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Basal and induced NO formation in the pharyngo-oral tract influences estimates of alveolar NO levels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
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 Medical Cell Biology, Integrative Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
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2009 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 106, no 2, 513-519 p.Article in journal (Refereed) Published
Abstract [en]

The present study analyzed how models currently used to distinguish alveolar from bronchial contribution to exhaled nitric oxide (NO) are affected by manipulation of NO formation in the pharyngo-oral tract. Exhaled NO was measured at multiple flow rates in 15 healthy subjects in two experiments: 1) measurements at baseline and 5 min after chlorhexidine (CHX) mouthwash and 2) measurements at baseline, 60 min after ingestion of 10 mg NaNO3/kg body wt, and 5 min after CHX mouthwash. Alveolar NO concentration (CalvNO) and bronchial flux (J′awNO) were calculated by using the slope-intercept model with or without adjustment for trumpet shape of airways and axial diffusion (TMAD). Salivary nitrate and nitrite were measured in the second experiment. CalvNO [median (range)] was reduced from 1.16 ppb (0.77, 1.96) at baseline to 0.84 ppb (0.57, 1.48) 5 min after CHX mouthwash (P < 0.001). The TMAD-adjusted CalvNO value after CHX mouthwash was 0.50 ppb (0, 0.85). The nitrate load increased J′awNO from 32.2 nl/min (12.2, 60.3) to 57.1 nl/min (22.0, 119) in all subjects and CalvNO from 1.47 ppb (0.73, 1.95) to 1.87 ppb (10.85, 7.20) in subjects with high nitrate turnover (>10-fold increase of salivary nitrite after nitrate load). CHX mouthwash reduced CalvNO levels to 1.15 ppb (0.72, 2.07) in these subjects with high nitrate turnover. All these results remained consistent after TMAD adjustment. We conclude that estimated alveolar NO concentration is affected by pharyngo-oral tract production of NO in healthy subjects, with a decrease after CHX mouthwash. Moreover, unknown ingestion of dietary nitrate could significantly increase estimated alveolar NO in subjects with high nitrate turnover, and this might be falsely interpreted as a sign of peripheral inflammation. These findings were robust for TMAD.

Place, publisher, year, edition, pages
2009. Vol. 106, no 2, 513-519 p.
Keyword [en]
exhaled nitric oxide, alveolar nitric oxide, salivary nitrite, breath test
National Category
Medical and Health Sciences Physiology
Identifiers
URN: urn:nbn:se:uu:diva-97886DOI: 10.1152/japplphysiol.91148.2008ISI: 000263120400024PubMedID: 19036899OAI: oai:DiVA.org:uu-97886DiVA: diva2:172985
Available from: 2008-11-27 Created: 2008-11-27 Last updated: 2013-04-02Bibliographically approved
In thesis
1. Nitric Oxide Exchange in Central and Peripheral Airways: Determinants in Health and Respiratory Disease
Open this publication in new window or tab >>Nitric Oxide Exchange in Central and Peripheral Airways: Determinants in Health and Respiratory Disease
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Exhaled nitric oxide (NO) is a marker of eosinophilic steroid-sensitive inflammation in the airways of patients with respiratory disease. Moreover, information about the localization of inflammation in the respiratory tree is obtained by estimates of bronchial and alveolar contributions to exhaled NO.

Aims: The main aim of this thesis was to identify the determinants of exhaled NO, as well as determinants of bronchial and alveolar contributions to exhaled NO in health and disease. Smoking history, degree of IgE sensitization and effects of modulating the pharyngo-oral tract production of NO were specifically studied in this context. Other specific aims were to determine the association of exhaled NO with the presence of asthma and pulmonary hypertension (PH).

Methods: Both population-based studies and experimental studies have been performed within the frame of the thesis. The population-based studies are based on data from the European Community Respiratory Health Survey II. NO measurements at several exhalation flow rates were performed in order to estimate alveolar and bronchial contributions to exhaled NO.

Results: Both current and previous smoking were associated with decreased exhaled NO and bronchial NO flux levels. Alveolar NO concentrations were decreased in current smokers. The degree of IgE sensitization was positively related to the levels of exhaled NO and its bronchial contribution. Exhaled NO appeared to be a more specific marker of allergic inflammation than of rhinitis or asthma. Both allergic and non-allergic asthma were associated with increased exhaled NO levels, but only in never-smoking persons. The estimated alveolar NO increased after ingestion of nitrate in individuals with high nitrate turnover in the pharyngo-oral tract. Pulmonary arterial hypertension, but not other forms of PH, was associated with decreased bronchial NO flux, whereas PH of all etiologies was related to increased alveolar NO concentrations.

Conclusion: Smoking history and IgE sensitization, that are known determinants of exhaled NO, affected the bronchial and alveolar contributions to exhaled NO differently. The limitations of the simple NO pulmonary exchange models were highlighted by the paradoxical effects on estimated alveolar NO when modulating the NO production proximally, in the pharyngo-oral tract. Predominance of non-eosinophilic inflammation in ever-smoking patients with asthma could explain the poor association between the presence of asthma and exhaled NO in these patients. Different pathophysiological changes in terms of bronchial NO production and exchange were related to the etiology of pulmonary hypertension.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 64 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 403
Keyword
exhaled nitric oxide, alveolar NO, bronchial NO flux, extended NO analysis, asthma, smoking, snus, IgE-sensitization, pharyngo-oral tract, nitrate, nitrite, pulmonary hypertension
Identifiers
urn:nbn:se:uu:diva-9416 (URN)978-91-554-7363-1 (ISBN)
Public defence
2008-12-19, Robergsalen, Akademiska Sjukhuset, Ingång 40, 4 tr., Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-11-27 Created: 2008-11-27Bibliographically approved

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Malinovschi, AndreiJanson, ChristerHolm, LenaNordvall, LennartAlving, Kjell

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