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New method for single-breath fraction of exhaled nitric oxide measurement with improved feasibility in preschool children with asthma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. (Pediatrisk inflammationsforskning/Alving)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. (Pediatrisk inflammationsforskning/Alving)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. (Pediatrisk inflammationsforskning/Alving)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
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2015 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 26, no 7, 662-667 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Respiratory societies recommend use of standardized methodologies for fraction of exhaled nitric oxide (FeNO) measurements in adults and children, but in preschoolers, feasibility remains a problem. The exhalation time needed to obtain steady-state FeNO is unclear. Our primary aim was to study the feasibility of an adapted single-breath FeNO method with age-adjusted exhalation times. We also studied the association between time to steady-state NO level and height, as well as FeNO in relation to asthma and current treatment with inhaled corticosteroids (ICS).

METHODS: Sixty-three children aged 3-10 years performed FeNO measurements with a hand-held electrochemical device with a newly developed flow-control unit. Exhalation times were pre-adapted to age. Exhaled air was simultaneously sampled to a chemiluminescence analyzer to measure time to steady-state NO level.

RESULTS: Eighty-one percent of the children achieved at least one approved measurement. From 4 years upwards, success rate was high (96%). Time to steady-state [NO] (median and interquartile range) was 2.5 s (2.4-3.5) at the age of 3-4 years and 3.5 s (2.7-3.8) at the age of 5-6 years. Height was associated with time to steady state (r(2)  = 0.13, p = 0.02). FeNO (geometric mean [95% CI]) was higher in ICS-naïve asthmatic children (n = 19): 15.9 p.p.b. (12.2-20.9), than in both healthy controls (n = 8) 9.1 p.p.b. (6.6-12.4) and asthmatic subjects on treatment (n = 24) 11.5 p.p.b. (9.7-13.6).

CONCLUSION: We found this adapted single-breath method with age-adjusted exhalation times highly feasible for children aged 4-10 years. ICS-naïve asthmatic children had FeNO levels under the current guideline cutoff level (20 p.p.b.), highlighting the importance of taking age into account when setting reference values.

Place, publisher, year, edition, pages
2015. Vol. 26, no 7, 662-667 p.
Keyword [en]
airway inflammation; asthma; biomarker; children; feasibility; fraction of exhaled nitric oxide; preschool
National Category
Respiratory Medicine and Allergy Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-270371DOI: 10.1111/pai.12447ISI: 000365410900013PubMedID: 26184580OAI: oai:DiVA.org:uu-270371DiVA: diva2:889630
Available from: 2015-12-27 Created: 2015-12-27 Last updated: 2017-12-01Bibliographically approved
In thesis
1. Towards Improved Diagnostics and Monitoring in Childhood Asthma: Methodological and Clinical Aspects of Exhaled NO and Forced Oscillation Technique
Open this publication in new window or tab >>Towards Improved Diagnostics and Monitoring in Childhood Asthma: Methodological and Clinical Aspects of Exhaled NO and Forced Oscillation Technique
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Asthma is a heterogeneous disease. Diagnosis relies on symptom evaluation and lung function tests using spirometry. Symptoms can be vague. Spirometry is effort-dependent and does not reliably evaluate small airways. Allergic asthma in preschool children is not easily separated from episodic wheeze.

Exhaled NO (FeNO) is a marker of allergic Th2-cytokine-driven airway inflammation. However, FeNO is not feasible in preschoolers with current devices and algorithms. Alveolar NO is an estimate of small airway involvement. Forced oscillometry (FOT) is an effort-independent lung function test assessing both large and small airways.

Aims: To study clinical and methodological aspects of FeNO, alveolar NO and lung function indices by FOT.

Methods: Asthmatic children and young adults and healthy controls, were included in the studies. FeNO at 50 mL/s was performed in all studies (in study III with an adapted single-breath method with age-adjusted exhalation times). FeNO at multiple exhalation flow rates were performed in studies I, II and IV to calculate alveolar NO, as was spirometry. FOT indices were assessed in study IV.

Results: The exhalation time needed to reach steady-state NO was < 4 s in subjects aged 3-4 years, and was related to subject height. FeNO was higher in ICS-naïve asthmatic children than in controls. ICS-naïve asthmatic preschool children had FeNO < 20 ppb. The oral contribution to FeNO was similar in asthmatic and healthy youths. Multiple flow rates and modelling of alveolar NO were feasible in children aged 10-18 years. Alveolar NO correlated to asthma characteristics, though not when axial diffusion correction was applied. FOT resistance measures were associated with asthma diagnosis, and small airway FOT measures were associated with asthma control, in adolescents.

Conclusion: An adapted FeNO method is feasible from 4 years, and exhalation time is related to child height. Our findings emphasise the need to refine clinical cut-offs for FeNO in younger children. FOT variables discriminate between asthmatics and controls, much like spirometry. The information provided by FOT is additive to that from spirometry. Further studies of exhaled NO dynamics and FOT indices of small airways are warranted to evaluate new treatment options and possibly improve asthma control.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 79 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1262
Keyword
asthma, children, exhaled NO, forced oscillation technique, airway inflammation, small airways, asthma diagnostics
National Category
Clinical Medicine
Research subject
Pediatrics; Lung Medicine
Identifiers
urn:nbn:se:uu:diva-304264 (URN)978-91-554-9710-1 (ISBN)
Public defence
2016-11-25, Robergsalen, Akademiska sjukhuset, Ingång 40, 4tr, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2016-11-03 Created: 2016-10-03 Last updated: 2016-11-21

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Heijkenskjöld-Rentzhog, CharlotteKalm-Stephens, PiaNordvall, LennartMalinovschi, AndreiAlving, Kjell

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