Measurement of Nasal Nitric Oxide

Abstract

The major part of nitric oxide (NO) in exhaled air originates from the nasal airways, with only minor contribution from the lower airways and the oral cavity. The physiological role of the very high local NO concentration in the paranasal sinuses is still unclear. The most widely used and best-standardized method to sample nasal NO in isolation from the lower respiratory tract is aspiration at a fixed flow through the nasal passages in series. Important technical considerations include the choice of the correct transnasal flow and the ability of children to perform a breath-holding manoeuvre.The effects of age and height on nasal NO values have yet to be defined in a larger population of healthy children using the recommended aspiration technique. Presently, there is no validated technique available to measure nasal NO in infants and small children.The measurement of nasal NO concentrations has evoked interest in its potential to serve as a non-invasive and simple diagnostic tool for upper and lower respiratory tract disorders. Measurements of nasal NO concentrations are helpful to screen children with clinical symptoms suggestive of primary ciliary dyskinesia and to exclude this disease in those with high nasal NO concentrations with high certainty. Nasal NO measurements are, however, of no diagnostic utility in distinguishing between other conditions such as asthma, cystic fibrosis, bronchiectasis, sinusitis or rhinitis, or in monitoring therapeutic interventions in any such disorder. Origin of Nasal Nitric OxideNitric oxide (NO) is produced endogenously within the respiratory tract and was first documented in exhaled air in humans and mammals in 1991 [1]. It was then shown that the major part of NO in exhaled air originates from the nasal airways, with only a minor contribution from the lower airways and the oral cavity [2]. NO is present in the nasal airways and paranasal sinuses in very high concentrations, close to the acute exposure levels set by occupational health guidelines for short-term exposure at the workplace [3,4]. Biochemical Pathway and Cellular OriginNO is generated from the semi-essential amino acid L-arginine by the enzyme NO synthase (NOS), which can be divided into two major categories: constitutive NOS (cNOS) and inducible NOS (iNOS). The constitutive enzyme, which according to its location may be named endothelial NOS (eNOS) or neuronal NOS (nNOS), is activated by calcium and calmodulin. It produces small amounts of NO to modulate physiological processes, and can be stimulated by bradykinin, acetylcholine, histamine, leukotrienes, and several other mediators. Calmodulin is an enzyme cofactor regulating electron transport. It is also identified in close juxtaposition to the cilia of the upper airway epithelium, and is thought to be involved in ciliary motility. The iNOS, which was first isolated in macrophages, is calciumand calmodulin-independent and activated by a variety of Hammer J, Eber E (eds): Paediatric Pulmonary Function Testing.