Nasal Nitric Oxide: A Comparison of Measurement Techniques

Abstract

Nasal nitric oxide measurement may be a surrogate marker of upper airway inflammation. There is, however, no standardized measurement technique; and this led us to examine measurement techniques for acceptability and reproducibility. In five subjects we examined the flow dependence of nasal NO. In 13 healthy volunteers, nasal NO was measured on-line by five methods: 1) Tidal nasal and oral breathing: NO sampling during exclusive nasal followed by exclusive oral tidal breathing; 2) Fixed flow exhalation: NO sampling during exclusive nasal followed by exclusive oral exhalation at 100 mL/second from total lung capacity; 3) Nasal-oral aspiration: air aspirated from the mouth via both nares at 100 mL/second with glottis closure; 4) Aspiration from one nares: air aspirated from one nares at 3.3 mL/second using nitric oxide analyzer sample line with velum closure; 5) Nasal Insufflation: NO sampled at one nares as air insufflated into the other nares at a flow of 100 mL/second with velum closure. Acceptability of all methods was assessed by subjects and technicians. Nasal NO concentration showed a significant inverse correlation with transnasal flow rate. All methods showed excellent reproducibility as assessed by the intraclass correlation coefficient except tidal breathing, which showed highly variable breath-to-breath NO levels, although mean breath values were reproducible. Mean nasal NO concentrations with methods 1, 2, 3, 4, and 5 were 32.1, 50.2, 62.8, 1381, and 60.0 ppb, respectively. Velum closure was not always achieved in methods 4 and 5, whereas methods 1 and 2 required separate nasal and oral procedures. Method 5 had reduced acceptability. NO concentrations were similar with methods that used the same airflow (2, 3, and 5). Nasal NO can be sampled in different ways with excellent reproducibility. In view of the flow dependence of nasal NO, it is vital to use a constant flow rate, and lower airway NO contribution must be excluded or subtracted. The fixed flow exhalation appears to be the preferred method as it is highly reproducible and acceptable.

Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements

“…Nasal (supravelum) measurement techniques have been extensively discussed and consensus has been reached on what methods should be used [14,16]. However, no clearcut explanations of what is being measured and why different measurements yield different NO outputs at different flow rates have been put forward [15,18,19]. In the present study healthy young subjects performing exhalations in a highly reproducible way were examined.…”

“…Thus, it could be argued that a nasal exhalation better reflects normal physiological conditions for transnasal airflow than the aspiration/insufflation methods. The single-breath method is widely accepted for oral exhalations and the nose-mask was well tolerated [19] and easily adapted to the setup for oral measurements.…”

Inhibition of nitric oxide synthase by nasal decongestants

“…By this means NO is thought to modulate nasal vascular conductance and nasal cavity volume, which are correlated to the nasal airway resistance [16,17]. It should be noted however, that recent investigations, using high flow rate insufflation, contradict the existence of such a relationship [31,32]. The difference in these results is thought to be due to underestimation of measured NO outputs as low flows were used instead of higher and probably more physiological transnasal airflows [33].…”

Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients

“…In contrast to the relatively high levels of inhaled NO used in these studies, clinical effects have been shown using levels as low as 100-150 parts per billion (ppb) in acute respiratory failure and ARDS [13][14][15]. The level of NO in the nasal cavity varies with the measurement method [16] but often exceeds 100 ppb. Autoinhalation of nasal NO occurs and has physiological effects as an airborne messenger [3,17].…”