The role of bronchial mucus layer thickness in radon dosimetry.

Abstract Radon is considered to be the second most important cause of lung cancer after smoking. Several investigations proved that at radon inhalation the most exposed parts are the central airways especially the carinal regions of these bifurcations. The radon progenies induced lung tumours show similar spatial distribution as the deposition density distribution of inhaled radon progenies. The bronchial mucus layer absorbs a significant part of the energy of the ionizing alpha-particles. Since the mucus layer thickness is not constant in the different airway generations, the microdosimetric parameters can be significantly influenced by the mucus thickness. Hence, it may be quite important to investigate the role of mucus layer thickness in radon microdosimetry, what is the main objective of this research. The major conclusions of this research are that the thickness of the mucus layer can basically influence the risk of inhaled radon progenies and the relationship between risk and exposure is slightly under linear in the analysed dose range applying an Initiation-Promotion Approach on a three-dimensional epithelium model. The effect of mucus thickness can be observed in every analysed microdosimetric quantities, hence mucus layer thickness cannot be neglected in radon dosimetry in the central airways

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. The results obtained suggest that in the vicinity of the carinal regions of the central airways the probability of multiple hits can be quite high, even at low average doses. Assuming a uniform distribution of activity there are practically no multiple hits and the hit probability as a function of dose exhibits a linear shape in the low dose range. The results are quite the opposite in the case of hot spots revealed by realistic deposition calculations, where practically all cells receive multiple hits and the hit probability as a function of dose is non-linear in the average dose range of 10–100 mGy

Centrális légúti radondepozíció és tisztulás

Abstract Most of the lung cancers of former uranium miners developed in the large central airways. Current computational fluid dynamics calculations indicate high primary deposition in this region. However, the cellular burden of the radon progenies deposited in the deep regions of the lung and clears up by the mucus layer may contribute to the health effects found in airway generations 2–5. In this work, the deposition distribution of inhaled radon progenies was computed by a developed version of the stochastic lung model. A clearance model was constructed to simulate the up clearing fractions of attached and non-attached radon progenies in each bronchial airway generations. Finally, the ratio of the primarily deposited and the up cleared fraction has been calculated in airway generation level at different breathing patterns and mucus velocities. The characteristic input data of the clearance model are the deposition pattern, the velocity of the mucus per generation, the length of the airways and the half life of radon progenies. Based on the results, in the central airways, the radiation burden of the up clearing, more deeply deposited, radon progenies can significantly be higher than the burden of the primarily deposited fraction in these central airways

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. Therefore, in the present study, the Radact version of the stochastic lung model was used to quantify the cellular radiation dose distribution at airway generation level and to simulate the kinetics of the deposited radon progeny resulting from the moving mucus layer. All simulations were performed assuming an isotope ratio typical for an average dwelling, and breathing mode characteristic of a healthy adult sitting man. The study demonstrates that the cell nuclei receiving high doses are non-uniformly distributed within the bronchial airway generations. The results revealed that the maximum of the radiation burden is at the first few bronchial airway generations of the respiratory tract, where most of the lung carcinomas of former uranium miners were found. Based on the results of the present simulations, it can be stated that regional lung models may not be fully adequate to describe the radiation burden due to radon progeny. A more realistic and precise calculation of the absorbed doses from the decay of radon progeny to the lung requires deposition and clearance to be simulated by realistic models of airway generations.(VLID)469743

Modeling of nursing care-associated airborne transmission of SARS-CoV-2 in a real-world hospital setting

Respiratory transmission of SARS-CoV-2 from one older patient to another by airborne mechanisms in hospital and nursing home settings represents an important health challenge during the COVID-19 pandemic. However, the factors that influence the concentration of respiratory droplets and aerosols that potentially contribute to hospital- and nursing care-associated transmission of SARS-CoV-2 are not well understood. To assess the effect of health care professional (HCP) and patient activity on size and concentration of airborne particles, an optical particle counter was placed (for 24 h) in the head position of an empty bed in the hospital room of a patient admitted from the nursing home with confirmed COVID-19. The type and duration of the activity, as well as the number of HCPs providing patient care, were recorded. Concentration changes associated with specific activities were determined, and airway deposition modeling was performed using these data. Thirty-one activities were recorded, and six representative ones were selected for deposition modeling, including patient’s activities (coughing, movements, etc.), diagnostic and therapeutic interventions (e.g., diagnostic tests and drug administration), as well as nursing patient care (e.g., bedding and hygiene). The increase in particle concentration of all sizes was sensitive to the type of activity. Increases in supermicron particle concentration were associated with the number of HCPs (r = 0.66; p < 0.05) and the duration of activity (r = 0.82; p < 0.05), while submicron particles increased with all activities, mainly during the daytime. Based on simulations, the number of particles deposited in unit time was the highest in the acinar region, while deposition density rate (number/cm(2)/min) was the highest in the upper airways. In conclusion, even short periods of HCP-patient interaction and minimal patient activity in a hospital room or nursing home bedroom may significantly increase the concentration of submicron particles mainly depositing in the acinar regions, while mainly nursing activities increase the concentration of supermicron particles depositing in larger airways of the adjacent bed patient. Our data emphasize the need for effective interventions to limit hospital- and nursing care-associated transmission of SARS-CoV-2 and other respiratory pathogens (including viral pathogens, such as rhinoviruses, respiratory syncytial virus, influenza virus, parainfluenza virus and adenoviruses, and bacterial and fungal pathogens)

Biophysical modelling of the effects of inhaled radon progeny on the bronchial epithelium for the estimation of the relationships applied in the two-stage clonal expansion model of carcinogenesis

There is a considerable debate between research groups applying the two stage clonal expansion model for lung cancer risk estimation, whether radon exposure affects initiation and transformation or promotion. The objective of the present study is to quantify the effects of radon progeny on these stages with biophysical models. For this purpose, numerical models of mutation induction and clonal growth were applied in order to estimate how initiation, transformation and promotion rates depend on tissue dose rate. It was found that rates of initiation and transformation increase monotonically with dose rate, while effective promotion rate decreases with time, but increases in a supralinear fashion with dose rate. Despite the uncertainty of the results due to the lack of experimental data, present study suggests that effects of radon exposure on both mutational events and clonal growth are significant, and should be considered in epidemiological analyses applying mathematical models of carcinogenesis