Information on the depo sition efficiency of aerosol particles in the nasal airways is used for optimizing the delivery of therapeutic aero sols into the nose and for risk assessment of toxic airborne pollutants inhaled through the nose into the respiratory system. Nasal particle depo sition is often studied using plastic replicas of nasal airways. Deposition efficiency in a nasal replica manufactu red by stereolithography has not been reported to date. We determined the inertial particle deposition efficiency of two replicas of the same nasal airways manufactured by different stereolithograph y machines and compared results with deposition efficiencies reported for models manufactured by other techniques from the same magnetic resonance imaging scans. Deposition in the replicas was measured for particles of aerodynamic diameter between 1 and 10 JLm and constant inspiratory flow rates ranging from 20-40 Ipm. Deposition efficiency of the replica s increased from nea rly 0-100 % with increasing particle inertia. For a range of particl e inertias, particle depo sition in the replica made with a higher resolution stereolithography machine was slightl y less th an in the replica mad e with a lower resolution stereolithography process. Th ese dat a showed lower deposition efficiency when compared with other deposition studies in nasal replicas based on the same magnetic resonance ima ging data. The differences in deposition efficiency can be attributed in part to differences in methods used to manufacture the replicas. There was little or no difference in deposition du e to cutti ng tool size, some difference due to the use

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Objectives 1. Quantify mucosal cooling (i.e., heat loss) spatially in the nasal passages of nasal airway obstruction (NAO) patients before and after surgery using computational fluid dynamics (CFD). 2. Correlate mucosal cooling with patient-reported symptoms, as measured by the Nasal Obstruction Symptom Evaluation (NOSE) and a visual analog scale (VAS) for sensation of nasal airflow. Study Design Prospective Setting Academic tertiary medical center. Subjects and Methods Computed tomography (CT) scans and NOSE and VAS surveys were obtained from 10 patients before and after surgery to relieve NAO. Three-dimensional models of each patient’s nasal anatomy were used to run steady-state CFD simulations of airflow and heat transfer during inspiration. Heat loss across the nasal vestibule and the entire nasal cavity, and the surface area of mucosa exposed to heat fluxes > 50 W/m2 were compared pre- and post-operatively. Results After surgery, heat loss increased significantly on the pre-operative most obstructed side (p values < 0.0002). A larger surface area of nasal mucosa was exposed to heat fluxes > 50 W/m2 after surgery. The best correlation between patient-reported and CFD measures of nasal patency was obtained for NOSE against surface area in which heat fluxes > 50 W/m2 (Pearson r = −0.76). Conclusion A significant post-operative increase in mucosal cooling correlates well with patients’ perception of better nasal patency after NAO surgery. CFD-derived heat fluxes may prove to be a valuable predictor of success in NAO surgery.

Atrophic rhinitis is a chronic disease of the nasal mucosa. The disease is characterized by abnormally wide nasal cavities, and its main symptoms are dryness, crusting, atrophy, fetor, and a paradoxical sensation of nasal congestion. The etiology of the disease remains unknown. Here, we propose that excessive evaporation of the mucous layer is the basis for the relentless nature of this disease. Airflow and water and heat transport were simulated using computational fluid dynamics (CFD) techniques. The nasal geometry of an atrophic rhinitis patient was acquired from computed tomography scans before and after a procedure to narrow the nasal cavity. Simulations of air conditioning in the atrophic nose were compared with similar computations performed within the nasal geometries of four healthy humans. The excessively wide cavity of the patient generated abnormal flow patterns, which led to abnormal patterns of water fluxes across the wall. Geometrically, the atrophic nose had a much lower surface area than the healthy nasal passages, which increased water fluxes per unit area. Nevertheless, the simulations indicated that the atrophic nose did not condition inspired air as effectively as the healthy geometries. These simulations of water transport in the nasal cavity are consistent with the hypothesis that excessive evaporation of mucus plays a key role in the pathophysiology of atrophic rhinitis. We conclude that the main goals of a surgery to treat atrophic rhinitis should be 1) to restore the original surface area of the nose, 2) to restore the physiological airflow distribution, and 3) to create symmetric cavities.

Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t-tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning.

Formaldehyde inhalation at 6 ppm and above causes nasal squamous cell carcinoma (SCC) in F344 rats. The human health implications of this effect are of significant interest since human exposure to environmental formaldehyde is widespread, though at lower concentrations than those that cause cancer in rats. In this article, which is part of a larger effort to predict the human cancer risks of inhaled formaldehyde, we describe biologically motivated quantitative modeling of the exposure-tumor response continuum in the rat. An anatomically realistic, three-dimensional fluid dynamics model of the F344 rat nasal airways was used to predict site-specific flux of formaldehyde from inhaled air into tissue, since both SCC and preneoplastic lesions develop in a characteristic site-specific pattern. Flux into tissue was used as a dose metric for two modes of action, direct mutagenicity and cytolethality-regenerative cellular proliferation (CRCP), which in turn were linked to key parameters of a two-stage clonal growth model. The direct mutagenicity mode of action was represented by a low dose linear dose-response model of DNA-protein cross-link (DPX) formation. An empirical J-shaped dose-response model and a threshold model fit to the empirical data were used for CRCP. In the clonal growth model, the probability of mutation per cell generation was a function of the tissue concentration of DPX while the rate of cell division was calculated from the CRCP data. Maximum likelihood methods were used to estimate parameter values. Survivor (a nontumor outcome) and tumor data for controls from the National Toxicology Program database and from two formaldehyde inhalation bioassays were used for likelihood calculations. The J-shaped dose-response for CRCP provided a better description of the SCC data than did the threshold model. Sensitivity analyses indicated that the rodent tumor response is due to the CRCP mode of action, with the directly mutagenic pathway having little, if any, influence. When evaluated in light of modeling and database uncertainties, particularly the specification of the clonal growth model and the dose-response data for CRCP, this work provides suggestive though not definitive evidence for a J-shaped dose-response for formaldehyde-mediated nasal SCC in the F344 rat.

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In the model, anterior septal deviations increased nasal resistance more than posterior deviations. This suggests, in agreement with the literature, that other causes of nasal obstruction (dysfunction of the nasal valve, allergy, etc.) should be carefully considered in patients with posterior septal deviations because such deviations may not affect nasal resistance. This study illustrates how computational modeling and virtual manipulation of the nasal geometry are useful to investigate nasal physiology.