The fraction of exhaled nitric oxide in exhaled air (FeNO) is considered to be a reliable marker of airway inflammation in asthma.1 High FeNO levels after withdrawal of inhaled corticosteroids (ICS) are associated with increased risk of impending asthma exacerbation.2 We conducted a prospective study in 103 6–16-year-old children with asthma (62% male, mean (SD) forced expiratory volume in 1 s (FEV₁) 101.0 (12.1) % predicted), who had been using ICS therapy (fluticasone 100–250 μg/day or equivalent) for persistent partly or completely controlled asthma, to examine whether a single FeNO measurement could predict exacerbations in the 12 months after the measurement. During a scheduled follow-up visit, FeNO was measured by NIOX MINO, and expressed in ppb. Patients were followed up prospectively for 12 months. Data on exacerbations requiring systemic steroids were collected during scheduled follow-up visits, and cross-checked against pharmacy prescription data. Ethical review was waived by the hospital's ethics committee because this was a study examining clinical routine.

During 1-year follow-up, an asthma exacerbation was observed in 10 patients (9.7%). Although FeNO levels at baseline were higher in patients who had exacerbations (median 41 ppb, IQR 33–71 ppb) than in those who did not (median 13, IQR 9–21 ppb, p<0.001), there was complete overlap of FeNO values between groups (figure 1).

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Figure 1

Fraction of exhaled nitric oxide (FeNO) values in children with asthma using inhaled corticosteroids who did or did not have an asthma exacerbation during 1-year follow-up.

The main limitation of our study is that we only measured FeNO once. It is possible that repeated FeNO measurements would allow a more reliable prediction of asthma exacerbations.1 However, titration of ICS dose according to daily FeNO measurements does not improve asthma control over a 30-week study period.3 Although mean FeNO levels in children with asthma decrease during ICS treatment, a considerable minority have persistent high FeNO levels despite high-dose ICS therapy.1 Equal distribution of these patients between the groups with or without an exacerbation in our study may have diluted an association between FeNO and exacerbations. The relatively low exacerbation rate could be considered an additional limitation, but this rate is comparable to the risk of having an exacerbation in ICS clinical trials in children. This suggests that close follow-up and repeated education and inhalation instruction in our clinic helps to maximise the efficacy of ICS in clinical practice.4

In conclusion, this study shows that although FeNO levels are significantly higher in children with partly or well controlled asthma who experienced an exacerbation during 1-year follow-up while on ICS maintenance therapy than in those who did not, the complete overlap of individual FeNO levels between groups renders measurement of FeNO useless in predicting asthma exacerbations.