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

Abstract

Background: Asthma is a process of chronic allergic inflammation that may be worsened by the activation of neutrophils during acute exacerbations.

Objective: We investigated our hypothesis that changes in cellular activation may be detectable in peripheral blood (PB) during late-phase asthma and during clinical exacerbations.

Methods: Twenty-one stable asthmatics (9 on treatment with beta2-agonists only, 12 using inhaled corticosteroids) and 10 nonasthmatic volunteers were first compared using flow cytometry to measure beta2-integrin (CD11b/CD18) expression. Production of reactive oxygen species (ROS) was evaluated employing chemiluminescence. Next, 8 mild asthmatics were assessed using similar methods before and after allergen-induced late asthmatic reactions (LARs). Finally, 4 asthmatic subjects were evaluated over 3 months, and symptoms, peak expiratory flow (PEF) and ROS production 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 production comparing the normal and asthmatic groups. However, after development of the LAR, significant reductions in CD11b neutrophil expression (mean fluorescence intensity; MFI) were observed [before: 994 +/- 102 MFI (mean +/- SEM) versus after: 424 +/- 81 MFI; p < 0.01]. Furthermore, strong associations 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 significantly associated with reductions in PEF (r = 0.5, p < 0.03).

Conclusions: In patients with mild stable asthma, no differences in the activation of circulating neutrophils were detectable compared to nonasthmatic individuals. During episodes of asthmatic airway obstruction, in the laboratory and in clinical disease, neutrophil activation decreased in PB, conceivably because activated cells may be preferentially sequestered in the lung.