Background: Raised concentrations of nitrate and nitrite have been found in exhaled breath condensate (EBC) in airway disease, and it has been postulated that this reflects increased nitric oxide (NO) metabolism. However, the chemical and anatomical origin of nitrate and nitrite in the airways has not yet been sufficiently studied. Methods: The fraction of exhaled NO at an exhalation flow rate of 50 ml/s (FE NO ) and nitrite and nitrate in EBC, nasal condensate, and saliva were measured in 17 tracheostomised and 15 non-tracheostomised subjects, all of whom were non-smokers without respiratory disease. Tracheal and oral samples were taken from the tracheostomised subjects and nasal (during velum closure) and oral samples from the nontracheostomised subjects. Measurements were performed before and after sodium nitrate ingestion (10 mg/kg) and use of antibacterial mouthwash (chlorhexidine 0.2%). Results: In tracheostomised subjects oral FE NO increased by 90% (p,0.01) while tracheal FE NO was not affected 60 minutes after nitrate ingestion. Oral EBC nitrite levels were increased 23-fold at 60 minutes (p,0.001) whereas the nitrite levels in tracheal EBC showed only a minor increase (fourfold, p,0.05). Nitrate was increased the same amount in oral and tracheal EBC at 60 minutes (2.5-fold, p,0.05). In non-tracheostomised subjects oral FE NO and EBC nitrite increased after nitrate ingestion and after chlorhexidine mouthwash they approached baseline levels again (p,0.001). Nasal NO, nitrate, and nitrite were not affected by nitrate intake or mouthwash. At baseline, mouthwash with deionised water did not affect nitrite in oral EBC or saliva, whereas significant reductions were seen after antibacterial mouthwash (p,0.05 and p,0.001, respectively). Conclusions: Besides the salivary glands, plasma nitrate is taken up by the lower airways but not the nasal airways. Nitrate levels in EBC are thus influenced by dietary intake. Nitrate is reduced to nitrite by bacterial activity which takes place primarily in the oropharyngeal tract of healthy subjects. Only oropharyngeal nitrite seems to contribute to exhaled NO in non-inflamed airways, and there is also a substantial contribution of nitrite from the oropharyngeal tract during standard collection of EBC.

Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation.Ten tracheotomized patients and seven healthy subjects were studied. The mean ¡ SEM fraction of exhaled NO from the nose, mouth and trachea was 56 ¡ 8, 14 ¡ 4 and 6 ¡ 1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64 ¡ 14, 11 ¡ 3 and 4 ¡ 1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation.There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.

Intragastric generation of NO requires continuous delivery of nitrite-containing saliva and is almost abolished in critically ill, intubated patients. Enteral supplementation with nitrite could however fully restore gastric NO levels. Future studies will reveal if low NO levels contribute to stress ulcers and gastric overgrowth of bacteria often seen in these patients and in turn if restoring gastric NO with nitrite could be a useful therapeutic approach.