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

Abstract

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.