Parameter characteristics in intranasal drug delivery: A key to targeting medications to the olfactory airspace.

BACKGROUND: The nose is a viable pathway for topical drug delivery to the olfactory cleft for treatment of obstructive smell loss and nose-to-brain drug delivery. This study investigates how variations in nasal vestibule morphology influence intranasal spray drug transport to the olfactory cleft and olfactory roof/bulb regions. METHODS: The unilateral nasal vestibule morphology in three healthy subjects with healthy normal nasal anatomy was classified as Elongated (Subject DN001), Notched (Subject DN002), and Standard (Subject DN003). Computational fluid and particle dynamics modelling were used to simulate nasal airflow and drug particle transport to the olfactory cleft and olfactory roof/bulb regions in each subject-specific nasal cavity. To evaluate highest drug depositions in these regions, the particle transport simulations involved extensive parameter combination analyses: 6 inspiratory flow rates mimicking resting to sniffing (10-50 L/min); 5 spray release locations (Top, Bottom, Central, Lateral, and Medial); 5 head positions (Upright, Tilted Forward, Tilted Back, Supine, and Mygind); 3 particle velocities (1, 5, and 10 m/s); 350,000 µm-particles (1-100 µm) and 346,500 nanoparticles (10-990 nm). FINDINGS: Particle size groups with highest depositions in olfactory cleft: DN001 left = 28.4% at 11-20 µm, right = 75.3% at 6-10 µm; DN002 left = 16.8% at 1-5 µm, right = 45.3% at 30-40 nm; DN003 left = 29.1% at 21-30 µm, right = 15.9% at 6-10 µm. Highest depositions in olfactory roof/bulb: DN001 left = 6.5% at 11-20 µm, right = 26.4% at 11-20 µm; DN002 left = 3.6% at 1-5 µm, right = 2.6% at 1-5 µm; DN003 left = 2.8% at 21-30 µm, right = 1.7% at 31-40 µm. INTERPRETATION: DN001 (Elongated nasal vestibule) had the most deposition in the olfactory regions. Micron-particles size groups generally had better deposition in the olfactory regions.

Nasal airway obstruction in patients with cleft lip nasal deformity: A systematic review.

BACKGROUND: Cleft lip nasal deformity (CLND)-associated nasal airway obstruction (CL-NAO) may be inadequately characterized, with its functional implications subsequently underappreciated and neglected. The purpose of this systematic review is to (1) summarize the available assessment results in CL-NAO, (2) evaluate the reliability of current assessment tools, and (3) identify ongoing gaps and inconsistencies for future study. METHODS: A systematic search of the MEDLINE, EMBASE, and Scopus databases was performed for articles studying CL-NAO. Articles focusing on noncleft populations or surgical techniques were excluded. Extracted data included information about study design, patient demographics, medical history, and assessment scores. RESULTS: Twenty-six articles met criteria for inclusion. Assessments included patient-reported outcome measures (PROMs), anatomic characterizations of CLND, and nasal airflow and resistance studies. Objective assessments were generally more reliable than subjective assessments in CLND. Unilateral CLND was better represented in the literature than bilateral CLND. For unilateral CLND, the cleft side was more obstructed than the noncleft side, with stereotyped patterns of anterior nasal deformity but varied middle and posterior deformity patterns. Overall, there was considerable heterogeneity in study design regarding stratification of CLND cohorts by age, cleft phenotype and laterality, and surgical history. CONCLUSIONS: A wide range of subjective and objective assessment tools were used to characterize CL-NAO, including PROMs, anatomic measurements, and airflow and resistance metrics. Overall, objective assessments of CL-NAO were more reliable than subjective surveys, which may have resulted from variable expectations regarding nasal patency in the CLND population combined with large heterogeneity in study design.

Finding the Potholes in Academic Career Pathways for Underrepresented Groups in Otolaryngology.

OBJECTIVE: To assess inequities in representation among ranks and odds of promotion by race in academic otolaryngology. STUDY DESIGN: Cross-sectional study. SETTING: US academic medical centers. METHODS: Demographic data was collected for medical students, residents, and faculty in the Association of American Medical Colleges and Accreditation Council for Graduate Medical Education databases for the academic year 2020 to 2021. The rank equity index (REI) was used to make pairwise comparisons between ranks to determine groups' representation between levels. Odds ratios (ORs) and 95% confidence intervals (CIs) demonstrating the likelihood that an individual of a particular rank/race would advance in their academic career were determined. RESULTS: Representation comparing medical students with full professors for black, Latine, and Asian otolaryngologists was below parity (REI: 0.27, 0.85, 0.85, respectively). Black (OR: 0.20, CI: 0.15, 0.26), Latine (OR: 0.61, CI: 0.50, 0.75), and Asian (OR: 0.62, CI: 0.55, 0.71) medical students all faced lower odds of becoming otolaryngology residents compared to their white counterparts. Similar findings occurred when comparing resident and assistant professor representation. American Indian/Alaskan Native (AIAN) and Native Hawaiian/Pacific Islander (NHPI) REIs and ORs could not be assessed as only 1 self-reported AIAN and no NHPI faculty are present in the studied data. CONCLUSION: Underrepresented in Medicine and Asian physicians faced worsening representation at each rung of the academic otolaryngology ladder. The greatest losses occurred when medical students transitioned to residents and residents transitioned to assistant professors. AIAN and NH faculty were absent in otolaryngology, indicating vital targets for recruitment efforts.

Limitations in Faculty Advancement for Underrepresented Groups in Academic Otolaryngology.

OBJECTIVE: Despite the increasing racial diversity of the United States, representation in academic medicine faculty does not reach concordance with the general population and worsens with higher rank. Few studies have examined this within academic Otolaryngology and surgical subspecialties. This project aims to compare rank equity in academic Otolaryngology on self-reported gender and race/ethnicity between the years 2000 and 2020. METHODS: Publicly available data were obtained from the Association of American Medical Colleges under the "Data & Reports" section for the years 2000 and 2020. The report comprised of full-time faculty from all U.S. medical schools. To determine parity between faculty ranks across gender and race/ethnicity, rank equity index (REI) was calculated for associate/assistant, professor/associate, and professor/assistant professor comparisons. RESULTS: The percentage of women faculty in Otolaryngology has increased from 21% in 2000 to 37% in 2020; however, they did not achieve parity at all rank comparisons for both years. On the contrary, men were above parity at all rank comparisons. Improvements in rank equity occurred for Black/African American (Black) and Hispanic Latino/Spanish Origin (Latine) faculty between the years 2000 and 2020; however, when accounting for gender, benefits were concentrated among men. CONCLUSION: Advancement along the academic ladder is limited for women of all racial groups in academic Otolaryngology. While improved rank equity was seen for Black and Latine faculty, these improvements were largely among men. Future directions should aim to identify barriers to recruitment, retention, and promotion for women and underrepresented in medicine (URiM) academic otolaryngologists and create interventions that diversify Otolaryngology faculty at all ranks. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1625-1632, 2024.

Insights into exercise-induced rhinitis based on nasal aerodynamics induced by airway morphology.

BACKGROUND: Exercise-induced rhinitis (EIR) is a poorly understood phenomenon that may be related to increased inspiratory airflow. Characterization of the development of EIR is important to understand contributing factors. OBJECTIVE: To characterize how different nasal morphologies respond to airflow-related variables during rapid/deep inspiratory conditions. METHODS: Subject-specific nasal airways were reconstructed from radiographic images. Unilateral airways were classified as Standard, Notched, or Elongated accord to their distinct nasal vestibule morphology. Computational fluid dynamics simulations were performed at various airflow rates. RESULTS: For all simulated flow rates, average resistance at the nasal vestibule, airflow velocity and wall sheer stress were highest in Notched. Average mucosal heat flux was highest in Standard. Notched phenotypes showed lower mean percent increases from 10 L/min to 50 L/min in all computed variables. CONCLUSION: Resistance values and airflow velocities depicted a more constricted nasal vestibule in the Notched phenotypes, while perception of nasal mucosal cooling (heat flux) favored the Standard phenotypes. Different nasal phenotypes may predispose to EIR.

Olfactory drug delivery with intranasal sprays after nasal midvault reconstruction.

Conductive olfaction and nose to brain drug delivery are important processes that remain limited by inadequate odorant or drug delivery to the olfactory airspace. Primary challenges include anatomic barriers and poor targeting to the olfactory region. This study uses computational fluid dynamics to investigate the effects of nasal midvault surgery on olfactory drug delivery with intranasal sprays. Soft tissue elevation, spreader flaps, and spreader grafts were performed on two fresh cadaveric specimens, using computed tomography for airway reconstruction. Nasal airflow and drug particle transport simulations were performed under these conditions: inhalation rate (15, 30 L/min), spray velocity (1, 5, 10 m/s), spray location (top, bottom, center, medial, lateral), head position (upright, supine, forward, backward), and particle size (1-100 µm). Simulation results were used to calculate drug particle deposition to the olfactory airspaces and bulbs. Total olfactory deposition was < 5% but attained a maximum of 36.33% when sorted by particle size. There was no association between nasal midvault surgery and olfactory deposition. No single parameter or technique demonstrated superior olfactory deposition, but smaller particle size, slower spray velocity, and higher inhalation rate tended to optimize olfactory deposition, providing important implications for future intranasal spray and drug design to target the olfactory airspace.

A computational analysis on the impact of multilevel laryngotracheal stenosis on airflow and drug particle dynamics in the upper airway.

Laryngotracheal stenosis (LTS) is a type of airway narrowing that is frequently caused by intubation-related trauma. LTS can occur at one or multiple locations in the larynx and/or trachea. This study characterizes airflow dynamics and drug delivery in patients with multilevel stenosis. Two subjects with multilevel stenosis (S1 = glottis + trachea, S2 = glottis + subglottis) and one normal subject were retrospectively selected. Computed tomography scans were used to create subject-specific upper airway models. Computational fluid dynamics modeling was used to simulate airflow at inhalation pressures of 10, 25, and 40 Pa, and orally inhaled drug transport with particle velocities of 1, 5, and 10 m/s, and particle size range of 100 nm-40 µm. Subjects had increased airflow velocity and resistance at stenosis with decreased cross-sectional area (CSA): S1 had the smallest CSA at trachea (0.23 cm2) and resistance = 0.3 Pa·s/mL; S2 had the smallest CSA at glottis (0.44 cm2), and resistance = 0.16 Pa·s/mL. S1 maximal stenotic deposition was 4.15% at trachea; S2 maximal deposition was 2.28% at glottis. Particles of 11-20 µm had the greatest deposition, 13.25% (S1-trachea) and 7.81% (S2-subglottis). Results showed differences in airway resistance and drug delivery between subjects with LTS. Less than 4.2% of orally inhaled particles deposited at stenosis. Particle sizes with most stenotic deposition were 11-20 µm and may not represent typical particle sizes emitted by current-use inhalers.

Gender Differences in Nasal Anatomy and Function Among Caucasians.

Background: Anatomical variations influence nasal physiology, yet sex differences in physiology remains unclear. Objective: To investigate sex differences among Caucasians using computational fluid dynamics. Methods: Adult subjects were selected with normal nasal cone beam computed tomography (CBCT) images and Nasal Obstruction Symptom Evaluation scores ≤30. The CBCT images were used to create subject-specific airway models. Nasal surface area (SA) and volume were computed, and airflow and heat transfer were simulated. Results: The CBCT scans were taken from 23 females and 12 males. The SA and volume (males: mean = 25.0 cm3; females: mean = 19.5 cm3; p < 0.001; Cohen's d = 1.51) were significantly larger for males, but SA-to-volume ratio did not differ significantly. Although unilateral nasal resistance did not vary greatly, females had higher bilateral resistance (males: mean = 0.04 Pa.s/mL; females: mean = 0.05 Pa.s/mL; p = 0.044; Cohen's d = 0.37). Females had higher heat flux (males: mean = 158.5 W/m2; females: mean = 191.8 W/m2; p = 0.012; Cohen's d = 0.79), but males had larger SA where mucosal heat flux exceeds 50 W/m2. Conclusions: These findings suggest differences in normal nasal anatomy and physiology between Caucasian males and females, which may be useful when assessing sex-specific functional outcomes after nasal surgery.

Comparison of Inhaled Drug Delivery in Patients With One- and Two-level Laryngotracheal Stenosis.

OBJECTIVES/HYPOTHESIS: Laryngotracheal stenosis (LTS) is a functionally devastating condition with high respiratory morbidity and mortality. This preliminary study investigates airflow dynamics and stenotic drug delivery in patients with one- and two-level LTS. STUDY DESIGN: A Computational Modeling Restropective Cohort Study. METHODS: Computed tomography scans from seven LTS patients, five with one-level (three subglottic, two tracheal), and two with two-level (glottis + trachea, glottis + subglottis) were used to reconstruct patient-specific three-dimensional upper airway models. Airflow and orally inhaled drug particle transport were simulated using computational fluid dynamics modeling. Drug particle transport was simulated for 1-20 µm particles released into the mouth at velocities of 0 m/s, 1 m/s, 3 m/s, and 10 m/s for metered dose inhaler (MDI) and 0 m/s for dry powder inhaler (DPI) simulations. Airflow resistance and stenotic drug deposition in the patients' airway models were compared. RESULTS: Overall, there was increased airflow resistance at stenotic sites in subjects with two-level versus one-level stenosis (0.136 Pa s/ml vs. 0.069 Pa s/ml averages). Subjects with two-level stenosis had greater particle deposition at sites of stenosis compared to subjects with one-level stenosis (average deposition 2.31% vs. 0.96%). One-level stenosis subjects, as well as one two-level stenosis subject, had the greatest deposition using MDI with a spacer (0 m/s): 2.59% and 4.34%, respectively. The second two-level stenosis subject had the greatest deposition using DPI (3.45%). Maximum deposition across all stenotic subtypes except one-level tracheal stenosis was achieved with particle sizes of 6-10 µm. CONCLUSIONS: Our results suggest that patients with two-level LTS may experience a more constricted laryngotracheal airflow profile compared to patients with one-level LTS, which may enhance overall stenotic drug deposition. LEVEL OF EVIDENCE: NA Laryngoscope, 133:366-374, 2023.

Opioid and non-opioid analgesic prescribing practices for pediatric adenotonsillectomy in a tertiary care center.

IMPORTANCE: The U.S. is in an opioid epidemic with greater than 40,000 deaths annually. Pediatric adenotonsillectomy is one of the most common and painful otolaryngology surgeries performed, often associated with opioid prescriptions. OBJECTIVE: To understand postoperative prescribing practices of adenotonsillectomy in a tertiary care institution and associated postoperative emergency department (ED) visits. DESIGN: Descriptive analysis of retrospective cohort data. SETTING: Tertiary academic healthcare institution. PARTICIPANTS: Pediatric patients <18yo undergoing adenotonsillectomy between 2013 and 2016. INTERVENTIONS/EXPOSURES: Postoperative analgesic regimens assessed including opioid and non-opioid analgesic prescriptions upon discharge from tonsillectomy surgery. MAIN OUTCOMES AND MEASURES: Main outcomes included ED presentation within 30-days of surgery and reoperation. Secondary outcomes included reason for ED presentation and relation to prescribed analgesics. Data was analyzed between November 2021-February 2022. RESULTS: 200 patients were included in the study with 69% prescribed opioids, and 51% prescribed non-opioid analgesics. Number of opioid doses ranged widely with a median of 37 (Q1, Q3: 0, 62). There were no demographic differences in patients prescribed opioids from those who were not. Of those patients who presented to the ED, 81% were not specifically prescribed acetaminophen (p < 0.001). Regression analysis models were not predictive of postoperative analgesic regimen or 30-day ED presentation (p > 0.05) CONCLUSIONS: Wide ranges of post tonsillectomy prescribing practices currently exist in our institution. Prescribing acetaminophen may help to reduce 30-day ED presentation rate. Larger prospective studies are needed to optimize pain control regimens and reduce variability of opioid prescribing practices. Standardization of postoperative pain medication doses may also reduce postoperative ED presentations.

Analyses on the influence of normal nasal morphological variations on odorant transport to the olfactory cleft.

OBJECTIVE: Olfaction requires a combination of sensorineural components and conductive components, but conductive mechanisms have not typically received much attention. This study investigates the role of normal nasal vestibule morphological variations in ten healthy subjects on odorant flux in the olfactory cleft. MATERIALS AND METHODS: Computed tomography images were used to create subject-specific nasal models. Each subject's unilateral nasal cavity was classified according to its nasal vestibule shape as Standard or Notched. Inspiratory airflow simulations were performed at 15 L/min, simulating resting inspiration using computational fluid dynamics modeling. Odorant transport simulations for three odorants (limonene, 2,4-dinitrotoluene, and acetaldehyde) were then performed at concentrations of 200 ppm for limonene and acetaldehyde, and 0.2 ppm for dinitrotoluene. Olfactory cleft odorant flux was computed for each simulation. RESULTS AND DISCUSSION AND CONCLUSION: Simulated results showed airflow in the olfactory cleft was greater in the Standard phenotype compared to the Notched phenotype. For Standard, median airflow was greatest in the anterior region (0.5006 L/min) and lowest in the posterior region (0.1009 L/min). Median airflow in Notched was greatest in the medial region (0.3267 L/min) and lowest in the posterior region (0.0756 L/min). Median olfactory odorant flux for acetaldehyde and limonene was greater in Standard (Acetaldehyde: Standard = 140.45 pg/cm2-s; Notched = 122.20 pg/cm2-s. Limonene: Standard = 0.67 pg/cm2-s; Notched = 0.65 pg/cm2-s). Median dinitrotoluene flux was greater in Notched (Standard = 2.86 × 10-4pg/cm2-s; Notched = 4.29 × 10-4 pg/cm2-s). The impact of nasal vestibule morphological variations on odorant flux at the olfactory cleft may have implications on individual differences in olfaction, which should be investigated further.

A systematic analysis of surgical interventions for the airway in the mature unilateral cleft lip nasal deformity: a single case study.

PURPOSE: Individuals with unilateral cleft lip nasal deformity (uCLND) often require rhinoplasty in adolescence to correct nasal obstruction. The intent of this study is to identify sites of greatest nasal obstruction and evaluate the effects of isolated and combinations of simulated surgical procedures on these sites using computational fluid dynamics (CFD). METHODS: Computed tomography imaging of an adolescent subject with uCLND was converted to an anatomically accurate three-dimensional nasal airway model. Initial analysis was performed to identify anatomic sites of obstruction based on CFD computed resistance values. Virtual surgery procedures corresponding to common uCLND surgical interventions were simulated. Resulting airspace models were then analyzed after conducting airflow and heat transfer simulations. RESULTS: The preoperative model had 21 obstructed sites with a nasal resistance of 0.075 Pa s/mL. Following simulated surgical procedures with functional interventions alone and in combinations, the three virtual surgery models with most improved nasal airflow were inferior turbinate reduction (ITR) with posterior septoplasty (resistance = 0.054 Pa s/ml, reduction in 14 of 21 obstructed sites), ITR with anterior septoplasty (resistance = 0.058 Pa s/ml, reduction in 8 of 21 obstructed sites), and ITR with both anterior and posterior septoplasty (resistance = 0.052 Pa s/ml, reduction in 17 of 21 obstructed sites). CONCLUSION: This study introduces a new technique for analysis of the impact of different simulated surgical interventions on uCLND-induced nasal obstruction. In this subject, simulated septoplasty with ITR on the non-cleft side provided maximal relief of nasal obstruction. The proposed technique can be further studied for possible utility in analyzing potential surgical interventions for optimal relief of nasal obstruction in patients with uCLND.

Analysis of nasal air conditioning in subjects with unilateral cleft lip nasal deformity.

This study evaluated the impact of unilateral cleft lip nasal deformity (uCLND) on the ability of the nasal passages to warm and humidify inspired environmental air using computational fluid dynamics (CFD) modeling. Nasal air conditioning was simulated at resting inspiration in ten individuals with uCLND and seven individuals with normal anatomy. The overall heat and water transfer through nasal mucosa was significantly greater (p = 0.02 for both heat and moisture fluxes) on the non-cleft side than on the cleft side. Unilateral median and interquartile range (IQR) for heat flux (W/m2) was 190.3 (IQR 59.9) on the non-cleft side, 160.9 (IQR 105.0) on the cleft side, and 170.7 (IQR 87.8) for normal subjects. For moisture flux (mg/(s·m2), they were 357.4 (IQR 112.9), 298.7 (IQR 200.3) and 320.8 (IQR 173.0), respectively. Significant differences of SAHF50 between cleft side of uCLND and normal existed except for anterior region. Nevertheless, air conditioning ability in subjects with uCLND was generally comparable to that of normal subjects.

Role of nasal vestibule morphological variations on olfactory airflow dynamics.

BACKGROUND: The conductive mechanisms of olfaction are typically given little priority in the evaluation of olfactory function. The objective of this study is to investigate the role of nasal vestibule morphological variations on airflow volume at the olfactory recess in healthy subjects. METHODS: Anatomically realistic three-dimensional nasal airway models were constructed from computed tomography scans in five subjects. Each individual's unilateral nasal cavity (10 total) was classified according to the shape of their nasal vestibule: Standard, Notched, or Elongated. Nasal airflow simulations were performed using computational fluid dynamics modeling at two inspiratory flow rates (15 L/min and 30 L/min) to reflect resting and moderate breathing rates. Olfactory airflow volume and cross-sectional flow resistance were computed. FINDINGS: Average olfactory airflow volumes (and percent airflow in olfactory) were: 0.25 L/min to 0.64 L/min (3.0%-7.7%; 15 L/min simulations) and 0.53 L/min to 1.30 L/min (3.2%-7.8%; 30 L/min simulations) for Standard; 0.13 L/min - 0.47 L/min (2.0%-6.8%; 15 L/min simulations) and 0.06 L/min - 0.82 L/min (1.7%-6.1%; 30 L/min simulations) for Notched; and 0.07 L/min - 0.39 L/min (1.2%-5.4%; 15 L/min simulations) and 0.30 L/min - 0.99 L/min (2.1%-6.7%; 30 L/min simulations) for Elongated. On average, relative difference in olfactory resistance between left and right sides was 141.5% for patients with different unilateral phenotypes and 82.2% for patients with identical unilateral phenotype. INTERPRETATION: Olfactory cleft airflow volume was highest in the Standard nasal vestibule phenotype, followed by Notched phenotype for 15 L/min simulations and Elongated phenotype for 30 L/min simulations. Further, intra-patient variation in olfactory cleft airflow resistance differs greatly for patients with different unilateral phenotypes compared to patients with identical unilateral phenotype.

Computational Analysis of Olfactory Airspace in Patients With Unilateral Cleft Lip Nasal Deformity.

OBJECTIVES: To evaluate the magnitude of olfactory recess opacity in patients with unilateral cleft lip nasal deformity (uCLND). DESIGN: Subject-specific 3-dimensional reconstruction of the nasal airway anatomy was created from computed tomography images in 11 (4 males and 7 females) subjects with uCLND and 7 (3 males, and 4 females) normal subjects. The volume and surface area of each subject's unilateral and bilateral olfactory airspace was quantified to assess the impact of opacification. Qualitatively speaking, patients with 75% to 100% olfactory recess opacification were classified as extreme, 50% to 75% as severe, 25% to 50% as moderate, and 0% to 25% as mild. RESULTS: Of the 11 subjects with uCLND, 5 (45%) were classified as having extreme olfactory recess opacification, 3 (27%) subjects had severe opacification, and 3 (27%) subjects had moderate opacification. Mean (±SD) bilateral olfactory recess volume was significantly greater in normal subjects than in subjects with uCLND (0.9668 cm3 ± 0.4061 cm3 vs 0.3426 cm3 ± 0.1316 cm3; P < .001). Furthermore, unilateral olfactory airspace volumes for the cleft and non-cleft sides in subjects with uCLND were considerably less than unilateral olfactory volume in subjects with normal anatomy (uCLND cleft side = 0.1623 cm3 ± 0.0933 cm3; uCLND non-cleft side = 0.1803 cm3 ± 0.0938 cm3; normal = 0.4834 cm3 ± 0.2328 cm3; P < .001). CONCLUSIONS: Our findings indicate a high prevalence of olfactory recess opacification among subjects with uCLND when compared to subjects with normal anatomy. The majority of subjects with uCLND had extreme olfactory recess opacity, which will likely influence their sense of smell.

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.

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.

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.

Computational Analysis of the Mature Unilateral Cleft Lip Nasal Deformity on Nasal Patency.

BACKGROUND: Nasal airway obstruction (NAO) due to nasal anatomic deformities is known to be more common among cleft patients than the general population, yet information is lacking regarding severity and variability of cleft-associated nasal obstruction relative to other conditions causing NAO. This preliminary study compares differences in NAO experienced by unilateral cleft lip nasal deformity (uCLND) subjects with noncleft subjects experiencing NAO. METHODS: Computational modeling techniques based on patient-specific computed tomography images were used to quantify the nasal airway anatomy and airflow dynamics in 21 subjects: 5 healthy normal subjects; 8 noncleft NAO subjects; and 8 uCLND subjects. Outcomes reported include Nasal Obstruction Symptom Evaluation (NOSE) scores, cross-sectional area, and nasal resistance. RESULTS: uCLND subjects had significantly larger cross-sectional area differences between the left and right nasal cavities at multiple cross sections compared with normal and NAO subjects. Median and interquartile range (IQR) NOSE scores between NAO and uCLND were 75 (IQR = 22.5) and 67.5 (IQR = 30), respectively. Airflow partition difference between both cavities were: median = 9.4%, IQR = 10.9% (normal); median = 31.9%, IQR = 25.0% (NAO); and median = 29.9%, IQR = 44.1% (uCLND). Median nasal resistance difference between left and right nasal cavities were 0.01 pa.s/ml (IQR = 0.03 pa.s/ml) for normal, 0.09 pa.s/ml (IQR = 0.16 pa.s/ml) for NAO and 0.08 pa.s/ml (IQR = 0.25 pa.s/ml) for uCLND subjects. CONCLUSIONS: uCLND subjects demonstrated significant asymmetry between both sides of the nasal cavity. Furthermore, there exists substantial disproportionality in flow partition difference and resistance difference between cleft and noncleft sides among uCLND subjects, suggesting that both sides may be dysfunctional.

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.