Characterization of aerosol nebulized by Aerogen Solo mesh nebulizer

Nebulizers are commonly used devices for inhalation treatment of various disorders. There are three main categories of medical nebulization technology: jet nebulizers, ultrasound nebulizer, and mesh nebulizer. The mesh nebulizers seem to be very promising since this technology should be able to produce aerosol with precisely determined particle size and is easy to use as well [1]. Aerosol generated from the mesh nebulizer Aerogen Solo was measured in this work. Particle size distribution with a mass median of aerodynamic diameter (MMAD) was determined by two different methods

Comparison of methods for flow border detection in images of smoke visualization

A separation of the flow region from the surroundings is an essential step in the analysis of smoke visualization images. The separation can be performed using several detection methods from the image segmentation group. This paper deals with the border detection of the air flow downstream of a benchmark automotive vent using different threshold-based detection methods. An assessment of the methods on the basis of the resulting image quality is also addressed. The quality level depends on the quantity and brightness of disturbances in the background area. The disturbance is usually an isolated region of smoke, which naturally cannot be a part of the flow. Three representative images of different quality levels were selected for the detection, and three methods were used for the evaluation. Each of the methods was used to determine the threshold differently (by the level, by the ratio, and by the change of brightness). It is demonstrated that the change-based method with an appropriately selected parameter is the most convenient for images with the worst quality level while level- and ratio-based methods are only applicable for images of good quality.A separation of the flow region from the surroundings is an essential step in the analysis of smoke visualization images. The separation can be performed using several detection methods from the image segmentation group. This paper deals with the border detection of the air flow downstream of a benchmark automotive vent using different threshold-based detection methods. An assessment of the methods on the basis of the resulting image quality is also addressed. The quality level depends on the quantity and brightness of disturbances in the background area. The disturbance is usually an isolated region of smoke, which naturally cannot be a part of the flow. Three representative images of different quality levels were selected for the detection, and three methods were used for the evaluation. Each of the methods was used to determine the threshold differently (by the level, by the ratio, and by the change of brightness). It is demonstrated that the change-based method with an appropriately selected parameter is the most convenient for images with the worst quality level while level- and ratio-based methods are only applicable for images of good quality

Experimental verification of boundary conditions for numerical simulation of airflow in a benchmark ventilation channel

Correct definition of boundary conditions is crucial for the appropriate simulation of a flow. It is a common practice that simulation of sufficiently long upstream entrance section is performed instead of experimental investigation of the actual conditions at the boundary of the examined area, in the case that the measurement is either impossible or extremely demanding. We focused on the case of a benchmark channel with ventilation outlet, which models a regular automotive ventilation system. At first, measurements of air velocity and turbulence intensity were performed at the boundary of the examined area, i.e. in the rectangular channel 272.5 mm upstream the ventilation outlet. Then, the experimentally acquired results were compared with results obtained by numerical simulation of further upstream entrance section defined according to generally approved theoretical suggestions. The comparison showed that despite the simple geometry and general agreement of average axial velocity, certain difference was found in the shape of the velocity profile. The difference was attributed to the simplifications of the numerical model and the isotropic turbulence assumption of the used turbulence model. The appropriate recommendations were stated for the future work

Simulation of Airway Deposition of an Aerosol Drug in COPD Patients

Medical aerosols are key elements of current chronic obstructive pulmonary disease (COPD) therapy. Therapeutic effects are conditioned by the delivery of the right amount of medication to the right place within the airways, that is, to the drug receptors. Deposition of the inhaled drugs is sensitive to the breathing pattern of the patients which is also connected with the patient's disease severity. The objective of this work was to measure the realistic inhalation profiles of mild, moderate, and severe COPD patients, simulate the deposition patterns of Symbicort((R)) Turbuhaler((R)) dry powder drug and compare them to similar patterns of healthy control subjects. For this purpose, a stochastic airway deposition model has been applied. Our results revealed that the amount of drug depositing within the lungs correlated with the degree of disease severity. While drug deposition fraction in the lungs of mild COPD patients compared with that of healthy subjects (28% versus 31%), lung deposition fraction characteristic of severe COPD patients was lower by a factor of almost two (about 17%). Deposition fraction of moderate COPD patients was in-between (23%). This implies that for the same inhaler dosage severe COPD patients receive a significantly lower lung dose, although, they would need more

Flow Behaviour of Inhaled Fibres – Equations of Motion and Preliminary Results of Real Trajectories Recorded by a High-Speed Camera

The ability to precisely predict the fate of inhaled fibres is important for toxicologists as well as for pharmaceutists struggling to utilize fibres as carriers of a medication. However, the complexity of fibre movement in human airways still represents a significant challenge for programmers of codes for simulation of fibre flow. This conference contribution introduces the theoretical equations of fibre motion which can be used for calculation of the fate of inhaled fibres, and also, in the second part, first results of high-speed camera recorded trajectories of fibres downstream of a realistic human airway bifurcation are presented as an illustration of the real behaviour of fibres in the lungs

Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

In this study, novel Trojan particles were engineered for direct delivery of doxorubicin (DOX) and miR-34a as model drugs to the lungs to raise local drug concentration, decrease pulmonary clearance, increase lung drug deposition, reduce systemic side effects, and overcome multi-drug resistance. For this purpose, targeted polyelectrolyte nanoparticles (tPENs) developed with layer-by-layer polymers (i.e., chitosan, dextran sulfate, and mannose-g-polyethyleneimine) were spray dried into a multiple-excipient (i.e., chitosan, leucine, and mannitol). The resulting nanoparticles were first characterized in terms of size, morphology, in vitro DOX release, cellular internalization, and in vitro cytotoxicity. tPENs showed comparable cellular uptake levels to PENs in A549 cells and no significant cytotoxicity on their metabolic activity. Co-loaded DOX/miR-34a showed a greater cytotoxicity effect than DOX-loaded tPENs and free drugs, which was confirmed by Actin staining. Thereafter, nano-in-microparticles were studied through size, morphology, aerosolization efficiency, residual moisture content, and in vitro DOX release. It was demonstrated that tPENs were successfully incorporated into microspheres with adequate emitted dose and fine particle fraction but low mass median aerodynamic diameter for deposition into the deep lung. The dry powder formulations also demonstrated a sustained DOX release at both pH values of 6.8 and 7.4. © 2023, The Author(s).Tomas Bata University in Zlin, TBU: RP/CPS/2022/005; Grantová Agentura České Republiky, GA ČR: GA 20-27653

Inhalers and nebulizers: basic principles and preliminary measurements

Inhalers are hand-held devices which are used for administration of therapeutic aerosols via inhalation. Nebulizers are larger devices serving for home and hospital care using inhaled medication. This contribution describes the basic principles of dispersion of aerosol particles used in various types of inhalers and nebulizers, and lists the basic physical mechanisms contributing to the deposition of inhaled particles in the human airways. The second part of this article presents experimental setup, methodology and preliminary results of particle size distributions produced by several selected inhalers and nebulizers

The role of the combined use of experimental and computational methods in revealing the differences between the micron -size particle deposition patterns in healthy and asthmatic subjects

Quantification of airway deposition of aerosol particles is essential for the assessment of health risks of detrimental particles. Knowledge of deposition distribution is important also in the case of treatment with aerosolised drugs. It is also worth considering that deposition of inhaled particles in severe asthmatics can be different from the deposition in healthy subjects due to the modified breathing parameters, airway geometry and lobar flow distribution. The aim of this study was to apply combined experimental and numerical techniques to quantify the upper airway and bronchial deposition of the inhaled microparticles in healthy individuals in comparison with asthma patients. Idealised and realistic physical and digital replicas of the human airways were constructed. Deposition fractions and efficiencies of inhaled polydisperse mannitol and chitosan particles in different airway sections were measured and calculated. Deposition fraction of polydisperse mannitol particles in the idealised airway geometry assuming breathing conditions of healthy subjects was 21.9% and 18.3% when determined experimentally and by numerical simulations, respectively. Experimental measurements of deposition fraction of chitosan particles in the same geometry, but assuming breathing parameters characteristic of severe asthmatics yielded 32%, while simulations provided 30.1% for the same conditions. Extrathoracic deposition fraction of mannitol particles in healthy subjects measured in the realistic geometry was 71.1%, while bronchial deposition fraction was 5.3%. The corresponding simulations yielded 76.2% and 8.9% deposition fractions in the upper and bronchial airways, respectively. There was a good agreement between the experimental and simulation deposition results also in the different predefined sections of the airways. Present pilot study proved that lobar flow redistribution due to severe asthma significantly modified the deposition distribution of micro-particles. Although the present results refer only to small groups of healthy and asthmatic individuals, it clearly demonstrates the capability of carefully validated models to simulate the deposition of micron-size particles in larger populations of both groups

Variations of flow in human airways as a consequence of lung diseases

The efficiency of drug delivery administered by inhalation depends, among other factors, such as size and shape of aerosol particles, significantly also on the flow in the airways. As many lung diseases change both the breathing pattern and the shape of airways, we focus in this study on the influence of several selected diseases on the distribution of flow between the lung lobes and on changes the diseases induce on the course of flowrate. First, we present results of a literature survey focused on the published records of pathological breathing patterns. In the second part, we describe the newly designed breathing simulator and the implementation of the patterns into it. The last part is focused on the experimental verification of fidelity of the simulated breathing patterns