Search

The objective of this study was to develop a new heated dryer system (HDS) for high efficiency lung delivery of nebulized aerosol and demonstrate performance with realistic in vitro testing for trans-nasal aerosol administration simultaneously with high-flow nasal cannula (HFNC) therapy and separately for direct oral inhalation (OI) of the aerosol. With the HDS-HFNC and HDS-OI platforms, new active synchronization control routines were developed to sense subject inhalation and coordinate drug aerosol delivery. In vitro experiments were conducted to predict regional drug loss and lung delivery efficiency in systems that included the HDS with various patient interfaces, realistic airway models, and simulated breathing waveforms. For the HDS-HFNC platform and a repeating breathing waveform, total system loss was 10%, extrathoracic deposition was approximately 6%, and best-case lung delivery efficiency was 75-78% of nebulized dose. Inclusion of randomized breathing with the HFNC system decreased lung delivery efficiency by ~ 10% and had no impact on nasal depositional loss. For the HDS-OI platform and best-case mouthpiece, total system loss was 8%, extrathoracic deposition was 1%, and lung delivery efficiency was 90% of nebulized dose. Normal vs. deep randomized oral inhalation had little impact on performance of the HDS-OI platform and environmental aerosol loss was negligible. In conclusion, both platforms demonstrated the potential for high efficiency lung delivery of the aerosol with the HDS-OI platform having the added advantages of nearly eliminating extrathoracic deposition, being insensitive to breathing waveform, and preventing environmental aerosol loss.

PURPOSE. The objective of this study was to optimize nose-to-lung aerosol delivery in an adult upper airway model using computational fluid dynamics (CFD) simulations in order to guide subsequent human subject aerosol delivery experiments. METHODS. A CFD model was developed that included a new high-flow nasal cannula (HFNC) and pharmaceutical aerosol delivery unit, nasal cannula interface, and adult upper airway geometry. Aerosol deposition predictions in the system were validated with existing and new experimental results. The validated CFD model was then used to explore aerosol delivery parameters related to synchronizing aerosol generation with inhalation and inhalation flow rate. RESULTS. The low volume of the new HFNC unit minimized aerosol transit time (0.2 s) and aerosol bolus spread (0.1 s) enabling effective synchronization of aerosol generation with inhalation. For aerosol delivery correctly synchronized with inhalation, a small particle excipient-enhanced growth delivery strategy reduced nasal cannula and nasal depositional losses each by an order of magnitude and enabled ~80% of the nebulized dose to reach the lungs. Surprisingly, nasal deposition was not sensitive to inhalation flow rate due to use of a nasal cannula interface with co-flow inhaled air and the small initial particle size. CONCLUSIONS. The combination of correct aerosol synchronization and small particle size enabled high efficiency nose-to-lung aerosol delivery in adults, which was not sensitive to inhalation flow rate.

This study evaluates the recently developed general framework for solution verification methods for large eddy simulation (LES) using implicitly filtered LES of periodic channel flows at friction Reynolds number of 395 on eight systematically refined grids. The seven-equation method shows that the coupling error based on Hypothesis I is much smaller as compared with the numerical and modeling errors and therefore can be neglected. The authors recommend five-equation method based on Hypothesis II, which shows a monotonic convergence behavior of the predicted numerical benchmark (S C ), and provides realistic error estimates without the need of fixing the orders of accuracy for either numerical or modeling errors. Based on the results from seven-equation and five-equation methods, less expensive three and four-equation methods for practical LES applications were derived. It was found that the new three-equation method is robust as it can be applied to any convergence types and reasonably predict the error trends. It was also observed that the numerical and modeling errors usually have opposite signs, which suggests error cancellation play an essential role in LES. When Reynolds averaged Navier-Stokes (RANS) based error estimation method is applied, it shows significant error in the prediction of S C on coarse meshes. However, it predicts reasonable S C when the grids resolve at least 80% of the total turbulent kinetic energy.

We present fluid flow and heat transfer of a slot jet impingement heat transfer at a small value of the nozzle-to-plate spacing at which a secondary peak in the Nusselt number is observed. Large eddy simulation has been performed with a finite-volume-based computational fluid dynamics code and using a dynamic Smagorinsky model. The optimum domain size and grid for large eddy simulation (LES) have been produced based on LES computations on a coarse mesh and Reynolds-averaged Navier–Stokes-based computations. Two inflow conditions, namely, using the vortex method and no perturbations, were compared. The present LES results, using the vortex method, capture the secondary peak in the Nusselt number better as compared to the case with no perturbations. Results show that mean velocity profile in the stagnation region deviates from the standard law of the wall. Further, large-scale vortical structures were observed near the location of the secondary Nusselt number peak. Increases in both the streamwise and wall ...

INTRODUCTION: Respiratory drug delivery is a surprisingly complex process with a number of physical and biological challenges. Computational fluid dynamics (CFD) is a scientific simulation technique that is capable of providing spatially and temporally resolved predictions of many aspects related to respiratory drug delivery from initial aerosol formation through respiratory cellular drug absorption. AREAS COVERED: This review article focuses on CFD-based deposition modeling applied to pharmaceutical aerosols. Areas covered include the development of new complete-airway CFD deposition models and the application of these models to develop a next generation of respiratory drug delivery strategies. EXPERT OPINION: Complete-airway deposition modeling is a valuable research tool that can improve our understanding of pharmaceutical aerosol delivery and is already supporting medical hypotheses, such as the expected under-treatment of the small airways in asthma. These complete-airway models are also being used to advance next generation aerosol delivery strategies, like controlled condensational growth. We envision future applications of CFD deposition modeling to reduce the need for human subject testing in developing new devices and formulations, to help establish bioequivalence for the accelerated approval of generic inhalers, and to provide valuable new insights related to drug dissolution and clearance leading to microdosimetry maps of drug absorption.

Evaluation of lung mechanics is the primary component for designing lung protective optimal ventilation strategies. This paper presents a machine learning approach for bedside assessment of respiratory resistance (R) and compliance (C). We develop machine learning algorithms to track flow rate and airway pressure and estimate R and C continuously and in real-time. An experimental study is conducted, by connecting a pressure control ventilator to a test lung that simulates various R and C values, to gather sensor data for validation of the devised algorithms. We develop supervised learning algorithms based on decision tree, decision table, and Support Vector Machine (SVM) techniques to predict R and C values. Our experimental results demonstrate that the proposed algorithms achieve 90.3%, 93.1%, and 63.9% accuracy in assessing respiratory R and C using decision table, decision tree, and SVM, respectively. These results along with our ability to estimate R and C with 99.4% accuracy using a linear regression model demonstrate the potential of the proposed approach for constructing a new generation of ventilation technologies that leverage novel computational models to control their underlying parameters for personalized healthcare and context-aware interventions.

We present a numerical investigation of hydrodynamic and heat transfer behaviors for Al2O3–water nanofluids for laminar and turbulent confined slot jets impingement heat transfer at nanoparticle volume fractions of 3% and 6%. A comparison of the nanofluid with the base fluid has been performed for the same Reynolds number and same jet inlet velocity. A single-phase fluid approach was used to model the nanofluid. Further, the thermo-physical properties of nanofluid were calculated using a recent approach. For the same value of Reynolds number, maximum increase in the average heat transfer coefficient at the impingement plate was found to be approximately 27% and 22% for laminar and turbulent slot impingements, respectively, for 6% volume fraction of nanofluid as compared to that of water. However, the pumping power curve showed a steep increase with the volume fraction with nearly five times increase in the pumping power observed for 6% volume fraction nanofluid. Further, the energy-based performance was assessed with the help of the performance evaluation criterion (PEC). PEC values indicate that nanofluids do not necessarily represent the most efficient coolants for this type of application. Moreover, at the same jet inlet velocity, a reduction in the heat transfer coefficient of 7% and 20% was observed for nanofluid as compared to base fluid for laminar and turbulent flows, respectively.

OBJECTIVE A comparison between flow and gas washout data for high-frequency percussive ventilation (HFPV) and pressure control ventilation (PCV) under similar conditions is currently not available. This bench study aims to compare and describe the flow and gas washout behavior of HFPV and PCV in a newly designed experimental setup and establish a framework for future clinical and animal studies. APPROACH We studied gas washout behavior using a newly designed experimental setup that is motivated by the multi-breath nitrogen washout measurements. In this procedure, a test lung was filled with nitrogen gas before it was connected to a ventilator. Pressure, volume, and oxygen concentrations were recorded under different compliance and resistance conditions. PCV was compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate the different variations in its clinical application. In the HFPV-Low mode, the peak pressures and drive pressures of HFPV and PCV are matched, whereas in the HFPV-High mode, the mean airway pressures (MAP) are matched. MAIN RESULTS HFPV-Low mode delivers smaller tidal volume (V T) as compared to PCV under all lung conditions, whereas HFPV-High delivers a larger V T. HFPV-High provides rapid washout as compared to PCV under all lung conditions. HFPV-Low takes a longer time to wash out nitrogen except at a low compliance, where it expedites washout at a smaller V T and MAP compared to PCV washout. SIGNIFICANCE Various flow parameters for HFPV and PCV are mathematically defined. A shorter washout time at a small V T in low compliant test lungs for HFPV could be regarded as a hypothesis for lung protective ventilation for animal or human lungs.

In this article, large eddy simulation (LES) is performed for a turbulent slot jet impingement heat transfer at a Reynolds number of 13,500 and a nozzle to plate spacing of 10. Various aspects of predicting a turbulent jet impinging flow in an optimum domain size and grid resolution for LES have been assessed. Two inflow conditions, one without any fluctuations and the other with fluctuations generated by the spectral synthesizer, were tested and comparisons of various mean flow, turbulence, and heat transfer data showed that LES without any inflow fluctuations provides good agreement with the corresponding experimental and numerical results reported in the literature. Further, various important dynamical flow structures have been visualized from the instantaneous computed data. Finally, mean flow and turbulence statistics have been presented in the wall jet region close to the stagnation point, which could be useful as data for validation of RANS-based turbulence models.

A review of the current status of computation of turbulent impinging jet heat transfer is presented. It starts with a brief introduction to flow and heat transfer characteristics of jet impinging flows considering the simplest jet impinging geometry: normal impingement of a single jet into a flat surface. Subsequently, a review of recent computational studies related to the same geometry is presented. The effects of different subgrid scale models, boundary conditions, numerical schemes, grid distribution, and size of the computational domain adopted in various large eddy simulations of this flow configuration are reviewed in detail. A review of direct numerical simulation of the same geometry is also presented. Further, some recent attempts in Reynolds-averaged Navier–Stokes modeling of impinging flows are also reviewed. A review of computation of other complex impinging flows is also presented. The review concludes with a listing of some important findings and future directions in the computation of impi...

The accuracy of turbulence models for the Reynolds-Averaged Navier-Stokes (RANS) equations in rough-wall flows is evaluated by comparing the model predictions with the data obtained from large-eddy simulations (LES). We have considered boundary layers in favourable and adverse pressure gradients mimicking those encountered in hydroturbines. We find that some features of the flow cannot be captured accurately by any model, due to the fundamental modelling assumptions. An example is the flow reversal that occurs in the roughness sublayer prior to separation, which cannot be predicted by the commonly used approaches, which bypass the roughness sublayer while modifying the boundary conditions. In mild pressure gradients most models are sufficiently accurate for engineering applications, but if strong favourable or adverse pressure gradients are applied (especially those leading to separation) the model performance rapidly degrades. A particularly difficult problem (both for rough- and smooth-wall cases) is the return to equilibrium after a strong perturbation, a known limitation of RANS models. Simulations of real configurations using commercial codes are also considered.