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- Zetterquist, Wilhelm
(författare)
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Exhaled nitrogen oxides and carbon monoxide in asthma and cystic fibrosis : markers of inflammation?
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Exhaled markers of airway inflammation have attracted much interest as potential tools for monitoring the bronchial inflammation of respiratory disease. Exhaled nitric oxide (NO), its metabolites nitrite and nitrate in breath condensate (EBC), and exhaled carbon monoxide (CO), have been suggested for this purpose. However, their site of origin has not been fully investigated and the enterosalivary circuit of nitrate, with its possible off springs of nitrite and NO, could constitute a confounding factor. Exhaled NO is increased in asthma, but its levels are unexpectedly low in cystic fibrosis (CF). Exhaled CO and EBC nitrite are instead elevated in both these conditions, where the latter could reflect an increased NO activity also in CF. Aims: The aim of study I was to compare the profiles and possible origins of exhaled NO and CO in children and adults with asthma and CF by the introduction of highly specific infrared technique and controlled flow rate for CO measurements. In study II we wanted to investigate the possible influence from salivary formation of NO on measurements in exhaled air. Study III was designed to evaluate the postulated link between nitrite and nitrate in EBC and exhaled NO in children with allergic asthma, also in relation to other disease markers. In study IV, these EBC metabolites were examined in relation to the salivary contents of the same in subjects with CF, to evaluate a possible influence from oral bacteria, which may reduce nitrate to nitrite. Methods: In study I, 56 children and adults with asthma, 16 with allergic rhinitis, 9 CF patients and 30 age-matched controls performed exhaled CO and NO measurements with two different flow rates. Study II was performed on ten healthy adults who ingested 240 mg of nitrate on empty stomach for consecutive measurements of exhaled and nasal NO and salivary nitrate and nitrite, followed by a series of mouthwash experiments. In study III, 27 children with allergic asthma and 21 age-matched controls were examined with exhaled NO, EBC nitrite and nitrate, blood eosinophils, spirometry and methacholine challenge. Whereas EBC and salivary nitrite and nitrate, together with exhaled NO, were studied before and after mouthwash with the anti-bacterial solution of chlorhexidine in15 CF patients and 15 controls in study IV. Results: Exhaled CO, was in contrast to NO, not elevated in asthma and allergic rhinitis, and both markers were negative in CF. The change of exhalation flow rate did, furthermore, not affect the levels of CO but gave a proportional change of NO. The intake of nitrate resulted in a 150% increase of exhaled NO after 2 h, whereas nasal NO was unaffected. This increase was largely abolished by chlorhexidine mouthwash, which also decreased baseline NO levels with 30%. EBC nitrite, but not nitrate, was significantly elevated in the children with allergic asthma, but no correlation was found to increased levels of NO or other disease markers. EBC nitrite was also significantly higher in the CF patients, as was salivary nitrite, but these levels were almost eradicated by chlorhexidine, which in addition reduced exhaled NO more in CF than in controls. Conclusions: The flow independence of exhaled CO proves that it has its origin in the alveoli and is therefore not a suitable marker for bronchial inflammation. There is a substantial salivary contribution to exhaled NO from the non-enzymatic reduction of nitrite, which can be greatly increased by the intake of nitrate-rich foods. There is also a most prominent salivary contribution to EBC nitrite in CF, and probably even in asthma, which indicates an altered activity of oral bacteria in these conditions, rather than increased NO metabolism, as an explanation for their higher levels of EBC nitrite.
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| 2. |
- Zetterquist, Wilhelm, et al.
(författare)
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Increased exhaled nitrite in children with allergic asthma is not related to nitric oxide formation
- 2008
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Ingår i: The Clinical Respiratory Journal. - 1752-6981 .- 1752-699X. ; 2:3, s. 166-174
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Tidskriftsartikel (refereegranskat)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.
(författare)
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Oral bacteria : the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis
- 2009
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 103:2, s. 187-193
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Tidskriftsartikel (refereegranskat)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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