Concomitant allergic Aspergillus sinusitis and allergic bronchopulmonary aspergillosis associated with familial occurrence of allergic bronchopulmonary aspergillosis

A 24-year-old male, who had nasal symptoms with occasional wheezing was evaluated for consolidation of the right lung which led to the diagnosis of concomitant allergic Aspergillus sinusitis (AAS) and allergic bronchopulmonary aspergillosis (ABPA), a rarely reported association. The patient's mother was a diagnosed case of ABPA. Dramatic relief of nasal and pulmonary symptoms resulted with prednisolone that could not be tapered off completely. No untoward effect of prednisolone was observed on the disease process in a follow-up of 2 years. A high index of suspicion is required for the diagnosis of AAS and family members with history of asthma and/or rhinitis should be investigated for ABPA and/or AAS.     

Contemporaneous occurrence of allergic bronchopulmonary aspergillosis, allergic Aspergillus sinusitis, and aspergilloma.

BACKGROUND: The clinical categories of Aspergillus-related respiratory disorders usually remain mutually exclusive. The coexistence of allergic bronchopulmonary aspergillosis (ABPA) with aspergilloma is uncommon, whereas concurrent ABPA and allergic Aspergillus sinusitis (AAS) is rare. The association of these 3 clinical entities has previously been documented only once in a patient who had earlier been operated on for an aspergilloma before the diagnoses of ABPA and AAS were established. OBJECTIVE: To describe an adult in whom ABPA, AAS, and aspergilloma were diagnosed simultaneously. METHODS: Spirometry, radiography, computed tomography, skin allergy testing with Aspergillus antigens, serum precipitins against Aspergillus, total and specific IgE, functional endoscopic sinus surgery, and fungal culture were performed. RESULTS: A 26-year-old man who had asthma and rhinitis since childhood presented with hemoptysis. Serial chest radiographs revealed transient pulmonary infiltrates and an aspergilloma. Computed tomography of the thorax confirmed the aspergilloma and showed bilateral central bronchiectasis along with patchy infiltrates. Strong bands of precipitins were detected against Aspergillus fumigatus, and intradermal testing with Aspergillus antigens elicited strong type I and III hypersensitivity reactions. Specific IgE and IgG antibodies against A fumigatus were positive, and total IgE levels were significantly elevated. Peripheral blood eosinophilia was also detected. Sinus involvement was confirmed on computed tomography, and pathologic material obtained by functional endoscopic sinus surgery demonstrated allergic mucin that contained fungal elements. In addition, A fumigatus was cultured. CONCLUSIONS: ABPA, AAS, and aspergilloma can occur simultaneously in the same patient.     

Perennial allergic rhinitis and chronic sinusitis: correlation with rhinologic risk factors

BACKGROUND: The reported association of allergy and sinusitis varies greatly between study, and the exact role of allergy in predisposing to sinusitis is not clear. We attempted to determine whether patients with perennial allergic rhinitis are at greater risk of developing sinusitis with respect to a control group, and to determine whether there is a correlation between rhinomanometry, endoscopy, and nasal swab, and computed tomography (CT) findings. METHODS: Forty adult patients with perennial allergic rhinitis underwent CT scans of the paranasal sinuses, and the results were then compared to CTs of the paranasal sinuses of 30 control subjects. All allergic patients underwent nasal endoscopy, nasal swab, and active anterior rhinomanometry, and the results were studied in relation to the CT findings. RESULTS: We found sinusitis in 67.5% of the allergic patients and in 33.4% of the controls, with a statistically significant difference between the two groups (P = 0.017). Twenty-three patients had a positive nasal swab; 22 showed increased nasal resistance on rhinomanometry, and 36 had positive endoscopy, but the association of CT findings with endoscopy, rhinomanometry, or nasal swab was not statistically significant (P = 0.583, P = 1.00, P = 0.506, respectively). CONCLUSIONS: Allergic rhinitis is often associated with sinusitis, but the underlying mechanism has yet to be determined. Evidently, factors other than classical pathogen growth and mechanical factors, such as the association of the various factors and immunologic mechanisms, may contribute to the pathogenesis of chronic sinusitis in allergic patients.     

Cystic fibrosis transmembrane conductance regulator gene mutations: do they play a role in the aetiology of allergic bronchopulmonary aspergillosis?

BACKGROUND: Previous work suggests that cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations may be implicated in the aetiology of allergic bronchopulmonary aspergilosis (ABPA). OBJECTIVE: To compare the frequency of CF gene mutations in asthmatics with ABPA of varying severity with asthmatics who were skin prick test (SPT)-positive to Aspergillus fumigatus (Af) without evidence of ABPA and asthmatics SPT-negative to Af. METHODS: Thirty-one Caucasian patients with ABPA were identified, together with asthmatics SPT positive to Af without evidence of ABPA (n = 23) and SPT negative to Af (n = 28). Genomic DNA was tested for 16 CF mutations accounting for approximately 85% of CF alleles in Caucasian New Zealanders. RESULTS: Four (12.9%) ABPA patients were found to be carriers of a CF mutation (DeltaF508 n = 3, R117H n = 1), one (4.3%) asthmatic SPT positive to Af without ABPA (DeltaF508), and one (3.6%) asthmatic SPT negative to Af (R117H). All patients with a CF mutation had normal sweat chloride (< 40 mM). There was no significant difference between the frequency of CF mutations in the ABPA patients and asthmatics without ABPA. However, the frequency of CF mutations in the ABPA patients was significantly different (P = 0.0125) to the expected carrier rate in the general population. CONCLUSION: These results lend further support to a possible link between CF mutations and ABPA.     

The spectrum of allergic fungal diseases of the upper and lower airways

Fungi cause a wide spectrum of fungal diseases of the upper and lower airways. There are three main phyla involved in allergic fungal disease: (1) Ascomycota (2) Basidiomycota (3) Zygomycota. Allergic fungal rhinosinusitis (AFRS) causes chronic rhinosinusitis symptoms and is caused predominantly by Aspergillus fumigatus in India and Bipolaris in the United States. The recommended treatment approach for AFRS is surgical intervention and systemic steroids. Allergic bronchopulmonary aspergillosis (APBA) is most commonly diagnosed in patients with asthma or cystic fibrosis. Long term systemic steroids are the mainstay treatment option for ABPA with the addition of an antifungal medication. Fungal sensitization or exposure increases a patient’s risk of developing severe asthma and has been termed severe asthma associated with fungal sensitivity (SAFS). Investigating for triggers and causes of a patient’s asthma should be sought to decrease worsening progression of the disease.     

IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus (Af) allergens and a hyper-immunoglobulin E (IgE) state compared with cystic fibrosis patients without ABPA. The IgE serologic differentiation of ABPA from atopic CF patients can be difficult. We propose as the reactivity with purified antigens varies qualitatively and quantitatively and that the antibody response is more specific than with crude Af antigen extract, the IgE responses to purified recombinant Af allergens may differentiate ABPA from atopic CF patients. METHODS: Serum IgE reactivity to seven recombinant purified allergens and to a crude extract of Af was measured in 15 ABPA, in 23 Af skin test positive (ST+), and in 19 Af skin test negative (ST-) CF patients. Four of the ABPA CF patients were studied before and after developing ABPA. Nine ABPA patients were studied during flares and remissions of ABPA. RESULTS: Allergic bronchopulmonary aspergillosis patients had significantly increased IgE reactivity to Asp f2, f3, f4, f6, and f16 compared with the Af ST+ and ST- non-ABPA CF patients. In the ABPA patients studied before and after developing ABPA, IgE reactivity also increased to Asp f2, f3, f4, and f6, and to the crude extract. In ABPA CF patients, IgE reactivity to Asp f1, f2, f3, and f6 significantly increased during periods of ABPA flares compared with periods of remission. Analysis of the receiver operating curve demonstrated that IgE reactivity to Asp f3 and f4 gave the best sensitivity and specificity and were better than IgE reactivity to a crude extract of Aspergillus. Furthermore, in ABPA patients studied during periods of remission the IgE reactivity to Asp f3 and f4 remained significantly elevated compared with Af ST+ non-ABPA patients. The IgE responses when considered either to be positive or negative to Asp f3 and f4 significantly differentiated ABPA from Af ST+ and ST- non-ABPA CF patients. In contrast, IgE reactivity was considered positive to the crude extract in 89% of ABPA, 61% of Af ST+, and 0% of Af ST- non-ABPA CF patients. CONCLUSIONS: Immunoglobulin E reactivity to a panel of purified Af allergens, especially to Asp f3 and f4, differentiates ABPA from atopic Af ST+ non-ABPA CF patients. Serial determinations of IgE reactivity to individual purified Aspergillus antigens, especially Asp f3, demonstrates that increases in IgE reactivity may provide improved distinction between stages of flares and remission compared with changes in IgE reactivity to a crude Aspergillus extract.     

Late sequelae of allergic bronchopulmonary aspergillosis

Seven patients with late sequelae of allergic bronchopulmonary aspergillosis (ABPA) are described. All seven had significant chronic symptoms from asthma. At the time of diagnosis of ABPA all patients had marked irreversible pulmonary function abnormalities; symptoms of chronic bronchitis were present in all. Pulmonary fibrosis was present in six of seven patients. Three patients have died from irreversible lung disease with terminal cardiac failure. Despite the difficulty in establishing an early diagnosis of ABPA, its importance must be emphasized in order to attempt to prevent progression of the disease to severe irreversible and potentially fatal end-stage lung disease.     

Chemokine receptor expression on allergen-specific T cells in asthma and allergic bronchopulmonary aspergillosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a rare variant of severe asthma resulting from hypersensitivity to Aspergillus fumigatus (Asp f) present in the airways. AIMS OF THE STUDY: We analyzed the expression of a panel of six chemokine receptors (CCR3, CCR4, CCR8, CCR5, CXCR3 and CXCR4) on total blood CD4(+) T cells and Asp f-specific-T cells in ABPA patients. We hypothesized that chemokine receptor pattern on T cells differs between ABPA patients, non-ABPA allergic asthmatics sensitized to Dermatophagoides pteronyssinus (Der p) or Phleum pratense (Phl p) and healthy controls. METHODS: We used the fluorescent dye PKH26, a membrane bound marker, to identify accumulated proliferating (cell-sorted PKH26(low)) CD4(+) T cells in response to allergens (Asp f, Der p, Phl p) or recall antigens (PPD and TT). Chemokine receptor expression was analyzed by flow cytometry on proliferating CD3(+) CD4(+) PKH26(low) cells. RESULTS: Stimulation of CD4(+) T cells with the relevant allergen resulted in different patterns of chemokine receptor expression in ABPA and non-ABPA allergic asthmatics. Upon Asp f exposure, proliferating CD4(+) T cells from ABPA patients down-regulated the expression of CCR4 and CXCR3 while CCR4 and CXCR3 were up-regulated in allergen-specific T cells from non-ABPA allergic asthmatics. Considering each group of patients, the pattern of chemokine receptors expressed on proliferating allergen-specific CD4(+) T cells was similar to that expressed by recall antigen-specific T cells. CONCLUSIONS: The down-regulation of CCR4 and CXCR3 after allergen exposure in Asp f-specific T cells seems to be a characteristic feature of ABPA patients and requires further evaluation.     

Unusual aspects of allergic bronchopulmonary fungal disease: Report of two cases due to Curularia organisms associated with allergic fungal sinusitis

We report two cases of allergic bronchopulmonary fungal disease (ABPFD) caused by Curvularia sp and associated with allergic fungal sinusitis (AFS). Curvularia lunata was cultured in one case and Curvularia senegalensis was cultured in the other. Based on these cases and a review of the literature, we discuss unusual clinical and pathologic features that can occur in ABPFD. Unusual clinical aspects of ABPFD include associated AFS, absence of asthma, progression to Churg-Strauss angiitis and granulomatosis, concomitant hypersensitivity pneumonitis, and underlying cystic fibrosis. Atypical pathologic features that may occur in ABPFD include follicular bronchiolitis, xanthomatous bronchiolitis, limited tissue invasion, fungus balls, and association with unusual fungi. Prominent follicular bronchiolitis and xanthomatous bronchiolitis were misleading histologic features in one of our cases and led to a delay in recognition of the diagnosis. Both patients presented primarily with AFS; ABPFD was detected subsequently. This suggests that a small subset of patients with AFS may be at risk for ABPFD. The goal of this review is to increase awareness of unusual clinical and pathologic manifestations of ABPFD. It is hoped that this will result in accurate diagnosis and proper therapy, especially for patients who present with atypical features. Unusual fungal species should be considered in patients who have clinical findings compatible with ABPFD but who do not demonstrate immunologic reactivity to Aspergillus sp, especially Aspergillus fumigatus. In addition, ABPFD should be considered in patients with AFS who develop new pulmonary lesions.     

Allergic Aspergillus sinusitis: a newly recognized form of sinusitis

The clinical and pathologic features of seven cases of a newly recognized form of chronic sinusitis are described. Most patients were young adults with a history of asthma, and all had chronic nasal polyps. Radiographically, there was opacification of multiple sinuses. Recurrent sinusitis was common, and several patients underwent numerous surgical drainage procedures. Histologically, a distinct mucinous material containing eosinophils, Charcot-Leyden crystals, and fungal hyphae was found in tissue resected from the sinuses. We believe that these findings constitute a distinct clinicopathologic entity that we term allergic Aspergillus sinusitis. This condition shares similar histopathologic features with allergic bronchopulmonary aspergillosis (ABPA) but affects the paranasal sinuses rather than the lung. Implications for therapy of this form of sinusitis and its possible relationship to allergic lung diseases are discussed.     

Increased sensitivity to IL-4 in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus allergens and a hyper-immunoglobulin (Ig)E state compared with cystic fibrosis patients without ABPA. We hypothesize that one reason for this response is increased sensitivity to interleukin (IL)-4 in ABPA resulting in increased expression of CD23 and CD86 and leading to a positive amplification mechanism that increases Th2 CD4+ T cell responses. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from seven ABPA CF and 19 non-ABPA CF patients and 16 nonatopic controls and stimulated with rIL-4 (range 0.1-10 ng/ml) and rIL-13 (range 1-10 ng/ml) for 48 h. The number of CD23 molecules and percentages of CD23+ B cells were quantified by flow cytometry. Both phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO) and antigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmic cytokine synthesis enumerated by cytokine staining using flow cytometry to measure Th2 and Th1 CD3+ T cells. RESULTS: The numbers of CD23 molecules on B-cells were significantly elevated at time 0 in ABPA CF patients compared with both non-ABPA CF patients and nonatopic controls. Following IL-4 stimulation in vitro, the numbers and percentages of CD23 expression on B cells were significantly up-regulated in ABPA CF patients compared with non-ABPA CF patients and controls. The IL-13 stimulation up-regulated CD23 expression; however, there was no significant difference in ABPA CF patients compared with non-ABPA CF patients and controls. The percentages of interferon (IFN)-gamma+ CD3+T cells following PMA/IO stimulation were significantly decreased in both ABPA and non-ABPA CF patients compared with controls. There were no significant differences of IL-4+ and IL-13+ CD3+ T cells between ABPA and non-ABPA CF patients. When tetanus toxoid stimulated T cells were examined, both ABPA and non-ABPA CF patients had significantly decreased IFN-gamma+ CD3+ T cells compared with controls. In Asp f2/f3/f4 stimulated T cells, ABPA CF patients had significantly increased IL-4+ CD3+ T cells compared with non-ABPA CF patients and controls. CONCLUSIONS: ABPA CF patients have increased sensitivity to IL-4 but not to IL-13 up-regulation of CD23 molecules compared with non-ABPA CF patients. There were decreased percentages of IFN-gamma+ and IL-2+ Th1 T cells in CF patients compared with nonatopic controls but similar percentages of IL-4+ Th2 T cells in all three groups. However, ABPA CF patients had increased frequency of Aspergillus-stimulated Th2 T cells. This indicated that there is skewing of Th2 T cells in ABPA CF patients. Thus, in CF ABPA patients there is increased Th2 T cells and increased sensitivity to IL-4.     

Recurrence of allergic bronchopulmonary aspergillosis after seven years of remission

A staging system has been presented previously to assist in the evaluation and management of allergic bronchopulmonary aspergillosis (ABPA). One of these stages is a remission stage in which patients are free from pulmonary infiltrates. It had been uncertain whether patients with ABPA in remission were at risk for recurrences. We now present a patient in whom recurrence of ABPA developed after 7 yr of remission that demonstrates that patients with ABPA are at risk for recurrences for a prolonged period of time.     

Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination

BACKGROUND: Aspergillus fumigatus is a pathogenic mould causing allergic and invasive respiratory diseases. Allergic bronchopulmonary Aspergillosis (ABPA) is a severe pulmonary complication resulting from hypersensitivity to A. fumigatus proteins. Aspergillus allergen Asp f6 is recognized by IgE from ABPA patients, but not from sensitized individuals, a fact that can be used to differentiate between these two groups of allergic patients. METHODS: Proteins from hyphae, resting and germinating conidia of A. fumigatus were compared by SDS-PAGE. Protein identification was performed using MALDI-TOF mass spectrometry. Recombinant A. fumigatus allergens were used to isolate specific monoclonal antibodies (mab) from a hybridoma bank generated against Aspergillus proteins. RESULTS: A hyphae-specific 23 kDa A. fumigatus protein was identified as the allergen Asp f6/manganese-dependent superoxide dismutase (MnSOD). Differential expression of MnSOD was confirmed by immunoblot using a specific mab. In contrast, Asp f8 another intracellular, but not ABPA-specific allergen, was detected in hyphae and conidia. CONCLUSIONS: Aspergillus fumigatus is able to colonize its environment by the formation of hyphae. Hyphae are found in the lung of ABPA patients, but not in patients suffering from atopic asthma. Our finding that Asp f6 is specifically expressed in hyphae might explain why an IgE response to Asp f6 is specific for ABPA patients.     

Anti-Candida albicans IgE and IgG subclasses in sera of patients with allergic bronchopulmonary aspergillosis (ABPA)

We performed immunoblotting experiments to determine specific IgE and IgG subclass responses to Candida albicans antigens in allergic bronchopulmonary aspergillosis (ABPA) patients. This is a first report describing C. albicans antigens recognized by serum IgE and IgG subclasses of ABPA patients sensitized to that yeast. Among the various antigens reacting with serum IgE, a 43-kDa component was recognized by all seven patients and can be considered a major antigen of C. albicans for this particular group of patients. By comparison, only 20% of a group of asthmatic atopics (25 patients) and 10% of a group of normal controls (10 subjects) were 43-kDa positive. Multiple banding patterns, revealing no major antigen, were observed for all four IgG subclasses except for IgG1 in one case. In particular, the 43-kDa component was not always recognized by all the patients. Furthermore, oral or inhaled steroid treatment appears to have no impact on the specific IgE immunopatterns obtained. Using immunoelectron-microscopy, we localized IgE-binding primarily in the mannoprotein-containing layers of the C. albicans cell wall. In conclusion, C. albicans-IgE and IgG subclasses may participate in the physiopathology of ABPA by exacerbating pulmonary infiltrates (IgE) and inducing eosinophil-mediated inflammatory reaction (IgG1, IgG3).     

Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease resulting from exposure to Aspergillus fumigatus allergens. Patients with ABPA show elevated Aspergillus-specific serum IgE, a major criterion used in the diagnosis of the disease. Crude culture filtrate and mycelial antigens have been used widely to demonstrate IgE antibody to Aspergillus in the sera of patients. While these antigens have been useful in the diagnosis of ABPA, occasionally they present inconsistency in their reactivity and lack of specificity. Although in recent years, a number of purified A. fumigatus allergens have been produced by molecular cloning, no attempt was made to evaluate them systematically. OBJECTIVE: To evaluate the recombinant proteins from A. fumigatus for their IgE antibody binding, we studied sera from ABPA patients and controls by antigen specific enzyme linked immunosorbent assay (ELISA). METHODS: Recombinant Aspergillus allergens Asp f 1, f 2, f 3, f 4, and f 6 were studied for their specific binding to IgE in the sera of ABPA patients, A. fumigatus skin prick test positive asthmatics, and normal controls from the USA and Switzerland. The sera were blinded and studied by ELISA in two different laboratories. RESULTS: All the recombinant allergens showed IgE antibody binding with sera from patients with ABPA, whereas only fewer asthmatics and normal sera showed significant binding. The three selected recombinant allergens together reacted with all the ABPA patients studied. CONCLUSIONS: The results demonstrate that Asp f 2, f 4, and f 6 can be used in the serodiagnosis of ABPA, while IgE antibody binding to Asp f 1 and f 3 was not specific.     

Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis

BACKGROUND: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF. METHODS: Accumulated data from a 5-year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non-ABPA group (n = 35). Patients in both groups were colonized with Aspergillus fumigatus (Af.), but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n = 177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non-ABPA group. RESULTS: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P = 0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P < 0.05), SPT positivity to Af. (P < 0.02), and Af. precipitins (P < 0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in-house RAST). The CAP level was one to two classes higher than the ML level; however, the results were comparable (r=0.66, P<0.005). IgE to Af. measured by CAP was the test which offered the highest positive predictive value (PPV) and negative predictive value (NPV). Optimal diagnostic cutoff levels for the diagnosis of ABPA were determined: class 2 for HR to Af., 200 kIU/l for total IgE, and 3.5 (titer) for precipitating antibodies to Af., and class 2 for IgE to Af. (by CAP System). CONCLUSIONS: Unspecific atopy markers were of limited value for the diagnosis of ABPA. Patients with ABPA do not seem to be more atopic to other aeroallergens than non-ABPA patients. The most valid parameters for the diagnosis of ABPA in CF are SPT to Af., IgE to Af. in combination with precipitating antibodies to Af., and/or total IgE.     

Allergy in patients with acute maxillary sinusitis

The occurrence of allergy was studied in 224 patients with verified acute maxillary sinusitis by means of an allergy questionnaire, skin testing, and nasal smears. Allergy was found in 56 patients (25%). In addition, allergy was considered probable in 14 patients (6.5%). The corresponding percentages in the control group were 16.5 and 3, respectively. The difference is statistically significant P less than 0.05). However, the frequency of allergy is lower in the present series than in those previously reported on chronic sinusitis. There were no differences between allergic and non-allergic patients in the number of prior acute sinusitis episodes or of previously performed sinus irrigations. Bacteriological and radiological findings did not differ significantly between the groups.     

Usefulness of Fungiflora Y to detect fungus in a frozen section of allergic mucin

Allergic fungal sinusitis is a non-invasive disease characterized by pansinusitis with nasal polyps, with most causative agents being members of the dematiaceous fungi. Reported herein is the ninth Japanese case of allergic fungal sinusitis; an Alternaria species was culturally identified as the etiological agent. The present patient, a 32-year-old man, presented with multiple sinusitis and nasal polyps. Allergic mucin, which is a histological hallmark of this disease, was examined intraoperatively on frozen section. Although characteristic histology, including laminated masses of mucin and aggregates of eosinophils, was seen in HE-stained sections, fungal hyphae were scarce and recognized merely as clear spaces. Because fluorescent stilbene derivatives seem useful for the rapid detection of fungi, Fungiflora Y, a commercially available staining kit that includes a fluorescent stilbene derivative, was applied to the sections, and hyphae were successfully visualized using a fluorescence microscope. This stain takes only several minutes to perform. It is concluded that Fungiflora Y should be used when fungal elements are hard to find on HE stain, especially in cases in which rapid detection of fungus is requested.     

Sequential serological responses to Aspergillus fumigatus in patients with cystic fibrosis. Use of antigen ''stretching'' to delineate IgG and IgE activity.

Immunogens from Aspergillus fumigatus were fractionated on the basis of molecular weight. Nine fractions ranging from 900 to 10 kDa were used in ELISA and in a radioallergosorbent test (RAST) with sera from cases of allergic bronchopulmonary aspergillosis (ABPA) and from cystic fibrosis (CF) patients with ABPA or other Aspergillus involvement and compared with control subjects. The profile of IgG reactivity to the nine fractions did not vary substantially for all Aspergillus-involved groups producing peaks at greater than 900 kD and 170 kD whereas the profile for control subjects had a peak at greater than 900 kD only. The IgE profile for CF patients with ABPA did not differ from the profile of the RAST-positive CF patients without ABPA and provided only one peak of activity at 24 kD. Recovery from an episode of ABPA in CF patients was accompanied by a fall in both IgG and IgE antibody levels to all nine fractions, whereas increases in IgG and IgE to all fractions were seen during an episode of ABPA. Although there was an exaggerated IgG increase to antigens in the 43-170 kD range during ABPA, a meaningful increase was also observed to unfractionated A. fumigatus antigen preparations. With IgE in one detailed study the 24-kD fraction provided a better indication of Aspergillus involvement than the unfractionated A. fumigatus antigens. Sequential studies of IgG and IgE levels were not able to predict an episode of ABPA but were useful in conjunction with clinical assessment in following the course of the illness.     

Experience with allergic bronchopulmonary aspergillosis: some unusual features

The clinical and immunologic features often patients with allergic bronchopulmonary aspergillosis (ABPA), observed over periods varying from 12 months to 10 years, are reported. Acute attacks of ABPA were characterized by several, or all of: increased cough and sputum, haemoptysis, pleuritic pain, expectoration of sputum plugs, and increasing airways obstruction. Peripheral blood eosinophilia and acutely elevated serum IgE levels were seen in all patients during acute attacks, sputum eosinophilia and recovery of Aspergillus in sputum was less common. However, blood eosinophilia was not present in all attacks of ABPA and sputum eosinophilia varied similarly from one attack to another. Six patients with previously documented multiple precipitin lines have had no demonstrable precipitins to Aspergillus on several occasions between attacks, three of these patients have also been negative during attacks. Five of the six patients have again developed positive precipitin lines. The total number of episodes in these ten patients was fifty two, three patients have had more than nine acute attacks of ABPA. There is no seasonal variation in this group of patients. Since diagnosis, only three patients have had an attack-free interval longer than 12 months. Two patients are steroid-dependent because of severe asthma, and nine have symptoms of bronchiectasis.