Nitric oxide in exhaled gas : studies on physiological regulation and measurements in infants and children

Nitric oxide (NO) is found in the exhaled gas of humans, starting from birth, and is increased in adult patients with bronchial asthma. This study assessed whether the measurement of NO in exhaled gas is technically feasible in infants and children. We studied a possible difference of exhaled NO levels between asthmatic children and healthy controls. Optimising existing sampling techniques, a link between clinical severity and levels of exhaled NO was sought. Adapting the sampling technique to the specific needs of infants, tidal analysis of inhaled and exhaled NO concentrations was performed. Finally, regulatory aspects of pulmonary NO synthesis were studied in an established rabbit model.

We found that NO in exhaled gas can be reliably measured in newborn infants and children and distinguished from nasally derived NO. In spite of comparable lung function parameters orally exhaled NO was significantly increased in asthmatic children in comparison with healthy controls. Even higher increases were seen in asthmatic children with recent clinical symptoms of airway obstruction, suggesting that exhaled NO measurements may be an early signal of asthmatic airway inflammation and useful to monitor the effectiveness of anti-inflammatory treatment. In newborn infants the range of autoinhaled NO concentrations made biological effects of NO in the lower respiratory tract conceivable. In the rabbit experiments adrenoceptor stimulation and high frequency oscillatory ventilation significantly increased pulmonary NO production. These findings are likely relevant to the understanding of the circulatory adaptation to extrauterine life. Increases of pulmonary NO production induced by mechanical stretch might influence bronchial function and ventilation perfusion matching.

List of scientific papers

I. Artlich A, Hagenah JU, Jonas S, Ahrens P, Gortner L. (1996). Exhaled nitric oxide in childhood asthma. Eur J Pediatr. 155:698-701.
https://pubmed.ncbi.nlm.nih.gov/8839728

II. Artlich A, Busch T, Lewandowski K, Jonas S, Gortner L, Falke KJ. (1999). Childhood asthma: exhaled nitric oxide in relation to clinical symptoms. Eur Respir J. 13:1396-401.
https://pubmed.ncbi.nlm.nih.gov/10445618

III. Artlich A, Jónsson B, Bhiladvala M, Lönnqvist PA, Gustafsson LE. Single breath analysis of endogenous nitric oxide (NO) in the newborn. [Submitted]

IV. Adding LC, Agvald P, Artlich A, Persson MG, Gustafsson LE. (1999). Beta-adrenoceptor agonist stimulation of pulmonary nitric oxide production in the rabbit. Br J Pharmacol. 126:833-9.
https://pubmed.ncbi.nlm.nih.gov/10188998

V. Artlich A, Adding C, Agvald P, Persson MG, Lönnqvist PA, Gustafsson LE. (1999). Exhaled nitric oxide increases during high frequency oscillatory ventilation in rabbits. Exp Physiol. 84:959-69.
https://pubmed.ncbi.nlm.nih.gov/10502663