Intranasal challenge with aspirin induces cell influx and activation of eosinophils and mast cells in nasal secretions of ASA-sensitive patients.

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) 12 mg, on separate occasions. Nasal lavages were obtained before, and then every 15 min 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%, postsaline 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 micrograms/L and 140.9 +/- 45.8 micrograms/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 pre-challenge: 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.

Diagnosis of pyrazolone drug sensitivity: clinical history versus skin testing and in vitro testing.

Pyrazolone drug hypersensitivity (PDH) may manifest as angioedema, urticaria, and/or life threatening anaphylactic shock. Although it has been suggested that PDH is an immunologic, probably IgE-mediated reaction, the diagnosis of PDH is still based on clinical history because there is no reliable in vitro diagnostic method currently used in clinical practice. The goal of this study was to evaluate the reliability of various methods to confirm a diagnosis of PDH. Twenty-eight patients with prior history of 71 reactions to pyrazolone drugs were studied. In all patients, pyrazolone drugs induced urticaria and angioedema. In addition, laryngeal edema occurred in 14 patients and anaphylactic shock with loss of consciousness in five patients. Skin prick test and intradermal tests using increasing concentrations of noraminophenazone were performed in 25 patients. Sera of all 28 patients were negative for pyrazolone-specific IgE as determined by an immunoenzymatic method. Peripheral blood mononuclear cells proliferative responses to pyrazolone were studied by a lymphocyte proliferation test with 3H-thymidine incorporation. Incubation of peripheral blood mononuclear cells with increasing concentrations of noraminophenazone did not induce any significant proliferation responses. Our study demonstrated that 1) intradermal skin tests correlate poorly with the clinical history of hypersensitivity reaction; and 2) in vitro tests are not useful in establishing a diagnosis of PDH.

Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients.

The mechanism of aspirin (acetylsalicylic acid [ASA]) sensitivity associated with severe asthma and chronic rhinosinusitis with nasal polyps ("aspirin triad") has been attributed to arachidonic metabolism alternations, although the putative biochemical defects have not been elucidated. The aim of this study was assessment of the hypothesis that local production of eicosanoids in the respiratory epithelium in patients with ASA-sensitive asthma/rhinosinusitis (ASARS) differs from that of ASA-tolerant patients with rhinosinusitis (ATRS). Nasal polyps were obtained from 10 patients with ASARS and 15 with ATRS during routine polypectomies, and epithelial cells (ECs) were cultured on bovine collagen type I matrix (Vitrogen 100), in medium supplemented with growth factors. The generation of eicosanoids in supernatants of confluent ECs (6 to 8 d of culture; purity > 98%) was quantified by immunoassays. Unstimulated ECs from ASARS patients generated significantly less prostaglandin E(2)(PGE(2)) compared with ATRS (0.8 +/- 0.3 versus 2. 4 +/- 0.5 ng/microg double-stranded deoxyribonucleic acid [dsDNA], respectively), although a similar relative increase in response to calcium ionophore and inhibition with ASA was observed in both groups. Basal levels of 15-hydroxyeicosatetraenoic acid (15-HETE) were not different between groups, and calcium ionophore enhanced its production to a similar extent. However, cells incubation with 200 microM ASA for 60 min resulted in a significant increase (mean +359%) in 15-HETE generation only in ASARS patients, whereas no effect of ASA on 15-HETE generation in ATRS patients was observed. PGF(2alpha) generation was similar in both groups, and no significant generation of PGD(2) or leukotriene C(4) (LTC(4)) was observed in epithelial cell cultures from either group. Our results indicate that nasal polyps ECs from ASA-sensitive patients have significant abnormality in basal and ASA-induced generation of eicosanoids which may be causally related to the mechanism of ASA sensitivity.