Elsevier

American Journal of Otolaryngology

Volume 22, Issue 1, January–February 2001, Pages 19-32
American Journal of Otolaryngology

Current Reviews
Nitric oxide in the nasal airway: A new dimension in otorhinolaryngology,,*,**

https://doi.org/10.1053/ajot.2001.20700Get rights and content

Abstract

The discovery that the gas nitric oxide (NO) is an important signaling molecule in the cardiovascular system earned its Nobel prize in 1998. NO has since been found to play important roles in a variety of physiologic and pathophysiologic processes in the body including vasoregulation, hemostasis, neurotransmission, immune defense, and respiration. The surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the field of otorhinolaryngology. NO provides a first-line defense against micro-organisms through its antiviral and antimicrobial activity and by its upregulation of ciliary motility. Nasal treatments such as polypectomy, sinus surgery, removal of hypertrophic adenoids and tonsils, and treatment of allergic rhinitis may alter NO output and, therefore, the microbial colonization of the upper airways. Nasal surgery aimed at relieving nasal obstruction may do the same but would also be expected to improve pulmonary function in patients with asthma and upper airway obstruction. NO output rises in a number of conditions associated with chronic airway inflammation, but not all of them. Concentrations are increased in asthma, allergic rhinitis, and viral respiratory infections, but reduced in sinusitis, cystic fibrosis, primary ciliary dysfunction, chronic cough, and after exposure to tobacco and alcohol. Therefore, NO, similar to several other inflammatory mediators, probably subserves different functions as local conditions dictate. At present, it seems that the measurement of NO in the upper airway may prove valuable as a simple, noninvasive diagnostic marker of airway pathologies. The objective of this review is to highlight some aspects of the origin, physiology, and functions of upper airway NO, and to discuss the particular methodological problems that result from the complex anatomy. (Am J Otolaryngol 2001;22:19-32. Copyright © 2001 by W.B. Saunders Company)

Section snippets

Exhaled NO (ENO)

NO was first shown in exhaled air in 1991.18 Two years later, Alving et al19 showed that exhaled NO (ENO) levels were elevated in asthmatics, and that they decreased after treatment with steroids. In the same study, Alving reported a high concentration of NO in upper airways.19

A large number of studies19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 have confirmed that ENO is increased in such airway inflammations as asthma,30, 39 bronchiectasis,40 viral

Nasal NO

The finding of high levels of NO in the nasal airways19 and paranasal sinuses73 in normal humans and animals74, 75 as compared with the lower airways evoked renewed interest in the physiology and respiratory role of the upper airways and its potential interaction with the lower airways. Some of the mechanisms of this link are controversial,76, 77 as is the function and physiologic role of the large, air-filled paranasal sinuses.78

A growing number of connections are being found between the

Biochemical pathway

NO is synthesized from the semiessential amino acid L-arginine by the action of one of several forms of nitric oxide synthase (NOS) with the production of L-citrulline. For this chemical reaction there are several cofactors, among which are oxygen and nicotinamide adenine dinucieotide phosphate (NADPH).86 The NO produced is oxidized to nitrite (NO2−), which can be used to monitor NO formation, nitrate (NO3−), and peroxynitrite (ONOO−) ions (Fig 1).87

. Nitric oxide synthesis.

The NOS exists in at

Production, absorption, and output of NO from the airways

The nasal airway protects the lower airway by humidifying, warming, and filtering the inspired air. The particular aerodynamic characteristics of the complex slit-like nasal airway results in maximum contact between the inspired air at the nasal mucosa. With this method, not only particles but also inhaled noxious gases are removed before they reach the delicate structures of the alveolar bed of the lungs. The efficiency of the removal of particles depends mainly on their size, whereas

Aerodynamic considerations relevant to nasal no output

Regardless of the measuring technique used, it is essential to record the NO concentration only when it has been ascertained that a steady-state plateau has been achieved. In several studies, nasal aspiration has been performed by using the built-in sampling flow of the analyzer, which is usually in the range from 0.2 to 0.7 L/min.5, 32, 58, 64, 103, 112, 115, 116, 117 At such low rates, laminar flow regimen will prevent air penetration to the deeper parts of the nose. Local turbulence is

NO in relation to nasal physiology and upper airway pathology

The nasal valves, acting as an anterior resistor, account for approximately half of the total airways resistance.135 They have important aerodynamic functions in inspiration and expiration. In the former, the abrupt increase in nasal dimensions within the cavum and its complicated geometry dissipate the laminar airflow and promote turbulence. This enhances mucosa-to-air contact. This change in airflow characteristics protects the lower airways from particles, noxious gases, and extreme

Measurement of nasal NO

Current knowledge suggests that the measurement of exhaled NO and/or some other gases such as CO,142 ethane, and penthane143 may have value as diagnostic tools for monitoring the cause of disease and in evaluating the impact of treatment. It is already used for the latter in asthma and rhinitis. Furthermore, the measurement of these gases from the airways may become important in assessing the effect of indoor and outdoor exposure to pollutants.

Because NO concentration is flow-dependent, it is

Methods for remote collection and delayed analysis of NO (offline)

NO can be passed through the analyzer as soon as it has been extracted from the nose or stored before analysis. The latter presents 2 problems. A suitable container must be used to store the gas. This must neither allow NO to escape nor permit other gases to diffuse in. Secondly, the NO sampling rate remains as critical as ever. The equipment used for direct online measurements of NO in air exhaled is technically advanced, expensive, and requires maintenance from skilled personnel. Therefore,

Conclusions

The discovery of higher NO concentrations in the sinuses and the nasal airway than anywhere else in the body suggests an important role for this gas in the local immune defense. Within the nose and sinuses, its bactericidal and virocidal activity supplement its augmentation of ciliary beat frequency and protect against some infections. Its tumoricidal action may account for the low incidence of malignancy observed in the Schneiderian muciosa. Nasal NO is transported by the inspired air to the

Acknowledgements

This work was performed as part of ongoing research by The Toronto Upper Airway Study Group in the Respiratory Research Laboratory at The Toronto Hospital in Canada. It was supported by the Departments of Otolaryngology and Respirology at St. Michael's Hospital, Toronto, Canada and the Departments of Otolaryngology at the Mt. Sinai Hospital and Hospital for Sick Children, Toronto, Canada. Furthermore, the authors wish to express their gratitude for financial support to The Norwegian Research

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    the Catholic University of Rio Grande do Sul, Porto Alegre, Brazil;

    Zhenjiang First People's Hospital, Jiangsu, People's Republic of China; and

    *

    §the Department of Otolaryngology, St. Michael's Hospital, University of Toronto, Canada.

    **

    Address reprint requests to James S.J. Haight, 197 Strathgowan Ave, Toronto M4N 1C4, Ontario, Canada.

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