PT - JOURNAL ARTICLE AU - Wang, Ran AU - Fowler, Stephen J. AU - Turner, Stephen W. AU - Drake, Sarah AU - Healy, Laura AU - Lowe, Lesley AU - Wardman, Hannah AU - Bennett, Miriam AU - Custovic, Adnan AU - Simpson, Angela AU - Murray, Clare S. TI - Defining the normal range of fractional exhaled nitric oxide in children – one size does not fit all AID - 10.1183/23120541.00319-2022 DP - 2022 Jan 01 TA - ERJ Open Research PG - 00319-2022 4099 - https://publications.ersnet.org//content/early/2022/06/30/23120541.00319-2022.short 4100 - https://publications.ersnet.org//content/early/2022/06/30/23120541.00319-2022.full AB - Background The normal range of fractional exhaled nitric oxide (FeNO) is influenced by demographic factors. However, single, fixed cut-off values are used for clinical interpretation in children despite rapid growth. We aimed to define the normal range of FeNO during childhood and evaluate its utility in the diagnostic setting.Method FeNO percentile charts were developed using data from non-asthmatic children in a population-based birth cohort (MAAS). Children were skin prick tested and FeNO measured at the age of 8, 11, 13–16 and 18 years and clinical information was collected. This chart was externally validated in the SEATON cohort before being prospectively tested in symptomatic, treatment-naïve patients with suspected asthma in a diagnostic setting (RADicA study).Results Height, weight, BMI and age were predictive of FeNO in univariate analysis using 1219 FeNO measurements. Only height remained significant after adjustment in the overall, non-atopic and atopic populations, and was included in the predictive equations for 50th, 75th 90th and 98th percentiles. The proposed percentile lines corresponded to the 57th (95%CI:53–61st), 80th (76–83rd), 90th (87–92nd) and 98th (96–99th) percentiles in the SEATON cohort (660 measurements). When tested in 73 symptomatic treatment-naïve children and young adults (median [IQR] age: 11 [8–14] years), a FeNO >90th percentile gave a 96% specificity and positive predictive value of 97%, identifying 59% of children who were subsequently diagnosed with asthma after extensive testing.Conclusion We developed a height-based FeNO percentile chart which quantifies the probability of asthma in symptomatic children and merits further validation towards clinical implementation.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Ran Wang has nothing to disclose.Conflict of interest: Stephen J Fowler has nothing to disclose.Conflict of interest: Stephen W Turner has nothing to disclose.Conflict of interest: Sarah Drake has nothing to disclose.Conflict of interest: Laura Healy has nothing to disclose.Conflict of interest: Lesley Lowe has nothing to disclose.Conflict of interest: Hannah Wardman has nothing to disclose.Conflict of interest: Miriam Bennett has nothing to disclose.Conflict of interest: Adnan Custovic has nothing to disclose.Conflict of interest: Angela Simpson has nothing to disclose.Conflict of interest: Clare S Murray has nothing to disclose.