Nasal nitric oxide flux from the paranasal sinuses.

PURPOSE OF REVIEW: Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and can be modulated by various airway inflammatory conditions, including allergic rhinitis and chronic rhinosinusitis - with and without polyposis. Paranasal sinuses serve as a NO 'reservoir', with concentrations typically exceeding those measured in lower airway (fractional exhaled NO or FeNO) by a few orders of magnitude. However, the dynamics of NO flux between the paranasal sinuses and main nasal airway, which are critical to respiratory NO emission, are poorly understood. RECENT FINDINGS: Historically, NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). However, recent anatomically-accurate computational modeling studies based on patients' CT scans showed that the ethmoid sinuses and diffusive transport dominate the process. SUMMARY: These new findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

Use of computational fluid dynamics (CFD) to model observed nasal nitric oxide levels in human subjects.

BACKGROUND: Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and nasal NO (nNO) levels typically exceed those in exhaled breath (fractional exhaled NO [FeNO]). Elevated concentrations of NO sampled from the nose, in turn, reflect even higher concentrations in the paranasal sinuses, suggesting a "reservoir" role for the latter. However, the dynamics of NO flux within the sinonasal compartment are poorly understood. METHODS: Data from 10 human subjects who had previously undergone both real-time nNO sampling and computed tomography (CT) scanning of the sinuses were analyzed using computational fluid dynamics (CFD) methods. Modeled and observed nNO values during the initial 2-s transient ("spike") during nasal exhalation were then compared. RESULTS: Examining the initial 2-s transient spike for each subject (as well as the pooled group), there was a statistically significant correlation between modeled and observed nNO levels, with r values ranging from 0.43 to 0.89 (p values ranging from <0.05 to <0.0001). Model performance varied between subjects, with weaker correlations evident in those with high background (FeNO) levels. In addition, the CFD simulation suggests that ethmoid sinuses (>60%) and diffusion process (>54%) contributed most to total nasal NO emissions. CONCLUSION: Analysis of this dataset confirms that CFD is a valuable modeling tool for nNO dynamics, and highlights the importance of the ethmoid sinuses, as well as the role of diffusion as an initiating step in sinonasal NO flux. Future model iterations may apply more generally if baseline FeNO is taken into account.

Computational modeling of nasal nitric oxide flux from the paranasal sinuses: Validation against human experiment.

BACKGROUND: Nitric oxide (NO) is important in respiratory physiology and airway defense. Although the paranasal sinuses are the major source of nasal NO, transport dynamics between the sinuses and nasal cavities are poorly understood. METHODS: Exhaled nasal NO tracings were measured in two non-asthmatic subjects (one with allergic rhinitis, one without) using NO analyzer connected via face mask. We subsequently performed computational fluid dynamics NO emission simulations based on individual CT scans and compared to the experimental data. RESULTS: Simulated exhaled NO tracings match well with experimental data (r > 0.84, p < 0.01) for both subjects, with measured peaks reaching 319.6 ppb in one subject (allergic-rhinitis), and 196.9 ppb in the other. The CFD simulation accurately captured the peak differences, even though the initial sinus NO concentration for both cases was set to the same 9000 ppb based on literature value. Further, the CFD simulation suggests that ethmoid sinuses contributed the most (>67%, other sinuses combined <33%) to total nasal NO emission in both cases and that diffusion contributes more than convective transport. By turning off diffusion (setting NO diffusivity to ~0), the NO emission peaks for both cases were reduced by >70%. CONCLUSION: Historically, nasal NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). Here, we showed that the ethmoid sinuses and diffusive transport dominate the process. These findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.

Association of Allergic Rhinitis With Change in Nasal Congestion in New Continuous Positive Airway Pressure Users.

Importance: Nasal congestion occurring after continuous positive airway pressure (CPAP) treatment initiation impairs CPAP adherence. Allergic rhinitis is associated with worsening nasal congestion in patients who are exposed to nonallergic triggers. Use of CPAP presents potential nonallergic triggers (eg, humidity, temperature, pressure, and airflow). Objective: To compare nasal congestion among CPAP users with allergic rhinitis, nonallergic rhinitis, and no rhinitis. We hypothesize that CPAP patients with baseline allergic rhinitis are more likely to experience a worsening of nasal congestion (or less improvement in nasal congestion) compared with patients with no baseline rhinitis. Design, Setting, and Participants: This prospective cohort study included consecutive patients newly diagnosed with obstructive sleep apnea in a tertiary sleep center who were using CPAP therapy 3 months after diagnosis. Baseline rhinitis status was assigned as allergic rhinitis, nonallergic rhinitis, or no rhinitis, based on questionnaire responses and past allergy testing. Data were collected from 2004 to 2008 and analyzed from July 2019 to February 2020. Main Outcomes and Measures: At baseline before CPAP exposure and again 3 months later, subjective nasal congestion was measured with the Nasal Obstruction Symptom Evaluation (NOSE) scale and a visual analog scale (VAS), each scored from 0 to 100 (100 = worst congestion). Changes in nasal congestion were tested over 3 months for the whole cohort, within each rhinitis subgroup (paired t test), and between rhinitis subgroups (multivariate linear regression). Results: The study cohort comprised 102 participants, of whom 61 (60%) were male and the mean (SD) age was 50 (13). The study included 23 (22.5%) participants with allergic rhinitis, 67 (65.7%) with nonallergic rhinitis, and 12 (11.8%) with no rhinitis. Nasal congestion improved from baseline to 3 months in the whole cohort (mean [SD] NOSE score, 38 [26] to 27 [23], mean [SD] change, -10 [23]; 95% CI, -15 to -6; mean [SD] VAS score, 41 [27] to 32 [28]; mean [SD] change, -10 [26]; 95% CI, [-15 to -4]) and in each rhinitis subgroup. Adjusted improvement in nasal congestion at 3 months was significantly less in the allergic rhinitis subgroup compared with the no rhinitis subgroup (positive difference means less improvement) compared with baseline: NOSE score 14 (95% CI, 1 to 28) and VAS score 15 (95% CI, 0 to 30). Conclusions and Relevance: Initiation of CPAP was associated with improved subjective nasal congestion, but less improvement in patients with baseline allergic rhinitis. Baseline allergic rhinitis may predict which patients are more vulnerable to potential congestive effects of CPAP.

Pilot evaluation of the nasal nitric oxide response to humming as an index of osteomeatal patency.

BACKGROUND: Paranasal sinuses are reservoirs for nitric oxide (NO), and humming facilitates nasal diffusion of NO. The nasal NO response to humming has previously been shown to be blunted with chronic sinusitis and nasal polyposis. We hypothesized that the nasal NO response to humming will be proportional to radiographic osteomeatal patency when comparing allergic rhinitis (AR) patients (without chronic sinusitis) with normal controls. METHODS: Nonsmoking subjects completed questionnaires and skin-prick testing. Subjects underwent sinus CT scanning, followed by exhaled (oral) and nasal NO sampling (with and without humming). Humming-to-quiet (H/Q) nasal NO ratios were calculated. Three-dimensional reconstructions were used to trace the osteomeatal complex (OMC) and measure minimum cross-sectional area. Lund-Mackay scores were also documented. RESULTS: A total of 33 subjects (22 women; mean age, 35.5 years) completed the study. Seventeen AR patients (5 IAR and 12 PAR) participated, as did 16 nonallergic controls. Among controls, quiet nasal NO levels--corrected for fractional exhaled NO--rose significantly with OMC area and fell significantly with Lund-Mackay scores (p < 0.05). However, we observed no proportionality between H/Q ratio and radiographic OMC patency. CONCLUSION: Analysis of nasal NO samples taken under quiet conditions from normal controls was consistent with the paranasal sinuses acting as a reservoir of nasal NO and with OMC patency acting as a significant factor in NO diffusion. However, our results did not support a relationship between the nasal NO response to humming and radiographic OMC patency in a sample excluding subjects with severe rhinosinusitis.

Nasal physiological reactivity of subjects with nonallergic rhinitis to cold air provocation: a pilot comparison of subgroups.

BACKGROUND: Noninfectious nonallergic rhinitis (NINAR) is characterized by self-reported hyperreactivity to nonspecific physical or chemical stimuli. The relationship between these two classes of triggers is not well established, however. We compared NINAR subjects with predominantly physical or chemical triggers versus normal controls with respect to subjective (symptomatic) and objective (obstructive) responses to cold, dry air challenge. METHODS: We studied 14 NINAR subjects and 10 normal controls. Exposures consisted of 15 minutes of cold dry air (0 degrees C/5% RH) or warm moist air (25 degrees C/50% RH) on two separate days a week apart. Subjects rated symptoms using visual analog scales and had their nasal airway resistance measured at baseline, immediately after, and at 15-minute intervals for 1 hour postexposure. RESULTS: The majority of NINAR subjects reported physical triggers as more troublesome than chemical. Immediately postprovocation, the mean net proportional change in nasal airway resistance from baseline was +0.18 in NINAR (physical), +0.05 in NINAR (chemical), and -0.01 in control subjects (NS). However, a pooled linear regression by number of physical triggers (0-5) revealed a 7.5% increase in cold air-induced nasal airway resistance per trigger reported (p<0.05). Similarly, raising the criterion number of physical triggers from >or=1 to >or=2 also distinguished NINAR subjects from controls in a bivariate analysis. CONCLUSION: Either considering self-reported physical triggers as a continuous scale (0-5) or requiring more physical triggers (>or=2 rather than >or=1) to define NINAR successfully predicts objective nasal reactivity to cold air provocation.