Exhaled Nasal Nitric Oxide During Humming: Potential Clinical Tool in Sinonasal Disease?

Abstract

The use of nasal nitric oxide (nNO) in sinonasal disease has recently been advocated as a potential tool to explore upper inflammatory airway disease. However, it is currently hampered by some factors including the wide range of measurement methods, the presence of various confounding factors and the heterogeneity of the study population. The contribution of nasal airway and paranasal sinuses communicating with the nose through the ostia represents the main confounding factor. There is accumulating evidence that nasal humming (which is the production of a tone without opening the lips or forming words) during nNO measurement increases nNO levels due to a rapid gas exchange in the paranasal sinuses. The aim of this review is to discuss the basic concepts and clinical applications of nNO assessment during humming, which represents a simple and noninvasive method to approach sinonasal disease.

Drug Delivery to Paranasal Sinuses Using Pulsating Aerosols

“…In previous studies, it has been shown that humming can release nitric oxide from the paranasal sinuses during exhalation. (14) Therefore, we studied sinus ventilation during humming and, as seen from Figure 2C, the maxillary sinuses are displayed on the anterior gamma camera images, confirming efficient sinus ventilation.…”

“…Ventilation and sinus drug delivery was also confirmed in studies by Maniscalco et al (12,14) In these studies, oscillatory airflow was induced during humming, and they could show release of nitric oxide from the sinuses and its suppression by inhalation of the nitric oxide synthase inhibitor L-NAME. But these studies require nasal inhalation, because humming can only be performed during exhalation.…”

“…(13) Recent studies have shown that pulsating, vibrating, or ''sonique'' air flows as well as humming can generate sufficient pressure gradients for ventilation of the sinus cavities or release of captured gases, such as nitric oxide. (14) Aerosolized Drug Delivery to the Respiratory Tract Aerosolized drug delivery to the respiratory tract, for either topical or systemic therapy, has been used for a long time. (15) The respiratory tract consists of several distinct functional units and, in general, we can distinguish the airways (upper and lower airways) and the pulmonary (alveolar) zone.…”

Extended analysis of exhaled and nasal nitric oxide for the evaluation of chronic cough

“…The sinuses, which contain a very high NO concentration [21], communicate with the nasal cavity through ostia, and there is a continuous NO gas exchange between these cavities [22]. Therefore, the possibility to detect alterations in nasal NO output is limited by the high background NO levels present in paranasal sinuses, which could easily blunt slight alteration of NO [23]. Moreover, the limited number of patients with sinusitis enrolled in our study may have influenced the statistical significance.…”

The Nasal Nitric Oxide Response to External Acoustic Energy: A Pilot Study of Sampling Dynamics

“…In addition to the above-cited studies linking radiographic and/or endoscopic OMC obstruction to a blunted nNO response to humming, this transient response has been shown to be normalize after effective medical therapy of nasal polyposis, consistent with restoration of OMC patency [34]. As noted above, however, in our earlier study of normal controls and allergic rhinitics without sinusitis, the magnitude of the humming-induced nNO transient did not correlate with radiographically-documented OMC cross-sectional area, leading one observer to characterize its blunting as a high-threshold, "all or none" response [31,35]. Given these uncertainties, along with the variability inherent in the humming maneuver, future clinical validation studies, in addition to including multiple clinical sub-groups to maximize external validity, might profitably examine whether the nNO response to external acoustic stimulation yields more clinically-coherent results than does the response to humming.…”