scholarly journals Prediction of Aerosol Deposition in the Human Respiratory Tract via Computational Models: A Review with Recent Updates

Atmosphere ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 137 ◽  
Author(s):  
Vu Khac Hoang Bui ◽  
Ju-Young Moon ◽  
Minhe Chae ◽  
Duckshin Park ◽  
Young-Chul Lee
Keyword(s):  
Respiratory Tract ◽  
Particle Deposition ◽  
Computational Models ◽  
Aerosol Particles ◽  
Three Dimensional ◽  
Aerosol Deposition ◽  
Research Area ◽  
Human Respiratory Tract

The measurement of deposited aerosol particles in the respiratory tract via in vivo and in vitro approaches is difficult due to those approaches’ many limitations. In order to overcome these obstacles, different computational models have been developed to predict the deposition of aerosol particles inside the lung. Recently, some remarkable models have been developed based on conventional semi-empirical models, one-dimensional whole-lung models, three-dimensional computational fluid dynamics models, and artificial neural networks for the prediction of aerosol-particle deposition with a high accuracy relative to experimental data. However, these models still have some disadvantages that should be overcome shortly. In this paper, we take a closer look at the current research trends as well as the future directions of this research area.

A theory of aerosol deposition in the human respiratory tract

1975 ◽  
Vol 38 (1) ◽  
pp. 77-85 ◽  
Author(s):  
D. B. Taulbee ◽  
C. P. Yu
Keyword(s):  
Particle Size ◽  
Respiratory Tract ◽  
Particle Deposition ◽  
Particle Concentration ◽  
Diffusion Mechanism ◽  
Aerosol Deposition ◽  
Lung Model ◽  
Brownian Diffusion ◽  
Human Respiratory Tract ◽  
Apparent Diffusion

The deposition of inhaled aerosol particles in the human respiratory tract is due to the mechanisms of inertia impaction, Brownian diffusion, and gravitational settling. A theory is developed to predict the particle deposition and its distribution in human respiratory tract for any breathing condition. A convection-diffusion equation for the particle concentration with a loss term is used to describe the transport and deposition of particles. In this equation, an apparent diffusion coefficient due to the velocity dispersion in the lung is present and found to be the dominant diffusion mechanism for the cases considered here. Expressions for deposition by various mechanisms are also derived. The governing equation is solved numerically with Weibel's lung model A. The particle concentration at the mouth is calculated during washin and washout and compared favorably with experimental recordings for 0.5-mum diameter di(2-ethylhexyl) sebacate particles. The total deposition in the lung for particle size ranging from 0.05 to 5 mum is also computed for a 500-cm-3 tidal volume and 15 breaths/min. The results in general agree with recent measurements of Heyder et al. However, a particle size of minimum deposition is found to exist theoretically near 0.3 mum.

Methodology for the measurement of mucociliary function in the mouse by scintigraphy

2001 ◽  
Vol 90 (3) ◽  
pp. 1111-1118 ◽  
Author(s):  
W. Michael Foster ◽  
Dianne M. Walters ◽  
Malinda Longphre ◽  
Kristin Macri ◽  
Laura M. Miller
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Particle Deposition ◽  
Time Course ◽  
Colloidal Particles ◽  
Intratracheal Instillation ◽  
Aerosol Inhalation ◽  
Mucociliary Function

The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by γ-camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., ∼60–80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and ≥80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.

scholarly journals Effects of Psa and F1 on the Adhesive and Invasive Interactions of Yersinia pestis with Human Respiratory Tract Epithelial Cells

2006 ◽  
Vol 74 (10) ◽  
pp. 5636-5644 ◽  
Author(s):  
Fengzhi Liu ◽  
Huaiqing Chen ◽  
Estela M. Galván ◽  
Melissa A. Lasaro ◽  
Dieter M. Schifferli
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Yersinia Pestis ◽  
Bacterial Adhesion ◽  
Wild Type Strain ◽  
Cell Types ◽  
Human Respiratory Tract ◽  
Bacterial Uptake

ABSTRACT Yersinia pestis, the causative agent of plague, expresses the Psa fimbriae (pH 6 antigen) in vitro and in vivo. To evaluate the potential virulence properties of Psa for pneumonic plague, an Escherichia coli strain expressing Psa was engineered and shown to adhere to three types of human respiratory tract epithelial cells. Psa binding specificity was confirmed with Psa-coated polystyrene beads and by inhibition assays. Individual Y. pestis cells were found to be able to express the capsular antigen fraction 1 (F1) concomitantly with Psa on their surface when analyzed by flow cytometry. To better evaluate the separate effects of F1 and Psa on the adhesive and invasive properties of Y. pestis, isogenic Δcaf (F1 genes), Δpsa, and Δcaf Δpsa mutants were constructed and studied with the three respiratory tract epithelial cells. The Δpsa mutant bound significantly less to all three epithelial cells compared to the parental wild-type strain and the Δcaf and Δcaf Δpsa mutants, indicating that Psa acts as an adhesin for respiratory tract epithelial cells. An antiadhesive effect of F1 was clearly detectable only in the absence of Psa, underlining the dominance of the Psa+ phenotype. Both F1 and Psa inhibited the intracellular uptake of Y. pestis. Thus, F1 inhibits bacterial uptake by inhibiting bacterial adhesion to epithelial cells, whereas Psa seems to block bacterial uptake by interacting with a host receptor that doesn't direct internalization. The Δcaf Δpsa double mutant bound and invaded all three epithelial cell types well, revealing the presence of an undefined adhesin(s) and invasin(s).

scholarly journals The BvgS PAS domain: an independent sensory perception module in theBordetellaBvgAS phosphorelay

2019 ◽  
Author(s):  
M. Ashley Sobran ◽  
Peggy A. Cotter
Keyword(s):  
Respiratory Tract ◽  
Bordetella Pertussis ◽  
Kinase Activity ◽  
Expression Patterns ◽  
Pas Domain ◽  
Human Respiratory Tract ◽  
Signal Perception ◽  
Two Component

AbstractTo detect and respond to the diverse environments they encounter, bacteria often use two-component regulatory systems (TCSs) to coordinate essential cellular processes required for survival. In pathogenicBordetellaspecies, the BvgAS TCS regulates expression of hundreds of genes, including those encoding all known protein virulence factors, and its kinase activity is essential for respiratory infection. Maintenance of BvgS kinase activity in the lower respiratory tract (LRT) depends on the function of another TCS, PlrSR. While the periplasmic venus fly-trap domains of BvgS have been implicated in responding to so-called modulating signalsin vitro(nicotinic acid and MgSO4), a role for the cytoplasmic Per-Arnt-Sim (PAS) domain in signal perception has not previously been demonstrated. By comparingB. bronchisepticastrains with mutations in the PAS domain-encoding region ofbvgSwith wild-type bacteriain vitroandin vivo, we found that although the PAS domain is not required to sense modulating signalsin vitro, it is required for the inactivation of BvgS that occurs in the absence of PlrS in the LRT of mice, suggesting that the BvgS PAS domain functions as an independent signal perception domain. Our data also indicate that the BvgS PAS domain is important for controlling absolute levels of BvgS kinase activity and the efficiency of the response to modulating signalsin vitro. Our results indicate that BvgS is capable of integrating sensory inputs from both the periplasm and the cytoplasm to control precise gene expression patterns in diverse environmental conditions.ImportanceDespite high rates of vaccination, Pertussis, a severe, highly contagious respiratory disease, caused by the bacteriumBordetella pertussis, has reemerged as a significant health threat. InBordetella pertussisand the closely related species,Bordetella bronchiseptica, activity of the BvgAS two-component regulatory system is critical for colonization of the human respiratory tract and other mammalian hosts, respectively. Here we show that the cytoplasmic PAS domain of BvgS can function as an independent signal perception domain that is capable of integrating environmental signals that influence overall BvgS activity. Our work is significant as it reveals a critical, yet previously unrecognized role, for the PAS domain in the BvgAS phosphorelay and provides a greater understanding of virulence regulation inBordetella.

scholarly journals Sex-dependent differences in central artery haemodynamics in normal and fibulin-5 deficient mice: implications for ageing

2019 ◽  
Vol 475 (2221) ◽  
pp. 20180076 ◽  
Author(s):  
Federica Cuomo ◽  
Jacopo Ferruzzi ◽  
Pradyumn Agarwal ◽  
Chen Li ◽  
Zhen W. Zhuang ◽  
...  
Keyword(s):  
Computational Models ◽  
Pulse Wave ◽  
Three Dimensional ◽  
Micro Computed Tomography ◽  
Central Artery ◽  
Wall Stiffness ◽  
Outflow Boundary ◽  
Deficient Mice

Mouse models provide unique opportunities to study vascular disease, but they demand increased experimental and computational resolution. We describe a workflow for combining in vivo and in vitro biomechanical data to build mouse-specific computational models of the central vasculature including regional variations in biaxial wall stiffness, thickness and perivascular support. These fluid–solid interaction models are informed by micro-computed tomography imaging and in vivo ultrasound and pressure measurements, and include mouse-specific inflow and outflow boundary conditions. Hence, the model can capture three-dimensional unsteady flows and pulse wave characteristics. The utility of this experimental–computational approach is illustrated by comparing central artery biomechanics in adult wild-type and fibulin-5 deficient mice, a model of early vascular ageing. Findings are also examined as a function of sex. Computational results compare well with measurements and data available in the literature and suggest that pulse wave velocity, a spatially integrated measure of arterial stiffness, does not reflect well the presence of regional differences in stiffening, particularly those manifested in male versus female mice. Modelling results are also useful for comparing quantities that are difficult to measure or infer experimentally, including local pulse pressures at the renal arteries and characteristics of the peripheral vascular bed that may differ with disease.

scholarly journals In VivoGene Essentiality and Metabolism inBordetella pertussis

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Laura A. Gonyar ◽  
Patrick E. Gelbach ◽  
Dennis G. McDuffie ◽  
Alexander F. Koeppel ◽  
Qing Chen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Murine Model ◽  
Whooping Cough ◽  
Critical Role ◽  
Respiratory Illness ◽  
Human Respiratory Tract ◽  
Content Type ◽  
Gene Essentiality

ABSTRACTBordetella pertussisis the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms ofB. pertussisgrowth and pathogenicity. While previous studies have provided insight intoin vitrogene essentiality of this organism, very little is known aboutin vivogene essentiality, a critical gap in knowledge, sinceB. pertussishas no previously identified environmental reservoir and is isolated from human respiratory tract samples. We hypothesize that the metabolic capabilities ofB. pertussisare especially tailored to the respiratory tract and that many of the genes involved inB. pertussismetabolism would be required to establish infectionin vivo. In this study, we generated a diverse library of transposon mutants and then used it to probe gene essentialityin vivoin a murine model of infection. Using the CON-ARTIST pipeline, 117 genes were identified as conditionally essential at 1 day postinfection, and 169 genes were identified as conditionally essential at 3 days postinfection. Most of the identified genes were associated with metabolism, and we utilized two existing genome-scale metabolic network reconstructions to probe the effects of individual essential genes on biomass synthesis. This analysis suggested a critical role for glucose metabolism and lipooligosaccharide biosynthesisin vivo. This is the first genome-wide evaluation ofin vivogene essentiality inB. pertussisand provides tools for future exploration.IMPORTANCEOur study describes the firstin vivotransposon sequencing (Tn-seq) analysis ofB. pertussisand identifies genes predicted to be essential forin vivogrowth in a murine model of intranasal infection, generating key resources for future investigations intoB. pertussispathogenesis and vaccine design.

Effect of pyocyanin and 1-hydroxyphenazine on in vivo tracheal mucus velocity

1989 ◽  
Vol 67 (1) ◽  
pp. 316-323 ◽  
Author(s):  
N. C. Munro ◽  
A. Barker ◽  
A. Rutman ◽  
G. Taylor ◽  
D. Watson ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Guinea Pigs ◽  
Bolus Dose ◽  
Ringer Solution ◽  
Human Respiratory Tract ◽  
Tracheal Mucus

Products of the bacterium Pseudomonas aeruginosa have been shown to slow the beating of human respiratory tract cilia in vitro. We have tested the effects of two of these compounds, pyocyanin and 1-hydroxyphenazine (given as a bolus dose dissolved in 2 microliters Ringer solution), on tracheal mucus velocity of radiolabeled erythrocytes in anesthetized guinea pigs. 1-Hydroxyphenazine (200 ng) caused a rapid slowing of tracheal mucus velocity (maximum fall 47% at 20 min) with recovery by 1 h. The effect of pyocyanin was slower in onset, 600 ng causing 60% reduction in tracheal mucus velocity at 3 h, and no recovery occurred. A combination of pyocyanin and 1-hydroxyphenazine produced an initial rapid slowing equivalent to the same dose of 1-hydroxyphenazine given alone, but the later slowing attributed to pyocyanin was greater than the same dose administered alone. This study demonstrates one mechanism by which products of P. aeruginosa may facilitate its colonization of the respiratory tract.

scholarly journals Analysis of Cigarette Smoke Deposition Within an In Vitro Exposure System for Simulating Exposure in the Human Respiratory Tract

2016 ◽  
Vol 27 (1) ◽  
Author(s):  
Shinkichi Ishikawa ◽  
Yasufumi Nagata ◽  
Takuya Suzuki
Keyword(s):  
Respiratory Tract ◽  
Cigarette Smoke ◽  
Chemical Exposure ◽  
Cigarette Smoke Exposure ◽  
Human Respiratory Tract ◽  
Exposure System ◽  
Direct Exposure ◽  
Air Liquid Interface

SummaryFor the risk assessment of airborne chemicals, a variety of in vitro direct exposure systems have been developed to replicate airborne chemical exposure in vivo. Since cells at the air-liquid interface are exposed to cigarette smoke as an aerosol in direct exposure systems, it is possible to reproduce the situation of cigarette smoke exposure in the human respiratory system using this device. However it is difficult to know whether the exposed cigarette smoke in this system is consistent with the smoke retained in the human respiratory tract. The purpose of this study is to clarify this point using the CULTEX

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