Nasal Nitric Oxide Concentration Research Articles

Low Levels of Nasal Nitric Oxide (NO) Correlate to Impaired Mucociliary Function in the Upper Airways

Findings in previous studies have suggested nitric oxide (NO) to be a regulator of mucociliary activity in the upper airways. The aim of the present investigation was to study whether a correlation exists between the nasal NO concentration and mucociliary function in patients suffering from respiratory tract diseases such as chronic sinusitis or recurrent pneumonia. Nasal NO was measured with a chemiluminescence analyser, 100 ppb (parts per billion) being adopted as the lower limit of the normal range on the basis of findings in an earlier study of healthy subjects. Mucociliary function was evaluated by measurements of ciliary beat frequency (CBF) in nasal brush samples, and the saccharin transport test. A subnormal level of nasal NO was found in 50% (9/18) of the patients. This correlated with a significantly impaired mucociliary function, regarding both CBF and the saccharin transport time. The median CBF was 10.6 Hz in the group with normal levels of nasal NO, as compared to 8.4 Hz in the subnormal NO group. AH patients with a normal nasal NO concentration had a mean CBF of s9.0 Hz in their nasal brush samples, but in the subnormal group the same measurements yielded a CBF of ≥9.0 Hz in only 22% (2/9) of the cases. As measured with the saccharin test, mucociliary transport was normal in 78% (7/9) in the normal nasal NO group, but the saccharin test was normal only in 11% (1/9) of the subnormal nasal NO group. Nasal NO levels were found to correlate with both CBF measurements (Spearman's rho, 0.80) and the saccharin transport test results (Spearman's rho, -0.61). The results of the present study provide further support for the view that NO is an important regulator of mucociliary function in the upper airways, and that measurements of the nasal NO concentration should be included in investigations of the mucociliary system.

Changes in Nasal Nitric Oxide Concentration Associated with Symptoms of Common Cold and Treatment with a Topical Nasal Decongestant

Nitric oxide (NO) is known to play a role in the non-specific host defence mechanism. Furthermore, it has been proposed that NO may be important in respiratory defence against the viruses which cause the common cold. Indeed, elevated NO levels have previously been observed in orally expired air during upper respiratory tract infection (URTI). We wanted to investigate further the role of NO in the host response to URTI. Total nasal airway resistance (tNAR) and nasal NO levels were obtained during symptomatic URTI in 97 subjects. Of these, 80 received treatment with either oxymetazoline or a placebo spray. Post-treatment tNAR and NO levels were obtained 60 min after treatment. Measurements of NO were also repeated 4-6 weeks later, when subjects were healthy, (n = 82). NO levels were measured using a chemiluminescence gas analyser whilst tNAR was measured using posterior rhinomanometry. The mean pre-treatment NO level (1063 ± 541 ppb) was shown to be reduced significantly after treatment with oxymetazoline (827 ± 373ppb), p < 0.0001. The mean pre-treatment tNAR, 0.42 Pa cm-3 sec-1, was also reduced significantly to 0.21 Pa cm-1 sec' (p < 0.001) after treatment with oxymetazoline. There was no significant correlation between the change in NO levels and change in tNAR following treatment with oxymetazoline (p, corrected for ties = 0.011, p = 0.98). No significant difference was found between NO levels obtained during URTI (1130 ± 444 ppb) when compared to values obtained when healthy (1197 ± 361 ppb), p =0.25. These results demonstrate that treatment with a topical nasal decongestant spray causes a reduction in nasal NO levels. We propose that this occurs as an indirect consequence of the vasoconstrictor actions of oxymetazoline. Since no change in NO levels was observed during URTI, we propose that the NO synthase responsible for NO production in the nose responds in a different manner to that in the lungs.

Endogenous nitric oxide in the upper airways of healthy newborn infants.

The endogenous production of nitric oxide (NO) in the upper airways was studied in healthy newborn infants within the first minutes after delivery (N = 2) and at postnatal ages of 1 and 24 h (N = 13). Measurements were made in infants born vaginally or by cesarean section and at various times after the rupture of membranes. Gas was sampled from the nose and pharynx, and NO concentrations were determined by a fast response chemiluminescence analyzer. Sampling from the nose at a constant flow of 20 mL/min gave 0.27 +/- 0.01 parts per million (mean +/- SEM, ppm) of NO, independent of age and mode of delivery (vaginal delivery and cesarean section). Allowing NO to accumulate in the nose for 15-120 s yielded peak concentrations up to 4.6 ppm. A 30% increase was noted between 1 and 24 h of age. We conclude that nasal peak NO concentrations in the ppm range can be demonstrated in the healthy newborn infant within the first hour after birth. Consequently autoinhalation of endogenously produced upper airway NO may play a role in the adaptation of the respiratory system to postnatal life in the human.

Calcium-independent and steroid-resistant nitric oxide synthase activity in human paranasal sinus mucosa

Nitric oxide (NO) is present in the human nasal airways and originates primarily from the paranasal sinuses. Immunohistochemical studies and messenger ribonucleic acid (mRNA) in situ hybridization indicate that a type-2 NO synthase (NOS) is constitutively expressed in healthy sinus epithelium. We have further characterized sinus NOS activity by studying the enzymatic conversion of L-arginine to L-citrulline in biopsies from sinus mucosa. Maxillary sinus biopsies were obtained from nine healthy subjects during reconstructive facial surgery. In addition, nasal NO concentrations in nine controls were compared with those found in five patients treated with high systemic doses of glucocorticosteroids. Finally, the effects of i.v. L-arginine infusion on nasal cavity NO concentrations were studied in six healthy subjects. Ca(2+)-independent NOS activity was found in all biopsies and was five times higher than Ca(2+)-dependent activity (179 +/- 64 and 36 +/- 17 pmol.g-1.min, respectively). There was no difference in nasal NO levels between controls (344 +/- 21 parts per billion (ppb)) and steroid-treated patients (342 +/- 36 ppb). Nasal NO levels increased up to 35% following i.v. infusion of L-arginine. We conclude that NOS activity in healthy sinus mucosa is predominantly Ca(2+)-independent and this NOS is not downregulated by systemic steroids. Furthermore, L-arginine infusion increases nasal airway NO excretion in vivo, indicating that the substrate concentration is a rate-limiting factor under basal conditions. These findings further support the notion that sinus NOS is identical or very closely related to the type-2 NOS; however, the regulation of expression seems to be fundamentally different from that described previously for this NOS isoform.