Effective Mechanical Properties of Periodic Cellular Solids with Generic Bravais Lattice Symmetry via Asymptotic Homogenization.

In this paper, the scope of discrete asymptotic homogenization employing voxel (cartesian) mesh discretization is expanded to estimate high fidelity effective properties of any periodic heterogeneous media with arbitrary Bravais's lattice symmetry, including those with non-orthogonal periodic bases. A framework was developed in Python with a proposed fast-nearest neighbour algorithm to accurately estimate the periodic boundary conditions of the discretized representative volume element of the lattice unit cell. Convergence studies are performed, and numerical errors caused by both voxel meshing and periodic boundary condition approximation processes are discussed in detail. It is found that the numerical error in periodicity approximation is cyclically dependent on the number of divisions performed during the meshing process and, thus, is minimized with a refined voxel mesh. Validation studies are performed by comparing the elastic properties of 2D hexagon lattices with orthogonal and non-orthogonal bases. The developed methodology was also applied to derive the effective properties of several lattice topologies, and variation of their anisotropic macroscopic properties with relative densities is presented as material selection charts.

In Vitro Measurements of Spiriva Respimat Dose Delivery in Mechanically Ventilated Tracheostomy Patients.

Background: For patients with severe chronic obstructive pulmonary disease under invasive mechanical ventilation, medication for aerosol therapy is delivered through tracheostomy or endotracheal airways. Typically, these medications (such as bronchodilators) are long-acting formulations that are delivered through Soft Mist™ Inhalers (SMI), or Pressurized Metered-Dose Inhalers. The Respimat® SMI has been shown to have increased efficiency because of its slow and prolonged aerosol mist and has gained popularity in clinical settings. However, the Respimat was not designed for drug delivery through artificial airways. Therefore, there is a need for SMI adapters in intensive care for use in mechanical ventilator circuits. The purpose of this study was to evaluate the performance of a new Respimat adapter (ODAPT™ for mechanical ventilator [ODAPT MV]) for use in mechanical ventilator circuits which, in combination with a Pulmodyne T-piece adapter, allows use without interruption of the circuit in case of medication replacement. Methods: Tiotropium delivery to the lungs, using Respimat, was assessed using the ODAPT MV adapter within an in vitro setup, including a three-dimensional printed trachea model and a mechanical ventilator. Medication deposition and losses were investigated using two commonly used tracheostomy tube (TT) sizes (6 and 8 mm inner canula) for two flow rates (45 and 60 L/min) under different conditions (30%-50%. and 100% relative humidity [RH]). Medication delivery using the ODAPT MV adapter was compared with the RTC-26C in-line adapter under similar conditions (8 mm TT size, 100% RH at 45 L/min). Results: It was found that 7.1%-13.4% of the nominal dose (ND) was lost in the ODAPT MV adapter for different TT size, RH, and flow rates used. Higher losses were found in the inhaler's mouthpiece ranging from 15.7% to 29.1% ND. The percentage of the delivered medication reaching the lungs was determined to be 13.7%-18.5% ND delivered without significant differences between the experimental conditions tested. The ODAPT MV performed well compared with the RTC-26C under similar conditions (17.9% and 16.6% ND, respectively). Conclusion: The medication delivered through mechanical ventilation using the ODAPT MV adapter represents about one third the dose delivered directly through the Respimat SMI in vivo.

In vitro investigation of the Flusso™ Bypass adapter efficiency upon ventilator circuit disconnect in a clinical simulated environment.

RATIONALE: Mechanically ventilated patients must be disconnected from the ventilator during intra-facility transfers. Intentional and accidental circuit disconnections represent a potential hazard to patients (sudden collapse and re-expansion of the alveoli) as well as to clinical staff (exposure to patient's unfiltered exhalation). Therefore, avoiding abrupt circuit disconnections could better protect the patient's health and reduce or eliminate contamination risks around clinical staff. OBJECTIVE: The purpose of this in-vitro work was to investigate and evaluate the potential for environmental exposure of Nitric Oxide (NO, as an indicator of any contamination exposure) before and after implementing the novel Flusso™ Bypass adapter during the disconnect procedure of a mechanical ventilator system. METHODS: A mechanical ventilator delivering NO was connected to a breathing simulator with and without the Flusso™ Bypass adapter. The ambient NO concentration was measured when the circuit was briefly disconnected (3 s) during inhalation and exhalation. Both volume and pressure ventilation modes were used. MEASUREMENTS AND MAIN RESULTS: Disconnecting the standard ventilator circuit (pressure-controlled mode) without the Flusso™ Bypass adapter produced higher NO escape to the surroundings (compared with the volume-controlled mode), leading to a longer NO dissipation time. No ambient NO traces were detected when the Flusso™ adapter was used. CONCLUSION: The usage of the Flusso™ adapter drastically decreases the unwanted exposure among clinical staff dealing with potentially hazardous airborne biological aerosols emanating from the circuit. Avoiding abrupt disconnection in the ventilator circuit could reduce lung injuries and alveolar over distension and collapse.

Experimental Study of Spiriva Respimat Soft Mist Inhaler Spray Characterization: Size Distributions and Velocity.

Background: Respiratory illnesses such as asthma, bronchitis, and chronic obstructive pulmonary disease (COPD) are considered to be debilitating diseases. A variety of inhalation devices have been used to deliver aerosol medication to patients in the treatment of those diseases. Soft Mist Inhalers (SMIs, for example, the Spiriva Respimat) are a new generation of propellant-free inhalers. In this type of inhalation device, inhalable droplets are generated from an aqueous solution. Droplet size and velocity are two of the most substantial factors that impact the deposition of SMI aerosol medication into the patient lungs. Methods: In this study, size and velocity of droplets generated from the Spiriva Respimat inhaler were measured using phase Doppler anemometry (PDA). Measurements were taken at four locations along the centerline of the Spiriva Respimat inhaler, in addition to three cross sections (free-spray configuration). In addition, measurements were also performed at a single cross section in confined spray configurations using two separate idealized mouth cavities. Results and Conclusions: Measurements along the centerline of the aerosol mist generated using the Spiriva Respimat inhaler (6.5, 25, 100, and 125 mm downstream of the inhaler nozzle' orifice) showed that droplets at the mouthpiece have the highest velocity of 10.95 m/s, decreasing to 1.33 m/s at the 125 mm location away from the nozzle. The mean diameter D10 values ranged from 3.97 to 3.67 µm at 6.5 and 125 mm locations, respectively. In addition, of the three probability density functions (PDFs) that were tested, the log-normal PDF showed better curve fitting for the empirical data (droplet size distributions) that were measured. The effect of spray confinement using two idealized mouth cavities shows that there was a drop in the particles' velocity for both models on each axes compared with the open-air environment (free-spray configuration).

Aerosolization of Zn-DTPA Decorporation Agent Using Jet and Ultrasonic Nebulizers.

BACKGROUND: Chelating agents such as diethylenetriamine pentaacetic acid (DTPA) can be used as a decorporation drug in the zinc (Zn) form to treat internal radioactive contamination after exposure to plutonium or americium in a nuclear accident. Although Zn-DTPA is normally administered intravenously, inhalation of Zn-DTPA in aerosol form is a better route for direct delivery to the lungs. This work investigates the feasibility of synthesizing Zn-DTPA from three common chemicals and aerosolizing it using a jet or ultrasonic nebulizer. METHODS: The particle size distribution (PSD) of this decorporation agent at different concentrations were tested in vitro using two different methods: inertial impaction and aerodynamic time of flight. The particles were generated using either a jet nebulizer or an ultrasonic nebulizer. Two parameters, namely the mass median aerodynamic diameter and the geometric standard deviation, were assessed to determine the PSD of the generated aerosols. These parameters were obtained for different concentrations of Zn-DTPA using both nebulizers. RESULTS AND CONCLUSIONS: Zn-DTPA was successfully synthesized for decorporation purposes. Aerosol particles within the inhalable range were successfully generated by both nebulizers from four different concentrations of Zn-DTPA. It was found that the medication concentration did not affect the PSD of Zn-DTPA. The ultrasonic nebulizer was observed to produce a slightly larger aerosol particle size and required slightly longer treatment periods to deliver an effective dose to the lungs when compared with the jet nebulizer. Both nebulizers can be sustainably run to administer the agent for effective decorporation treatment of a large population after any major nuclear accident.

Characterization of Medication Velocity and Size Distribution from Pressurized Metered-Dose Inhalers by Phase Doppler Anemometry.

BACKGROUND: Particle size and velocity are two of the most significant factors that impact the deposition of pressurized metered-dose inhaler (pMDI) sprays in the mouth cavity. pMDIs are prominently used around the world in the treatment of patients suffering from a variety of lung diseases such as asthma and chronic obstructive pulmonary disease. Since their introduction in the field, and as a result of their effectiveness and simplicity of usage, pMDIs are considered to be the most widely prescribed medical aerosol delivery system. METHODS: In the current study, particle velocity and size distribution were measured at three different locations along the centerline of a pMDI spray using Phase Doppler Anemometry. pMDIs from four different pharmaceutical companies were tested, each using salbutamol sulfate as the medication. RESULTS AND CONCLUSIONS: Measurements along at the pMDI centerline (at 0, 75, and 100 mm downstream of the inhaler mouthpiece) showed that the spray velocities were bimodal in time for all four pMDI brands. The first peak occurred as the spray was leaving the mouthpiece, while the second peak (at the same location, 0 mm) occurred at around 60, 95, 95, and 115 milliseconds later, respectively, for the four tested inhalers, with a drop in the velocity between the two peaks. Three probability density functions (PDFs) were tested, and the Rosin-Rammler PDF best fit the empirical data, as determined using a chi-squared test. These results suggest that there is a difference in the mean particle velocities at the centerline for the tested pMDIs and the diameter of released particles varied statistically for each brand.

Nonuniform Deposition of Pressurized Metered-Dose Aerosol in Spacer Devices.

BACKGROUND: Pressurized metered-dose inhalers (pMDIs) are commonly used to administer medication to patients suffering from chronic lower respiratory tract diseases such as asthma. Inhaling medication directly from a pMDI can prove difficult for some patients and, as a result, add-on devices (or spacers) have been designed to aid in the delivery of medication. Although spacers increase the percentage of medication that reaches the patient, medication will also nonsymmetrically deposit on the walls of the device and will be lost to the device itself. METHODS: The deposition of medication, salbutamol sulfate, within a large- and a small-volume spacer, has been studied through an experimental and numerical analysis. Experiments were conducted at inspiratory flow rates ranging from 30 to 60 L/min. The amount of deposition of the medication on the walls of the spacer was quantified through an application of spectrophotometry. Computational fluid dynamics was used to quantify the deposition numerically. Simulations were conducted by implementing mean flow and turbulent tracking of particles using unsteady Reynolds-averaged Navier-Stokes (URANS) equations with a shear stress transport turbulence model. Regions of deposition are of interest, as well as how the method of deposition varied for different inhalation flow rates. RESULTS AND CONCLUSIONS: The deposition of salbutamol sulfate in the Volumatic® and OptiChamber® spacers was found to be greater in the lower half as opposed to the upper half of the spacer due to a downward spray angle. With an increased flow rate, these spacers demonstrated a slight increase in medication delivered to the inline filter, which is analogous to that reaching the patient, and an increase in distal deposition. For the numerical analysis, the results indicated that inertial impaction is the most likely method of deposition for the Volumatic spacer, and turbulence is more likely to cause deposition in the OptiChamber spacer.

Characterization of the spray velocities from a pressurized metered-dose inhaler.

BACKGROUND: Pressurized metered dose inhalers (pMDIs) are widely used to deliver aerosolized medications to the lungs, most often to relieve the symptoms of asthma. Over the past decade, pMDIs have been modified in several ways to eliminate the use of chlorofluorocarbons in their manufacture while increasing efficacy. Numerical simulations are being used more frequently to predict the flow and deposition of particles at various locations, both inside the respiratory tract as well as in pMDIs and add-on devices. These simulations require detailed information about the spray generated by a pMDI to ensure the validity of their results. METHODS: This paper presents detailed, spatially resolved velocity measurements of the spray emitted from salbutamol sulfate pMDIs obtained using optically triggered particle image velocimetry (PIV). Instantaneous planar velocity measurements were taken and ensemble-averaged at nine different times during the spray event ranging from 1.3 to 100 msec after a pneumatically controlled actuation. RESULTS AND CONCLUSIONS: The mean spray velocities were shown to be bimodal in time, with two velocity peaks and velocity magnitudes found to be much lower than published data from instantaneous single point measurements. Planar velocity data at each time step were analyzed to produce prescriptive velocity profiles suitable for use in numerical simulations. Spray geometry data are also reported. Statistical comparisons from several thousand individual spray events indicate that there is no significant difference in measured velocity among (1) two brands of pMDI canisters, (2) two pMDIs of the same brand but having different lot numbers, and (3) a full pMDI versus an almost empty pMDI. The addition of a secondary air flow of 30 SLPM (to represent simultaneous inhalation and spray actuation) deflected the spray downward but did not have a significant effect on flow velocity. Further experiments with an added cylindrical spacer revealed that within the spacer, the spray direction and cone angle were altered, although the peak velocities remained similar.

Improving prediction of aerosol deposition in an idealized mouth using large-Eddy simulation.

Monodisperse aerosol deposition in an idealized mouth geometry with a relatively small inlet diameter (D (in) = 3.0 mm) was studied numerically using a standard Large Eddy Simulation (LES). A steady inhalation flow rate of Q = 32.2 L/min was used. Thousands of particles (2.5, 3.7, and 5.0 microm in diameter and rho (f) = 912.0 kg/m(3) density) were released separately in the computational domain and aerosol deposition was determined. The total aerosol deposition results in this idealized mouth were in relatively good agreement when compared with measured data obtained in separate experiments, showing considerable improvement over the standard RANS/EIM (Reynolds Averaged Navier-Stokes/Eddy Interaction Model) approach.