Titrating Steroids on Exhaled Nitric Oxide in Children With Asthma: A Randomized, Controlled Trial

Purpose of the Study. To evaluate whether titrating inhaled corticosteroids (ICSs) on the fraction of nitric oxide in exhaled air (FeNO) improves asthma management in children. Study Population. A total of 85 children (aged 6–18 years) with asthma who had been using ICSs at a constant dose for at least 3 months. Methods. Children were randomly allocated to 1 of 2 groups stratified for baseline FeNO and dose of ICSs. In one group, ICS doses were determined by FeNO and symptoms according to an algorithm; in the other group, only symptoms influenced ICS dosing. The study duration was 12 months, with 5 visits at 3-month intervals. FeNO was measured at each visit, and the ICS dose was then adapted to FeNO and/or symptom scores that were recorded during the previous 2 weeks. Results. The cumulative ICS dose was not different between groups. Within the FeNO group, no significant change in FeNO was found, whereas in the symptom group there was a significant increase in FeNO (P = .035). In the FeNO group, hyperresponsiveness improved more than in the symptom group (2.5 vs 1.1 methacholine doubling dose; P = .04). Eight prednisone courses were prescribed for 7 patients in the FeNO group versus 18 courses in 10 patients in the symptom group, but this difference was not statistically significant (P = .60). There was no difference between groups in forced expiratory volume in 1 second (FEV1) or symptom scores. Conclusion. In children with asthma, 1 year of steroid titration on FeNO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation. Reviewer Comments. I am still not sure what to make of eNO. If monitoring FeNO and making treatment decisions on the basis of the values leads to better asthma outcomes, then it would be a useful tool. Because the FeNO group did not end up receiving a higher cumulative ICS dose, we have to assume that they got more when they needed it and less when they did not. However, the clinical results seem inconsistent. I suppose it is a good thing to have a higher methacholine PD20 (the dose provoking a 20% fall in FEV1) and a lower FeNO, but I would have been happier to see a difference in FEV1 and symptom scores, or if the difference in the number of episodes requiring prednisone courses had been statistically significant. Although I am not sure that I can share the authors’ conclusion that “the time has come to introduce FeNO in to the routine assessment of children with asthma,” I believe we should pay attention to future studies on FeNO monitoring and clinical asthma outcomes.