Abstract

Background: The paranasal sinuses serve as a reservoir of nitric oxide (NO), contributing to baseline nasal NO (nNO) levels. nNO has also been shown to increase transiently with humming, a response that may be blunted in severe rhinosinusitis. Blunting of the acoustically-induced nNO transient (“spike”) has been proposed as a screening test for osteomeatal complex (OMC) obstruction in sinusitis. Preparatory to conducting a clinical evaluation study, to eliminate variation in patient effort during this maneuver, we evaluated the use of external acoustic energy—in place of humming—to elicit nNO transients, documenting the effects of varying stimulus amplitude and gas sampling rates. Methods: Non-smoking, non-asthmatic subjects with no history of chronic sinusitis or nasal polyposis underwent nNO measurements in triplicate under: (1) control (quiet) conditions, and (2) with 128 Hz external acoustic energy. In Experiment 1, twelve subjects were exposed to two different intensities of external acoustic energy at 3 L/min sampling rate. In Experiment 2, a subset of nine subjects was sampled with and without acoustic stimulation at three different gas sampling rates (1, 2, and 3 L/min). Results: Experiment 1: Subjects, as a group, showed intensity-related increases in nNO with increasing acoustic amplitude (p < 0.01). Experiment 2: independently, both applied acoustic energy and lower nasal gas sampling rates increased measured nNO levels (p < 0.05 to p < 0.0001). Longitudinally, baseline (quiet) nNO obtained on a repeated basis in the two experiments (n = 9) was highly reproducible (R2 = 0.84; p < 0.001), and acoustically-stimulated nNO was moderately so (R2 = 0.50; p < 0.05). Conclusions: Application of external acoustic energy is a practical alternative to humming for mobilizing NO from the paranasal sinuses, and could be more objectively applied in any future validation studies involving clinical sinusitis and/or OMC obstruction.

Highlights

  • Nitric oxide (NO), an endogenously produced gas in the human airway, has vasodilatory, bacteriostatic, and ciliastimulatory effects [1]

  • In chronic rhinosinusitis, baseline nasal NO (nNO) has often been found to be paradoxically low despite widespread mucosal inflammation, and nNO levels can rise after appropriate medical or surgical treatment, suggesting restoration of osteomeatal complex (OMC) patency [13,14,15,16,17,18,19,20]

  • Individual mean nasal NO levels sampled at 3 L/min ranged from 66–182 ppb under quiet conditions, 106–386 ppb with low-amplitude acoustic stimulation (128 Hz; 64 dBA @ 30 cm), and 122–750 ppb at higher amplitude (128 Hz; 78 dBA @ 30 cm)

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Summary

Introduction

Nitric oxide (NO), an endogenously produced gas in the human airway, has vasodilatory, bacteriostatic, and ciliastimulatory effects [1]. The paranasal sinuses act as a major source for nNO, osteomeatal complex (OMC) obstruction can isolate sinus NO flux from the nasal cavity [10,11,12]. The paranasal sinuses serve as a reservoir of nitric oxide (NO), contributing to baseline nasal NO (nNO) levels. Preparatory to conducting a clinical evaluation study, to eliminate variation in patient effort during this maneuver, we evaluated the use of external acoustic energy—in place of humming—to elicit nNO transients, documenting the effects of varying stimulus amplitude and gas sampling rates. In Experiment 1, twelve subjects were exposed to two different intensities of external acoustic energy at 3 L/min sampling rate. Experiment 2: independently, both applied acoustic energy and lower nasal gas sampling rates increased measured nNO levels (p < 0.05 to p < 0.0001).

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