Predictors for Identifying the Efficacy of Systemic Steroids on Sustained Exhaled Nitric Oxide Elevation in Severe Asthma

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Background: Some patients with asthma have high levels of exhaled nitric oxide fraction (FE_NO) despite inhaled corticosteroids (ICS) therapy. Early studies suggested that this might be explained by the presence of heterogeneous airway inflammation. We aimed to assess the predictors for identifying the efficacy of systemic corticosteroids on residual FE_NO elevations in severe asthma.
Methods: Twenty severe asthmatics with persistent FE_NO elevation (≥40ppb) despite maintenance therapy including high-daily-dose ICS were enrolled. Asthma Control Questionnaire (ACQ), lung function, blood eosinophils, and FE_NO were assessed before and after 14 days treatment with 0.5mg/kg oral prednisolone/day.
Results: ACQ, blood eosinophils, FE_NO level, FVC, FEV₁, FEV₁/FVC ratio and the slope of the single nitrogen washout curve (ΔN₂) were significantly improved by treatment with prednisolone. 70% of the subjects showed ≥20% reductions in the FE_NO levels. The reduction in FE_NO levels was significantly correlated with the improvements in ACQ (p < 0.0001), FVC (p < 0.01), FEV₁ (p < 0.0001), and ΔN₂ (p < 0.05). Among the measurements at baseline, the FE_NO levels and blood eosinophil numbers were identified as significant predictors of ≥20% reductions in the FE_NO levels by systemic steroid therapy.
Conclusions: Systemic corticosteroids could suppress the residual FE_NO elevations in more than half of the patients with severe asthma and the reduction in FE_NO levels was associated with improvements in asthma control and airflow limitation. The FE_NO levels and blood eosinophil numbers were the predictors of improved residual airway inflammation by systemic steroid therapy in severe asthma.