Report of the first workshop on the genetic map of bovine chromosome 1

Allergic bronchopulmonary aspergillosis (ABPA), occurring primarily in patients with asthma or cystic fibrosis (CF), is a hypersensitivity reaction to Aspergillus fumigatus (Af), and is characterized by increased serum IgE levels and peripheral blood and pulmonary eosinophilia. We evaluated the IgE and cytokine profile in ABPA through enzyme-linked immunosorbent assay (ELISA), and evaluated eosinophil activity with the eosinophil peroxidase (EPO) assay. IgE and cytokines were measured in supernatants from cultures of peripheral blood mononuclear cells (PBMC) from three subject groups: ABPA patients, patients with asthma, and healthy individuals. All cultures for the three subject groups were studied in the presence and absence of two purified Af antigens (the 35-kD antigen and heat shock protein 1). We found that increased in vitro levels of IgE in unstimulated PBMC culture supernatants correlated significantly with serum IgE concentrations in ABPA patients. We measured a decrease in IgE levels of up to 75% of baseline values in supernatants from PBMC cultured with Af antigens. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) concentrations in cultures with Af were increased in ABPA, whereas concentrations of IL-4 did not differ in the three subject groups. An inverse relation was noted between the changes in IgE and IFN-gamma measured in 4 of 5 ABPA patients. The PBMC supernatants also promoted EPO activity in purified eosinophils from ABPA patients, and to a lesser extent in purified eosinophils from healthy subjects. These results show that the 35-kD antigen and HSP1 from Af downregulate IgE in vitro but are capable of inducing eosinophilia in ABPA. Further studies could result in the characterization of epitopes leading to these disparate effects. An identification of the IgE-down-regulating epitopes in Af antigens might have therapeutic significance.     

Prevalence of allergic bronchopulmonary aspergillosis and atopy in adult patients with cystic fibrosis

BACKGROUND: Underestimation of allergic bronchopulmonary aspergillosis (ABPA) prevalence in the cystic fibrosis (CF) population is suspected due to nonuniform diagnostic criteria, nonspecific signs and symptoms, assessment during asymptomatic intervals, and physician nonaggressiveness in making the diagnosis. OBJECTIVE: To define the prevalence of ABPA in adult patients with CF, as the increased duration of bronchiectasis may increase the probability of Aspergillus fumigatus (Af) colonization. We also sought to determine whether atopy increases the prevalence of ABPA in adults with CF. METHODS: We examined a cross-sectional population of adult patients with CF at the University of Washington for 1 year. RESULTS: Information was collected on 53 of 65 (82%) patients. Fifteen of 51 (29%) had an immediate skin test reaction to Af, and 30 of 51 (59%) had at least one positive skin test. Increased total serum IgE (>450 IU/mL) was present in 0 of 53; increased IgE-Af and IgG-Af were found in 12 of 53 (23%) and 9 of 53 (17%), respectively; 24 of 53 (45%) had Af-precipitins. Peripheral blood eosinophilia was present in one patient. Eight of 49 (16%) patients' sputum cultures grew Af. ABPA-CB (ABPA-central bronchiectasis) was present in one patient and ABPA-S (ABPA-seropositive) in no patients. Atopy was present in 20 of 51 (39%). CONCLUSION: There was a low prevalence of ABPA in the adult CF population despite frequent immunologic responses to Af. The prevalence of ABPA was too small to determine an association with atopy.     

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.     

The correlational analysis assessment of exacerbation in bronchial asthma and treatment efficacy

Blood and sputum eosinophils, eosinophilic cation protein (ECP) in the serum and OPV1 were measured in 30 patients with atopic bronchial asthma (BA) of moderate severity showing eosinophilia at the beginning and the end of treatment week 1 and 4, respectively. In exacerbation of BA relative number of blood eosinophils averaged 10.4 + -1.4%, sputum 35.2 + -5.6%. Serum concentration of ECP, OPV1, IgE averaged 42.6% + -11.9%, 66.8 + -6.3%, 753.7 + -114 IU/ml, respectively. In exacerbation a strong correlation is noted between relative number of eosinophils in the blood and sputum, between the levels of IgE and ECP. At the end of the treatment OPV1 was higher while ECP level in the serum went down. Reduced eosinophilia in the blood and sputum correlated with OPV1 increment. In BA patients with high blood and sputum eosinophilia function of the lungs depends on eosinophilic number, while in normalization of blood eosinophil concentration and in a sharp fall of sputum eosinophil number OPV1 changes correlation with changes in ECP in the course of treatment. A close correlation between changes in eosinophil count, FVD indices, IgE and ECP levels during the treatment indicate relief of inflammation in BA patients.     

Invasive pulmonary aspergillosis caused by Aspergillus ochraceus

Invasive pulmonary aspergillosis (IPA) is a frequent complication in patients with severe neutropenia resulting from cytotoxic chemotherapy. In Europe, Aspergillus fumigatus is most common pathogen of IPA. In our case, IPA was recognised in 54 year old female suffering from acute lymphoblastic leukemia with pancytopenia. The patient developed severe granulocytopenia during chemotherapy. Chest radiograph revealed progressive bilateral infiltrations with cavitation. In sputum culture Aspergillus ochraceus was found. The results of precipitating tests were positive for A. ochraceus and A. fumigatus. Treatment with amphotericin B was used successfully leading soon to clinical improvement, yet radiological lesions remained largely unchanged. The patient received itraconazole, which was very effective and caused almost complete regression. Two episodes of IPA recurrence were treated with antifungal therapy with good results.     

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.     

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 granulomatous angiitis associated with cerebral infarction, myo-pericarditis and acute respiratory failure due to eosinophilic pneumonia

We encountered a 23-year-old woman with allergic granulomatous angiitis (AGA) associated with cerebral infarction, myo-pericarditis, and acute respiratory failure due to extended eosinophilic pneumonia. She underwent emergency treatment at our hospital because of right hemiparesis and impaired consciousness. AGA was suspected because the patient had a history of bronchial asthma accompanied by pulmonary infiltrations with eosinophilia, and presented with diffuse pulmonary infiltrates, pericardial effusion, diffuse hypokinesis of myocardium, cerebral infarction and marked peripheral eosinophlia. Pulmonary eosinophilia was confirmed by examination of broncho-alveolar lavage fluid. Myocardial tissue biopsy specimens revealed fibrous granulation indicative of myocarditis. The patient responded well to corticosteroid therapy.     

A case of acute eosinophilic pneumonia due to Sho-saiko-to

A 16-year-boy who had taken a common over-the-counter cold remedy containing Sho-saiko-to, presented with fever, severe cough, sputum and dyspena. Two days later, he was admitted because a negative density, pulmonary edema-like shadow was noted on chest X-ray. A diagnosis of drug-induced pneumonia was strongly suspected, because an arterial blood gas analysis showed severe hypoxemia and leukocytosis with eosinophilia, and the chest X-ray showed a diffuse negative density pulmonary edema like shadow bilaterally. The findings on microscopic examination of transbronchial lung biopsy specimens were compatible with eosinophilic pneumonia. The eosinophil percentage in the bronchoalveolar lavage fluid was high. The result of a lymphocyte-stimulation test was positive for Sho-saiko-to, and Sho-saiko-to-induced pneumonia was strongly suspected. The patient ceased taking the cold remedy, and prednisolone was given. The clinical symptoms, severe hypoxemia, and chest X-ray findings markedly improved. To the best of our knowledge, there have been no previous reports of acute eosinophilic pneumonia induced by Sho-saiko-to.     

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).     

The problem of allergic pulmonary aspergillosis in children in light of personal observations

67 children (age range 4-17 years) with severe asthma were examined for the presence of allergic pulmonary aspergillosis 28 of these underwent long term steroid therapy. The following parameters were analysed: medical history, clinical state, chest radiograms, microbiological examination of the sputum, precipitating IgG antibodies, skin prick tests with aspergillus, level of specific IgE antibodies. The authors did not find any single child that met the diagnostical criteria of allergic pulmonary aspergillosis. Only in 4 serum specific IgE antibodies were found but the precipitin and skin prick tests were negative. The children did not present typical clinical symptoms of pulmonary allergic aspergillosis. It seems worthwhile to re-examine these children in a few years.     

A patient with allergic bronchopulmonary candidiasis showing a high serum level of soluble interleukin 2 receptors

An 84-year-old man was admitted to Yonezawa City Hospital with fever, cough, hemoptysis and progressive dyspnea. He had complained of wheezing asthmatoid and exertional dyspnea for the previous 10 years, regardless of the season. On admission, chest radiographs revealed a diffuse ground-glass shadow, fibrotic change, and volume reduction. Arterial blood gas analysis showed extreme hypoxemia. A computed tomographic (CT) scan of the chest showed not only faint ground-glass opacities and dense patches in the whole lung field, but also central bronchiectasis. Laboratory tests revealed that both total serum levels of IgE and specific IgE for Candida albicans were elevated. In the bronchoalveolar lavage fluid, lymphocyte, neutrophil and eosinophil percentages were high, and the CD4/CD8 ratio was low. We diagnosed the fibrotic stage of allergic bronchopulmonary candidiasis. During treatment with hydrocortisone and fluconazole, eosinophilia in the peripheral blood was observed, and serum candida antigen was positive. In addition, high serum levels of soluble interleukin 2 receptors were observed in this patient.     

Immunological characterization of Asp f 2, a major allergen from Aspergillus fumigatus associated with allergic bronchopulmonary aspergillosis

The 37-kDa recombinant protein Asp f 2, encoding an allergen of Aspergillus fumigatus, was expressed in a prokaryotic expression system and immunologically evaluated for its functional and structural properties. The open reading frame for a 310-amino-acid-long protein was shown to encode a signal peptide of 31 amino acids. A native 37-kDa culture filtrate protein and a 55-kDa mycelial glycoprotein (gp55) exhibited complete N-terminal sequence homology to Asp f 2. A GenBank search for homologous proteins revealed 60 and 44% sequence homologies to the cytosolic protein ASPND1 from Aspergillus nidulans and fibrinogen binding protein from Candida albicans, respectively. The glycosylation sites and cysteine molecules are conserved in all the three proteins. The extracellular matrix protein laminin showed a dose-dependent interaction with Asp f 2. This protein, expressed as a major cell-associated protein within 24 h of in vitro fungal culture, comprises 20 to 40% of total fungal protein. Furthermore, both native and recombinant Asp f 2 exhibited specific immunoglobulin (IgE) binding with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis-ABPA patients, whereas A. fumigatus-sensitized allergic asthma and normal control subjects failed to show IgE binding with Asp f 2. These results indicate that Asp f 2 is a major allergen of A. fumigatus exhibiting IgE antibody binding with sera from patients with ABPA. The antigen should be explored further for its potential role in the differential diagnosis of A. fumigatus-associated allergic diseases.     

Successful treatment of chronic eosinophilic pneumonia with suplatast tosilate

The patient was a 59-year-old woman who complained of coughing, sputum production, and dyspnea. Abnormal moving shadows were found by chest radiography. There was prolonged eosinophilia in blood. Eosinophilia was also found in bronchoalveolar lavage fluid, and examination of a specimen obtained by transbronchial lung biopsy revealed eosinophil infiltration in alveolar septal walls, which led to a diagnosis of chronic eosinophilic pneumonia. Because of an attack of bronchial asthma and a high level of IL-5 in serum on admission, the patient was given suplatast tosilate. Symptoms were relieved, eosinophil counts in blood and in bronchoalveolar lavage fluid decreased, and the radiographic abnormality disappeared. The patient was not treated with steroids, and there has been no reccurrence to date, one year after discharge.     

Pulmonary hypertension. Response of vasoactive peptides to a nonionic contrast medium in patients undergoing pulmonary angiography

A 46-years-old male was admitted to our hospital because of productive cough and infiltrates on the chest roentogenogram. The patient had a history of left upper bullectomy ten years prior to the admission. The CT scan of the chest on admission showed infiltrats with cavitation in the left apex and multiple bullae in almost whole lung. Microscopical examination of smears of sputum and bronchoalveolar lavage fluid revealed acid-fast bacilli. They were identified as Mycobacterium szulgai by DNA-DNA hybridization method. The patient was treated with isoniazid, streptomycin and rifampicin. After treatment for about a month, the culture of sputum converted to negative for M. szulgai. After about three months hospitalization, the infiltrates decreased and the cavity wall became thin, and no recurrence sign has been observed after the discharge. There are a few case reports of pulmonary infection due to M. szulgai associated with bullous disease of the lung in Japan.     

A case of spontaneous remission of paragonimiasis miyazakii

A 52-year-old man was admitted with fever and chest pain. Chest X-ray showed a soft infiltration in the right lung and bilateral pleural effusions. A strong tuberculin reaction was elicited. Significant laboratory findings included eosinophilia (37% in peripheral blood and 78% in pleural fluid) and elevated IgE levels (577 IU/ml in sera and 6700 IU/ml in pleural fluid). Adenosine deaminase activity in the pleural fluid was high. No helminth eggs were detected after repeated examination of the pleural fluid and sputum. No definitive diagnosis was made. Three months of chemotherapy with INH and rifampicin resulted in little improvement. Corticosteroid was then administered orally under a tentative diagnosis of idiopathic eosinophilic pleurisy, which proved to be a successful treatment and resulted in a marked reduction of pleural fluid volume. Two years after discharge, the patient's chest X-ray was normal and laboratory findings were normal including the eosinophil count and IgE level. The pleural fluid obtained at the first admission and kept frozen was subjected to immunological analysis for anti-parasite antibody activity. The pleural fluid showed an unexpectedly high titer of antibody activity (x6400 dilution) against Paragonimus miyazakii antigen assayed by double diffusion Ouchterlony method. Examination of the sera obtained from the patient two years after discharge, however, revealed no detectable antibody activity against the parasite antigens assayed either by Ouchterlony or ELISA method. We concluded from the clinical as well as laboratory findings that the patient had recovered from Paragonimiasis miyazakii without specific intervention for the disease.     

Atopy and IgE in a pediatric allergy practice

In children under six years of age referred to a pediatric allergy practice the usefulness of serum IgE assay was evaluated in relation to age, symptoms, nasal eosinophilia, skin tests and family history. In more than 60% of the children the initial symptom, usually rhinorrhea, had occurred before one year of age. In infancy the diagnosis was more difficult, gastrointestinal complaints were more frequent and nasal eosinophilia less frequent than in the older children. Many infants had positive skin tests to foods and to environmental allergens. There was a significant correlation between elevated serum IgE level and age, nasaeosinophilia, the number of positive skin tests and the probability of immunotherapy being prescribed. Although no clear diagnostic level is seen, an IgE level above 100 micron/ml at any age and an IgE level above 20 micron/ml in infants strongly suggest the possibility of atopic disease. However, a low IgE level does not exclude atopic disease.     

Development of the role of occupational health nursing in the U.S. and future perspectives in the U.S. and Japan

From 1988 to 1995, a bronchial washing was performed on 118 cases of middle lobe syndrome at the National Himeji Hospital. Twenty cases (16.9%) were positive for Mycobacterium avium complex (MAC). All cases were middle-aged (mean age 54.8), non-smoking women. Fourteen cases were asymptomatic and showed only abnormal shadow on chest X-ray film, while others complained cough, sputum or hemosputum. CT examinations were done on 13 patients, and pulmonary infiltrations were found in addition to right middle lobe or lingula in many cases. It is important to note that MAC infection might be one of causes of middle lobe syndrome.     

Ruptured Salmonella mycotic aneurysm of the extracranial carotid artery

Alternative strategies for screening tuberculosis (TB) suspects are needed in sub-saharan Africa. Ambulatory adult TB suspects who were seen in the chronic cough room of Queen Elizabeth Central Hospital, Blantyre, Malawi, were assessed with respect to appropriateness of referral. Appropriate referrals (patients with cough 3 weeks or longer, weight loss and no antibiotic response) were screened by 3 sputum specimens for microscopy and culture of Mycobacterium tuberculosis and chest radiography (CXR). Hypothetical strategy A (screening by sputum smear examination followed by CXR in patients with negative sputum smears) was compared with strategy B (screening by CXR followed by sputum smear examination in patients with a CXR consistent with TB) in terms of diagnostic efficacy and cost. Of 1127 patients referred to the cough room, 402 (38%) were appropriate TB suspect referrals. Of these, 111 (28%) were sputum smear-positive, 213 (53%) were culture-positive, and 221 (55%) had smear and/or culture-positive evidence of TB. Routine CXR was consistent with pulmonary (P) TB in 230 patients (57%). With strategy A, 243 (60%) patients were diagnosed as PTB, but 40 (25%) of those not diagnosed as PTB had positive mycobacterial cultures. With strategy B, 230 patients (57%) were diagnosed as PTB, but 53 (31%) of those not diagnosed as PTB had positive mycobacterial cultures, including 13 with smear-positive sputum. The cost per diagnosed case of PTB was US$ 4.63 with strategy A and US$ 5.44 with strategy B. Screening patients with good criteria of TB has high diagnostic sensitivity, but screening by CXR is less effective and more costly than screening by sputum smear microscopy.     

Reed-Sternberg cells in sputum from a patient with Hodgkin''s disease. A case report

A patient with stage IV Hodgkin's disease developed severe dyspnea and was found to have pulmonary infiltrates one year following his initial diagnosis of nodular sclerosing Hodgkin's disease, stage IIB. Two separate cell block sputum cytology samples demonstrated Reed-Sternberg cells. The patient died of respiratory failure. At autopsy the main findings were extensive confluent nodules of Hodgkin's disease nearly replacing the pulmonary parenchyma of both lungs. Cytology of sputum or bronchial washings may reveal diagnostic Reed-Sternberg cells and establish the diagnosis of pulmonary Hodgkin's disease without a lung biopsy.