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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Although the mechanism of aspirin-sensitivity seems to be related to inhibition of cyclo-oxygenase by aspirin (ASA), the chain of biochemical events leading to the ASA-induced adverse reaction is not clear, and the contribution of particular mediators and inflammatory cells has not been elucidated.Objectives To investigate the involvement of secretory, vascular and cellular mechanisms in the pathophysiology of nasal reactions to aspirin.Methods Six patients with ASA-sensitive asthma/rhinosinusitis and seven ASA-tolerant patients were challenged intranasaly with saline and lysine-acetylsalicylic acid (Lys-ASA) 12mg, on separate occasions. Nasal lavages were obtained before, and then every 15min after challenges, and analysed for biochemical and cellular composition.Results Lys-ASA challenge caused rhinorrhoea. sneezing and nasal congestion with parallel increases in total protein and albumin concentration, albumin % and lysozyme activity in the nasal secretions of ASA-sensitive patients. Concomitant with clinical symptoms, an influx of leucocytes into nasal secretions occurred with significant enrichment in eosinophils (mean prechallenge: 24 ± 12%, postsatine 27±9%, postLys-ASA 51 ± 10%; P 〈 0.03). The influx of eosinophils into nasal secretions was associated with a remarkable increase in Eosinophil Cationic Protein (ECP) immunoreactivity in five of six patients (mean 9.3 ± 3.8 μg/L and 140.9 ± 45.8 μg/mL before and after Lys-ASA, respectively). At the peak of ASA-induced symptoms an increase in the tryptase level was also observed in five of six patients (mean prechallenge: 2 ± 0.1 U/L; postLys-ASA 16 ± 5 U/L; P 〈 0.01) suggesting activation of mucosal mast cells. In ASA-tolerant patients Lys-ASA did not induce significant symptoms or changes in the biochemical and cellular composition of nasal secretions.Conclusion The results show that the ASA-induced nasal adverse reaction involves changes in vascular permeability and serous cell secretion. Both activated eosinophils and mast cells may contribute to the pathophysiology of the ASA-induced reaction in the nasal mucosa.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Patients with aspirin-hypersensitive rhinosinusitis/asthma suffer from a severe form of hyperplastic rhinosinusitis with recurrent polyposis. We aimed to assess the presence of apoptotic cells in nasal polyps from aspirin-hypersensitive (AH) and aspirin-tolerant (AT) patients with rhinosinusitis as related to the characteristics of local inflammation.Methods: Nasal polyps obtained from 16 AH patients and 36 AT patients (17 atopic and 19 nonatopic) were stained for eosinophils and metachromatic cells, and in parallel immunocytochemistry was performed to detect CD45RO+, HLA-DR+, CD8+ and CD68+ positive cells. Apoptotic cells were detected by a nick-end labelling technique, TUNEL.Results:  The density of apoptotic cells in AH polyps (5.5 + 1.5 cells/mm2) was significantly lower as compared to both atopic (18.7 + 3.8 cells/mm2; P 〈 0.02;) and nonatopic (21.3 + 5.2 cells/mm2; P 〈 0.01) AT polyps. The number of eosinophils, mast cells, and CD45RO+ cells were significantly increased in AH compared to AT polyps (P 〈 0.001), and the density of HLA-DR+ cells in AH patients was higher than in nonatopic (P 〈 0.02), but not in atopic AT patients. While in AH patients the duration of rhinosinusitis correlated inversely with the number of apoptotic cells (r = − 0.67; P 〈 0.04), in contrast, in AT atopic patients the duration of rhinosinusitis showed positive correlation with apoptosis (r = 0.89; P 〈 0.003).Conclusions:  We conclude, that decreased apoptosis of inflammatory cells in nasal polyps from ASA-hypersensitive patients, reflects a distinct mechanisms of local inflammation and may be related to persistence and severity of the disease in these patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 40 (1985), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The hypothesis that increased reactivity to polymyxin B in asthmatic patients is not limited to the bronchi but also exists in basophils was investigated in 26 atopic asthmatic subjects. Quantification of basophil degranulation induced by polymyxin B was performed using a flow-cytometric method. Significant degranulation was noted in 17 patients, but in none of 10 healthy controls. There was close relationship between basophil “releasability” to polymyxin B and bronchial reactivity to inhaled polymyxin B. These findings support the hypothesis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  We have previously demonstrated that aspirin triggers specific generation of 15-hydroxyeicosateraenoic acid (15-HETE) from nasal polyp epithelial cells and peripheral blood leukocytes (PBL) from aspirin-sensitive (AS) but not aspirin-tolerant (AT) patients with asthma/rhinosinusitis. The goal of this study was to assess the diagnostic value of ASA-induced 15-HETE generation measurement to identify AS patients.Methods:  PBL were obtained from 43 AS patients with asthma and rhinosinusitis, 35 AT asthmatics and 17 healthy control (HC) subjects. PBL were incubated with 2–200 μM aspirin (ASA) and 15-HETE release was measured in cell supernatants with competitive ELISA.Results:  Unstimulated PBL from all three groups of patients generated similar amount of 15-HETE. Incubation with 200 μM ASA resulted in an increase in an 15-HETE generation (mean increase +421%) in AS-asthmatics but small and nonsignificant response in AT-asthmatics or control subjects. Receiver operating curve (ROC) analysis revealed that the sensitivity of the test for confirmation of ASA-sensitivity was 83% and the specificity 82%. Positive predictive value was 0.79 and negative predictive value was 0.86. Naproxen induced a significant increase in 15-HETE only in some AS-asthmatics, but not in AT-asthmatics.Conclusion:  Our data demonstrate that ASA-induced 15-HETE generation by PBL is a specific and sensitive aspirin-sensitive patients identification test (ASPITest).
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In order to elucidate the mechanism responsible for infiltration of nasal mucosa by granulocytes, we tested neutrophil chemotactic activity (NCA) in nasal lavages, by the modified Boyden chamber method, in 16 patients with perennial allergic rhinitis (AR), six ASA-sensitive patients with chronic rhinosinusitis (CRS), and seven normal, nonatopic control subjects (NC). Nasal secretions from all three groups showed significant NCA (mean 157.1±54.0, 62.2±20.7, and 39.4 ± 11.4% of FMLP chemotactic activity for AR, CRS, and NC subjects, respectively). Nasal secretions from patients with AR expressed significantly higher NCA (P〈0.02) than did secretions from NA patients.NCA was unchanged by heating at 56°C for 60 min and was not susceptible to degradation by trypsin. Nasal challenge with Dermatophagoides pteronyssinus antigen induced clinical symptoms and resulted in significant increases in total protein and albumin concentrations in nasal lavages in AR patients, but failed to change the mean NCA activity for up to 40 min after the challenge. These results indicate that nasal secretions from both atopic and nonatopic patients express NCA, but its relation to allergic inflammation remains to be established.
    Type of Medium: Electronic Resource
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