| 1. |
- Marteus, Helena
(author)
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Oropharyngeal origin of markers in exhaled breath
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Normal NO formation in the human airways occurs primarily in the nasal airways, where it is catalyzed by inducible NO synthase (iNOS), and in the oropharyngeal tract, via as yet not fully defined pathways. This NO can be detected in exhaled breath and when inflammation is present in the airways, for example in asthma, the concentration of NO is increased. Although most studies on non-invasive measurements of airway inflammation have focused on NO in exhaled breath, there has also been an increasing interest in measurements of compounds in exhaled breath condensate. For example, levels of nitrite and ammonia in condensate are altered in patients with asthma. Finding out where in the respiratory tract exhaled aerosol particles and gaseous products primarily originate is an important challenge, as is elucidation of to what extent the oropharyngeal compartment contributes to markers of physiological status. We wanted to determine the contribution of NO from the nasal, oral and lower airway compartment both during exhalation and inhalation. We also investigated low levels of exhaled NO in smokers to determine whether this effect is due to an effect in the oropharyngeal tract. Furthermore, we wanted to elucidate the chemical and anatomical origin of nitrite and nitrate measured in nasal and exhaled breath condensate and their relation to NO formation. Finally, we wished to study the chemical and anatomical origin of ammonia measured in exhaled breath condensate and its possible influence on pH. We show a substantial contribution of both nasal and oral NO during both exhalation and inhalation, and that nasal NO output is higher during inhalation compared to exhalation. We were not able to show a relation between NO formation from nitrite in saliva and the low levels of exhaled NO seen in smokers. However, we do find indications for a significant iNOSmediated NO formation in the squamous epithelium of the oropharyngeal tract. Thus, the reduced exhaled NO levels observed in smokers could still be due to an effect in the oropharyngeal tract. A major part of the nitrite measured in exhaled breath condensate originates above the upper trachea, indicating a proximal generation of respiratory droplets, and is primarily a product of the bacterial reduction of nitrate. Additionally, we show that plasma nitrate is taken up from the circulation by the lower airways, but not by the nasal airways. Moreover, we found that pH measured in exhaled breath condensate is strongly affected by oral ammonia formed by urea-splitting bacteria, thus refuting that pH measurements in exhaled breath condensate would reflect pH homeostasis in the lower airways. In conclusion, the oropharyngeal tract is a major site of origin for many biological markers found in exhaled breath, in the gaseous as well as in the aqueous phase. Some of these exhaled markers (nitrite and ammonia) are formed by bacteria, and since the levels of these markers are altered in asthma, the collected data indicate that patients with airway disease have abnormal bacterial activity in the oropharyngeal tract.
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| 2. |
- Zetterquist, Wilhelm, et al.
(author)
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Increased exhaled nitrite in children with allergic asthma is not related to nitric oxide formation
- 2008
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In: The Clinical Respiratory Journal. - 1752-6981 .- 1752-699X. ; 2:3, s. 166-174
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Journal article (peer-reviewed)abstract
- Introduction: Nitrite sampled from the upper airways could originate from inflammation-induced nitric oxide (NO), as reports of elevated nitrite in exhaled breath condensate (EBC) from asthmatics suggest, but also through bacterial action in the pharyngo-oral tract. Objectives: To correlate EBC nitrite and nitrate to exhaled NO (FENO, fraction Of expired NO) and other markers of disease activity in children with allergic asthma and thereby further investigate their role and origin. Materials and methods: EBC was collected from 27 asthmatic subjects (ages 6-17 years, all immunoglobulin E-positive for aeroallergens) and 21 age-matched non-atopic healthy controls for fluorometric analysis of nitrite and nitrate. These markers were compared with measurements of FENO, blood eosinophil count (EOS), methacholine reactivity (PD20) and baseline spirometry. Results: EBC nitrite, in contrast to nitrate, was significantly increased (P < , 0.01) in the asthmatic children. They also had increased levels of FENO (P < , 0.001) and EOS (P < , 0.001) along with decreased PD20 (P < , 0-001) and FEV1/FVC (p < , 0.01). However, there was no correlation between EBC nitrite and FENO (r = 0.05) or any other marker of disease activity in the asthmatic children, whereas between the other markers correlations could be established. Conclusion: EBC nitrite is elevated in childhood asthma but the lack of correlation to FENO and other markers, together with simultaneously normal levels of nitrate, make its origin as a metabolite of inflammation-induced NO questionable.
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| 3. |
- Zetterquist, Wilhelm, et al.
(author)
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Oral bacteria : the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis
- 2009
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 103:2, s. 187-193
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nitrite in exhaled breath condensate (EBC) has been shown to be elevated in cystic fibrosis (CF), while exhaled nitric oxide (FENO) is paradoxically low. This has been argued to reflect increased metabolism of NO while its diffusion is obstructed by mucus. However, we wanted to study the possible influence of salivary nitrite and bacterial nitrate reduction on these parameters in CF patients by the intervention of an anti-bacterial mouthwash. METHODS: EBC and saliva were collected from 15 CF patients (10-43 years) and 15 controls (9-44 years) before and 5 min after a 30s chlorhexidine mouthwash, in parallel with measurements of FENO. Nitrite and nitrate concentrations were measured fluorometrically. RESULTS: EBC nitrite, but not nitrate, was significantly higher in the CF patients (median 3.6 vs 1.3 microM in controls, p<0.05) and decreased after mouthwash in both groups (3.6-1.4 microM, p<0.01; 1.3-0.5 microM, p<0.01). Salivary nitrite correlated significantly to EBC nitrite (r=0.60, p<0.001) and decreased correspondingly after chlorhexidine, whereas salivary nitrate increased. FENO was lower in CF and the difference between patients and controls was accentuated after mouthwash (5.4 vs 8.4 ppb in controls, p<0.05). CONCLUSION: EBC nitrite mainly originates in the pharyngo-oral tract and its increase in CF is possibly explained by a regional change in bacterial activity. The limited lower airway contribution supports the view of a genuinely impaired formation and metabolism of NO in CF, rather than poor diffusion of the molecule.
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