Original Article
FeNO and Exercise Testing in Children at Risk of Asthma

https://doi.org/10.1016/j.jaip.2017.10.014Get rights and content

Background

Exercise testing is the gold standard for diagnosing exercise-induced bronchoconstriction in children, but requires considerable cooperation and medical resources. Therefore, fraction of exhaled nitric oxide (FeNO) has been proposed as a tool to predict the need for exercise testing.

Objective

The objective of this study was to investigate the relationship between FeNO, exercise test results, and a history of respiratory symptoms during exercise in children at risk of asthma.

Methods

FeNO measurement, exercise testing, and interview about respiratory symptoms during exercise were completed in 224 seven-year-old children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood2000 birth cohort. The associations between FeNO, exercise test results, and reported respiratory symptoms during exercise were analyzed adjusting for gender, respiratory infections, and inhaled corticosteroid treatment. The associations were also analyzed stratified by asthma and atopic status.

Results

Of the 224 children, 28 (13%) had an established asthma diagnosis and 58 (26%) had a positive exercise test (≥15% drop in forced expiratory volume in 1 second [FEV1] from baseline). FeNO and bronchial obstruction after exercise were linearly associated with a doubling of FeNO corresponding to a 2.4% drop in FEV1 (95% confidence interval, 0.8-4.1; P < .01). However, a receiver operating characteristic curve analysis showed that the best cutoff of FeNO for predicting exercise test outcome among children who reported respiratory symptoms during exercise was 17 ppb, which only had 74% negative predictive value. There was no association between FeNO and reported respiratory symptoms during exercise (odds ratio = 1.3 [0.8-1.9]; P = .29) or reported symptoms during exercise and exercise test results (odds ratio = 1.0 [1.0-1.1]; P = .12).

Conclusions

A history of respiratory symptoms during exercise was not associated with either elevated FeNO or a positive exercise test in children at risk of asthma. FeNO and exercise test results were linearly associated traits, but FeNO could not reliably be used dichotomized to predict the need of exercise testing.

Section snippets

Study design

Participants comprised children of COPSAC2000: a single-center, prospective clinical birth cohort study of 411 children born to mothers with a history of asthma. The children were enrolled between August 1998 and December 2001 at 1 month of age and were closely monitored by scheduled visits to the COPSAC clinical research unit every 6 months till the age of 7. The recruitment and baseline characteristics of the participants have previously been described in detail.11, 12, 13, 14

Ethics

The Copenhagen

Baseline

Of the 411 children in the COPSAC2000 cohort, 327 (80%) attended the 7-year visit, and of these children, 224 (69%) completed exercise testing, FeNO measurement, and a structured clinic interview about respiratory symptoms during exercise (see the study group flow chart in Figure 1). The number of children with a positive exercise test (postexercise FEV1 drop ≥15% from baseline) was 58 (26%), 29 (13%) reported respiratory symptoms during exercise, and 28 (13%) had asthma. The mean (standard

Primary findings

FeNO and exercise test results were linearly associated traits in 7-year-olds at risk of asthma comprising children both with and without an established diagnosis of asthma, suggesting that exercise-induced bronchoconstriction develops as a continuum from health to disease. However, the study also shows that FeNO cannot be used in clinical practice to predict exercise test outcome, as the most optimal cutoff for FeNO only had the potential to exclude a positive exercise test in 74% of children

Conclusions

FeNO and bronchial obstruction after the exercise test are linearly associated traits in our at-risk population of 7-year-old children with and without an established asthma diagnosis, suggesting that exercise-induced bronchoconstriction develops as a continuum from health to disease. However, FeNO cannot reliably be used dichotomized in clinical practice to predict the need of exercise testing.

Acknowledgements

We express our deepest gratitude to the children and families of the COPSAC2000 cohort study for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team.

The guarantor of the study is HB, from conception and design to conduct of the study and acquisition of data, data analysis, and interpretation of data. A-MMS, CFC, and BLC have written the first draft of the manuscript. All co-authors have provided important intellectual input and

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    All funding received by COPSAC is listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (Grant no 0603-00280B); and the Capital Region Research Foundation have provided core support to the COPSAC research center.

    Conflicts of interest: K. Bønnelykke has received consultancy fees from ALK Abello; has received research support from the Lundbeck Foundation, Novo Nordisk Foundation, danish Ministry of Health, and Danish Strategic Research Foundation; has an approved but unpaid patent for Diagnosing asthma and other wheezing disorders by genotyping of CDHR3 variants (Danish patent no. PA 2012 00368). H. Bisgaard has received research support from the Danish Ministry of Health, Lundbeck Foundation, Danish Council for Strategic Research, Danish Advanced Technology Foundation, Danish State Budget; and has received consultancy fees from Chiesi Pharmaceuticals and Boehringer Ingelheim. The rest of the authors declare that they have no relevant conflicts of interest.

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