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

Abstract

BackgroundThe 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.MethodFeNO 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).ResultsHeight, 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.ConclusionWe developed a height-based FeNO percentile chart which quantifies the probability of asthma in symptomatic children and merits further validation towards clinical implementation.

Use of exhaled nitric oxide in the diagnosis and monitoring of childhood asthma: myth or maxim?

“…While F ENO is usually expressed in parts per billion, attempts have been made to standardise concentrations, similar to percentage predicted or z-score values of forced expiratory volume in 1 s (FEV 1 ). One group standardised F ENO for height using data from two UK populations and found that concentrations above the 90th centile (equivalent to 25 ppb in a 10-year-old boy of average height) has 59% sensitivity, 96% specificity, 97% positive predictive value and 50% negative predicted value [ 35 ].…”

Fractional exhaled nitric oxide in the assessment of exercise‐induced bronchoconstriction: A multicenter retrospective analysis of UK‐based athletes

“…For example, females have been reported to have approximately 25% lower FeNO values compared to males. 21,22 Further, height, 23,24 age, 24,25 and atopic status 24,26 may all act as confounders. Personalized normal values for FeNO that account for these factors have therefore been proposed 24 ; however, the diagnostic value of such personalized normal values in the context of EIB is yet to be evaluated.…”