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Alveolar and exhaled NO in relation to asthma characteristics: effects of correction for axial diffusion
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 Medical Sciences, Respiratory Medicine and Allergology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
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2014 (English)In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 69, no 8, 1102-1111 p.Article in journal (Refereed) Published
Abstract [en]

Background: Inflammation in the small airways might contribute to incomplete asthma disease control despite intensive treatment in some subgroups of patients. Exhaled NO (FeNO) is a marker of inflammation in asthma and the estimated NO contribution from small airways (Calv(NO)) is believed to reflect distal inflammation. Recent studies recommend adjustments of Calv(NO) for trumpet model and axial diffusion (TMAD-adj). This study aimed to investigate the clinical correlates of Calv(NO), both TMAD-adjusted and unadjusted. Methods: Asthma symptoms, asthma control, lung function, bronchial responsiveness, blood eosinophils, atopy and treatment level were assessed in 410 subjects, aged 10-35 years. Exhaled NO was measured at different flow-rates and Calv(NO) calculated, with TMAD-adjustment according to Condorelli. Results: Trumpet model and axial diffusion-adjusted Calv(NO) was not related to daytime wheeze (P = 0.27), FEF50 (P = 0.23) or bronchial responsiveness (P = 0.52). On the other hand, unadjusted Calv(NO) was increased in subjects with daytime wheeze (P < 0.001), decreased FEF50 (P = 0.02) and with moderate-to-severe compared to normal bronchial responsiveness (P < 0.001). All these characteristics correlated with increased FeNO (all P < 0.05). Unadjusted Calv(NO) was positively related to bronchial NO flux (J'aw(NO)) (r = 0.22, P < 0.001) while TMAD-adjCalv(NO) was negatively related to J'awNO (r = -0.38, P < 0.001). Conclusions: Adjusted Calv(NO) was not associated with any asthma characteristics studied in this large asthma cohort. However, both FeNO and unadjusted Calv(NO) related to asthma symptoms, lung function and bronchial responsiveness. We suggest a potential overadjustment by current TMAD-corrections, validated in healthy or unobstructed asthmatics. Further studies assessing axial diffusion in asthmatics with different degrees of airway obstruction and the validity of proposed TMAD-corrections are warranted.

Place, publisher, year, edition, pages
2014. Vol. 69, no 8, 1102-1111 p.
Keyword [en]
alveolar nitric oxide, asthma, axial diffusion, exhaled nitric oxide, peripheral inflammation
National Category
Pediatrics Respiratory Medicine and Allergy
Identifiers
URN: urn:nbn:se:uu:diva-231109DOI: 10.1111/all.12430ISI: 000339436200013PubMedID: 24894594OAI: oai:DiVA.org:uu-231109DiVA: diva2:744182
Available from: 2014-09-07 Created: 2014-09-04 Last updated: 2017-12-05
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, CharlotteNordvall, LennartJanson, ChristerBorres, Magnus P.Alving, KjellMalinovschi, Andrei

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