Current ReviewsNitric oxide in the nasal airway: A new dimension in otorhinolaryngology†,‡,*,**
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
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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Cited by (0)
- †
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.