Upper airway reconstruction using long-range optical coherence tomography: Effects of airway curvature on airflow resistance.

OBJECTIVES: Adenotonsillectomy (AT) is commonly used to treat upper airway obstruction in children, but selection of patients who will benefit most from AT is challenging. The need for diagnostic evaluation tools without sedation, radiation, or high costs has motivated the development of long-range optical coherence tomography (LR-OCT), providing real-time cross-sectional airway imaging during endoscopy. Since the endoscope channel location is not tracked in conventional LR-OCT, airway curvature must be estimated and may affect predicted airway resistance. The study objective was to assess effects of three realistic airway curvatures on predicted airway resistance using computational fluid dynamics (CFD) in LR-OCT reconstructions of the upper airways of pediatric patients, before and after AT. METHODS: Eight subjects (five males, three females, aged 4-9 years) were imaged using LR-OCT before and after AT during sedated endoscopy. Three-dimensional (3D) airway reconstructions included three airway curvatures. Steady-state, inspiratory airflow simulations were conducted under laminar conditions, along with turbulent simulations for one subject using the k-ω turbulence model. Airway resistance (pressure drop/flow) was compared using two-tailed Wilcoxon signed rank tests. RESULTS: Regardless of the airway curvatures, CFD findings corroborate a surgical end-goal with computed post-operative airway resistance significantly less than pre-operative (P < 0.01). The individual resistances did not vary significantly for different airway curvatures (P > 0.25). Resistances computed using turbulent simulations differed from laminar results by less than ∼5%. CONCLUSIONS: The results suggest that reconstruction of the upper airways from LR-OCT imaging data may not need to account for airway curvature to be predictive of surgical effects on airway resistance. Lasers Surg. Med. 51:150-160, 2019. © 2018 Wiley Periodicals, Inc.

Radiologic changes in the aging nasal cavity.

BACKGROUND: With an aging population, it is important to understand age-related anatomic changes in the nasal cavity and cribriform plate (CP) that may have clinical implications. METHODOLOGY: Computed tomography (CT) scans obtained for non-rhinologic conditions were divided into a young cohort (N=35, 18-34 years old) and an older adult cohort (N=32, 80-99 years old). Intranasal airspace volumes and bony anatomy of the CP were manually segmented using OsiriX software. The CP was assessed for mean Hounsfield Units (HU) and percentage of olfactory foramina. Deformation based morphometry (DBM) was then performed on the same cohort and correlated with manual measurements. RESULTS: Individual nasal cavity volumes increased 17-75% with age. Regression analysis of all scans revealed age to be the predominant variable influencing intranasal volume differences when controlling for sex and head size. Mean HU of the CP negatively correlated with age. No age-related differences in bone stenosis of olfactory foramina were identified. Automated DBM measurements of intranasal volumes, as well as CP and zygoma mean HU correlated with manual measurements. CONCLUSION: Older subjects have a global increase in intranasal volumes and diffuse bone density loss in the CP. The clinical impact of age-related anatomic changes in the nasal cavity and CP requires further investigation.

The N-terminal domain allosterically regulates cleavage and activation of the epithelial sodium channel.

The epithelial sodium channel (ENaC) is activated upon endoproteolytic cleavage of specific segments in the extracellular domains of the α- and γ-subunits. Cleavage is accomplished by intracellular proteases prior to membrane insertion and by surface-expressed or extracellular soluble proteases once ENaC resides at the cell surface. These cleavage events are partially regulated by intracellular signaling through an unknown allosteric mechanism. Here, using a combination of computational and experimental techniques, we show that the intracellular N terminus of γ-ENaC undergoes secondary structural transitions upon interaction with phosphoinositides. From ab initio folding simulations of the N termini in the presence and absence of phosphatidylinositol 4,5-bisphosphate (PIP2), we found that PIP2 increases α-helical propensity in the N terminus of γ-ENaC. Electrophysiology and mutation experiments revealed that a highly conserved cluster of lysines in the γ-ENaC N terminus regulates accessibility of extracellular cleavage sites in γ-ENaC. We also show that conditions that decrease PIP2 or enhance ubiquitination sharply limit access of the γ-ENaC extracellular domain to proteases. Further, the efficiency of allosteric control of ENaC proteolysis is dependent on Tyr(370) in γ-ENaC. Our findings provide an allosteric mechanism for ENaC activation regulated by the N termini and sheds light on a potential general mechanism of channel and receptor activation.

Olfactory deposition of inhaled nanoparticles in humans.

CONTEXT: Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. OBJECTIVES: This article aims to (i) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (ii) compare the olfactory dose in humans with our earlier dose estimates for rats. MATERIALS AND METHODS: An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1-100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. RESULTS: In humans, olfactory dose of inhaled nanoparticles is highest for 1-2 nm particles with ∼1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. DISCUSSION AND CONCLUSION: Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans in the 1--7 nm size range due to the larger inhalation rate in humans. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles.

Effects of airway surface liquid height on the kinetics of extracellular nucleotides in airway epithelia.

Experimental techniques aimed at measuring the concentration of signaling molecules in the airway surface liquid (ASL) often require an unrealistically large ASL volume to facilitate sampling. This experimental limitation, prompted by the difficulty of pipetting liquid from a very shallow layer (~15 µm), leads to dilution and the under-prediction of physiologic concentrations of signaling molecules that are vital to the regulation of mucociliary clearance. Here, we use a computational model to describe the effect of liquid height on the kinetics of extracellular nucleotides in the airway surface liquid coating respiratory epithelia. The model consists of a reaction-diffusion equation with boundary conditions that represent the enzymatic reactions occurring on the epithelial surface. The simulations reproduce successfully the kinetics of extracellular ATP following hypotonic challenge for ASL volumes ranging from 25 µl to 500 µl in a 12-mm diameter cell culture. The model reveals that [ATP] and [ADO] reach 1200 nM and 2200 nM at the epithelial surface, respectively, while their volumetric averages remain less than 200 nM at all times in experiments with a large ASL volume (500 µl). These findings imply that activation of P2Y2 and A2B receptors is robust after hypotonic challenge, in contrast to what could be concluded based on experimental measurements of volumetric concentrations in large ASL volumes. Finally, given the central role that ATP and ADO play in regulating mucociliary clearance, we investigated which enzymes, when inhibited, provide the greatest increase in ATP and ADO concentrations. Our findings suggest that inhibition of NTPDase1/highTNAP would cause the greatest increase in [ATP] after hypotonic challenge, while inhibition of the transporter CNT3 would provide the greatest increase in [ADO].

Effects of Mucosal Decongestion on Nasal Aerodynamics: A Pilot Study.

OBJECTIVE: Mucosal decongestion with nasal sprays is a common treatment for nasal airway obstruction. However, the impact of mucosal decongestion on nasal aerodynamics and the physiological mechanism of nasal airflow sensation are incompletely understood. The objective of this study is to compare nasal airflow patterns in nasal airway obstruction (NAO) patients with and without mucosal decongestion and nondecongested healthy subjects. STUDY DESIGN: Cross-sectional study of a convenience sample. SETTING: Academic tertiary medical center. METHODS: Forty-five subjects were studied (15 nondecongested healthy subjects, 15 nondecongested NAO patients, and 15 decongested NAO patients). Three-dimensional models of the nasal anatomy were created from computed tomography scans. Steady-state simulations of airflow and heat transfer were conducted at 15 L/min inhalation rate using computational fluid dynamics. RESULTS: In the narrow side of the nose, unilateral nasal resistance was similar in decongested NAO patients and nondecongested healthy subjects, but substantially higher in nondecongested NAO patients. The vertical airflow distribution within the nasal cavity (inferior vs middle vs superior) was also similar in decongested NAO patients and nondecongested healthy subjects, but nondecongested NAO patients had substantially less middle airflow. Mucosal cooling, quantified by the surface area where heat flux exceeds 50 W/m2, was significantly higher in decongested NAO patients than in nondecongested NAO patients. CONCLUSION: This pilot study suggests that mucosal decongestion improves objective measures of nasal airflow, which is consistent with improved subjective sensation of nasal patency after decongestion.

Impact of posture and CPAP on nasal airflow.

Obstructive sleep apnea (OSA) patients who use continuous positive airway pressure (CPAP) often complain of nasal dryness and nasal obstruction as side effects of CPAP. The physiological mechanisms by which CPAP may cause nasal dryness and nasal obstruction remain poorly understood. It has been hypothesized that CPAP interferes with the nasal cycle, abolishing the resting phase of the cycle and leading to nasal dryness. We performed rhinomanometry measurements in 31 OSA patients sitting, laid supine, and supine after 10 min of CPAP at 10 cmH2O. A posture change from sitting to supine led to more symmetric airflow partitioning between the left and right nostrils in the supine position. CPAP did not have a significant impact on nasal resistance, unilateral airflows, or airflow partitioning. Our results suggest that airflow partitioning becomes more symmetric immediately after changing to a supine position, while CPAP had no effect on nasal airflow, thus preserving the nearly symmetric airflow partitioning achieved after the posture change.

Estimation of Nasal Airway Cross-sectional Area From Endoscopy Using Depth Maps: A Proof-of-Concept Study.

OBJECTIVE: Endoscopy is routinely used to diagnose obstructive airway diseases. Currently, endoscopy is only a visualization technique and does not allow quantification of airspace cross-sectional areas (CSAs). This pilot study tested the hypothesis that CSAs can be accurately estimated from depth maps created from virtual endoscopy videos. STUDY DESIGN: Cross-sectional. SETTING: Academic tertiary medical center. METHODS: Virtual endoscopy and depth map videos of the nasal cavity were digitally created based on anatomically accurate three-dimensional (3D) models built from computed tomography scans of 30 subjects. A software tool was developed to outline the airway perimeter and estimate the airspace CSA from the depth maps. Two otolaryngologists used the software tool to estimate the nasopharynx CSA and the nasal valve minimal CSA (mCSA) in the left and right nasal cavities. Model validation statistics were performed. RESULTS: Nasopharynx CSA had a median percent error of 3.7% to 4.6% when compared to the true values measured in the 3D models. Nasal valve mCSA had a median percent error of 22.7% to 33.6% relative to the true values. Raters successfully used the software tool to identify subjects with nasal valve stenosis (ie, mCSA < 0.20 cm2) with a sensitivity of 83.3%, specificity ≥ 90.7%, and classification accuracy ≥ 90.0%. Interrater and intrarater agreements were high. CONCLUSION: This study demonstrates that airway CSAs in 3D models can be accurately estimated from depth maps. The development of artificial intelligence algorithms to compute depth maps may soon allow the quantification of airspace CSAs from clinical endoscopies.

Inhaled fosamprenavir for laryngopharyngeal reflux: Toxicology and fluid dynamics modeling.

Objectives: Approximately 25% of Americans suffer from laryngopharyngeal reflux (LPR), a disease for which no effective medical therapy exists. Pepsin is a predominant source of damage during LPR and a key therapeutic target. Fosamprenavir (FOS) inhibits pepsin and prevents damage in an LPR mouse model. Inhaled FOS protects at a lower dose than oral; however, the safety of inhaled FOS is unknown and there are no inhalers for laryngopharyngeal delivery. A pre-Good Lab Practice (GLP) study of inhaled FOS was performed to assess safety and computational fluid dynamics (CFD) modeling used to predict the optimal particle size for a laryngopharyngeal dry powder inhaler (DPI). Methods: Aerosolized FOS, amprenavir (APR), or air (control) were provided 5 days/week for 4 weeks (n = 6) in an LPR mouse model. Organs (nasal cavity, larynx, esophagus, trachea, lung, liver, heart, and kidney) were assessed by a pathologist and bronchoalveolar lavage cytokines and plasma cardiotoxicity markers were assessed by Luminex assay. CFD simulations were conducted in a model of a healthy 49-year-old female. Results: No significant increase was observed in histologic lesions, cytokines, or cardiotoxicity markers in FOS or APR groups relative to the control. CFD predicted that laryngopharyngeal deposition was maximized with aerodynamic diameters of 8.1-11.5 µm for inhalation rates of 30-60 L/min. Conclusions: A 4-week pre-GLP study supports the safety of inhaled FOS. A formal GLP assessment is underway to support a phase I clinical trial of an FOS DPI for LPR. Level of Evidence: NA.

Biophysical model of ion transport across human respiratory epithelia allows quantification of ion permeabilities.

Lung health and normal mucus clearance depend on adequate hydration of airway surfaces. Because transepithelial osmotic gradients drive water flows, sufficient hydration of the airway surface liquid depends on a balance between ion secretion and absorption by respiratory epithelia. In vitro experiments using cultures of primary human nasal epithelia and human bronchial epithelia have established many of the biophysical processes involved in airway surface liquid homeostasis. Most experimental studies, however, have focused on the apical membrane, despite the fact that ion transport across respiratory epithelia involves both cellular and paracellular pathways. In fact, the ion permeabilities of the basolateral membrane and paracellular pathway remain largely unknown. Here we use a biophysical model for water and ion transport to quantify ion permeabilities of all pathways (apical, basolateral, paracellular) in human nasal epithelia cultures using experimental (Ussing Chamber and microelectrode) data reported in the literature. We derive analytical formulas for the steady-state short-circuit current and membrane potential, which are for polarized epithelia the equivalent of the Goldman-Hodgkin-Katz equation for single isolated cells. These relations allow parameter estimation to be performed efficiently. By providing a method to quantify all the ion permeabilities of respiratory epithelia, the model may aid us in understanding the physiology that regulates normal airway surface hydration.

A mechanochemical model for auto-regulation of lung airway surface layer volume.

We develop a proof-of-principle model for auto-regulation of water volume in the lung airway surface layer (ASL) by coupling biochemical kinetics, transient ASL volume, and homeostatic mechanical stresses. The model is based on the hypothesis that ASL volume is sensed through soluble mediators and phasic stresses generated by beating cilia and air drag forces. Model parameters are fit based on the available data on human bronchial epithelial cell cultures. Simulations then demonstrate that homeostatic volume regulation is a natural consequence of the processes described. The model maintains ASL volume within a physiological range that modulates with phasic stress frequency and amplitude. Next, we show that the model successfully reproduces the responses of cell cultures to significant isotonic and hypotonic challenges, and to hypertonic saline, an effective therapy for mucus hydration in cystic fibrosis patients. These results compel an advanced airway hydration model with therapeutic value that will necessitate detailed kinetics of multiple molecular pathways, feedback to ASL viscoelasticity properties, and stress signaling from the ASL to the cilia and epithelial cells.

A workflow for viewing biomedical computational fluid dynamics results and corresponding data within virtual and augmented reality environments.

Researchers conducting computational fluid dynamics (CFD) modeling can spend weeks obtaining imaging data, determining boundary conditions, running simulations and post-processing files. However, results are typically viewed on a 2D display and often at one point in time thus reducing the dynamic and inherently three-dimensional data to a static image. Results from different pathologic states or cases are rarely compared in real-time, and supplementary data are seldom included. Therefore, only a fraction of CFD results are typically studied in detail, and associations between mechanical stimuli and biological response may be overlooked. Virtual and augmented reality facilitate stereoscopic viewing that may foster extraction of more information from CFD results by taking advantage of improved depth cues, as well as custom content development and interactivity, all within an immersive approach. Our objective was to develop a straightforward, semi-automated workflow for enhanced viewing of CFD results and associated data in an immersive virtual environment (IVE). The workflow supports common CFD software and has been successfully completed by novice users in about an hour, demonstrating its ease of use. Moreover, its utility is demonstrated across clinical research areas and IVE platforms spanning a range of cost and development considerations. We are optimistic that this advancement, which decreases and simplifies the steps to facilitate more widespread use of immersive CFD viewing, will foster more efficient collaboration between engineers and clinicians. Initial clinical feedback is presented, and instructional videos, manuals, templates and sample data are provided online to facilitate adoption by the community.

Quantifying strategies to minimize aerosol dispersion in dental clinics.

Many dental procedures are aerosol-generating and pose a risk for the spread of airborne diseases, including COVID-19. Several aerosol mitigation strategies are available to reduce aerosol dispersion in dental clinics, such as increasing room ventilation and using extra-oral suction devices and high-efficiency particulate air (HEPA) filtration units. However, many questions remain unanswered, including what the optimal device flow rate is and how long after a patient exits the room it is safe to start treatment of the next patient. This study used computational fluid dynamics (CFD) to quantify the effectiveness of room ventilation, an HEPA filtration unit, and two extra-oral suction devices to reduce aerosols in a dental clinic. Aerosol concentration was quantified as the particulate matter under 10 µm (PM10) using the particle size distribution generated during dental drilling. The simulations considered a 15 min procedure followed by a 30 min resting period. The efficiency of aerosol mitigation strategies was quantified by the scrubbing time, defined as the amount of time required to remove 95% of the aerosol released during the dental procedure. When no aerosol mitigation strategy was applied, PM10 reached 30 µg/m3 after 15 min of dental drilling, and then declined gradually to 0.2 µg/m3 at the end of the resting period. The scrubbing time decreased from 20 to 5 min when the room ventilation increased from 6.3 to 18 air changes per hour (ACH), and decreased from 10 to 1 min when the flow rate of the HEPA filtration unit increased from 8 to 20 ACH. The CFD simulations also predicted that the extra-oral suction devices would capture 100% of the particles emanating from the patient's mouth for device flow rates above 400 L/min. In summary, this study demonstrates that aerosol mitigation strategies can effectively reduce aerosol concentrations in dental clinics, which is expected to reduce the risk of spreading COVID-19 and other airborne diseases.

Mandibular advancement reduces pharyngeal collapsibility by enlarging the airway rather than affecting velopharyngeal compliance.

Mandibular advancement devices (MADs) are frequently prescribed for obstructive sleep apnea (OSA) patients, but approximately one third of patients experience no therapeutic benefit. Understanding the mechanisms by which MADs prevent pharyngeal collapse may help optimize MAD therapy. This study quantified the relative contributions of changes in airspace cross-sectional area (CSA) versus changes in velopharyngeal compliance in determining MAD efficacy. Sixteen patients with moderate to severe OSA (mean apnea-hypopnea index of 32 ± 15 events/h) underwent measurements of the velopharyngeal closing pressure (PCLOSE ) during drug induced sedated endoscopy (DISE) via stepwise reductions in nasal mask pressure and recording of the intraluminal pressure with a catheter. Airspace CSA was estimated from video endoscopy. Pharyngeal compliance was defined as the slope of the area-pressure relationship of the velopharyngeal airspace. MAD therapy reduced PCLOSE from a median of 0.5 cmH2 O pre-advancement to a median of -2.6 cmH2 O post-advancement (p = 0.0009), increased the minimal CSA at the velopharynx by approximately 20 mm2 (p = 0.0067), but did not have a statistically significant effect on velopharyngeal compliance (p = 0.23). PCLOSE had a strong correlation with CSA but did not correlate with velopharyngeal compliance. Our results suggest that MADs reduce velopharyngeal collapsibility by increasing airway size as opposed to affecting velopharyngeal compliance. This contradicts the speculation of previous literature that the effectiveness of MADs is partially due to a reduction in velopharyngeal compliance resulting from stretching of the soft palate. These findings suggest that quantification of velopharyngeal CSA pre- and post-MAD advancement has potential as a biomarker to predict the success of MAD therapy.

Anatomical determinants of upper airway collapsibility in obstructive sleep apnea: A systematic review and meta-analysis.

Upper airway (UA) collapsibility is one of the key factors that determine the severity of obstructive sleep apnea (OSA). Interventions for OSA are aimed at reducing UA collapsibility, but selecting the optimal alternative intervention for patients who fail CPAP is challenging because currently no validated method predicts how anatomical changes affect UA collapsibility. The gold standard objective measure of UA collapsibility is the pharyngeal critical pressure (Pcrit). A systematic literature review and meta-analysis were performed to identify the anatomical factors with the strongest correlation with Pcrit. A search using the PRISMA methodology was performed on PubMed for English language scientific papers that correlated Pcrit to anatomic variables and OSA severity as measured by the apnea-hypopnea index (AHI). A total of 29 papers that matched eligibility criteria were included in the quantitative synthesis. The meta-analysis suggested that AHI has only a moderate correlation with Pcrit (estimated Pearson correlation coefficient r = 0.46). The meta-analysis identified four key anatomical variables associated with UA collapsibility, namely hyoid position (r = 0.53), tongue volume (r = 0.51), pharyngeal length (r = 0.50), and waist circumference (r = 0.49). In the future, biomechanical models that quantify the relative importance of these anatomical factors in determining UA collapsibility may help identify the optimal intervention for each patient. Many anatomical and structural factors such as airspace cross-sectional areas, epiglottic collapse, and palatal prolapse have inadequate data and require further research.

Computational model for the regulation of extracellular ATP and adenosine in airway epithelia.

Extracellular nucleotides are key components of the signaling network regulating airway clearance. They are released by the epithelium into the airway surface liquid (ASL) to stimulate cilia beating activity, mucus secretion and airway hydration. Understanding the factors affecting their availability for purinoceptor activation is an important step toward the development of new therapies for obstructive lung diseases. This chapter presents a mathematical model developed to gain predictive insights into the regulation of ASL nucleotide concentrations on human airway epithelia. The parameters were estimated from experimental data collected on polarized primary cultures of human nasal and bronchial epithelial cells. This model reproduces major experimental observations: (1) the independence of steady-state nucleotide concentrations on ASL height, (2) the impact of selective ectonucleotidase inhibitors on their steady-state ASL concentrations, (3) the changes in ASL composition caused by mechanical stress mimicking normal breathing, (4) and the differences in steady-state concentrations existing between nasal and bronchial epithelia. In addition, this model launched the study of nucleotide release into uncharted territories, which led to the discovery that airway epithelia release, not only ATP, but also ADP and AMP. This study shows that computational modeling, coupled to experimental validation, provides a powerful approach for the identification of key therapeutic targets for the improvement of airway clearance in obstructive respiratory diseases.

Toward automatic atlas-based surgical planning for septoplasty.

PURPOSE: Surgery for nasal airway obstruction (NAO) has a high failure rate, with up to 50% of patients reporting persistent symptoms postoperatively. Virtual surgery planning has the potential to improve surgical outcomes, but current manual methods are too labor-intensive to be adopted on a large scale. This manuscript introduces an automatic atlas-based approach for performing virtual septoplasties. METHODS: A cohort of 47 healthy subjects and 26 NAO patients was investigated. An atlas of healthy nasal geometry was constructed. The automatic virtual septoplasty method consists of a multi-stage registration approach to fit the atlas to a target NAO patient, automatically segment the patient's septum and airway, and deform the patient image to have a non-deviated septum. RESULTS: Our automatic virtual septoplasty method straightened the septum successfully in 18 out of 26 NAO patients (69% of cases). In these cases, the ratio of the higher to the lower airspace cross-sectional areas in the left and right nasal cavities improved from 1.47 ± 0.45 to 1.16 ± 0.33 in the region surrounding the septal deviation, showing that the nasal airway became more symmetric after virtual septoplasty. CONCLUSION: This automated virtual septoplasty technique has the potential to greatly reduce the effort required to perform computational fluid dynamics (CFD) analysis of nasal airflow for NAO surgical planning. Future studies are needed to investigate if virtual surgery planning using this method is predictive of subjective symptoms in NAO patients after septoplasty.

Effects of Surface Smoothness on Inertial Particle Deposition in Human Nasal Models.

Computational fluid dynamics (CFD) predictions of inertial particle deposition have not compared well with data from nasal replicas due to effects of surface texture and the resolution of tomographic images. To study effects of geometric differences between CFD models and nasal replicas, nasal CFD models with different levels of surface smoothness were reconstructed from the same MRI data used to construct the nasal replica used by Kelly et al. (2004) [Aerosol Sci. Technol. 38:1063-1071]. One CFD model in particular was reconstructed without any surface smoothing to preserve the detailed topology present in the nasal replica. Steady-state inspiratory airflow and Lagrangian particle tracking were simulated using Fluent software. Particle deposition estimates from the smoother models under-predicted nasal deposition from replica casts, which was consistent with previous findings. These discrepancies were overcome by including surface artifacts that were not present in the reduced models and by plotting deposition efficiency versus the Stokes number, where the characteristic diameter was defined in terms of the pressure-flow relationship to account for changes in airflow resistance due to wall roughness. These results indicate that even slight geometric differences have significant effects on nasal deposition and that this information should be taken into account when comparing particle deposition data from CFD models with experimental data from nasal replica casts.

Narrowed Posterior Nasal Airway Limits Efficacy of Anterior Septoplasty.

Background: Predicting symptomatic relief after septoplasty has been difficult. Minimal cross-sectional area (mCSA) measured by acoustic rhinometry and airflow resistance (R) measured by rhinomanometry have been used to select surgical candidates with mixed success. An important assumption is that mCSA and resistance are tightly coupled, but studies have reported weak or no correlation. Recently, we proposed the Bernoulli Obstruction Theory as an explanation, where tight coupling between mCSA and R is only predicted below a critical mCSA (Acrit). Methods: The nasal airway and septum of 10 healthy subjects were reconstructed from computed tomography scans. Simulated anterior septal deviations of increasing severity were created. Computational fluid dynamics simulations were performed to quantify mCSA, resistance, and flow in the healthy septum model and four simulated septal deviation models for each subject (total of 50 models). Results: A tighter coupling between mCSA and resistance was found below Acrit, estimated to be 0.20 cm2 (a very severe deviation). Above Acrit, enlarging the mCSA had a smaller effect in patients with narrower cross-sectional area in the postvalve region (CSAPV). Conclusions: Two patterns of flow increase are expected with septoplasty. Below Acrit, enlarging mCSA predictably increases flow. Above Acrit, the effect size of increasing mCSA depends on CSAPV. Unrecognized small CSAPV may explain persistent sensation of nasal obstruction after septoplasty. Our data suggest that inferior turbinate reduction ipsilateral to a septal deviation may amplify airflow benefits after septoplasty in patients with a narrow CSAPV.

Rhinomanometry Versus Computational Fluid Dynamics: Correlated, but Different Techniques.

BACKGROUND: Past studies reported a low correlation between rhinomanometry and computational fluid dynamics (CFD), but the source of the discrepancy was unclear. Low correlation or lack of correlation has also been reported between subjective and objective measures of nasal patency. OBJECTIVE: This study investigates (1) the correlation and agreement between nasal resistance derived from CFD (RCFD) and rhinomanometry (RRMN), and (2) the correlation between objective and subjective measures of nasal patency. METHODS: Twenty-five patients with nasal obstruction underwent anterior rhinomanometry before and after mucosal decongestion with oxymetazoline. Subjective nasal patency was assessed with a 0-10 visual analog scale (VAS). CFD simulations were performed based on computed tomography scans obtained after mucosal decongestion. To validate the CFD methods, nasal resistance was measured in vitro (REXPERIMENT) by performing pressure-flow experiments in anatomically accurate plastic nasal replicas from 6 individuals. RESULTS: Mucosal decongestion was associated with a reduction in bilateral nasal resistance (0.34 ± 0.23 Pa.s/ml to 0.19 ± 0.24 Pa.s/ml, p = 0.003) and improved sensation of nasal airflow (bilateral VAS decreased from 5.2 ± 1.9 to 2.6 ± 1.9, p < 0.001). A statistically significant correlation was found between VAS in the most obstructed cavity and unilateral airflow before and after mucosal decongestion (r = -0.42, p = 0.003). Excellent correlation was found between RCFD and REXPERIMENT (r = 0.96, p < 0.001) with good agreement between the numerical and in vitro values (RCFD/REXPERIMENT = 0.93 ± 0.08). A weak correlation was found between RCFD and RRMN (r = 0.41, p = 0.003) with CFD underpredicting nasal resistance derived from rhinomanometry (RCFD/RRMN = 0.65 ± 0.63). A stronger correlation was found when unilateral airflow at a pressure drop of 75 Pa was used to compare CFD with rhinomanometry (r = 0.76, p < 0.001). CONCLUSION: CFD and rhinomanometry are moderately correlated, but CFD underpredicts nasal resistance measured in vivo due in part to the assumption of rigid nasal walls. Our results confirm previous reports that subjective nasal patency correlates better with unilateral than with bilateral measurements and in the context of an intervention.