Defining the normal range of fractional exhaled nitric oxide in children – one size does not fit all
- Ran Wang1,2,
- Stephen J. Fowler1,2,
- Stephen W. Turner3,4,
- Sarah Drake1,2,
- Laura Healy1,2,
- Lesley Lowe1,2,
- Hannah Wardman5,
- Miriam Bennett1,2,
- Adnan Custovic6,
- Angela Simpson1,2,7⇑ and
- Clare S. Murray1,2,7
- 1Division of Immunology, Immunity to infection & Respiratory Medicine, School of Biological Sciences, The University of Manchester. Manchester Academic Health Science Centre, Manchester, UK
- 2Manchester University NHS Foundation Trust, Manchester, UK
- 3Women and Children's Division NHS Grampian, Aberdeen, Scotland
- 4Child Health, University of Aberdeen, Aberdeen
- 5University of Manchester, Centre for Primary Care and Health Services Research, Manchester, UK
- 6Faculty of Medicine, National Heart & Lung Institute, Imperial College London, UK
- 7joint senior authors
- Corresponding author: Angela Simpson (Angela.Simpson{at}manchester.ac.uk)
Abstract
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.
Footnotes
This 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.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received June 29, 2022.
- Accepted July 3, 2022.
- Copyright ©The authors 2022
This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org