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 r elated 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 involveme nt of secretory, vascular and cellular mechanisms in the pathophysiolo gy of nasal reactions to aspirin. Methods Six patients with ASA-sensit ive asthma/rhinosinusitis and seven ASA-tolerant patients were challen ged 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 c ellular composition. Results Lys-ASA challenge caused rhinorrhoea, sne ezing and nasal congestion with parallel increases in total protein an d albumin concentration, albumin % and lysozyme activity in the nasal secretions of ASA-sensitive patients. Concomitant with clinical sympto ms, an influx of leucocytes into nasal secretions occurred with signif icant enrichment in eosinophils (mean prechallenge: 24 +/- 12%, postsa line 27 +/- 9%, postLys-ASA 51 +/- 10%; P < 0.03). The influx of eosin ophils 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 mu g/L and 140.9 +/- 45.8 mu g/mL before an d after Lys-ASA, respectively). At the peak of ASA-induced symptoms an increase in the tryptase level was also observed in five of six patie nts (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 pati ents Lys-ASA did not induce significant symptoms or changes in the bio chemical and cellular composition of nasal secretions. Conclusion The results show that the ASA-induced nasal adverse reaction involves chan ges in vascular permeability and serous cell secretion. Both activated eosinophils and mast cells may contribute to the pathophysiology of t he ASA-induced reaction in the nasal mucosa.