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  • 1
    Digitale Medien
    Digitale Medien
    The Effect of Aspirin during Aspirin “Desensitisation” on Compound 48/80 and Histamine-Induced Skin Responses in Aspirin-Sensitive Asthmatics (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 40 (1985), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: In a group of aspirin-sensitive asthmatics we studied skin weal and flare responses to intradermal injections of compound 48/80 and histamine during oral aspirin (ASA) provocation and after ASA “desensitisation”. During provocation (bronchospasm accompanied by naso-ocular symptoms) the mean weal area after compound 48/80 increased to about 42.4% (P 〈 0.05). Neither the threshold (provocative) doses of ASA nor 600 mg ASA, when given after ASA-desensitisation, significantly influenced the weal reactions to compound 48/80 (mean changes of area were –1.8% and –16.5% respectively). Aspirin did not change flare reactions to compound 48/80 and weal and flare reactions to histamine on any of the three study occasions. Initial (pre-aspirin) weal reactions to compound 48/80 after desensitisation to the threshold ASA doses were significantly reduced, but after desensitisation to 600 mg ASA were significantly increased as compared with the reactions before. These data suggest that ASA-“desensitisation” may influence the skin reactivity to non-specific mast cell degranulating stimulus in ASA-sensitive asthmatics.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.1985.tb02672.x
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  • 2
    Digitale Medien
    Digitale Medien
    Decreased apoptosis and distinct profile of infiltrating cells in the nasal polyps of patients with aspirin hypersensitivity (2002)
    Oxford, UK : Munksgaard International Publishers
    Allergy 57 (2002), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1034/j.1398-9995.2002.13508.x
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  • 3
    Digitale Medien
    Digitale Medien
    Intranasal challenge with aspirin induces cell influx and activation of eosinophils and mast cells in nasal secretions of ASA-sensitive patients (1996)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 26 (1996), S. 0 
    Details
    ISSN: 1365-2222
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1365-2222.1996.tb00612.x
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  • 4
    Digitale Medien
    Digitale Medien
    Neutrophil chemotactic activity (NCA) in nasal secretions from atopic and nonatopic subjects (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 48 (1993), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.1993.tb00738.x
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  • 5
    Digitale Medien
    Digitale Medien
    Aspirin Tolerance Induced in Aspirin-Sensitive Asthmatics (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 39 (1984), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Twenty-nine patients with asthma and aspirin-sensitivity were studied in an attempt to induce tolerance to aspirin (ASA). Starting with the smallest ASA doses eliciting bronchial obstruction (threshold doses) we doubled the doses on subsequent days and finally achieved good tolerance of 600 mg ASA per day in 27 patients. It was more difficult to achieve tolerance in patients with low ASA-thresholds than in patients with high ones. Daily ASA administration led to prolongation of the refractory state but when the intervals between consecutive doses were increased aspirm hypersensitivity recurred. The pause sufficient for a recurrence of sensitivity to ASA was measured in 16 patients and ranged from 24 h to 9 days Twelve patients challenged with indomethauen after ASA-desensitisation showed good drug tolerance.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.1984.tb02621.x
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  • 6
    Digitale Medien
    Digitale Medien
    β2-ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Association and linkage studies of β2-adrenergic receptor (β2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of β2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: −47, −20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different β2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when β2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with β2-ADR haplotype −47T/−20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual β2-ADR SNP or β2-ADR haplotype might affect disease manifestation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00869.x
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  • 7
    Digitale Medien
    Digitale Medien
    Aspirin-triggered 15-HETE generation in peripheral blood leukocytes is a specific and sensitive Aspirin-Sensitive Patients Identification Test (ASPITest) (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 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).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00836.x
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  • 8
    Digitale Medien
    Digitale Medien
    Standard skin prick testing and sensitization to inhalant allergens across Europe – a survey from the GA2LEN network (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal 〉3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan-European core SPT panel.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00895.x
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  • 9
    Digitale Medien
    Digitale Medien
    Inhibition of nasal polyp mast cell and eosinophil activation by desloratadine (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Nasal polyp tissue which contains mast cells and eosinophils is similar to the inflamed airway mucosa in cellular composition and mediator content. This investigation assessed the effect of desloratadine (DL), on activation of cells in nasal polyp tissue. Polyps were obtained from 22 patients with chronic rhinosinusitis [nine aspirin acetylosalitic acid (ASA)-sensitive and 13 ASA-tolerant]. Polyp tissue was dispersed by digestion, and preincubated with DL and incubated with anti-immunoglobulin E (IgE) or calcium ionophore. LTC4, eosinophil cationic protein (ECP) and tryptase concentrations in supernatants were measured by immunoassays. Desloratadine (1, 10 and 50 μM) inhibited calcium ionophore-induced LTC4 release by a mean of 29%, 50% and 63% respectively, and anti-IgE-induced LTC4 release by a mean of 27%, 35% and 39% respectively. Calcium ionophore-induced tryptase release was inhibited 60% and 69% by 10 and 50 μM of DL, respectively, and anti-IgE-induced tryptase release was inhibited 33%, 47% and 66% for 1, 10 and 50 μM of DL. Desloratadine 10 μM and 50 μM inhibited ECP release by and 45% and 48% respectively. Polyp tissue from ASA-sensitive patients when compared with ASA-tolerant patients released at baseline significantly more ECP (medians 120.0 μg/ml, range: 69.0–182.0 vs 63.4 μg/ml, range: 3.7–172.0; P 〈 0.05), but similar amounts of tryptase and LTC4. This study demonstrated that DL inhibits activation of both eosinophils and mast cells derived from a site of airway mucosal inflammation.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00642.x
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  • 10
    Digitale Medien
    Digitale Medien
    Tolerance to acetylsalicylic acid (ASA) induced in ASA-sensitive asthmatics does not depend on initial adverse reaction (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 42 (1987), S. 0 
    Details
    ISSN: 1398-9995
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: A state of tolerance to aspirin (ASA) was induced in 10 aspirin-sensitive patients by daily administration of incremental doses of ASA. No adverse reactions were reported. The initial dose (from 5 to 60 mg) was gradually increased each day up to 300 mg and then doubled. 50 mg indomethacin given the day after administration of 600 mg ASA did not elicit any symptom of intolerance. The authors discuss a possible mechanism of tolerance to aspirin in ASA-sensitive asthmatics after ASA administration, suggesting that it might be connected either with inhibition of the lipooxygenetic pathway of arachidonic acid metabolism or with blockade of the cyclooxygenase supplementary binding site by salicylic acid, a product of acetylsalicylic acid hydrolysis. This would prevent aspirin from binding with the catalytic cyclooxygenase site.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1398-9995.1987.tb02197.x
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