A novel aerosol-mediated drug delivery system for inner ear therapy: intratympanic aerosol methylprednisolone can attenuate acoustic trauma.

We developed a novel aerosol-mediated drug delivery system for inner ear therapy by using a silicon-based multiple-Fourier horn nozzle. Intratympanic aerosol (ITA) methylprednisolone (MP) delivery can protect hearing after acoustic trauma. The highest concentration of MP (38.9 ± 5.47 ppm) appeared at 2 h and declined rapidly within 10 h. The concentrations of MP remained at a relatively low level for more than 10 h. Compared to the baseline, the auditory brainstem response (ABR) thresholds shifted markedly at 1 h after noise exposure in all groups (p < 0.05). From the cochleograms, it can be noted that the main lesions encompassed the 2-20 kHz frequency range. Significant differences ( ) were observed for the range between 5 and 8 kHz in the cell loss of outer hair cells (OHCs). The losses for IHCs were lower than for OHCs. The MP movement in the middle ear was simulated by a convection diffusion equation with a relaxation time. The relaxation time was 0.5 h, and the concentration threshold of MP on the round window membrane (RWM) in the middle ear (C T) was 8900 ppm. Using the unit hydrograph (UH) method, we obtained a proper boundary concentration on the RWM at the cochlea, which resulted in a well-fit concentration. Finally, a linking mechanism between the middle ear and the cochlea was established by the RWM. The adjustable permeability and concentration threshold provide the flexibility to match the peak times and peak values of the concentration on the RWM in the middle ear and the cochlea.

Computational fluid dynamics study of the inspiratory upper airway and clinical severity of obstructive sleep apnea.

The apnea-hypopnea index (AHI) is a widely accepted measure for the severity of obstructive sleep apnea (OSA). Current methods to determine AHI fail to provide anatomic information for treatment decisions. In this report, we studied three-dimensional models of upper airways acquired by computed tomographic scanning with geometric measurements and computational fluid dynamics (CFD) analysis and evaluated the correlations with AHI.Participants had CT scans of their upper airways after standard polysomnography studies. Three-dimensional surface models of upper airways were generated for cross-sectional area measurements of the choanae (ACH) and the smallest cross-sectional area (Amin). Computational fluid dynamic analysis was then performed by using this three-dimensional model. Pressure differences required to set tidal volume during inspiration (ΔPmin-INSP) and expiration (ΔPmax-EXP) and minimum negative pressure produced in the level of ACH (Pmin-INSP at ACH) and Amin (Pmin-INSP at Amin) were calculated. Correlations of these parameters and the body mass index with AHI were analyzed. Statistical differences between groups of different AHI ranges were also compared.The pressure distribution simulated by CFD demonstrated abrupt pressure drops in Amin level, and this phenomenon was more significant in severe OSA. All parameters except ACH and Pmin-INSP at Amin significantly correlated with the AHI, and there were significant statistical differences between the OSA groups and the normal group. The results indicate that, in our study group, the geometry of pharyngeal airway and its CFD simulation correlate well with AHI. This model may be further applied for clinical evaluation.

Computational fluid dynamic study on obstructive sleep apnea syndrome treated with maxillomandibular advancement.

Maxillomandibular advancement is one of the treatments available for obstructive sleep apnea. The influence of this surgery on the upper airway and its mechanism are not fully understood. The present research simulates the flow fields of narrowed upper airways of 2 patients with obstructive sleep apnea treated with maxillomandibular advancement. The geometry of the upper airway was reconstructed from computed tomographic images taken before and after surgery. The consequent three-dimensional surface model was rendered for measurement and computational fluid dynamics simulation. Patients showed clinical improvement 6 months after surgery. The cross-sectional area of the narrowest part of the upper airway was increased in all dimensions. The simulated results showed a less constricted upper airway, with less velocity change and a decreased pressure gradient across the whole conduit during passage of air. Less breathing effort is therefore expected to achieve equivalent ventilation with the postoperative airway. This study demonstrates the possibility of computational fluid dynamics in providing information for understanding the pathogenesis of OSA and the effects of its treatment.