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PubMed1989

Pulmonary eosinophilia with and without allergic bronchopulmonary aspergillosis.

Sixty five patients with pulmonary eosinophilia attending one respiratory unit were reviewed. All had fleeting radiographic abnormalities and peripheral blood eosinophil counts greater than 500 x 10(6)/l. Eighteen had a single episode and 47 recurrent episodes during a median follow up period of 14 years. Thirty three patients had allergic bronchopulmonary aspergillosis on the basis of a positive skin test response to Aspergillus fumigatus, serum precipitins, or culture of A fumigatus from sputum, or a combination of these. All but seven patients had asthma, six of the seven being in the group who did not have allergic bronchopulmonary aspergillosis. The patients with allergic bronchopulmonary aspergillosis were more often male and had a greater incidence of asthma and an earlier age of onset of asthma than those without aspergillosis. The patients with aspergillosis had lower mean blood eosinophil counts and more episodes of pulmonary eosinophilia and more commonly had radiographic shadowing that suggested fibrosis or bronchiectasis (20 v 7). Pulmonary eosinophilia associated with allergic bronchopulmonary aspergillosis appears to be a distinct clinical syndrome resulting in greater permanent radiographic abnormality despite lower peripheral blood eosinophil counts.

Adolescent↗

PubMed1984

Evaluation of a rapid enzyme-linked immunosorbent assay for IgG antibodies to Aspergillus fumigatus in the serological diagnosis of allergic aspergillosis.

A range of 6 somatic and culture filtrate antigens of Aspergillus fumigatus were evaluated in a rapid ELISA procedure for anti-A. fumigatus IgG where the component incubation times had been reduced to 10 min. Sera from patients with allergic aspergillosis, patients with suspected allergic aspergillosis, and asthmatic patients with or without A. fumigatus precipitins were tested. For all antigens, levels of anti-A. fumigatus IgG were higher in patients with allergic aspergillosis than in the other 3 groups. Low levels of specific IgG were, however, detected in asthmatic patients who had no precipitins against A. fumigatus. None of the antigen preparations enabled all patients with proven or suspected allergic aspergillosis to be separated from the other 2 groups of asthmatic patients. Positive-negative discrimination in ELISA was achieved by the inclusion of 10 pools of precipitin test-negative sera from the 50 asthmatics without A. fumigatus precipitins. The number of sera that were classed as positive in ELISA ranged from 9 to 15 in the allergic aspergillosis group, depending on the antigen used; in the suspected aspergillosis group, the number of positive reactions ranged from 1 to 8, while in the asthmatics with precipitins, the number ranged from 0 to 2.

Antibodies, Fungal↗

PubMed2005

Current approaches to diagnosis and treatment of invasive aspergillosis.

Filamentous fungi (moulds) are ubiquitous soil inhabitants whose conidia are inhaled into the respiratory tract, where they may cause life-threatening infections. Among these infections is invasive aspergillosis, which is a major cause of morbidity and mortality in the severely immunocompromised. Risk factors for invasive aspergillosis include prolonged and severe neutropenia, hematopoietic stem cell and solid organ transplantation, advanced AIDS, and chronic granulomatous disease. Invasive aspergillosis most commonly involves the sinopulmonary tract reflecting inhalation as the principal portal of entry. Chest computed tomography scans and new non-culture-based assays such as antigen detection and polymerase chain reaction may facilitate the early diagnosis of invasive aspergillosis, but have limitations. Reflecting an important unmet need, there has been a significant expansion in the antifungal armamentarium. The second-generation triazole, voriconazole, was superior to conventional amphotericin B as primary therapy for invasive aspergillosis, and is the new standard of care for this infection. There is significant interest in combination antifungal therapy pairing an echinocandin with either an azole or amphotericin B formulation as therapy for invasive aspergillosis. In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials.

Animals↗

PubMed2000

A comparative clinicopathologic study of endogenous mycotic endophthalmitis: variations in clinical and histopathologic changes in candidiasis compared to aspergillosis.

PURPOSE: Endophthalmitis caused by endogenous Candida and Aspergillus species has emerged as a visually threatening complication in patients with immune deficiency of various causes. Twenty-five patients who underwent enucleation, 13 with endogenous Aspergillus endophthalmitis and 12 with endogenous Candida intraocular infections, were evaluated. Both clinical features and intraocular spread of the fungi were studied to determine which clinical and/or histopathologic features could help distinguish aspergillosis from Candida infections. METHODS: Clinical information was sought from each case to determine whether there was any underlying systemic condition and to delineate the characteristic clinical features seen at initial presentation. The results of vitreous and other tissue cultures for bacteria and fungi were evaluated. Patients with AIDS were excluded. The enucleated globes were processed for histopathologic analysis to detect location of the fungal elements, inflammatory response, and vascular invasion by the fungi. RESULTS: With respect to the various predisposing systemic conditions, Candida species endophthalmitis was noted in patients with a history of gastrointestinal surgery, hyperalimentation, or diabetes mellitus, whereas aspergillosis was present in patients who had undergone organ transplantation or cardiac surgery. The vitreous was the primary focus of infection for Candida, whereas subretinal or sub-retinal pigment epithelium infection was noted in eyes with aspergillosis. Retinal and choroidal vessel wall invasion by fungal elements was noted in cases of aspergillosis but not in cases with candidiasis. The high rate of cerebral and cardiac infection in patients with Aspergillus endophthalmitis was not seen in those with Candida infection. CONCLUSIONS: The present study indicates that unlike Candida endophthalmitis, aspergillosis is seen in organ transplant or cardiac surgery patients, and its initial clinical presentation includes extensive areas of deep retinitis/choroiditis. Contrary to the findings in Candida endophthalmitis, vitreous biopsy may not yield positive results in aspergillosis. Aspergillus endophthalmitis is usually associated with a high rate of mortality caused by cerebral and cardiac complications.

Adult↗

PubMed1990

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.

Aspergillosis, Allergic Bronchopulmonary↗

PubMed1990

[Fatal hemoptysis during bronchial aspergillosis with multiple pulmonary artery aneurysms].

Aspergillosis with fatal outcome are usually pulmonary invasive aspergillosis with or without dissemination, developed in patients with severe immunosuppression. We report a fatal case of bronchial necrotizing aspergillosis in a young woman with diabetes mellitus, who developed similar lesions to "Semi-invasive Aspergillosis", so-called "Chronic Necrotizing Pulmonary Aspergillosis". This aspergillosis was complicated by large pulmonary artery aneurysms requiring an hemostatic lobectomy. These aneurysms, secondary to the bronchial lesions, contrast with infectious aneurysms (so-called mycotic) secondary to septic embols. They differ from Rasmussen's aneurysms, due to tuberculosis, by their size, fusiform shape and extent. Lesions of vessels' walls and parietal fungal invasion in the vicinity of an endo-bronchial aspergilloma explain the vascular rupture. The multiplicity of these aneurysms, showed on C T Scan, is responsible for death by post-surgical recurrence of hemoptysis.

Adult↗

PubMed1995

[The epidemiological surveillance network for nosocomial invasive aspergillosis of the Assistance Publique-Hôpitaux de Paris].

Since January 1990, a epidemiology surveillance network has been set up by the Paris hospitals for nosocomial invasive aspergillosis. The network includes 39 high risk clinics (haematology, bone marrow graft, organ transplantation) in 19 hospitals. Over the first 3 years of surveillance (1990-1992), 132 cases of aspergillosis have been registered as probably invasive and nosocomial. The incidence of nosocomial invasive aspergillosis invasive aspergillosis has been estimated at 1.16 per 1,000 patient-days in haematology wards, at 4.56% in bone marrow graft and at 1.57 in liver transplantation. Mortality was 57% for all cases registered and 75% for bone marrow transplant patients; 97% of these patients were immunodepressed. Room air filtration with an absolute filter system had been installed for only 32% of the patients at diagnosis of invasive nosocomial aspergillosis. Work areas were in the environment of 68% of the cases reported. Surveillance led to the establishment of incidence and mortality data and emphasized the importance of the problem in terms of public health. In addition, three main elements were recognized concerning the disease: the number of immunodepressed patients in increasing in the hospitals, room air filtration equipment is inadequate, unavoidable work areas in hospitals have a significant effect. A practical guide for the prevention of invasive nosocomial aspergillosis in case of work areas in the hospital was published in 1993. Nevertheless, the proposed measures must be integrated into a global prevention strategy to eliminate sources of contamination and improve food facilities, architecture, air conditioning, internal organization and personnel training in high risk clinics.

Aspergillosis↗

PubMed1996

[Diagnosis of pulmonary aspergillosis in cases with cavity as sequela of tuberculosis].

Non-invasive pulmonary aspergillosis is frequently seen in cases with cavity as sequela of tuberculosis. Diagnosis of non-invasive pulmonary aspergillosis is not easy except for cases whose chest X-ray findings show a typical fungus ball. How to diagnose pulmonary aspergillosis was studied in 21 patients who showed changes in the radiological findings of cavity as sequela of tuberculosis. We made sputum culture of Aspergillus, measurement of precipitin antibody titer to Aspergillus fumigatus and measurement of PASTOREX ASPERGILLUS in serum and sputum on the 21 patients (group A). PASTOREX ASPERGILLUS in sputum was evaluated in three grades: 1+ approximately 3+. We diagnosed 14 patients as pulmonary aspergillosis (PA group) among the 21 patients taking into account the chest X-ray findings and the results of the above-stated investigations. The types of chest X-ray findings of these 14 patients were fungus ball type (FB) in 2 patients, productive aspergilloma on the inner wall of a cavity (PAIC) in 8, mixed type with FB and PAIC in 2 and non-specific change in 2. However, there were 3 patients with the chest X-ray findings suggestive of PAIC in 7 patients (non-PA group) who were not diagnosed as pulmonary aspergillosis. Sputum culture were positive in 11 patients of PA group (79%) and negative in all patients of non-PA group. Precipitin antibody were positive in 8 patients of PA group (67%) and negative in all patients of non-PA group. PASTOREX ASPERGILLUS in serum were negative in all 21 patients. PASTOREX ASPERGILLUS in sputum were 3+ (+3) in all 14 patients of PA group and in 2 patients of non-PA group and 2+ (+2) in 2 patients of non-PA group. 12 patients of PA group were treated by antifungal agents and 11 patients responded well to the treatment. We also made sputum culture of Aspergillus and measurement of PASTOREX ASPERGILLUS in sputum on 14 patients (group B) who had respiratory diseases with stable cavities and 17 patients (group C) who had respiratory diseases without a cavity. In group B, sputum culture were positive in 1 patient and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 2 patients, 2+ (+2) in 1 and 1+ (+) in 2. In group C, sputum culture were negative in all patients and PASTOREX ASPERGILLUS in sputum were 3+ (+3) in 1 patient, 2+ (+2) in 3 and 1+ (+) in 2. Measurement of PASTOREX in sputum was a useful tool to diagnose non-invasive aspergillosis in addition to sputum culture and measurement of precipitin antibody titer. The sensitivity of PASTOREX in sputum was high but its specificity was low, however, its specificity could be raised by applying semi-quantitative analysis of PASTOREX in sputum.

Adult↗

PubMed1998

[Invasive aspergillosis in AIDS: findings with high-resolution computerized tomography].

PURPOSE: To review the early CT findings of invasive aspergillosis in AIDS patients who are at high risk for developing this infection. Early recognition of invasive fungal disease is imperative in these patients, and longer survival can be achieved with early CT detection and prompt institution of high-dose antifungal therapy. MATERIAL AND METHODS: February, 1992 to December, 1994, sixteen cases of invasive pulmonary aspergillosis in AIDS patients were retrospectively reviewed. All patients underwent a chest radiograph and high-resolution Computed Tomography (HRCT) and the results were confirmed by pathology. RESULTS: 11/16 cases (68.8%) showed angioinvasive aspergillosis, characterized by nodules surrounded by the halo sign and cavitations; the remaining 5 patients (31.2%) showed invasive aspergillosis of the airways with centrilobular nodules and/or peribronchial consolidations. Five cases of extrapulmonary fungal dissemination were also observed. CONCLUSIONS: HRCT is a sensitive noninvasive method for evaluating early angioinvasive aspergillosis because the halo sign is characteristic enough to allow an early presumptive diagnosis. Invasive aspergillosis of the airways presents no characteristic radiologic pattern. However, the association of the clinical and radiologic pattern allows prompt institution of high-dose antifungal therapy.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Invasive central nervous system aspergillosis in bone marrow transplantation recipients: an overview.

Invasive central nervous system aspergillosis is being seen with an increased frequency, particularly due to the increased number of immunosuppressed patients. The major cause of invasive central nervous system aspergillosis is bone marrow transplantation. In most cases, aspergillosis develops in the paranasal sinuses and in the lungs, and secondarily spreads to the brain. Imaging of cerebral aspergillosis may present different patterns depending on the lesion's age and the immunologic status of the patient. Lesions of the spinal cord are far less common but has been encountered in our series. In this article we review the clinical and radiologic features of aspergillosis affecting the central nervous system in patients who underwent bone marrow transplantation. Different CT and MR patterns are presented, including pertinent clinical and pathologic material. Significant morbidity and mortality can be associated with this fungal infection, and it is therefore incumbent upon the radiologist to identify intracranial aspergillosis as early as possible so that appropriate therapy can be administered.

Adult↗

PubMed1976

An aspergillus immunodiffusion test in the early diagnosis of aspergillosis in adult leukemia patients.

An Aspergillus fumigatus immunodiffusion test was performed biweekly for one year on 80 hospitalized patients with acute leukemia to determine if serologic conversion accompanied clinical aspergillosis. A micro-ouchterlony technique with agarose was used. The antigens were prepared from concentrated A. fumigatus culture filtrates and the sera were concentrated 3-fold before testing. Of 80 patients, 10 were proved at autopsy, lung biopsy, or closed space culture to have invasive aspergillosis. Six of 10 patients converted from a negative to a positive immunodiffusion test, whereas a seventh patient's weakly positive test became strongly positive. Three patients with documented aspergillosis did not develop a positive immunodiffusion test. Four of the patients who converted from a negative to a positive test were treated early and successfully with amphotericin B. A fifth patient developed immunodiffusion test antibody late in the course and died despite therapy. A sixth patient died of concomitant mucormycosis despite early therapy. Six additional patients who converted from a negative to a positive immunodiffusion test could not be evaluated because of inadequate documentation of aspergillosis. In severely immunosuppressed patients, our immunodiffusion test proved to be a specific but not always a sensitive test for aspergillosis. In 4 patients, biweekly tests showed conversion associated with invasive aspergillosis, which was diagnosed early and treated successfully.

Acute Disease↗

PubMed2005

Role of collectins in innate immunity against aspergillosis.

The protective role of lung surfactant proteins SP-A, SP-D and MBL in the host defense against both allergic and invasive aspergillosis was identified and established by a series of in vitro and in vivo studies. Therapeutic administration of SP-D and MBL proteins in a murine model of pulmonary invasive aspergillosis rescued mice from death. In mice mimicking human allergic bronchopulmonary aspergillosis, SP-A and SP-D suppressed IgE levels, eosinophilia, pulmonary cellular infiltration and cause a marked shift from a pathogenic Th2 to a protective Th1 cytokine profile. SP-A and SP-D knock-out mice studies made significant contributions in understanding the mechanisms by which SP-A and SP-D modulate the host defense response in patients suffering from pulmonary allergies and infections. The results suggested that individuals with any structural or functional defects in these innate immune molecules due to genetic variations might be susceptible to aspergillosis. SNPs in SP-A2 and MBL genes showed significant associations with patients of allergic bronchopulmonary aspergillosis in an Indian population. The patients carrying either one or both of GCT and AGG alleles of SP-A2 and patients with A allele at position 1011 of MBL had markedly higher eosinophilia, total IgE antibodies and lower FEV1 (the clinical markers of ABPA). Our results show that collectins play an important role in Aspergillus mediated allergies and infections.

Animals↗

PubMed1992

Serum precipitins in pulmonary aspergillosis: preliminary results.

Definitive diagnosis of pulmonary aspergillosis is difficult to establish. Thus, confirmative evidence of active fungal aggression is imperative. In this study, an immunodiffusion test was carried out on 36 cases of pulmonary aspergillosis and two groups of subjects comprising 133 patients with non-fungal diseases and 134 healthy volunteers as controls. The test was positive in 92.3% of the patients with mycetoma, in 50% of the patients with allergic bronchopulmonary aspergillosis, and in 25% of the patients with invasive aspergillosis. Results were negative in all subjects in the two control groups. The findings indicate the efficacy of the test under study for supporting the diagnosis of pulmonary aspergillosis.

Adult↗

PubMed2003

[Invasive aspergillosis: clinical manifestations and treatment].

During the last decade the incidence of invasive aspergillosis has substantially grown due to the increasing use of powerful immunosupressive drugs in more patients. Unfortunately, the associated mortality with this infection is still very high and has not decreased in recent years. Pulmonary aspergillosis is by far the most frequent clinical picture of this infection, followed by sinus, tracheo-bronchial and central nervous system disease. The degree of immunosupression is the main factor influencing the evolution and dissemination of aspergillosis. Conventional amphotericin B has been the first-line therapy of invasive aspergillosis for the last 30 years, and most authors have long considered amphotericin B related toxicity as one of the main causes for the poor results obtained in the outcome of patients who developed this infection. Fortunately, in the last few years new safer and more effective drugs have been developed for the treatment of this entity. However, if we are really trying to substantially decrease invasive aspergillosis associated-mortality we should use these drugs earlier in the development of the infection, using new more sensitive diagnostic tests and/or a riskbase strategy which could identify patients at the highest risk to develop this infection.

Amphotericin B↗

PubMed1991

Aspergillosis and lung defenses.

Aspergillosis refers to any of the illnesses caused by fungi that are members of the genus Aspergillus. The diseases range from allergic responses that occur in the absence of fungal growth (asthma, hypersensitivity pneumonitis), to colonization with or without an allergic component (allergic bronchopulmonary aspergillosis, aspergilloma, saprophytic involvement of infarcted tissue), to invasion and destruction of lung parenchyma (invasive aspergillosis, chronic necrotizing pulmonary aspergillosis). The development of lung infection and/or disease depends on interaction among three factors: the characteristics of the fungus (virulence factors), the status of host defense mechanisms, and the type of exposure. The purpose of this article is to review these factors and their relationship to the clinical syndromes of aspergillosis.

Alveolitis, Extrinsic Allergic↗

PubMed2002

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.

Adolescent↗

PubMed1985

Aspergillosis of the central nervous system: clinicopathological analysis of 17 patients.

The clinical, laboratory, and pathological features of aspergillosis of the central nervous system (CNS) were studied in a series of 17 autopsied patients. Two groups were defined. Group A consisted of 8 patients with diseases commonly associated with CNS aspergillosis: leukemia, lymphoma, aplastic anemia, and renal transplantation. Group B contained 9 patients with various illnesses not generally known to be associated with CNS aspergillosis. CNS aspergillosis was diagnosed and treated before death in only 1 patient. Patients in Group A received cytotoxic drugs, often had granulocytopenia, less commonly had focal neurological deficits, and seldom had seizures. Group B patients were not granulocytopenic, received no cytotoxic agents, underwent nontransplant surgery, and more frequently had focal neurological deficits. Eleven of the 17 patients (65%) had focal deficits, most of them hemiparesis. Meningeal signs were rare, but the cerebrospinal fluid was usually abnormal. The principal neuropathological process was Aspergillus invasion of blood vessels causing hemorrhagic infarction. Focal clinical deficits correlated neuroanatomically with Aspergillus lesions. In 2 patients, such lesions were detected by 99mTc-DTPA or cerebral angiography before computed tomographic scanning. The lungs were the usual portal of entry, but isolated CNS lesions occurred in 2 patients. CNS aspergillosis should be considered as a cause of new onset of focal neurological deficits in patients with illnesses that are more diverse than has generally been appreciated.

Adolescent↗

PubMed1979

Paranasal sinus aspergillosis.

Four cases of aspergillosis of the paranasal sinuses seen recently at the North Carolina Baptist Hospital are reported. Paranasal sinus aspergillosis is prone to develop in patients living in the southeastern states because those states 1. have an agricultural economy and 2. have a hot, humid climate that causes a high incidence of nasal and sinus disorders. The increasing use of immunosuppressive and oncological drugs should further increase the incidence of aspergillosis. Diagnosis of aspergillosis of the paranasal sinuses requires a high index of suspicion which should be present particularly for a patient who has unilateral sinusitis that does not respond to routine therapy, or who has a localized sinus mass or bony erosion. Immunodiffusion tests are specific for aspergillosis. Treatment consists of surgical removal of the diseased mucosa and adequate aeration and drainage of the sinus. Culture of the specimen on Sabouraud's agar will confirm the diagnosis.

Aged↗