Defining the normal range of fractional exhaled nitric oxide in children – one size does not fit all

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.