09 Mar Nitric Oxide and the Paranasal Sinuses: NO testing is an essential accompaniment to spirometry.
The discovery within the paranasal sinuses for the production of nitric oxide (NO) has altered the traditional explanations of sinus physiology. The role of NO in the sinuses is likely to enhance local host defence mechanisms via direct inhibition of pathogen growth and stimulation of mucociliary activity. This NO can be measured noninvasively in exhaled breath by means of a Fractional Expired Nitric Oxide (FENO) test and can provide clinicians with added data regarding upper airway inflammation when basic spirometry is normal.
In 1991, Gustafsson et al. showed that NO gas was present in exhaled breathe of experimental animals and humans. The initial line of thinking was that exhaled NO originated from the alveolar region. However, subsequent studies by Alving et al. (1993) showed that NO levels were higher during nasal breathing compared with oral exhalations, a finding that suggested the contribution of upper airways. Refining these findings, Lundberg et al. (1994) demonstrated that single-breathe measurements showed low-NO levels when exhaling via tracheostomy, intermediate levels from the mouth and high levels in nasal exhalations.
Research had clearly demonstrated that the nasal passages were the main source of NO in healthy people, however, it was still not clear exactly where this NO was coming from and by which cells it was produced. Experiments with topical NO synthase inhibitors in the nose gave the first clue. Surprisingly, these agents did not affect nasal NO levels to greater extent. This led researchers to speculate that a major NO source must be situated somewhere in the nasal region but out of reach for NOS inhibitors administrated via the inhalation route. The paranasal sinuses seemed like plausible candidates; these cavities lie adjacent to the nose, but they would not be readily accessible to topical drug administration. Further research by Lundberg et al. (1995, 1996) showed this was indeed the case.
Scientists now know that NO is constantly produced apically in the sinus epithelium. Interestingly, nitric oxide synthase is the same enzyme used by activated white blood to produce NO in response to invasion or virus or bacteria. The central role of iNOS in these cells is clearly illustrated in genetically engineered animals lacking this enzyme. Those animals are more susceptible to bacterial and viral infections (MacMicking et al., 1995; Wei et al., 1995).
The levels of NO in the nose and upper airway can easily be measured noninvasively by simply aspirating air from the nostril or by a nasal exhalation. Sensitive electrochemical analysers, such as FeNO, measure exhaled NO levels. It has been shown that nasal NO is altered in several airway disorders including allergic rhinitis and sinusitis. Intriguingly, this NO can function as an “aerocrine” hormone to enhance pulmonary oxygen uptake and reduce pulmonary vascular resistance. Thus, a physiological role of the paranasal sinuses in regulation of pulmonary function is suggested.
The Wesley Lung Function Laboratory include FENO testing as standard with every lung function test.
Reference source:
Lundberg, J. O. (2008), Nitric Oxide and the Paranasal Sinuses. Anat Rec, 291: 1479–1484. doi: 10.1002/ar.20782