Reduced activation of peripheral blood neutrophils after late-phase asthmatic responses but not in mild stable asthma

Background, Asthma is a process of chronic allergic inflammation that may b e worsened by the activation of neutrophils during acute exacerbations. Obj ective: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and dur ing clinical exacerbations. Methods: Twenty-one stable asthmatics (9 on tre atment with beta (2)-agonists only, 12 using inhaled corticosteroids) and 1 0 nonasthmatic volunteers were first compared using flow cytometry to measu re beta (2)-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asth matics were assessed using similar methods before and after allergen-induce d late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evalu ated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS produc tion were measured. Episodes of respiratory morbidity (exacerbations) were identified and their association with ROS production was examined. Results: No differences were detected in adhesion molecule expression and ROS produ ction comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fl uorescence intensity; MR) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p <0.01]. Furthermore, strong associatio ns were found between decreases in CD11b and the severity of the LAR (r = 0 .9; p <0.02). In the clinical study, ROS production was significantly lower during exacerbations (median 43%; p <0.05). Again, this measurement was si gnificantly associated with reductions in PEF(r = 0.5, p <0.03). Conclusion s:ln patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individual s. During episodes of asthmatic airway obstruction, in the laboratory and i n clinical disease, neutrophil activation decreased in PB, conceivably beca use activated cells may be preferentially sequestered in the lung. Copyrigh t (C) 2001 S. Karger AG, Basel.