Persistent elevation of exhaled nitric oxide and modification of corticosteroid therapy in asthma

Background: Persistent airway inflammation, detected by fractional exhaled nitric oxide (FE_NO), is occasionally observed in asthmatic patients, even in those treated with inhaled corticosteroids (ICS). However, improvement in residual airway inflammation and pulmonary function through modification of corticosteroid therapy has not been proven. Methods: Thirteen asthmatic patients whose FE_NO levels were over 40 parts per billion (ppb), despite dry-powder ICS therapy, were enrolled. A 3-step change in steroid treatment was undertaken until FE_NO was less than 40ppb. In the first step, the powder formula was changed to an ultra-fine particle compound as an equipotent ICS dose. In the second step, the ICS dose was doubled. In the third step, oral corticosteroids were added. We measured pulmonary function and FE_NO and alveolar NO concentrations (CAlvNO). Results: Doubling the ICS dose and changing the ICS formula significantly improved FVC (p<0.001), FEV1 (p<0.05), the slope of the single nitrogen washout curve (dN₂) (p<0.01), FE_NO (p<0.001), and CAlvNO (p<0.05), relative to baseline. The reductions in FE_NO were significantly associated with the improvement in airflow limitation assessed by dN₂ (r=0.73, p=0.007). The remaining FE_NO elevation, even after doubling the ICS dose, did not decrease after oral corticosteroid administration. Conclusions: These results suggest that modification of ICS therapy can suppress residual FE_NO elevation, and that reduction in FE_NO levels is associated with improvement in airflow limitation. However, steroid-resistance mechanisms may exist in some asthmatic patients with sustained FE_NO elevations.