What is a clinically meaningful change in exhaled nitric oxide for children with asthma?

Introduction: Fractional exhaled nitric oxide (F_ENO) may be a useful objective measurement to guide asthma treatment. What remains uncertain is what change in F_ENO is clinically significant. Methods: An individual patient data analysis was performed using data from seven randomized clinical trials which used F_ENO to guide asthma treatment. The absolute and percentage intra-subject change in F_ENO measurements over “stable” and also “unstable” 3-month periods were described. Results: Data were available in 1112 randomized controlled trial participants and ≥1 stable period was present for 665 individuals. The interquartile range (IQR) and limits of agreement (LoA) for change in absolute F_ENO among individuals whose initial F_ENO was <50 parts per billion (ppb) were −7 to +9 ppb and −43 to +50 ppb, and for those with initial F_ENO ≥50 ppb IQR was −29 to +17 ppb and LoA was −80 to +76 ppb. For percentage change in F_ENO, the IQR and LoA for individuals whose initial F_ENO was <50 ppb were −33% to +51% and −157% to +215%, and for those with initial F_ENO ≥50 ppb were −33% to +35% and −159% to +192%. The variation in F_ENO values for a stable period was similar irrespective of whether it was followed by a stable or unstable period. Conclusions: Over a 3-month period where F_ENO is initially <50 ppb, a rise of <10 ppb or of <50% (based on IQR) is unlikely to be related to asthma. When F_ENO is initially ≥50 ppb an percentage change of <50% (based on IQR) is unlikely to be asthma-related.