Oral bacteria--the missing link to ambiguous findings of exhaled nitrogen oxides in cystic fibrosis.

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.

Increased exhaled nitrite in children with allergic asthma is not related to nitric oxide formation.

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 (PD(20)) 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 PD(20) (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.