Exhaled Nitric Oxide Measurement may Predict Asthma Exacerbation after Stepping down Formoterol/Budesonide Combination Therapy inAdult Asthma

Objective: The Global Initiative for Asthma (GINA) guidelines state that when asthma control is maintained for at least 3 months, treatment can be stepped down; however, prediction tools have not been established for the reappearance of symptoms and increased risk of exacerbation on stepping down treatment. This study was designed to assess whether FeNO measurement predicts asthma exacerbation after stepping down from fixed dose formoterol/budesonide combination (FBC)9/320 μg bid to 4.5/160 μg bid (UMIN000005406). Methods: Subjects included 37 patients receiving a fixed-dose FBC 9/320 μg bid for at least 3 months, and achieving controlled asthma (GINA) in conjunction with an Asthma Control Questionnaire (5-item version (ACQ5) score ≤ 0.75). Based on the FeNO value at stepping down, patients were classified into 25 patients with FeNO<37 ppb and 12 with FeNO ≥ 37 ppb. The primary endpoint was the occurrence of asthma exacerbation within 8 weeks and from 8 weeks until 12 months. Secondary endpoints, including ACQ5, FeNO, and pulmonary function tests, were measured at baseline and until 8 weeks. Results: There was no difference in the incidence of exacerbation between patients with FeNO ≥ 37 ppb and those with FeNO<37 ppb within 8 weeks; however, in a long-term follow up until 12 months, the incidence was significantly higher in patients with FeNO ≥ 37 ppb than in those with FeNO<37 ppb (odds ratio 11.33, 95% confidence interval 1.45 to 88.52).There was no statistically significant differencein changes in ACQ5, pulmonary functions, and FeNO between the 2 groups by 2-way repeated measures analysis of variance. Conclusions: Higher FeNO levels may predict asthma exacerbation not within a short period of time, but in a long-term follow-up after stepping down FBC therapy in adult asthma.