The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase.

High values (800-6000 parts per billion) of nitric oxide (NO) in expelled air from the stomach were shown in humans by chemiluminescence technique. These NO values were more than 100 times higher than those found in orally exhaled air. Intragastric NO production is probably non-enzymatic, requiring an acidic environment, as NO in expelled air was reduced by 95% after pretreatment with the proton pump inhibitor omeprazole. Furthermore, large amounts of NO were formed in vitro from lettuce and saliva when placed in hydrogen chloride (pH < 2). In conclusion, large amounts of NO are formed intragastrically in humans and this source of NO may be of importance for the integrity of the gastric mucosa in health and disease. Measurements of NO in expelled air might be of value as a non-invasive method for estimation of gastric acidity.

The exact origin of nitric oxide (NO) in exhaled air is not known. We wanted to further investigate at what site exhaled NO is produced and to determine whether children with Kartagener's syndrome exhibited altered levels of exhaled NO. NO was measured by chemiluminescence technique in air sampled directly from the nose and in normally exhaled air of four children (2.5-13 years old) with Kartagener's syndrome, 20 healthy children, four healthy adults, and four conscious tracheostomized adults. NO was almost absent (98% reduced) in air sampled directly from the nose in four children with Kartagener's syndrome (4 +/- 1 parts per billion (ppb)), compared to age-matched controls (221 +/- 14 (ppb)). Tracheostomized adult subjects had considerably higher NO values in nasally (22 +/- 3 ppb) and orally (14 +/- 2 ppb) exhaled air, compared to levels in air exhaled through the tracheostomy (2 +/- 0 ppb). Treatment with intranasal corticosteroids for 14 days, or with antibiotics for 1 week, did not affect exhaled NO. These results clearly show that, basically, all NO in exhaled air of healthy subjects originates from the upper respiratory tract, with only a minor contribution from the lower airways. Furthermore, the absence of nasal NO in children with Kartagener's syndrome could be of use as a simple noninvasive diagnostic test.

Measurement of fractional exhaled nitric oxide in exhaled air is an exciting innovative technique that gives new insights in to the pathophysiology of lung disease and asthma in particular, with many potential clinical applications. Careful standardisation of measurement techniques will facilitate the use of this new measurement in paediatric respiratory medicine; this Task Force was set up for this purpose. Methodologies, for use in all age groups, are already available and there are abundant questions relating to interpretation and application of fractional exhaled nitric oxide waiting to be addressed. Noninvasiveness and instantaneous results potentially make it a suitable monitoring instrument for use in children. Exhaled nitric oxide measurement has definitely found its way into clinical research in paediatric respiratory medicine. Evidence for clinically-useful applications is accumulating, and the merits of this new technique must now be demonstrated in larger studies, using standardised methodology in an appropriate setting.