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

Persistent airway inflammation, detected by fractional exhaled nitric oxide (FENO), 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.

Thirteen asthmatic patients whose FENO 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 FENO 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 FENO and alveolar NO concentrations (CAlvNO).

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), FENO (p<0.001), and CAlvNO (p<0.05), relative to baseline. The reductions in FENO were significantly associated with the improvement in airflow limitation assessed by dN2 (r=0.73, p=0.007). The remaining FENO elevation, even after doubling the ICS dose, did not decrease after oral corticosteroid administration.

These results suggest that modification of ICS therapy can suppress residual FENO elevation, and that reduction in FENO levels is associated with improvement in airflow limitation. However, steroid-resistance mechanisms may exist in some asthmatic patients with sustained FENO elevations.