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PubMed1999

Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients.

OBJECTIVE: The purpose of this study was to assess the accuracy of high-resolution CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. MATERIALS AND METHODS: The high-resolution CT scans of 44 asthmatic patients with allergic bronchopulmonary aspergillosis and 38 asthmatic patients without allergic bronchopulmonary aspergillosis were analyzed retrospectively and randomly by two independent observers for these features: bronchial wall thickening, bronchiectasis, centrilobular nodules, mucoid impaction, mosaic perfusion, atelectasis, and consolidation. Each observer made a final diagnosis with a stated degree of confidence. The results are expressed as the average number of observations by the two observers. RESULTS: Findings seen more commonly in patients with allergic bronchopulmonary aspergillosis than in patients with asthma alone included bronchiectasis, centrilobular nodules, and mucoid impaction (p < .01, chi-square test). Bronchiectasis was present in 42 (95%) of 44 patients with allergic bronchopulmonary aspergillosis, centrilobular nodules in 41 (93%), and mucoid impaction in 29.5 (67%) (average of two observers). In the asthmatic control group, bronchiectasis was detected in 11 (29%) of 38 patients, centrilobular nodules in 10.5 (28%), and mucoid impaction in 4%. Bronchiectasis was seen in 184 (70%) of 264 lobes of patients with allergic bronchopulmonary aspergillosis compared with 19.5 (9%) of 228 lobes in asthmatic controls (p < .001, chi-square test). CONCLUSION: In asthmatic patients, bronchiectasis affecting three or more lobes, centrilobular nodules, and mucoid impaction are findings on high-resolution CT that are highly suggestive of allergic bronchopulmonary aspergillosis.

Adult↗
PubMed2005

Cardiac aspergillosis in patients with acquired immunodeficiency syndrome: a case report and review of the literature.

Cardiac aspergillosis is uncommon in patients with acquired immunodeficiency syndrome (AIDS) in the absence of open heart surgery. We report a unique case of a 62-year-old man with AIDS who developed Aspergillus pancarditis with Aspergillus vegetations on mitral valve without evidence of pulmonary aspergillosis. There was extensive embolization to the brain and multiple foci of Aspergillus infection in kidneys and adrenal glands. There are only 10 documented cases of cardiac aspergillosis in the literature (1966-2003) in severely immunocompromised AIDS patients with CD4 T-lymphocyte counts ranging from 10 to 121 cells/muL. The cardiac aspergillosis could result from invasive pulmonary aspergillosis, either by hematogenous dissemination or by direct invasion, and skin Aspergillus infection can be carried through the bloodstream to the right heart in intravenous drug abusers. Most of the reported cases of cardiac aspergillosis were diagnosed at autopsy. Mortality among AIDS patients with cardiac aspergillosis is 100%, despite appropriate therapy.

AIDS-Related Opportunistic Infections↗
PubMed2003

CNS-aspergillosis: are there new treatment options?

Invasive aspergillosis is an increasing cause of morbidity and mortality in immunocompromised patients. Extension of invasive aspergillosis to the central nervous system (CNS) is associated with an exceeding high mortality which approaches 100%. One major factor contributing to this devastating outcome is a poor penetration into the CNS of frequently used antifungal drugs, such as amphotericin B or itraconazole. Voriconazole, a new triazole with broad activity against various fungi, including Aspergillus species, shows superior activity in invasive aspergillosis compared to treatment with conventional amphotericin B. Voriconazole readily penetrates the blood-brain barrier yielding fungicidal drug concentrations within the CNS. A growing number of patients with CNS aspergillosis has been successfully treated with voriconazole in recent years. The pharmacological properties, the broad antifungal activity and the promising clinical data suggest that the use of voriconazole in CNS aspergillosis might improve the outcome in this otherwise devastating clinical condition. However, additional clinical data are needed to determine more precisely the role of voriconazole in CNS aspergillosis. In this review, we have compiled the available pharmacological and clinical data on CNS aspergillosis.

Amphotericin B↗
PubMed2004

[The diagnosis and surgical treatment for 56 cases with pulmonary and pleural aspergillosis].

OBJECTIVE: To summarize the experience of diagnosis and surgical treatment for pulmonary and pleural aspergillosis. METHODS: The clinical data of cases with pulmonary and pleural aspergillosis were analyzed retrospectively between September 1972 and June 2003. There were 53 cases with pulmonary aspergillosis and 3 cases with pleural aspergillosis. Aspergillus was found preoperatively in 8 patients by sputum culture (5 cases) or needle biopsy of the lung (2 cases) or fibro-bronchoscopic biopsy (1 case). All patients were treated with surgical procedures following X-ray film or CT scan. RESULTS: Of 53 cases with pulmonary aspergillosis, 42 lobectomies, 3 segment-Pneumonectomies, and 8 wedge resections were performed. Of three cases with pleural aspergillosis following eliminating their diseased foci in residual pleural space, two underwent thoracoplasty, one underwent postoperative closed chest drainage for one and an half month with fluconazole injected into residual pleural space repeatedly for 1 month (200 mg/100 ml, 1 time per 2 or 3 days). No operative death and major postoperative complications occurred. None of the patients had recurrent symptoms at follow-up. CONCLUSION: We recommend aggressive surgical resection for pulmonary and pleural aspergillosis, and the surgical result is excellent.

Adult↗
PubMed2005

[Diagnosis and treatment of chronic pulmonary aspergillosis in 4 children].

OBJECTIVE: Chronic pulmonary aspergillosis is different from acute pulmonary aspergillosis in clinical picture, radiogram, diagnostic procedures and prognosis. Four patients with chronic pulmonary aspergillosis had been misdiagnosed as having pneumonia or pulmonary tuberculosis for a long time before admission to the hospital. The purpose of this report was to summarize the clinical manifestations and laboratory findings for correct diagnosis of chronic pulmonary aspergillosis. METHODS: Four patients with chronic pulmonary aspergillosis seen between October 2002 and October 2004 were retrospectively studied. Their clinical manifestations, chest radiographic feature, immune status, diagnostic procedure, therapy and prognosis were reviewed. RESULTS: The chief complaints of these patients were chronic cough and fever for 3 to 12 months. Chest wall abscess developed in the late course in case 1 and 4. Fine moist rales were heard and hepatosplenomegaly was found in case 1 and 2. No abnormal sign was found in case 3 and 4. Chest radiographic feature: lobar consolidation with adjacent pleural thickening was present in all cases. In early phase, solitary or multiple small nodules were found in 2 cases. Case 1-3 had normal IgG, IgM, IgA, IgE, T Cell subsets and NBT test. Case 4 had chronic granulomatous disease. Etiologic evidences: culture was positive for Aspergillus (A.) fulmigatus in sputum and in chest wall abscess in case 1 and 4; for A. niger in sputum and spore existing in lung tissue in case 2; for A. fulmigatus in sputum and hypha existing in lung tissue in case 3. All patients were treated with combination of amphotericin B and itraconazole. Their symptoms were controlled 10-30 d after treatment. In case 1 the disease relapsed 6 months later and the patient died at last due to giving up treatment by his parents. Case 2 was free of symptom for 12 months and his chest radiographic lesion disappeared completely 6 months later. Treatment of case 4 was given up. Case 3 continued to receive treatment and observation. CONCLUSION: Chronic pulmonary aspergillosis should be considered in children with long period fever and cough and lobar consolidation associated with adjacent pleural thickening or with nodular infiltration. The diagnosis of chronic pulmonary aspergillosis depended on identification of aspergillus from sputum or lung tissue. Combined amphotericin B and itraconazole might control the disease.

Amphotericin B↗
PubMed2006

[Diagnosis and treatment of invasive aspergillosis infection following orthotopic liver transplantation].

OBJECTIVE: To explore the treatment and appropriate management of invasive aspergillosis infection following orthotopic liver transplantation. METHODS: The clinical data of 576 cases who underwent orthotopic liver transplantation consecutively between January 2000 and January 2005 were analyzed retrospectively. RESULTS: The prevalence of invasive aspergillosis infection was 1.74 (9/576), included 8 cases with pulmonary aspergillosis and 1 case with cerebral aspergillosis. The interval between transplantation and diagnosis were from 10 days to 2 months. Persistent or discontinuous low fever maybe the main clinical presentation after operation. Liposomal amphotericin B (AmBisome) is the mainly treatment for invasive aspergillosis infections, 5 patients were cured and 2 patients developed multi-organ aspergillosis infection died. CONCLUSIONS: The clinical features of invasive aspergillosis infection following orthotopic liver transplantation were un-typical presentations in the early stage and easy to disseminate. Appropriate modification of immunosuppression therapy and early, high dose and long-term application of antifungal treatment is effective and safe to cure the disease.

Adult↗
PubMed1991

[Invasive aspergillosis in patients infected by the human immunodeficiency virus].

Invasive aspergillosis is a disease that affects immunosuppressed patients, in close relationship with the presence and duration of neutropenia. Although formerly included among the AIDS definition criteria, it was thereafter dropped out because of its very low prevalence. We describe here four cases of invasive aspergillosis in HIV infected patients, diagnosed at our institution. Three patients presented with invasive pulmonary aspergillosis, including one patient with chronic ulcerative pulmonary aspergillosis. The fourth patient developed aspergillosis of the brain. Taking into account the difficulties in establishing a diagnosis of this infection before death (most of published cases were from autopsy reports) and because of the paramount importance of early diagnosis for improving survival, we support the use of invasive pulmonary aspergillosis diagnostic criteria in a similar way as used in patients suffering lymphoproliferative disorders. Although classic treatment of this infection is based on the use of amphotericin B (with or without 5 fluorocytosine), the potential usefulness of itraconazole (a new imidazole drug) has to be considered. In spite of the low number of published cases, we believe that invasive aspergillosis among HIV infected patients has to be included as a likely diagnosis, specially in view of the prolonged survival and widespread use of cancer chemotherapy in this population.

Adult↗
PubMed1985

[Invasive aspergillosis in patients who died from acute leukemia].

The necropsy material with acute leukosis (166 deceased) was studied in order to establish the incidence of invasive aspergillosis. It was established in 16 of the deceased (9,64%): aspergillosis pneumonia--in 5 cases, aspergillosis sepsis--in II, with invasion of lungs, brain, spleen, liver, myocardium and other organs. Clinically aspergillosis was not distinguished. Continuous septic temperature, not influenced by antibiotic therapy should draw the attention to the presence of aspergillosis. The factors, preconditioning aspergillosis infection are stressed upon: immune-suppressive treatment in acute leukosis, granulocytopenia, continuous preceding antibiotic therapy, etc. The difficulties in the clinical differentiation of the infection are emphasized. With a view to the high incidence and lethality of aspergillosis in acute leukosis, the introduction of modern diagnostic methods and treatment are underlined to be necessary.

Acute Disease↗
PubMed1994

[Therapy of invasive aspergillosis with itraconazole: our own experiences and review of the literature].

Invasive aspergillosis is one of the most threatening infections in immunocompromised patients of risk. The classical standard therapy of deep-seated mycoses--amphotericin B as monotherapy or in combination with 5-fluorocytosine--shows a response rate in aspergillosis of 55-60%. The new triazole compound itraconazole demonstrating a high in vitro activity against Aspergillus species was used in the recent years in several studies in the treatment of invasive aspergillosis. We report on our own experiences of itraconazole therapy in invasive aspergillosis with 20 patients suffering from well-known classical underlying diseases and factors of risk. Diagnosis was based on clinical symptomatology and was serologically and culturally proved. Special efforts were made for an early diagnosis according to clinical criteria. Therefore, in numerous cases clinical diagnosis was made several days prior to mycological confirmation, and antimycotic therapy could be started. The mean dosis administered was 400 mg itraconazole per day. With four patients no therapy response could be observed. In one patient a partial remission was obtained. In 15 patients aspergillosis was cured. In our patients the rate of complete remission, therefore, amounted to 75%. In evaluating 12 published studies on itraconazole therapy of invasive aspergillosis (including our own patients) a response rate of 63% (169 of 269 patients) could be calculated. Therefore, increasing experience is indicating that itraconazole therapy might be an alternative to classical amphotericin B therapy of invasive aspergillosis.

AIDS-Related Opportunistic Infections↗
PubMed1976

[Pathomorphology of pulmonary aspergillosis in tuberculosis patients based on according to resection material].

To investigate various manifestations of broncho-pulmonary aspergillosis and to ascertain its association with a previous disease there were carried out histotopographic, histological and mycological studies of specimens of the lung tissue resected in 37 patients in connection with aspergillomas of the lungs and broncho-pulmonary aspergillosis. The investigations showed that aspergillosis was one of the forms of dysbacteriosis in the human organism and could develop against the background of post-tuberculous, tuberculous and nonspecific changes. The development of aspergillosis following post-tuberculous changes should be considered as a second nonspecific disease pathogenetically associated with tuberculosis, but with an etiological factor ot its own. There are the following forms of broncho-pulmonary aspergillosis: aspergillomas, isolated aspergillosis of the bronchi, extensive aspergillosis of the bronchi and cyst-like cavities, aspergillous pneumonia.

Aspergillosis↗
PubMed2005

Cerebral aspergillosis in the critically ill: two cases of successful medical treatment.

OBJECTIVE: Invasive aspergillosis is associated with a poor prognosis, especially in critically ill patients with cerebral involvement. We present two cases of cerebral invasive aspergillosis successfully treated in the intensive care unit with combination antifungal therapies and without surgery. CASE PRESENTATION: The first patient was a 49-year-old man with rheumatoid arthritis who received corticosteroid and cyclophosphamide treatment and developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole the patient had a successful outcome with voriconazole and liposomal amphotericin B therapy. The patient returned home after an 8-month hospital stay. The second patient was a 54-year-old woman with pulmonary neoplasia and corticosteroid treatment who developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole and liposomal amphotericin B therapy the patient had a favorable outcome with liposomal amphotericin B and caspofungin therapy. The patient died 10 months after initial diagnosis of cardiac tamponade unrelated to fungal infection. DISCUSSIONS: These cases illustrate the improving prognosis of invasive aspergillosis due to the availability of new treatments, especially in cases of cerebral involvement. It also demonstrates that the outcome of critically ill patients requiring mechanical ventilation for invasive aspergillosis can be favorable. The treatment of patients with invasive cerebral aspergillosis in the intensive care setting should be encouraged.

Amphotericin B↗
PubMed2005

[Role of surgery in the treatment of pulmonary aspergillosis].

INTRODUCTION: This article reviews the different forms of pulmonary disease caused by aspergillus and discusses the possible surgical treatments. The most well known is the classic aspergilloma which develops as a fungal ball in the centre of a pre-existing pulmonary cavity. STATE OF KNOWLEDGE: One can distinguish simple (few symptoms, thin walled cavity without immediate complications) and complex forms (patient generally unwell, thick cavity, complications). In the complex form, surgical intervention must be considered as a last resort. In the simple form, surgery is relatively benign and prevents disease progression. Pleural aspergillosis can occur, usually following the surgical removal of a cavity either in the short or medium term. Given the loss of lung parenchyma thoracoplasty is often the only option. OUTLINES: Two different scenarios occur in acute invasive aspergillosis where surgery may be indicated: firstly, surgery can be considered in the event of haemoptysis related to vascular erosion; secondly, resection of mycotic sequestrations before intensification or resumption of therapy may prevent a relapse. Semi-invasive aspergillosis usually occurs in territories of post-radiation fibrosis: after a phase of invasion equivalent to a lobar pneumonia, a secondary cavity appears containing a small fungal ball. Thoracoplasty is often the only surgical option. Ulcerating tracheobronchial aspergillosis has been observed following (cardio-) pulmonary transplant and this may progress to a characteristic invasive aspergillosis. CONCLUSIONS: Finally, rare observations of parietal aspergillosis could be treated by surgical resection and associated with systemic antifungal therapy. Optimum management of these patients requires a multidisciplinary approach.

Acute Disease↗
PubMed2000

Aspergillosis among people infected with human immunodeficiency virus: incidence and survival. Adult and Adolescent Spectrum of HIV Disease Project.

Aspergillosis is a life-threatening fungal infection in immunocompromised people, including people infected with human immunodeficiency virus (HIV). We determined the incidence of aspergillosis among HIV-infected people and survival after aspergillosis diagnosis by use of a national HIV surveillance database. Among 35,252 HIV-infected patients, the incidence of aspergillosis was 3.5 cases per 1000 person-years (p-y; 95% confidence interval [CI], 3.0-4.0 per 1000 p-y). Incidence was higher among people aged > or =35 years (4.1 per 1000 p-y, 95% CI, 3. 5-4.8), among people with CD4 counts of 50-99 cells/mm(3) (5.1 per 1000 p-y, 95% CI, 2.8-7.3), or CD4 counts of <50 cells/mm(3) (10.2 per 1000 p-y, 95% CI, 8.0-12.2), versus people with CD4 counts of >200 cells/mm(3), people with > or =1 acquired immune deficiency syndrome-defining opportunistic illness (8.6 per 1000 p-y, 95% CI, 7.4-9.9), and people who were prescribed at least one medication associated with neutropenia (27.7 per 1000 p-y, 95% CI, 21.0-34.3). Median survival time after diagnosis of aspergillosis was 3 months, and 26% survived for > or =1 year. These findings suggest that aspergillosis is uncommon, occurs especially among severely immunosuppressed or leukopenic HIV-infected people, and is associated with poor survival.

AIDS-Related Opportunistic Infections↗
PubMed2005

Voriconazole for invasive bone aspergillosis: a worldwide experience of 20 cases.

UNLABELLED: BACKGROUND; Bone aspergillosis remains a rare but potentially devastating fungal disease. Although voriconazole is effective for invasive pulmonary aspergillosis, evidence of its efficacy for aspergillosis located in bone is limited. METHODS: We report our experience with voriconazole in 4 cases of invasive bone aspergillosis. In addition, all cases of probable and definite bone aspergillosis from the Pfizer clinical database were reviewed and analyzed to determine the safety and efficacy of voriconazole treatment. Global response was evaluated at the end of therapy on the basis of a composite assessment of overall clinical, radiological, and mycological responses. RESULTS: Twenty patients are described, of whom 18 had definite bone involvement diagnosed (spondylodiskitis in 9, sternum/rib osteomyelitis in 6, and peripheral bone involvement in 5). Of 20 patients, 14 were immunocompromised. Oral or intravenous voriconazole was given as salvage therapy for 18 patients; 2 patients received voriconazole as first-line therapy. Median duration of voriconazole treatment was 83.5 days (range, 4-395 days). Global response at end of therapy was satisfactory in 11 (55%) of 20 patients, including complete responses in 4 patients and partial responses in 7 patients; there were no relapses of infection in the 4 patients with complete response to therapy with voriconazole. Treatment was generally well tolerated. CONCLUSIONS: Long-term voriconazole treatment is a new therapeutic option for invasive aspergillosis with bone involvement.

Adolescent↗
PubMed1992

The spectrum of pulmonary aspergillosis.

Aspergillus species can produce a wide range of pulmonary disorders. Classically, pulmonary aspergillosis has been categorized into invasive, saprophytic, and allergic forms, all of which differ in their manifestations and therapy. More recently, however, other types of infection by this fungus have been recognized that do not fit into these traditional categories; an example is semi-invasive (chronic necrotizing) aspergillosis. In fact, these forms have features that are intermediate between those of the invasive and saprophytic types. The various types of aspergillosis can be regarded as constituting a continuous spectrum, ranging from invasive disease in the severely immunosuppressed patient to hypersensitivity reactions such as allergic bronchopulmonary aspergillosis (and bronchocentric granulomatosis) in the hyperreactive patient. Between these extremes are chronic necrotizing disease seen in midly immunocompromised hosts, and the noninvasive aspergilloma, which is due to saprophytic growth within a previously diseased area of lung in an otherwise normal host. Other intermediate forms may be encountered, their behavior being determined by the host immune status in combination with the underlying lung morphology. The radiographic and clinical features of these various forms of pulmonary aspergillosis are reviewed, including the more recently reported forms of infection such as Aspergillus tracheobronchitis and aspergillosis associated with acquired immunodeficiency syndrome and cystic fibrosis. The proposed concept of a disease spectrum is emphasized.

Aspergillosis↗
PubMed2006

Cytokine profiling of pulmonary aspergillosis.

Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly destructive form of pulmonary aspergillosis, without immunocompromise. We hypothesized that CCPA cytokine gene polymorphisms would differ from patients with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls. We have profiled functional cytokine gene polymorphisms for interleukin (IL)-10, IL-15, transforming growth factors (TGF)-beta1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in patients with CCPA (n = 24) who were compared with other forms of aspergillosis (mostly ABPA) (n = 15) and with ethnically matched controls (n = 65-330). Results are described with reference to the high-producing genotype in each case. Susceptibility to aspergillosis (all patients compared with normal controls) was associated with higher frequency of the IL-15 +13689*A allele (OR = 2.37, P = 0.0028) and A/A genotype (chi(2) = 10.31, P < 0.001), with a lower frequency of the TNF-alpha-308*A/A genotype (chi(2) = 11.05, P < 0.01). Within the aspergillosis patients, CCPA is associated with lower frequency of the IL-10 -1082*G allele (OR = 0.38, P = 0.0006) and G/G genotype (chi(2) = 22.45, P < 0.001) and with a lower frequency of the TGF-beta1 +869 *T allele (OR +0.42, P < 0.0029) and T/T genotype (chi(2) = 17.82, P < 0.001) compared with non-CCPA patients and normal controls. Patients infected with Aspergillus appear to be higher producers of IL-15, a Th2-promoting cytokine, and lower producers of TNF-alpha, a cytokine central in protective responses. CCPA occurs in patients who are genetically lower producers of both IL-10 and TGF-beta1. As these cytokines are regulatory and anti-inflammatory, CCPA may be a consequence of poor inflammatory response control in the lung.

Adult↗
PubMed1995

Varied radiologic appearances of pulmonary aspergillosis.

Pulmonary aspergillosis represents a common, potentially lethal opportunistic infection that has four unique forms: allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and invasive and semi-invasive aspergillosis. In individuals who are at risk, pulmonary aspergillosis is characterized by a spectrum of clinical and radiographic findings that are intrinsically related to the status of the immune system or the presence of structural lung disease. ABPA, occurring almost exclusively in asthma patients, is characterized radiographically by fleeting pulmonary alveolar opacities caused by deposition of immune complexes and inflammatory cells within the lung parenchyma. Mucus plugging and bronchial wall thickening can be expected in time. Aspergilloma, occurring in patients with structural lung disease, typically appears radiographically as a focal intracavitary mass and is characterized initially by an increase in the wall thickness of a preexisting cavity or cyst. Invasive aspergillosis, which occurs primarily in profoundly immunocompromised patients, may exhibit nonspecific patchy nodular opacities or lobar-type air-space disease in cases with vascular invasion. Computed tomography may reveal a halo or ground-glass attenuation and is more accurate in the detection of early disease. Cavitation often develops with time and typically results in the air crescent sign. Semi-invasive aspergillosis is radiographically similar to the invasive form but differs in clinical course, being associated with mild immunosuppression or chronic illness and typically progressing over the course of months rather than weeks.

Aspergillosis↗
PubMed1996

Evaluation of the diagnostic value of the measurement of (1-->3)-beta-D-glucan in patients with pulmonary aspergillosis.

The value of the measurement of (1-->3)-beta-D-glucan, a major and common cell wall constituent of fungi, for diagnosing pulmonary aspergillosis was assessed in comparison with that of conventional examinations. The concentrations of (1-->3)-beta-D-glucan in sera was elevated in 7 out of 8 patients with active aspergillosis, but not in cases without active diseases, except for one sample. Further, the concentrations well reflected the activity of the aspergillosis in each case. Regarding conventional examinations, with the immunodiffusion test it was difficult to detect the present activity of the disease. The radioallergosorbent test was useful for diagnosing bronchopulmonary aspergillosis, but not for other types of aspergillosis. The Aspergillus-specific component, galactomannan, was insensitive and the enzyme-linked immunosorbent assay gave highly variable results. Thus, although the assessment of the specificity of the assay is still necessary, compared with other tests, the assay of (1-->3)-beta-D-glucan has the advantage of diagnosing pulmonary aspergillosis and also of assessing the disease activity.

Antibodies, Fungal↗