Management of allergic bronchopulmonary aspergillosis without maintenance oral corticosteroids: a fifteen-year follow-up

Five non-smoking patients were diagnosed as having allergic bronchopulmonary aspergillosis in 1978/9. All have been treated since then with inhaled corticosteroids, using short courses of self-administered oral corticosteroids for symptomatic exacerbations. Over a mean 15 years of follow-up, they have required on average less than one course of oral drugs per annum. Regular monitoring of spirometry has shown no evidence of deterioration, and all have close to normal gas transfer. All have some localized bronchiectasis on CT scanning, in two cases probably occurring after treatment started, but in no case is there any respiratory disability. We conclude that this is a safe and effective method for the management of allergic bronchopulmonary aspergillosis when diagnosed before persistent hyphal colonization of the airways has occurred.     

A fatal case of ovarian hyperstimulation syndrome with cerebral infarction

BACKGROUND: A 76-year-old man developed allergic bronchopulmonary aspergillosis initially presenting with cough variant asthma. Symptoms worsened after exposure to ground mulch which was an identifiable source of Aspergillus fumigatus. Symptoms improved after corticosteroids and avoidance measures were instituted. OBJECTIVE: To report a case of allergic bronchopulmonary aspergillosis presenting as cough variant asthma with identifiable source of Aspergillus fumigatus. METHODS: Single case report. Serum precipitating antibodies against Aspergillus fumigatus were tested using gel diffusion techniques. Total IgE, specific IgE, and IgG indices were measured by ELISA. Cutaneous reactivity to Aspergillus fumigatus was also tested. RESULTS: Skin test and serum precipitating antibodies to Aspergillus fumigatus were positive. Precipitins were also detected between Aspergillus fumigatus and the mulch. Total serum IgE was 538 IU/mL (1290 ng/mL) which declined to 228 IU/mL (544 ng/mL) after corticosteroid therapy. IgE index = 1.10 and IgG index = 2.86. CONCLUSION: Allergic bronchopulmonary aspergillosis can present as cough variant asthma. Identification of exacerbating factors such as sources of Aspergillus fumigatus are important in management.     

Allergic bronchopulmonary aspergillosis

A 38 year old male was diagnosed to have allergic bronchopulmonary aspergillosis which responded remarkably to prednisolone therapy.     

Allergic bronchopulmonary mycosis caused by Pseudallescheria boydii

Two cases of allergic bronchopulmonary pseudallescheriosis (ABPP) are described. These are the first cases of this allergic bronchopulmonary mycosis (ABPM) reported in which the clinical and serologic criteria are described. The first case was in a patient with mild asthma, and it resolved spontaneously after expectoration of a mucous plug. The second was in a patient with recurrent allergic bronchopulmonary aspergillosis with an exacerbation of ABPM caused by Pseudallescheria boydii. The total serum IgE, IgG, and IgE antibodies against P. boydii and the clinical picture well define ABPP. This diagnosis may be important to recognize in order to prevent a progression of the patient's lung disease.     

Histopathological study of experimental recurrent pulmonary aspergillosis--the comparative study of steroid and cyclophosphamide induced models

A new animal model of recurrent pulmonary aspergillosis was established using cyclophosphamide (CPM) instead of cortisone acetate for reconstitution of immunosuppression, and histopathological findings were compared with those of the previous model. A recurrence of pulmonary aspergillosis, according to granulocytopenic conditions was much more rapid and uniform in this model than that of steroid induced model shown. In histopathologically, invasive and massive proliferation of Aspergillus hyphae was observed in lungs of rats 5-7 days after the CPM treatment and hyphal invasion into pulmonary vessels which suggested rapid systemic spreading of the infection was also found. This model considered to be good for the simulation of recurrent aspergillosis in patients with severe immunosuppression and also useful for studies of new diagnostic and therapeutic methods of recurrent pulmonary aspergillosis.     

Allergic bronchopulmonary aspergillosis in a patient with no symptoms of asthma until after bronchial lavage

An asymptomatic 56-year-old man was admitted to our hospital because of an abnormal shadow on a chest X-ray film. Allergic bronchopulmonary aspergillosis was diagnosed on the basis of five findings: eosinophilia, immediate skin reactivity to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, a high concentration of IgE in serum, and central bronchiectasis. He had no symptoms of asthma at the time of diagnosis, but did a few days after he underwent bronchial lavage. We speculate that the asthma attack was related to the bronchial Lavage as follows: First, drainage of mucus plugs by bronchial lavage may have exposed the bronchial epithelium, which had already been sensitized, to aspergillus antigens. Second, the scattered antigen may have dose-dependently stimulated the bronchi. Third, the infection may have increased bronchial responsiveness to the antigen. Symptoms of bronchial asthma are not necessary for the diagnosis of allergic bronchopulmonary aspergillosis.     

Functionalized 1,3-teraryls as a new class of hepatoprotectants. Part V

A 29-year-old man was admitted to the hospital because of a high fever and dyspnea. He had a history of bronchial asthma and had had a bullectomy of the right lung at 15 years of age. He had visited a family physician because of fever and non productive coughing. Medications had no effect on his symptoms, and dyspnea developed. A chest X-ray film showed total collapse of the right lung, and he was referred to our hospital. Laboratory data showed eosinophilia and a high titer of IgE. Total obstruction of the right main stem bronchus by mucous plug was found during fiberoptic bronchoscopy. Aspergillus was detected by pathological examination of bronchial lavage fluid. Tests for aspergillus-specific IgE and IgG antibody were positive, as was immediate skin reactivity to Aspergillus. Allergic bronchopulmonary aspergillosis (ABPA) was diagnosed. Infusion and inhalation of a corticosteroid and fluconazole were effective; the symptoms resolved and X-ray findings improved. While migratory infiltration, proximal bronchiectasis and segmental or subsegmental atelectasis caused by a mucous plug are common X-ray findings in allergic bronchopulmonary aspergillosis, total collapse is rare.     

Tumor necrosis factor alpha enhances antifungal activities of polymorphonuclear and mononuclear phagocytes against Aspergillus fumigatus

Invasive aspergillosis is a serious complication in immunocompromised patients. The effects of recombinant human tumor necrosis factor alpha (TNF-alpha) on antifungal activities of human neutrophils (polymorphonuclear leukocytes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macrophages (PAMs) against Aspergillus fumigatus were studied. The percentage of PMN-induced hyphal damage was increased after 30 min of incubation of PMNs with 0.1 ng of TNF-alpha per ml at 37 degreesC (P = 0.043). At 0.1 to 10 ng/ml, TNF-alpha also increased superoxide anion (O2-) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN phagocytosis of conidia in the presence of serum. By comparison, TNF-alpha induced only a slight increase in O2- production by MNCs in response to phorbol myristate acetate (P = 0.05) and no concomitant increase in the percentage of MNC-induced hyphal damage. Incubation of MNCs with TNF-alpha at 0.001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal activity. By contrast, incubation of PAMs with TNF-alpha at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-alpha augments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity against conidia. As such, TNF-alpha may have an important role in host defense against aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis.     

Severe small airways disease resistant to medical treatment in a child with cystic fibrosis

At the age of 12, a child with cystic fibrosis developed severe small airways obstruction of unknown aetiology, in the absence of significant bronchiectasis. He remained resistant to medical treatment until, following an exacerbation of allergic bronchopulmonary aspergillosis 18 months later, he responded to high dose oral steroids. He now remains steroid-dependent, and suffering from multiple side-effects. Possible aetiology and further therapeutic strategies are discussed.     

Chronic systemic aspergillosis in a patient with acute myeloid leukemia

Systemic aspergillosis is a well-recognized complication of chemotherapy-induced neutropenia. In this report a patient with acute myeloid leukemia is described in whom a chronic aspergillosis with systemic involvement developed after recovery from neutropenia following intensive chemotherapy and allogeneic bone marrow transplantation. The clinical features of a chronic course of systemic aspergillosis suggest a distinct clinical entity comparable to chronic systemic candidiasis.     

New concepts in atopic dermatitis

Allergic bronchopulmonary aspergillosis (ABPA) occurs in 1-2% of patients with asthma and in 10% of patients with cystic fibrosis. We introduce the acronym "ARTEPICS" in this review article on ABPA to facilitate its diagnosis: A: Asthma; R: Roentgenographic infiltrates; T: Tests for Aspergillus fumigatus (Af) positive in the skin; E: Eosinophilia; P: Precipitating antibody to Af; I: IgE in serum elevated; C: Central bronchiectasis; and S: Serum specific IgE-Af and IgG-Af elevated (ARTEPICS).     

Structure-based design of ligands for protein basic domains: application to the HIV-1 Tat protein

OBJECTIVES: to describe the clinical, microbiological and pathological features of invasive sinus aspergillosis affecting immunocompetent hosts, and to identify the risk factors for mortality. METHODS: we report three apparently immunocompetent patients with invasive sinus aspergillosis, and review all cases reported in the English literature since 1987, the year in which the triazole antifungal agents were introduced. RESULTS: twenty-nine patients (including three of our own) were identified. The presenting symptoms were non-specific and indistinguishable from viral, bacterial or allergic causes of sinusitis. The findings on computed tomography scan were also non-specific, and histopathology and culture of sinus tissue biopsy had low yield. These factors, along with the mistaken impression that Aspergillus can only affect immunocompromised hosts, frequently delayed the diagnosis. Fifty-nine percent of patients either failed therapy or died. The following factors were associated with a poor prognosis: delayed diagnosis, intracranial extension of infection, and histopathology demonstrating hyphal invasion of blood vessel or tissue. Complete surgical extirpation was the key element of successful therapy; antifungal agents played an adjunctive role. CONCLUSIONS: invasive sinus aspergillosis carries high morbidity and mortality, even in immunocompetent hosts. To improve outcome, the diagnosis must be recognized early, before the organism can invade the central nervous system or vascular structures. Aggressive surgical resection of the infected areas is of utmost importance in the management of this infection.     

Allergic bronchopulmonary aspergillosis effectively treated with itraconazole

A 23-year-old man with bronchial asthma presented with fever, cough, and sputum. A chest X-ray examination showed pulmonary infiltrations in the left upper and lower lung fields with central bronchiectasis. Although his temperature came down with antibiotics, pulmonary infiltrations persisted with cough and sputum. Following bronchoscopy and an allergological examination, the patient was given a diagnosis of allergic bronchopulmonary aspergillosis (ABPA) based on Rosenberg's criteria, including peripheral blood eosinophilia, a high serum IgE level, immediate skin reaction to Aspergillus antigen, positive precipitating antibodies, and Aspergillus fumigatus in sputum. The patient was treated with itraconazole instead of corticosteroids. His respiratory symptoms, eosinophilia, and pulmonary infiltration then disappeared, and his IgE serum level gradually decreased. An antifungal agent alone was effective in treating this ABPA patient.     

Gastrointestinal ulceration and pulmonary aspergillosis in a llama treated for parelaphostrongylosis

A 9-year-old llama examined because of hind limb paresis was found to have parelaphostrongylosis. Despite treatment with ivermectin, fenbendazole, cimetidine, and ceftiofur, the llama developed gastrointestinal ulceration and pulmonary aspergillosis and was euthanatized. Parelaphostrongylus tenuis is a parasite of white-tailed deer, but ruminants can serve as aberrant or dead-end hosts after accidentally ingesting snails or slugs carrying third-stage larvae of the parasite. Gastrointestinal ulceration and pulmonary aspergillosis can develop secondarily in llamas with chronic disease. Treatment of gastrointestinal ulceration in llamas is difficult, because efficacy of commonly used antiulcer drugs in llamas has not been established.     

The risk of seizures associated with tramadol

Several substances including proteases and restrictocin have been suggested as candidates for virulence determinants in invasive pulmonary aspergillosis. However, the roles of such substances are not well understood. This study compared the in vitro suppressive effects of Aspergillus fumigatus culture filtrates (ACFs), on the functions of human polymorphonuclear leukocytes (PMNLs), the principal cells in the host defence against aspergillus hyphae, from a clinically isolated wild-type and isogenic mutant strains which lack production of elastolytic alkaline protease (Alp) and/or restrictocin. ACFs were obtained by culturing conidia of each strain in Medium- 199 at 37 degrees C for 5 days. ACFs of the wild-type significantly (p<0.01) suppressed chemotaxis, superoxide anion (O2-) release and PMNL-mediated hyphal damage, compared with the control (Medium-199). ACFs of the mutant strains that lack Alp or restrictocin significantly (p<0.01) suppressed chemotaxis and O2(-)-release, but did not suppress hyphal damage, compared with the control. The wild-type significantly (p<0.01) suppressed chemotaxis of PMNLs compared with the mutant strains lacking Alp or restrictocin, whereas there were no significant differences in suppression of O2(-)-release and hyphal damage by PMNLs. ACF of a mutant strain that lacks both Alp and restrictocin had much less activity, but significantly (p<0.01) suppressed chemotaxis of PMNLs compared with the control. In conclusion, alkaline protease and restrictocin may play roles in the suppressive effect of Aspergillus fumigatus culture filtrates on the functions of human polymorphonuclear leukocytes. Other antiphagocytic substances produced by Aspergillus fumigatus remain to be identified.     

Changes in sputum composition during sputum induction in healthy and asthmatic subjects

BACKGROUND: Home oxygen therapy improves survival and quality of life in adults with chronic obstructive airways disease. The few studies about home oxygen therapy in children show improvements in weight gain, school performance and decreases in hospitalization expenses. AIM: To report our experience in home oxygen therapy in children followed for six months to four years. PATIENTS AND METHODS: Fifty five children, less than 15 years old, discharged from a University hospital with the diagnosis of chronic respiratory failure, were followed up at their homes. RESULTS: Discharge diagnoses were bronchopulmonary dysplasia in 36% of children, postinfectious pulmonary damage in 22%, neonatal distress in 13%, chronic aspiration in 9%, cystic fibrosis in 7% and miscellaneous in 13%. Forty six completed at least 6 months of follow up, five moved to other hospitals, three required ventilatory support and one died. Oxygen was discontinued in 33 patients, and this occurred before the ninth month of follow up in 88% of those children. Neonatal distress and bronchopulmonary dysplasia had the best prognoses, and oxygen was discontinued at 4 +/- 1 and 5.7 +/- 3 months respectively. Patients with postinfectious pulmonary disease had a higher incidence of bronchoneumoniae, and those with bronchopulmonary dysplasia a higher incidence of acute bronchiolitis, that motivated hospital admissions. Expenses due to home oxygen were lower than hospitalization costs. No adverse effects were detected. CONCLUSIONS: Infants and newborns on home oxygen therapy have a good prognosis, specially those with reversible diseases. This type of therapy allows an earlier hospital discharge with considerable cost reductions.     

Cutaneous purulent aspergillosis in a young man with chronic granulomatous disease

We describe a case of cutaneous purulent aspergillosis in a 19-year-old man with chronic granulomatous disease (CGD) treated successfully with a 6-month regimen of itraconazole. The therapeutic effect of the drug was seen after 1 month of administration. Surgical treatment of the skin lesions, although first planned, was not necessary.     

Immunodominant peptide epitopes of allergen, Asp f 1 from the fungus Aspergillus fumigatus

Aspergillus fumigatus ribotoxin Asp f 1 is a major allergen with IgE binding activity to serum of a majority of patients with allergic bronchopulmonary aspergillosis (ABPA). The IgE binding epitopes or the T-cell stimulatory peptides of this molecule have not been studied. In the present investigation, we have synthesized linear decapeptides spanning the whole molecule of Asp f 1 and analyzed their IgE binding properties. We have also synthesized peptides based on their possible T-cell stimulatory properties and studied the stimulation of peripheral blood mononuclear cells from ABPA patients and normal controls. Several peptides demonstrated distinct IgE antibody binding response against sera from ABPA patients and proliferative response against peripheral blood mononuclear cells from the patients. From the results, it can be concluded that the carboxy-terminal region of Asp f 1 representing amino acid residues 115-149 involved in both humoral and cell mediated immunoresponses in ABPA.     

Comparison of anaesthetic and non-anaesthetic effects on depolarization-evoked glutamate and GABA release from mouse cerebrocortical slices

The aim of the study was to investigate whether patients with Aspergillus-induced lung disease can be monitored by immunoblot analysis to detect antibodies to Aspergillus fumigatus (Af). Immunoblotting was performed by incubating 57 longitudinally collected sera from 13 patients on nitrocellulose sheets, blotted with Af antigen, separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Bound antibodies were demonstrated by peroxidase-labelled antihuman immunoglobulins (Ig)G and IgA antiserum and diaminobenzidine plus H2O2 as substrate. The immunoblot patterns were related to the patients' clinical status and time. Each patient had a characteristic immunoblot pattern that varied with time. There was a relationship between disease activity or clinical response and changes in immunoblot antibody patterns: a rise in anti-Af IgG and IgA antibodies was seen in sera collected during active disease, compared with before active disease, and a significant decline in anti-Af IgG and IgA was demonstrated in sera collected during recovery, compared with during active disease. Only in the acute stage of allergic bronchopulmonary aspergillosis were IgA antibodies against Af antigens of <20,000 Da demonstrated. Immunoblot analysis can be used to monitor the disease activity and the responses to treatment of patients with Aspergillus-induced lung diseases. Changes in specific immunoglobulin A may be more informative than specific immunoglobulin G.     

Psychological morbidity associated with abdominal aortic aneurysm screening

The case of a 46 years old man presenting a chronic history of right upper lobe pneumonia is reported. The clinical presentation associated with nodular pulmonary computed tomographic scan lesions, highly suggested a malignant bronchopulmonary process. A lobectomy was performed. Histological analysis revealed an inflammatory pseudotumor. This inflammatory process may be a particular end stage disease of pulmonary infectious disease.