Mucolytic treatment of chronic rhinosinusitis in a murine model of primary ciliary dyskinesia.

Background: Genetic defects in motile cilia cause primary ciliary dyskinesia (PCD), a rare disease with no specific therapeutics. Individuals with PCD often have impaired fertility and laterality defects and universally suffer from upper and lower airway diseases. Chronic rhinosinusitis is a universal feature of PCD, and mucus accumulation and subsequent infections of the sinonasal cavity cause significant morbidity in individuals with PCD. Despite this, there are no approved treatments that specifically target mucus. Objective: The goals of this study were to determine whether computed tomography (CT) imaging could be used to quantify mucus accumulation and whether the use of a mucolytic agent to reduce disulfide cross-links present in mucins would improve the effectiveness of nasal lavage at removing mucus in a murine model of PCD. Methods: Adult mice with a deletion of the axonemal dynein Dnaic1 were imaged using CT scanning to characterize mucus accumulation. The animals were then treated by nasal lavage with saline, with/without the disulfide-reducing agent tris(2-carboxyethyl)phosphine. Post-treatment CT scans were used to quantify improvement in the sinonasal cavity. Results: Mucus accumulation in the nasal cavity was readily quantified by CT. Compared to sham-treated control animals, nasal lavage with/without a mucolytic agent resulted in a significant reduction of accumulated mucus (p < 0.01). Treatment with the mucolytic agent showed a greater reduction of accumulated mucus than treatment with saline alone. Conclusion: The results suggest that inclusion of a mucolytic agent may increase the effectiveness of nasal lavage at reducing mucus burden in PCD.

Updating the biologically based dose-response model for the nasal carcinogenicity of inhaled formaldehyde in the F344 rat.

Chronic inhalation of formaldehyde by F344 rats causes nasal squamous cell carcinoma (SCC). This outcome is well-characterized: including dose-response and time course data for SCC, mechanistic endpoints, and nasal dosimetry. Conolly et al. (Toxicol. Sci. 75, 432-447, 2003) used these resources to develop a biologically based dose-response (BBDR) model for SCC in F344 rats. This model, scaled up to humans, has informed dose-response conclusions reached by several international regulatory agencies. However, USEPA concluded that uncertainties precluded its use for cancer risk assessment. Here, we describe an updated BBDR model that addresses uncertainties through refined dosimetry modeling, revised analysis of labeling index data, and an extended dataset where both inhaled (exogenous) and endogenous formaldehyde (exogF, endoF) form DNA adducts. Further, since Conolly et al. (ibid) was published, it has become clear that, when controls from all F344 inhalation bioassays are considered, accounting for over 4000 rats, at most one nasal SCC occurred. This low spontaneous incidence constrains possible contribution of endoF to the formation of nasal SCC via DNA reactivity. Further, since both exogF and endoF form DNA adducts, this constraint also applies to exogF. The revised BBDR model therefore drives SCC formation through the cytotoxicity of high concentration exogF. An option for direct mutagenicity associated with DNA adducts is retained to allow estimation of an upper bound on adduct mutagenicity consistent with the lack of a spontaneous SCC incidence. These updates represent an iterative refinement of the 2003 model, incorporating new data and insights to reduce identified model uncertainties.

Relative contributions of endogenous and exogenous formaldehyde to formation of deoxyguanosine monoadducts and DNA-protein crosslink adducts of DNA in rat nasal mucosa.

Understanding the dose-response for formaldehyde-induced nasal cancer in rats is complicated by (1) the uneven distribution of inhaled formaldehyde across the interior surface of the nasal cavity and, (2) the presence of endogenous formaldehyde (endoF) in the nasal mucosa. In this work, we used computational fluid dynamics (CFD) modeling to predict flux of inhaled (exogenous) formaldehyde (exogF) from air into tissue at the specific locations where DNA adducts were measured. Experimental work has identified DNA-protein crosslink (DPX) adducts due to exogF and deoxyguanosine (DG) adducts due to both exogF and endoF. These adducts can be considered biomarkers of exposure for effects of endoF and exogF on DNA that may be part of the mechanism of tumor formation. We describe a computational model linking CFD-predicted flux of formaldehyde from air into tissue, and the intracellular production of endoF, with the formation of DPX and DG adducts. We assumed that, like exogF, endoF can produce DPX. The model accurately reproduces exogDPX, exogDG, and endoDG data after inhalation from 0.7 to 15 ppm. The dose-dependent concentrations of exogDPX and exogDG are predicted to exceed the concentrations of their endogenous counterparts at about 2 and 6 ppm exogF, respectively. At all concentrations examined, the concentrations of endoDPX and exogDPX were predicted to be at least 10-fold higher than that of their DG counterparts. The modeled dose-dependent concentrations of these adducts are suitable to be used together with data on the dose-dependence of cell proliferation to conduct quantitative modeling of formaldehyde-induced rat nasal carcinogenicity.

Anatomic Optical Coherence Tomography (aOCT) for Evaluation of the Internal Nasal Valve.

OBJECTIVES/HYPOTHESIS: To establish the utility of anatomic optical coherence tomography (aOCT) in evaluating internal nasal valve (INV). STUDY DESIGN: Anatomic specimen imaging study. METHODS: Fresh-harvested human specimen heads were evaluated using both computed tomography (CT) imaging as well as using aOCT. Scans were performed at three time points: 1) After septoplasty for cartilage harvest, 2) after placement of butterfly graft (BFG), and 3) after placement of bilateral spreader grafts (SG). Imaging data were then converted into 3D models of the nasal airway. CT- and aOCT-generated models were compared by both static volumetric analysis and computational fluid dynamics (CFD) to predict nasal resistance and pressure. RESULTS: Scans using aOCT showed comparable results to CT in terms of volumetric parameters both before and after intervention. Analysis of aOCT data by CFD demonstrated decrease in pressure after SG or BFG intervention. No statistically significant difference was observed when comparing CT- and aOCT-generated calculations of pressure or resistance. CONCLUSION: The INV can be imaged in a static fashion using aOCT technology. Advantages over traditional CT imaging include lack of exposure to radiation and rapid scan time. In addition, in-office use is possible as aOCT technology develops. Further investigation will be necessary to define the role of aOCT in the dynamic evaluation of this vital component of the nasal airway. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2148-2156, 2022.

Lung inflammation and simulated airway resistance in infants with cystic fibrosis.

Cystic fibrosis (CF) is characterized by small airway disease; but central airways may also be affected. We hypothesized that airway resistance estimated from computational fluid dynamic (CFD) methodology in infants with CF was higher than controls and that early airway inflammation in infants with CF is associated with airway resistance. Central airway models with a median of 51 bronchial outlets per model (interquartile range 46,56) were created from chest computed tomography scans of 18 infants with CF and 7 controls. Steady state airflow into the trachea was simulated to estimate central airway resistance in each model. Airway resistance was increased in the full airway models of infants with CF versus controls and in models trimmed to 33 bronchi. Airway resistance was associated with markers of inflammation in bronchoalveolar lavage fluid obtained approximately 8 months earlier but not with markers obtained at the same time. In conclusion, airway resistance estimated by CFD modeling is increased in infants with CF compared to controls and may be related to early airway inflammation.

Radiologic Analysis of Balloon Sinuplasty in a Human Cadaver Model: Observed Effects on Sinonasal Anatomy.

BACKGROUND: Balloon sinuplasty is increasingly used in the outpatient clinic for treatment of chronic rhinosinusitis, but radiologic analysis of its effects on sinonasal anatomy is largely uncharacterized in the known literature. OBJECTIVE: The purpose of this study is to examine the anatomic effects of balloon sinuplasty in a cadaveric model. METHODS: Five fresh cadaver heads underwent sequential endoscopic balloon dilation of maxillary ostia, frontal recess outflow tracts, and sphenoid ostia bilaterally by fellowship-trained rhinologists. Pre- and post-procedural CT imaging was obtained. CT scans were imported into Mimics™ software and sinonasal anatomy was analyzed systematically. RESULTS: Visual confirmation of balloon dilation was achieved in all 3 sites bilaterally in each cadaver. Radiologic analysis demonstrated that the frontal sinus outflow tract was appropriately dilated 60% (6/10 sites) of the time while the agger was inadvertently dilated 30% of the time (3/10). The sphenoid os was successfully dilated 70% (7/10 sites) of the time. In two cases, a posterior sphenoethmoid (Onodi) cell was dilated instead of the sphenoid. Successful dilation of maxillary os was noted 60% of the time (6/10 sites). No significant change in maxillary os was noted after balloon dilation. Normal middle turbinates were significantly medialized following balloon dilation 75% (6/8 sites) of the time. CONCLUSIONS: While the goal of balloon sinuplasty is to improve natural sinonasal drainage by dilating existing outflow tracts, as evidenced by radiologic evaluation the procedure appears not to achieve this in all cases, while occasionally creating unintended changes in sinonasal anatomy as well. These unrecognized changes in anatomy may be responsible for the post-procedure change in symptomatology that some patients experience.

Numerical evaluation of spray position for improved nasal drug delivery.

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.

Nasal Airflow Changes With Bioabsorbable Implant, Butterfly, and Spreader Grafts.

OBJECTIVES/HYPOTHESIS: Internal nasal valve compromise is a major cause of nasal obstruction, with a growing number of ways to treat this condition. In this study, we compared the effects of butterfly graft, spreader graft, and the bioabsorbable nasal implant on nasal airflow resistance. STUDY DESIGN: Cadaver study. METHODS: Computational fluid dynamics (CFD) simulations were completed from nine preoperative and postoperative cadaveric subjects. Each cadaveric head underwent placement of a bioabsorbable nasal implant (BNI) (Spirox Latera; Stryker ENT, Plymouth, MN), butterfly graft, or spreader graft. Pre- and postoperative computed tomography (CT) scans were used to generate three-dimensional models of the nasal airway used in steady-state CFD simulations of airflow and heat transfer during inspiration. RESULTS: Butterfly graft placement resulted in a mean improvement in nasal airway resistance of 24.9% (±7.3), whereas BNI placement resulted in a 6.7% (±1.2) improvement, and spreader graft placement also resulted in a consistent improvement of 2.6% (±13.5). Pressure within the main nasal cavity was consistently lower following butterfly graft placement versus a spreader graft or BNI. Butterfly and spreader graft placement also resulted in modest improvements in airflow allocation, whereas BNI demonstrated more variation (-1% to 12%). Heat flux was not significantly different; however, a small improvement in total heat flux was seen with all three interventions. CONCLUSIONS: The results of this study demonstrate reduction in nasal airway resistance in all three surgical interventions, with the butterfly graft demonstrating superiority to the other two techniques. However, these data only reflect a static environment and not dynamic changes in airflow seen during respiration. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E817-E823, 2020.

Virtual septoplasty: a method to predict surgical outcomes for patients with nasal airway obstruction.

PURPOSE: A deviated nasal septum is the most common etiology for nasal airway obstruction (NAO), and septoplasty is the most common surgical procedure performed by ear-nose-throat surgeons in adults. However, quantitative criteria are rarely adopted to select patients for surgery, which may explain why up to 50% of patients report persistent or recurrent symptoms of nasal obstruction postoperatively. This study reports a systematic virtual surgery method to identify patients who may benefit from septoplasty. METHODS: One patient with symptoms of NAO due to a septal deviation was selected to illustrate the virtual surgery concept. Virtual septoplasty was implemented in three steps: (1) determining if septal geometry is abnormal preoperatively, (2) virtually correcting the deviation while preserving the anatomical shape of the septum, and (3) estimating the post-surgical improvement in airflow using computational fluid dynamics. Anatomical and functional changes predicted by the virtual surgery method were compared to a standard septoplasty performed independently from the computational analysis. RESULTS: A benchmark healthy nasal septum geometry was obtained by averaging the septum dimensions of 47 healthy individuals. A comparison of the nasal septum geometry in the NAO patient with the benchmark geometry identified the precise locations where septal deviation and thickness exceeded the healthy range. Good agreement was found between the virtual surgery predictions and the actual surgical outcomes for both airspace minimal cross-sectional area (0.05 cm2 pre-surgery, 0.54 cm2 virtual surgery, 0.50 cm2 actual surgery) and nasal resistance (0.91 Pa.s/ml pre-surgery, 0.08 Pa.s/ml virtual surgery, 0.08 Pa.s/ml actual surgery). CONCLUSIONS: Previous virtual surgery methods for NAO were based on manual edits and subjective criteria. The virtual septoplasty method proposed in this study is objective and has the potential to be fully automated. Future implementation of this method in virtual surgery planning software has the potential to improve septoplasty outcomes.

Intranasal Corticosteroids: Patient Administration Angles and Impact of Education.

INTRODUCTION: Intranasal corticosteroids sprays (INCS) are first line treatment for allergic rhinitis and are frequently used for chronic rhinosinusitis. Improperly aiming INCS increases the risk of epistaxis and may decrease the efficacy of the medication. The goal of this study was to determine how patients position INCS for drug delivery and if verbal or written instructions improve their positioning. METHODS: Patients in rhinology clinics were photographed while administering a generic spray bottle. The angle of the spray bottle relative to the patients' head and a fixed background was determined. RESULTS: A total of 46 participants were included. The average spray angle for the right naris was 10.1° towards the septum and 67.2° below the Frankfurt Horizontal plane. The average spray angle for the left naris was 4.5° towards the septum and 62.2° below the Frankfurt horizontal plane. The angle of the spray bottle ranged from 50° toward the septum to 43° away from the septum. Only 8 patients aimed away from the septum for both nares. Patients who recalled receiving verbal and written instructions aimed the INCS bottle at the lateral wall and inferior turbinate in contrast to patients who only received one form of instruction or no instructions. CONCLUSIONS: Most patients (83%) incorrectly aim INCS when compared to current guidelines. There was statistically significant improvement in the positioning of patients who reported receiving both verbal and written instruction; however, this study highlights a greater need for patient education.

Normative ranges of nasal airflow variables in healthy adults.

PURPOSE: Virtual surgery planning based on computational fluid dynamics (CFD) simulations of nasal airflow has the potential to improve surgical outcomes for patients with nasal airway obstruction (NAO). Virtual surgery planning requires normative ranges of airflow variables, but few studies to date have quantified inter-individual variability of nasal airflow among healthy subjects. This study reports CFD simulations of nasal airflow in 47 healthy adults. METHODS: Anatomically accurate three-dimensional nasal models were reconstructed from cone beam computed tomography scans and used for steady-state inspiratory airflow simulations with a bilateral flowrate of 250 ml/s. Normal subjective sensation of nasal patency was confirmed using the nasal obstruction symptom evaluation and visual analog scale. Healthy ranges for several CFD variables known to correlate with subjective nasal patency were computed, including unilateral airflow, nasal resistance, airspace minimal cross-sectional area (mCSA), heat flux (HF), and surface area stimulated by mucosal cooling (defined as the area where HF > 50 W/m2). The normative ranges were targeted to contain 95% of the healthy population and computed using a nonparametric method based on order statistics. RESULTS: A wide range of inter-individual variability in nasal airflow was observed among healthy subjects. Unilateral airflow varied from 60 to 191 ml/s, airflow partitioning ranged from 23.8 to 76.2%, and unilateral mCSA varied from 0.24 to 1.21 cm2. These ranges are in good agreement with rhinomanometry and acoustic rhinometry data from the literature. A key innovation of this study are the normative ranges of flow variables associated with mucosal cooling, which recent research suggests is the primary physiological mechanism of nasal airflow sensation. Unilateral HF ranged from 94 to 281 W/m2, while the surface area stimulated by cooling ranged from 27.4 to 64.3 cm2. CONCLUSIONS: These normative ranges may serve as targets in future virtual surgery planning for patients with NAO.

Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients.

BACKGROUND: Topical intranasal drugs are widely prescribed for chronic rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). METHODS: Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of 3 subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-µm to 120-µm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-µm to 30-µm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. RESULTS: Among nebulized droplet sizes, 11-µm to 14-µm droplets achieved at least 50% of MSDF in all 6 sinonasal cavities. Four of 6 sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. CONCLUSION: Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement.

Impact of endoscopic craniofacial resection on simulated nasal airflow and heat transport.

BACKGROUND: Endoscopic craniofacial resections (CFR) are performed for extensive anterior skull base lesions. This surgery involves removal of multiple intranasal structures, potentially leading to empty nose syndrome (ENS). However, many patients remain asymptomatic postoperatively. Our objective was to analyze the impact of CFR on nasal physiology and airflow using computational fluid dynamics (CFD). This is the first CFD analysis of post-CFR patients. METHODS: Three-dimensional sinonasal models were constructed from 3 postoperative images using MimicsTM . Hybrid computational meshes were created. Steady inspiratory airflow and heat transport were simulated at patient-specific flow rates using shear stress transport k-omega turbulent flow modeling in FluentTM . Simulated average heat flux (HF) and surface area where HF exceeded 50 W/m2 (SAHF50) were compared with laminar simulations in 9 radiographically normal adults. RESULTS: Three adults underwent CFR without developing ENS. Average HF (W/m2 ) were 132.70, 134.84, and 142.60 in the CFR group, ranging from 156.24 to 234.95 in the nonoperative cohort. SAHF50 (m2 ) values were 0.0087, 0.0120, and 0.0110 in the CFR group, ranging from 0.0082 to 0.0114 in the radiographically normal cohort. SAHF50 was distributed throughout the CFR cavities, with increased HF at the roof and walls compared with the nonoperative cohort. CONCLUSION: Average HF was low in the CFR group compared with the nonoperative group. However, absence of ENS in most CFR patients may be due to large stimulated mucosal surface area, commensurate with the nonoperative cohort. Diffuse distribution of stimulated area may result from turbulent mixing after CFR. To better understand heat transport post-CFR, a larger cohort is necessary.

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.

Geometric Validation of Continuous, Finely Sampled 3-D Reconstructions From aOCT and CT in Upper Airway Models.

Identification and treatment of obstructive airway disorders (OADs) are greatly aided by imaging of the geometry of the airway lumen. Anatomical optical coherence tomography (aOCT) is a promising high-speed and minimally invasive endoscopic imaging modality for providing micrometer-resolution scans of the upper airway. Resistance to airflow in OADs is directly caused by the reduction in luminal cross-sectional area (CSA). It is hypothesized that aOCT can produce airway CSA measurements as accurate as that from computed tomography (CT). Scans of machine hollowed cylindrical tubes were used to develop methods for segmentation and measurement of airway lumen in CT and aOCT. Simulated scans of virtual cones were used to validate 3-D resampling and reconstruction methods in aOCT. Then, measurements of two segments of a 3-D printed pediatric airway phantom from aOCT and CT independently were compared to ground truth CSA. In continuous unobstructed regions, the mean CSA difference for each phantom segment was 2.2 ± 3.5 and 1.5 ± 5.3 mm2 for aOCT, and -3.4 ± 4.3 and -1.9 ± 1.2 mm2 for CT. Because of the similar magnitude of these differences, these results support the hypotheses and underscore the potential for aOCT as a viable alternative to CT in airway imaging, while offering greater potential to capture respiratory dynamics.

A hierarchical stepwise approach to evaluate nasal patency after virtual surgery for nasal airway obstruction.

BACKGROUND: Despite advances in medicine and expenditures associated in treatment of nasal airway obstruction, 25-50% of patients undergoing nasal surgeries complain of persistent obstructive symptoms. Our objective is to develop a "stepwise virtual surgery" method that optimizes surgical outcomes for treatment of nasal airway obstruction. METHODS: Pre-surgery radiographic images of two subjects with nasal airway obstruction were imported into Mimics imaging software package for three-dimension reconstruction of the airway. A hierarchical stepwise approach was used to create seven virtual surgery nasal models comprising individual (inferior turbinectomy or septoplasty) procedures and combined inferior turbinectomy and septoplasty procedures via digital modifications of each subject's pre-surgery nasal model. To evaluate the effects of these procedures on nasal patency, computational fluid dynamics modeling was used to perform steady-state laminar inspiratory airflow and heat transfer simulations in every model, at resting breathing. Airflow-related variables were calculated for virtual surgery models and compared with dataset containing results of healthy subjects with no symptoms of nasal obstruction. FINDINGS: For Subject 1, nasal models with virtual septoplasty only and virtual septoplasty plus inferior turbinectomy on less obstructed side were within the healthy reference thresholds on both sides of the nasal cavity and across all three computed variables. For Subject 2, virtual septoplasty plus inferior turbinectomy on less obstructed side model produced the best result. INTERPRETATION: The hierarchical stepwise approach implemented in this preliminary report demonstrates computational fluid dynamics modeling ability to evaluate the efficiency of different surgical procedures for nasal obstruction in restoring nasal patency to normative level.

An Interactive, Patient-Specific Virtual Surgical Planning System for Upper Airway Obstruction Treatments.

Upper airway obstructions leading todifficulty breathing are significant problems that often require surgery to improve patient quality of life. However, these surgeries often have poor outcomes with little symptom improvement. This paper outlines the design of an interactive, patient-specific virtual surgical planning system that uses patient CT scans to generate three-dimensional representations of the airways and incorporates computational fluid dynamics (CFD) as a part of the surgical planning process. Individualized virtual surgeries can be performed by editing these models, which are then analyzed using CFD to compare pre- and post- surgery flow characteristics to assess patient symptom improvement. The prototype system shows significant promise by being intuitive, interactive, with a potential fast flow solver that provides near real-time feedback to the clinician.

Relationship between degree of obstruction and airflow limitation in subglottic stenosis.

OBJECTIVES: Subglottic stenosis (SGS) is one of the most common airway disorders in pediatric patients. Currently, treatment decisions rely primarily on the Cotton-Myer scale, which classifies SGS severity based on percentage reduction in airspace cross-sectional area (CSA). However, the precise relationship between upper airway resistance and subglottic CSA is unknown. We hypothesize that airway resistance can be described by the Bernoulli Obstruction Theory, which predicts that airway resistance is inversely proportional to airspace CSA ( R∝A-1) in cases of severe constriction. METHODS: Computed tomography (CT) scans of six healthy subjects and five SGS patients were used to create three-dimensional models of the respiratory tract from nostrils to carina. Cylindrical segments of varying lengths and varying diameters were digitally inserted in the subglottis of the healthy subjects to create simulated SGS models. Computational fluid dynamics simulations were run, and airway resistance was computed in the simulated SGS models and actual SGS models. RESULTS: Constriction diameter had a greater impact in airway resistance than constriction length. In agreement with the Bernoulli Obstruction Theory, airway resistance in the simulated SGS models was well represented by the power law R=aAb, where a is a constant and the exponent b ranged from -0.85 to -1.07. The percentage reduction in airflow (QOBSTRUCTIONQHEALTHY) at a constant pressure drop was found to be directly proportional to the percentage reduction in CSA (AOBSTRUCTIONAHEALTHY) in the limit of severe constrictions, namely QOBSTRUCTIONQHEALTHY=kAOBSTRUCTIONAHEALTHY, where k=2.25 ± 0.15. Airway resistances in the simulated SGS models were similar to resistances in models based on CT scans of actual SGS patients, suggesting that our simulated SGS models were representative of airway resistance in actual SGS patients. CONCLUSION: Our computer simulations suggest that the degree of airflow limitation in SGS patients may be estimated based on anatomic measurements alone. Future studies are recommended to test these predictions in larger cohorts. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1551-1557, 2018.

On computational fluid dynamics models for sinonasal drug transport: Relevance of nozzle subtraction and nasal vestibular dilation.

Generating anatomically realistic 3-dimensional (3D) models of the human sinonasal cavity for numerical investigations of sprayed drug transport presents a host of methodological ambiguities. For example, subject-specific radiographic images used for 3D reconstructions typically exclude spray bottles. Subtracting a bottle contour from the 3D airspace and dilating the anterior nasal vestibule for nozzle placement augment the complexity of model building. So we explored the question: how essential are these steps to adequately simulate nasal airflow and identify the optimal delivery conditions for intranasal sprays? In particular, we focused on particle deposition patterns in the maxillary sinus, a critical target site for chronic rhinosinusitis. The models were reconstructed from postsurgery computed tomography scans for a 39-year-old Caucasian male, with chronic rhinosinusitis history. Inspiratory airflow patterns during resting breathing are reliably tracked through computational fluid dynamics-based steady-state laminar-viscous modeling, and such regimes portray relative lack of sensitivity to inlet perturbations. Consequently, we hypothesized that the posterior airflow transport and the particle deposition trends should not be radically affected by the nozzle subtraction and vestibular dilation. The study involved 1 base model and 2 derived models; the latter 2 with nozzle contours (2 different orientations) subtracted from the dilated anterior segment of the left vestibule. We analyzed spray transport in the left maxillary sinus for multiple release conditions. Similar release points, localized on an approximately 2 mm × 4.5 mm contour, facilitated improved maxillary deposition in all 3 test cases. This suggests functional redundancy of nozzle insertion in a 3D numerical model for identifying the optimal spray release locations.

Ideal Particle Sizes for Inhaled Steroids Targeting Vocal Granulomas: Preliminary Study Using Computational Fluid Dynamics.

Objectives Vocal fold granulomas are benign lesions of the larynx commonly caused by gastroesophageal reflux, intubation, and phonotrauma. Current medical therapy includes inhaled corticosteroids to target inflammation that leads to granuloma formation. Particle sizes of commonly prescribed inhalers range over 1 to 4 µm. The study objective was to use computational fluid dynamics to investigate deposition patterns over a range of particle sizes of inhaled corticosteroids targeting the larynx and vocal fold granulomas. Study Design Retrospective, case-specific computational study. Setting Tertiary academic center. Subjects/Methods A 3-dimensional anatomically realistic computational model of a normal adult airway from mouth to trachea was constructed from 3 computed tomography scans. Virtual granulomas of varying sizes and positions along the vocal fold were incorporated into the base model. Assuming steady-state, inspiratory, turbulent airflow at 30 L/min, computational fluid dynamics was used to simulate respiratory transport and deposition of inhaled corticosteroid particles ranging over 1 to 20 µm. Results Laryngeal deposition in the base model peaked for particle sizes 8 to 10 µm (2.8%-3.5%). Ideal sizes ranged over 6 to 10, 7 to 13, and 7 to 14 µm for small, medium, and large granuloma sizes, respectively. Glottic deposition was maximal at 10.8% for 9-µm-sized particles for the large posterior granuloma, 3 times the normal model (3.5%). Conclusion As the virtual granuloma size increased and the location became more posterior, glottic deposition and ideal particle size generally increased. This preliminary study suggests that inhalers with larger particle sizes, such as fluticasone propionate dry-powder inhaler, may improve laryngeal drug deposition. Most commercially available inhalers have smaller particles than suggested here.