebo (p < 0.03). Meta-analysis of data from both trials showed that itraconazole treated patients were more likely to have decline in serum IgE over 25% or more (Peto OR 3.30; 95% confidence intervals 1.30 to 8.15). REVIEWERS' CONCLUSIONS: Itraconazole modifies the immunologic activation associated with allergic bronchopulmonary aspergillosis and improves clinical outcome, at least over the period of 16 weeks. Adrenal suppression with inhaled corticosteroids and itraconazole is a potential concern.

Antifungal Agents↗