Paradoxical eosinophilic and cytokine responses to oral corticosteroid treatment in patients with asthma exacerbations.

ABSTRACT

Background: Thymic stromal lymphopoietin (TSLP) orchestrates eosinophilic inflammation, which may increase during asthma exacerbations. In contrast, microRNA-1 (miR-1) inhibits TSLP-mediated eosinophil trafficking in lung endothelium. Whether the balance of TSLP and miR-1 levels determines the response to oral corticosteroids (OCSs) during the treatment of asthma exacerbations remains unknown. Objective: Our aim was to investigate the involvement of TSLP/miR-1 axis in inflammatory response to OCS treatment for asthma exacerbations. Methods: We measured the concentrations of TSLP and other inflammatory cytokines and miR-1 expression during acute asthma exacerbations treated with standard OCSs in a real-life setting. A total of 28 consecutive patients with acute asthma exacerbations treated with OCS (prednisolone 30 mg/d) for 1 week at the emergency department were studied prospectively. Steroid responders were identified by a significant reduction in blood eosinophil counts, whereas paradoxical responders (PRs) showed no markedly decreased or even increased absolute blood eosinophil counts after OCS treatment. Differential white blood cell counts, blood cytokine levels, and miR-1 expression within and between groups were compared before and after OCS treatment. The baseline cytokine concentrations in both groups were compared with those of patients with stable asthma. Results: OCS treatment significantly reduced TSLP levels in steroid responders, whereas this effect did not occur in PRs (P = .006 and P = .742, respectively). In contrast, miR-1 expression was unchanged in steroid responders in response to OCS, whereas it was markedly reduced in the PRs, despite higher expression at baseline than in patients with stable asthma, which may account for slower resolution of the exacerbation. Conclusions: In some asthmatic patients with acute exacerbations who do not suppress eosinophils after a course of OCS, there is a paradoxical decrease in plasma miR-1 level and increase in TSLP level versus in steroid responders, which may result in slower clinical recovery.