human respiratory tract
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2022 ◽  
Vol 8 (1) ◽  
pp. 75
Author(s):  
Kustrim Cerimi ◽  
Udo Jäckel ◽  
Vera Meyer ◽  
Ugarit Daher ◽  
Jessica Reinert ◽  
...  

Microbial volatile organic compounds (mVOC) are metabolic products and by-products of bacteria and fungi. They play an important role in the biosphere: They are responsible for inter- and intra-species communication and can positively or negatively affect growth in plants. But they can also cause discomfort and disease symptoms in humans. Although a link between mVOCs and respiratory health symptoms in humans has been demonstrated by numerous studies, standardized test systems for evaluating the toxicity of mVOCs are currently not available. Also, mVOCs are not considered systematically at regulatory level. We therefore performed a literature survey of existing in vitro exposure systems and lung models in order to summarize the state-of-the-art and discuss their suitability for understanding the potential toxic effects of mVOCs on human health. We present a review of submerged cultivation, air-liquid-interface (ALI), spheroids and organoids as well as multi-organ approaches and compare their advantages and disadvantages. Furthermore, we discuss the limitations of mVOC fingerprinting. However, given the most recent developments in the field, we expect that there will soon be adequate models of the human respiratory tract and its response to mVOCs.


2022 ◽  
Vol 15 (1) ◽  
pp. 61
Author(s):  
Mohamed Talaat ◽  
Xiuhua Si ◽  
Jinxiang Xi

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.


2021 ◽  
Vol 29 (6) ◽  
pp. 24-32
Author(s):  
Liliya Minvagizovna Fatkhutdinova ◽  
Gyuzel Abdulkhalimovna Timerbulatova ◽  
Evgeniy Pavlovich Bocharov ◽  
Elena Petrovna Sizova ◽  
Gulnaz Faezovna Gabidinova ◽  
...  

Introduction. Air pollution with particulate matter (PM) is a serious global problem. In the Russian Federation, regular field measurements of PMs in the ambient air are carried out only in a few cities, and the data, as a rule, are not systematized. Aim of the study: long-term analysis of the data set on concentrations of fine particles in the ambient air of the city of Kazan. Material and methods. Long-term analysis of ambient air pollution by fine particles in the city of Kazan for the period from 2016 to 2020 has been carried out. To study the effect of separate factors (year, measurement time during the day, climatic conditions, the presence of other pollutants) on the levels of PM10 and PM2.5, regression analysis was applied based on the method of mixed models. To characterize the elemental composition of the PM2.5 fraction, sampling of atmospheric air on PVC filters was carried out by use of 100 NR impactor (TSI, USA). The step function and MPPD model were applied to calculate the number of particles and the mass of the deposited fraction of fine particulate matter in different regions of the human respiratory tract. Results. The PM10 concentrations remained stable over a 5-year period, while the PM2.5 concentrations decreased. At the same time, an increase in the maximum annual concentrations of both fractions was observed. The concentrations of PM10 and PM2.5 significantly depended on climatic conditions. The presence of nitrogen oxides and organic carbon in the ambient air was significantly associated with higher concentrations of PM10 and PM2.5. The elemental composition of PM2.5 fraction was represented mainly by carbon (C) (from 86.16% to 93.45%). Mathematical modeling has shown that PM10 is mainly deposited in the upper respiratory tract, and their presence in the tracheobronchial and alveolar zones is insignificant. PM2.5 particles reach the lower respiratory tract and alveolar area. Conclusion. A statistically significant upward long-term trend in the maximum annual ambient concentrations for both fractions of fine particles can increase health risks. Secondary pollutants (nitrogen oxides, organic carbon) are important factors for the formation of secondary particles in the ambient air. The results obtained indicate that when assessing the risks to public health, it is necessary not only to use the concentrations of fine particles in ambient air, but also to consider the degree of deposition of separate fractions in different parts of the human respiratory tract, considering the alleged pathogenesis and priority target cells characteristic of individual diseases.


2021 ◽  
Author(s):  
Michael C. W. Chan ◽  
Kenrie PY Hui ◽  
John Ho ◽  
Man-chun Cheung ◽  
Ka-chun Ng ◽  
...  

Abstract Emergence of SARS-CoV-2 variants of concern (VOC) with progressively increased transmissibility between humans is a threat to global public health. Omicron variant also evades immunity from natural infection or vaccines1. It is unclear whether its exceptional transmissibility is due to immune evasion or inherent virological properties.We compared the replication competence and cellular tropism of the wild type (WT) virus, D614G, Alpha, Beta, Delta and Omicron variants in ex vivo explant cultures of human bronchus and lung. Dependence on TMPRSS2 for infection was also evaluated. We show that Omicron replicated faster than all other SARS-CoV-2 in the bronchus but less efficiently in the lung parenchyma. All VOCs had similar cellular tropism as the WT. Delta was more dependent on serine protease than other VOCs tested.Our findings demonstrate that Omicron is inherently able to replicate faster than other variants known to date and this likely contributes to its inherently higher transmissibility, irrespective of its ability to evade antibody immunity. The lower replication competence of Omicron in human lung may be compatible with reduced severity but the determinants of severe disease are multifactorial. These findings provide important biological clues to the transmissibility and pathogenesis of SARS-CoV-2 VOCs.


2021 ◽  
Vol 8 (4) ◽  
pp. 21-32
Author(s):  
T.V. Shestakova ◽  
I.A. Kirshchina

RELEVANCE. Bronchial asthma, along with cardiovascular and oncological diseases, is one of the three most common chronic non- communicable diseases. For the most part, anti-asthmatic drugs (LP) are presented in the form of aerosols, powders, solutions for inhalation and other dosage forms intended for administration directly into the human respiratory tract. It is obvious that misunderstanding of the method of application and / or insufficient effectiveness of LP due to improper use can lead to a decrease in patients’ adherence to the prescribed therapy. In this regard, the availability of pharmaceutical information in the instructions becomes important, i.e. the more accessible the information in the instructions is to the patient, the higher the probability of proper use of the drug, maintaining patient compliance and preserving the patient’s quality of life. PURPOSE. The aim of the study was to analyze the completeness of pharmaceutical information provided in the instructions for the medical use of anti-asthmatic drugs (LP) and on the websites of manufacturing companies, from the standpoint of patients’ compliance with the rules for the use of LP. The main objectives of the analysis were: identification of the proportion of anti- asthmatic drugs that have a detailed scheme of use in the instructions; analysis of the instructions of anti-asthmatic drugs from the position of having indications of additional features of the use / use of drugs; analysis of instructions for anti-asthmatic drugs, the use of which is possible for groups of patients with physical or cognitive disabilities; identification of the share of companies producing anti-asthmatic drugs that support patients by conducting a specialized consulting service on the use of drugs. METHODS. The assessment of the quality of pharmaceutical information for patients was carried out on the basis of an analysis of 165 instructions for the medical use of pharmacotherapeutic groups of drugs designated in GINA-2021 (Global Initiative for Asthma-2021) and Federal Clinical Guidelines for the Treatment of Bronchial Asthma of the Russian Respiratory Society (2019) as anti-asthmatic drugs. The analysis was also carried out in relation to the information content of the websites of anti-asthmatic LP manufacturers, additionally, by creating a direct search query, the presence of a private page on the Internet for specific LP was determined. In the course of the research, methods of logical, comparative analysis, as well as generalization and grouping were used. To process the results obtained, the Excel computer program of the Microsoft Office 10 package was used. RESULTS. As a result of the analysis, it was revealed that the vast majority of anti-asthmatic drugs of all the studied pharmacotherapeutic groups are intended for administration directly into the respiratory tract, the article presents the results of a study on the ratio of inhaled and non-inhaled dosage forms in the context of the analyzed pharmacotherapeutic groups. The article presents data on the proportion of anti-asthmatic drugs that have a detailed description in the instructions in addition to the standard method of application (figure, diagram, pictogram) the method of introduction / use of LP. The fact of the absence of a detailed method of application in the instructions of various pharmacotherapeutic groups has been established. The results of the analysis of the number of instructions with the additional properties of LP indicated in them, allowing the use of LP data in patients with physical or cognitive characteristics (limitations), are presented. The number of companies producing anti-asthmatic drugs that have posted detailed information for consumers regarding the use of these drugs on their websites, as well as the number of drugs that have their own website, has been revealed. CONCLUSION. The information in the instructions for the medical use of anti-asthmatic drugs and on the official websites of the manufacturing companies (holders of registration certificates) of the studied drugs is not always exhaustive in terms of the use of inhaled dosage forms, which does not fully ensure the safe and effective receipt of anti-asthmatic pharmacotherapy. According to the authors, improving the quality of information for patients about the rules of using drugs for the treatment of bronchial asthma will simplify the use of dosage forms specific for its therapy, increase patients’ adherence to prescribed pharmacotherapy, reduce the risks from insufficient effectiveness of anti-asthmatic pharmacotherapy and preserve the quality of life of patients associated with the disease.


Atmosphere ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1675
Author(s):  
Ruilian Yu ◽  
Yiling Lin ◽  
Jiahui Zou ◽  
Yangbin Dan ◽  
Chen Cheng

In recent years, atmospheric ozone pollution has become more and more serious in many areas of China due to the rapid development of industrialization and urbanization. The increase in atmospheric ozone concentration will not only cause harm to the human respiratory tract, nervous system and immune system, but also cause obvious harm to crops, which will lead to reductions in crop production. Therefore, the study of atmospheric ozone pollution should not be ignored in research on the atmospheric environment. In this paper, we summarized the formation mechanisms of atmospheric ozone, the spatiotemporal distribution characteristics of atmospheric ozone in some areas of China, the relationship between atmospheric ozone and its precursors, and the main factors affecting the concentration of atmospheric ozone. Then, the control countermeasures against atmospheric ozone pollution were put forward in combination with the actual situation in China.


Pharmacia ◽  
2021 ◽  
Vol 68 (4) ◽  
pp. 899-905
Author(s):  
Nattika Nimmano ◽  
Safura Binti Mohd Mohari

The properties of aerosols generated from salbutamol sulfate solution (1 mg/mL) using an air-jet nebulizer were evaluated using Next Generation Impactor (NGI), a full cascade impactor, and Fast Screening Impactor (FSI), an abbreviated impactor measurement (AIM). Both impactors were operated under the same experimental conditions. The samples were recovered and assayed using validated high performance liquid chromatography (HPLC). The study investigated AIM-Human Respiratory Tract (HRT) concept by comparing key parameters of aerosolization i.e. fine particle dose (FPD) and fine particle fraction (FPF) measured using FSI, with NGI as baseline. The results showed that FSI yielded different but comparable values for FPD and FPF, indicating that it is alternative impactor to NGI. Despite the fact that FSI could not replace NGI, it may be used as an alternative impactor for simple and rapid aerosol characterization of formulations in some pharmaceutical development and quality control processes.


2021 ◽  
Vol 21 (3) ◽  
pp. 141-146
Author(s):  
Ekaterina A. Stepanova ◽  
Ekaterina A. Bazhenova ◽  
Elena V. Krutikova ◽  
Nataliya V. Larionova ◽  
Irina V. Kiseleva ◽  
...  

BACKGROUND: Up to date Russian live attenuated influenza vaccines are produced in developing chicken embryos. During passaging in embryos, the virus isolated from the human respiratory tract undergoes adaptation to the receptors in embryos. The population of the virus, at any passage in chicken embryos, is heterogeneous and contains variants of viruses with one or another set of adaptive substitutions. Before preparing the vaccine strain, the population of the epidemic virus is cloned and the genetic sequence of the hemagglutinin and neuraminidase clones is analyzed. The growth characteristics of the vaccine strain and its antigenic properties depend on the correct choice of the variant of the virus. AIM: The aim of the study was to select the variant of the H3N2 subtype virus for the preparation of a vaccine reassortant based on data on the composition of the population and an assessment of its growth properties. MATERIALS AND METHODS: Viruses were cloned in developing chicken embryos, sequencing of the hemagglutinin and neuraminidase genes of the clones was performed. On the basis of the clones selected based on the results of the analysis of the population, strains of a live influenza vaccine were obtained by the reassortment in the chicken embryos. The growth characteristics of the strains, the phenotype in eggs, and the antigenic properties by hemagglutination inhibition test were evaluated. RESULTS: The influenza virus A/Kansas/14/2017 recommended by WHO for the epidemic season 2019-2020 acquired a pair of D190N + N246T substitutions dominating in the population at the 7th passage in eggs. From the population of A/Kansas/14/2017-like strain A/Brisbane/34/2018, from the third passage in the eggs, it was possible to obtain a variant of the virus with substitutions G186V + S219Y in hemagglutinin. The growth characteristics of the strain based on A/Kansas/14/2017 (passage E7) were significantly inferior to the characteristics of the strain based on A/Brisbane/34/2018 (passage E3), in the absence of differences in antigenic properties. CONCLUSIONS: The variant of egg adaptation of hemagglutinin G186V in strains of clade 3c.3a is preferable for the preparation of live influenza vaccine strains; variant N246T is not optimal. When preparing strains, it is necessary to analyze the composition of the virus population by cloning and choose the most optimal option for preparing strains. The persistence of egg-adaptive substitutions in passaged variants of the virus is not always optimal for strains of live influenza vaccine, and therefore it is preferable to use the population as close as possible to the initial variant to start work on the strain.


2021 ◽  
Vol 54 ◽  
Author(s):  
Kanognudge Wuttanachamsri ◽  
Nattapol Oangwatcharaparkan

In the human respiratory tract, air breathed in is often contaminated with strange particles such as dust and chemical spray, which may cause people respiratory diseases. However, the human body has an innate immune system that helps to trap the debris by secreting mucus to catch the foreign particles, which are removed from the body by the movement of tiny hairs lining on the surface of the epithelial cells in the immune system. The layer containing the tiny hairs or cilia is called Periciliary Layer (PCL). In this research, we find the velocity of the fluid in the PCL moved by a ciliary beating by using the Navier-Stokes-Brinkman equations. We apply the Galerkin finite element method to determine numerical solutions. For the steady linear case of the equation, the numerical result is in good agreement with an exact solution. Including the time derivative and nonlinear terms, we show that the velocity of the liquid is affected by the velocity of the solid, which follows the physical meaning of the fluid flow. The result can be applied as a bottom boundary condition of the mucous layer to be able to find the velocity of mucus in the human lungs.


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