Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated droplets and aerosol particles.

The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Internal microdosimetry of alpha-emitting radionuclides.

At the tissue level, energy deposition in cells is determined by the microdistribution of alpha-emitting radionuclides in relation to sensitive target cells. Furthermore, the highly localized energy deposition of alpha particle tracks and the limited range of alpha particles in tissue produce a highly inhomogeneous energy deposition in traversed cell nuclei. Thus, energy deposition in cell nuclei in a given tissue is characterized by the probability of alpha particle hits and, in the case of a hit, by the energy deposited there.

The degree of inhomogeneity of the absorbed cell nucleus doses in the bronchial region of the human respiratory tract.

Inhalation of short-lived radon progeny is an important cause of lung cancer. To characterize the absorbed doses in the bronchial region of the airways due to inhaled radon progeny, mostly regional lung deposition models, like the Human Respiratory Tract Model (HRTM) of the International Commission on Radiological Protection, are used. However, in this model the site specificity of radiation burden in the airways due to deposition and fast airway clearance of radon progeny is not described.

Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization and - lung deposition results.

The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation ways - carrier-based, carrier-free, and novel combined formulation - and thereby to compare their physicochemical and aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrier-based and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs. The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied.

Novel dry powder inhaler formulation containing antibiotic using combined technology to improve aerodynamic properties.

Dry Powder Inhaler (DPI) could offer a propellant-free, easy-to-use powder form ensuring better stability than liquid dosage forms. Therefore the development of traditional carrier-based and carrier-free new generation systems is a determinative factor in the field of DPI formulation. The purpose of our research work was to combine these two systems, utilizing their beneficial properties to produce a novel pulmonary drug delivery system containing ciprofloxacin hydrochloride (CIP).

Experimental and computational study of the effect of breath-actuated mechanism built in the NEXThaler dry powder inhaler.

The breath-actuated mechanism (BAM) is a mechanical unit included in NEXThaler with the role of delaying the emission of the drug until the inhalation flow rate of the patient is sufficiently high to detach the drug particles from their carriers. The main objective of this work was to analyse the effect of the presence of BAM on the size distribution of the emitted drug and its airway deposition efficiency and distribution. Study of the hygroscopic growth of the emitted drug particles and its effect on the deposition was another goal of this study.

Comparison of airway deposition distributions of particles in healthy and diseased workers in an Egyptian industrial site.

The objective of this study is the prediction and comparison of airway deposition patterns of an industrial aerosol in healthy workers and workers suffering from silicosis. Mass concentrations and related size distributions of particulate matter were measured in the industrial area of Samalut in Minia, Egypt. A novel stochastic lung deposition model, simulating the symptoms of silicosis by chronic bronchial (Br) obstruction and emphysema in the acinar (Ac) region, was applied to compute mass deposition fractions, deposition density, deposition rate and deposition density rate distributions in healthy and diseased workers.

Significance of breath-hold time in dry powder aerosol drug therapy of COPD patients.

Aerosol drugs are effectively used to treat chronic respiratory diseases. The efficiency of the therapy depends also on the amount and distribution of drug deposited within the airways. The objective of this study is to apply numerical techniques to analyse the effect of the duration of breath-hold after the inhalation of six different commercialized dry powder drugs on their lung deposition.

Aerodynamic properties and in silico deposition of meloxicam potassium incorporated in a carrier-free DPI pulmonary system.

Dry powder inhalers (DPIs) have been among the fastest developing inhaler forms in the past decades. Researches are focusing on the formulation of carrier-free powders to obtain a higher deep-lung deposition and hereby to increase the effectiveness of the medicine. The aim of our study was to prepare a carrier-free dry powder formulation of meloxicam potassium (MP), a novel salt form of meloxicam, using a one-step co-spray drying technology.

Numerical simulation of emitted particle characteristics and airway deposition distribution of Symbicort(®) Turbuhaler(®) dry powder fixed combination aerosol drug.

One of the most widespread dry powder fixed combinations used in asthma and chronic obstructive pulmonary disease (COPD) management is Symbicort(®) Turbuhaler(®). The aim of this study was to simulate the deposition distribution of both components of this drug within the airways based on realistic airflow measurements. Breathing parameters of 25 healthy adults (11 females and 14 males) were acquired while inhaling through Turbuhaler(®).

Computer modeling of airway deposition distribution of Foster(®) NEXThaler(®) and Seretide(®) Diskus(®) dry powder combination drugs.

Asthma is a serious global health problem with rising prevalence and treatment costs. Due to the growing number of different types of inhalation devices and aerosol drugs, physicians often face difficulties in choosing the right medication for their patients. The main objectives of this study are (i) to elucidate the possibility and the advantages of the application of numerical modeling techniques in aerosol drug and device selection, and (ii) to demonstrate the possibility of the optimization of inhalation modes in asthma therapy with a numerical lung model by simulating patient-specific drug deposition distributions.

Development and application of a complex numerical model and software for the computation of dose conversion factors for radon progenies.

A more exact determination of dose conversion factors associated with radon progeny inhalation was possible due to the advancements in epidemiological health risk estimates in the last years. The enhancement of computational power and the development of numerical techniques allow computing dose conversion factors with increasing reliability. The objective of this study was to develop an integrated model and software based on a self-developed airway deposition code, an own bronchial dosimetry model and the computational methods accepted by International Commission on Radiological Protection (ICRP) to calculate dose conversion coefficients for different exposure conditions.

3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: direct versus bystander effects.

Purpose: The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies.

Materials And Methods: State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation.

Results: The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities.

Mutation induction by inhaled radon progeny modeled at the tissue level.

The observable responses of living systems to ionizing radiation depend on the level of biological organization studied. Understanding the relationships between the responses characteristic of the different levels of organization is of crucial importance. The main objective of the present study is to investigate how some cellular effects of radiation manifest at the tissue level by modeling mutation induction due to chronic exposure to inhaled radon progeny.

Quantification of airway deposition of intact and fragmented pollens.

Although pollen is one of the most widespread agents that can cause allergy, its airway transport and deposition is far from being fully explored. The objective of this study was to characterize the airway deposition of pollens and to contribute to the debate related to the increasing number of asthma attacks registered after thunderstorms. For the quantification of the deposition of inhaled pollens in the airways computer simulations were performed.

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses.

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events.

Right main bronchus perforation detected by 3D-image.

A male metal worker, who has never smoked, contracted debilitating dyspnoea in 2003 which then deteriorated until 2007. Spirometry and chest x-rays provided no diagnosis. A 3D-image of the airways was reconstructed from a high-resolution CT (HRCT) in 2007, showing peribronchial air on the right side, mostly along the presegmental airways.

Simulation and minimisation of the airway deposition of airborne bacteria.

Respiratory infections represent one of the most important bioaerosol-associated health effects. Bacteria are infectious micro-organisms that may, after inhalation, cause specific respiratory diseases. Although a large number of inhalable pathogenic bacteria have been identified and the related respiratory symptoms are well known, their airway transport and deposition are still not fully explored.

Non-linear relationship of cell hit and transformation probabilities in a low dose of inhaled radon progenies.

Cellular hit probabilities of alpha particles emitted by inhaled radon progenies in sensitive bronchial epithelial cell nuclei were simulated at low exposure levels to obtain useful data for the rejection or support of the linear-non-threshold (LNT) hypothesis. In this study, local distributions of deposited inhaled radon progenies in airway bifurcation models were computed at exposure conditions characteristic of homes and uranium mines. Then, maximum local deposition enhancement factors at bronchial airway bifurcations, expressed as the ratio of local to average deposition densities, were determined to characterise the inhomogeneity of deposition and to elucidate their effect on resulting hit probabilities.

Stochastic aspects of primary cellular consequences of radon inhalation.

In this study, a composite, biophysical mechanism-based microdosimetric model was developed for the assessment of the primary cellular consequences of radon inhalation. Based on the concentration of radio-aerosols in the inhaled air and the duration of exposure, this mathematical approach allows the computation of the distribution of cellular burdens and the resulting distribution of cellular inactivation and oncogenic transformation probabilities within the epithelium of the human central airways. The composite model is composed of three major parts.

Three-dimensional model for aerosol transport and deposition in expanding and contracting alveoli.

Particle transport and deposition within a model alveolus, represented by a rhythmically expanding and contracting hemisphere, was modeled by a three-dimensional analytical model for the time-dependent air velocity field as a superposition of uniform and radial flow components, satisfying both the mass and momentum conservation equations. Trajectories of particles entrained in the airflow were calculated by a numerical particle trajectory code to compute simultaneously deposition by inertial impaction, gravitational sedimentation, Brownian diffusion, and interception. Five different orientations of the orifice of the alveolus relative to the direction of gravity were selected.

Quantification of particle deposition in asymmetrical tracheobronchial model geometry.

The primary objective of this study was to quantify the local inspiratory and expiratory aerosol deposition in a highly asymmetric five-generation tracheobronchial tree. User-enhanced commercial codes and self-developed software was used to compute the air velocity field as well as particle deposition distributions for a large size range of inhalable particles. The numerical model was validated by comparison of our results with experimental flow measurements and particle deposition data available in the open literature.

Modelling of cell deaths and cell transformations of inhaled radon in homes and mines based on a biophysical and microdosimetric model.

Purpose: In this study a biophysical mechanism-based microdosimetric model was applied to predict the biological effects of inhaled radon progenies in homes and in uranium mines.

Materials And Methods: The radon daughter concentrations of more than 2000 homes were averaged in case of home exposure and the New Mexico uranium mine data were used in case of exposure in mines. The complex microdosimetric model applied in this work was developed by combining a computational fluid and particle dynamics (CFPD) lung model with a lung dosimetry model that quantify the local distribution of radiation burden and the Unit-Track-Length Model, which characterizes the biological outcome of the exposure.

Effect of inhomogeneous activity distributions and airway geometry on cellular doses in radon lung dosimetry.

The human tracheobronchial system has a very complex structure including cylindrical airway ducts connected by airway bifurcation units. The deposition of the inhaled aerosols within the airways exhibits a very inhomogeneous pattern. The formation of deposition hot spots near the carinal ridge has been confirmed by experimental and computational fluid and particle dynamics (CFPD) methods.