Intranasal Spray Characteristics for Best Drug Delivery in Patients With Chronic Rhinosinusitis.

OBJECTIVES: To determine parameter combinations for effective drug delivery of intranasal spray steroids to the ostiomeatal complex (OMC) and maxillary sinus (MS) in patients with chronic rhinosinusitis (CRS). METHODS: Each patient's sinonasal cavity was reconstructed from computed tomography scans. Intranasal airflow and drug particle transport were simulated using computational fluid dynamic modeling. Airflow simulations were performed at 15 Pascal inhalation pressure. Intranasal spray particles of 1-100 µm were simulated at release speeds of 1, 5, and 10 m/s from 6 release locations (Bottom, Center, Top, Lateral, Lateral-Bottom, and Lateral-Top) at a nozzle insertion depth of 15 mm. Drug delivery simulations were performed in the head tilted forward position. RESULTS: Maximal OMC deposition was 0.78%-12.44%, while maximal MS deposition was 0.02%-1.03% across all simulations. In general, particles between 6 and 10 µm had the best OMC (at 1 m/s particle velocity) and MS (at 10 m/s particle velocity) deposition. Particles ranging from 21 to 30 µm also had superior OMC deposition. The lateral and lateral-top spray release locations produced maximum OMC deposition, but no one release location demonstrated an increase in MS deposition. CONCLUSION: This preliminary study suggests that it is challenging to determine a common set of intranasal spray parameter combinations for effective drug delivery to the OMC and MSs. Although drug particle size and spray particle velocity seem to impact particle deposition patterns, spray release location appears to vary with anatomical differences between subjects, particularly when the MS is the target location for particle deposition. Laryngoscope, 133:1036-1043, 2023.

Characterizing Olfactory Dysfunction in Patients with Unilateral Cleft Lip Nasal Deformities.

Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.

The role of normal nasal morphological variations from race and gender differences on respiratory physiology.

This study identifies anatomical and airflow-induced relationships based on nasal morphological variations due to inter- and intra-racial differences and gender. Subject-specific nasal airway reconstruction was created from computed tomography images in 16 subjects: 4 subjects from each ethnic group (Black, East Asian, Caucasian, and Latino) comprising of 2 males and 2 females. Volume, surface area and nasal index were calculated, as well as airflow rate and nasal resistance after computational fluid dynamics simulations in the nasal airway. Results showed that nasal airspace surface area (p = 0.0499) and volume (p = 0.0281) were significantly greater in males than in females. Nasal volume was greatest in East Asians (Median = 20.38cm3, Interquartile Range [IQR] = 4.58 cm3), Latinos had the greatest surface area (Median = 219.70cm2, IQR = 29.56cm2). On average, East Asian and Black females had larger nasal index than their male counterparts. Caucasians had the highest median nasal resistance (0.050 Pa.s/mL, IQR = 0.025 Pa.s/mL). Results indicate that there exist anatomical variabilities based on race and gender. However, these variabilities may not significantly influence nasal function.

Orally Inhaled Drug Particle Transport in Computerized Models of Laryngotracheal Stenosis.

OBJECTIVE: Adjuvant management for laryngotracheal stenosis (LTS) may involve inhaled corticosteroids, but metered dose inhalers are designed for pulmonary drug delivery. Comprehensive analyses of drug particle deposition efficiency for orally inhaled corticosteroids in the stenosis of LTS subjects are lacking. STUDY DESIGN: Descriptive research. SETTING: Academic medical center. METHODS: Anatomically realistic 3-dimensional reconstructions of the upper airway were created from computed tomography images of 4 LTS subjects-2 subglottic stenosis and 2 tracheal stenosis subjects. Computational fluid dynamics modeling was used to simulate airflow and drug particle transport in each airway. Three inhalation pressures were simulated, 10 Pa, 25 Pa, and 40 Pa. Drug particle transport was simulated for 100 to 950 nanoparticles and 1 to 50 micron-particles. Particles were released into the airway to mimic varying inhaler conditions with and without a spacer chamber. RESULTS: Based on smallest to largest cross-sectional area ratio, the laryngotracheal stenotic segment shrunk by 57% and 47%, respectively, for subglottic stenosis models and by 53% for both tracheal stenosis models. Airflow resistance at the stenotic segment was lower in subglottic stenosis models than in tracheal stenosis models: 0.001 to 0.011 Pa.s/mL vs 0.024 to 0.082 Pa.s/mL. Drug depositions for micron-particles and nanoparticles at stenosis were 0.06% to 2.48% and 0.10% to 2.60% for subglottic stenosis and tracheal stenosis models, respectively. Particle sizes with highest stenotic deposition were 6 to 20 µm for subglottic stenosis models and 1 to 10 µm for tracheal stenosis models. CONCLUSION: This study suggests that at most, 2.60% of inhaled drug particles deposit at the stenosis. Particle size ranges with highest stenotic deposition may not represent typical sizes emitted by inhalers.

Anatomic Variations in Temporal Bones Affect the Intensity of Nystagmus During Warm Caloric Irrigation.

HYPOTHESIS: Anatomic variables within the mastoid will correlate with intensity of caloric responses. BACKGROUND: During caloric irrigation, heat is transferred from the external auditory canal to the lateral semicircular canal (LSCC) through aerated mastoid bone. Temporal bone airspace volume and bone volume vary widely but the effect of this variation on caloric irrigation testing is not well characterized. Understanding this effect is necessary to understand how mastoid surgery may alter caloric irrigation results. METHODS: Twenty-two mastoid airspace and bones, as well as LSCC, were reconstructed from computed tomography scans of 11 subjects with normal anatomy who underwent vestibular function evaluation. Respective surface area (SA) and volume (V) of the mastoid airspace, bones, LSCC, and distance from LSCC to tympanic membrane (LSCC-TM) were calculated. In addition, computed values from these anatomic structures were correlated with the maximum velocity of slow phase nystagmus during warm caloric irrigation (MVwarm). RESULTS: Our results showed that the combined effect of airspace SA:V, bone SA:V, LSCC SA:V, and LSCC-TM distance accounted for 69.5% of the variation in MVwarm. Airspace SA:V (R = 0.22) and LSCC SA:V (R2 = 0.02) positively correlated with MVwarm, while bone SA:V (R = 0.17) demonstrated an inverse correlation with MVwarm. CONCLUSION: Preliminary results from this pilot study suggest that a substantial amount of the variability in MVwarm can be explained by temporal bone anatomy. Results also indicate that the denser the bone, the more heat is transferred to the LSSC, whereas increased airspace serves as an insulator. A larger study is necessary to confirm our findings.