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The fraction of NO in exhaled air and estimates of alveolar NO in adolescents with asthma: methodological aspects
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
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2012 (English)In: Pediatric Pulmonology, ISSN 8755-6863, E-ISSN 1099-0496, Vol. 47, no 10, 941-949 p.Article in journal (Refereed) Published
Abstract [en]

Rationale

This study investigated the oral contribution to exhaled NO in young people with asthma and its potential effects on estimated alveolar NO (CalvNO), a proposed marker of inflammation in peripheral airways. Secondary aims were to investigate the effects of various exhalation flow-rates and the feasibility of different proposed adjustments of (CalvNO) for trumpet model and axial diffusion (TMAD).

Methods

Exhaled NO at flow rates of 50–300 ml/sec, and salivary nitrite was measured before and after antibacterial mouthwash in 29 healthy young people (10–20 years) and 29 with asthma (10–19 years). CalvNO was calculated using the slope–intercept model with and without TMAD adjustment.

Results

Exhaled NO at 50 ml/sec decreased significantly after mouthwash, to a similar degree in asthmatic and healthy subjects (8.8% vs. 9.8%, P = 0.49). The two groups had similar salivary nitrite levels (56.4 vs. 78.4 µM, P = 0.25). CalvNO was not significantly decreased by mouthwash. CalvNO levels were similar when flow-rates between 50–200 or 100–300 ml/sec were used (P = 0.34 in asthmatics and P = 0.90 in healthy subjects). A positive association was found between bronchial and alveolar NO in asthmatic subjects and this disappeared after the TMAD-adjustment. Negative TMAD-adjusted CalvNO values were found in a minority of the subjects.

Conclusions

Young people with and without asthma have similar salivary nitrite levels and oral contributions to exhaled NO and therefore no antibacterial mouthwash is necessary in routine use. TMAD corrections of alveolar NO could be successfully applied in young people with asthma and yielded negative results only in a minority of subjects.

Place, publisher, year, edition, pages
2012. Vol. 47, no 10, 941-949 p.
Keyword [en]
exhaled nitric oxide, alveolar nitric oxide, nitrite, TMAD-adjustment, pediatric asthma
National Category
Pediatrics Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-172352DOI: 10.1002/ppul.22556ISI: 000308714100002PubMedID: 22467536OAI: oai:DiVA.org:uu-172352DiVA: diva2:514086
Available from: 2012-04-05 Created: 2012-04-05 Last updated: 2017-12-07Bibliographically 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, CharlotteAlving, KjellKalm-Stephens, PiaNordvall, LennartMalinovschi, Andrei

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