Human Respiratory Tree Research Articles

Glucocorticoids are differentially synthesized along the murine and human respiratory tree.

Synthetic glucocorticoids (GC) are effective in the treatment of inflammatory diseases of the lung. However, long-term use leads to severe side effects. Endogenous GC can be synthesized locally, either de novo from cholesterol in a 11β-hydroxylase (Cyp11b1)-dependent manner, or by reactivation from 11-dehydrocorticosterone/cortisone by 11β-hydroxysteroid dehydrogenase 1 (Hsd11b1). We aimed to define the molecular pathways of endogenous GC synthesis along the respiratory tree to provide a basis for understanding how local GC synthesis contributes to tissue homeostasis. Expression of steroidogenic enzymes in murine lung epithelium was analyzed by macroscopic and laser capture microdissection, followed by RT-qPCR. Flow cytometry analysis was performed to identify the cellular source of steroidogenic enzymes. Additionally, the induction of steroidogenic enzyme expression in the lung was analyzed after lipopolysaccharide (LPS) injection. mRNA and protein expression of steroidogenic enzymes was confirmed in human lung tissue by RT-qPCR and immunohistochemistry. Furthermore, GC synthesis was examined in ex vivo cultures of fresh tissue from mice and human lobectomy patients. We observed that the murine and human lung tissue differentially expresses synthesis pathway-determining enzymes along the respiratory tree. We detected Hsd11b1 expression in bronchial, alveolar, club and basal epithelial cells, whereas Cyp11b1 expression was detectable only in tracheal epithelial cells of mice. Accordingly, de novo synthesis of bioactive GC occurred in the large conducting airways, whereas reactivation occurred everywhere along the respiratory tree. Strikingly, Cyp11b1 but not Hsd11b1 expression was enhanced in the trachea upon LPS injection in mice. We report here the differential synthesis of bioactive GC along the murine and human respiratory tree. Thus, extra-adrenal de novo GC synthesis and reactivation may differentially contribute to the regulation of immunological and inflammatory processes in the lung.

Quantitative and qualitative analysis of operator inhaled aerosols during routine motorised equine dental treatment.

Routine equine odontoplasty is performed by both Veterinary Surgeons and Equine Dental Technicians. The production of aerosolised particulates from motorised equipment has been well documented in human orthodontics but has yet to be investigated in the veterinary industry. To assess the size, quantity and composition of particulates produced during routine motorised odontoplasty and to model their deposition in the human respiratory tree. Analytic observational study. Fifteen-minute routine motorised odontoplasties were performed on cadaver heads with monitoring equipment placed 30cm away from the oral cavity to simulate the position of the operator's face. For quantitative analysis, an active air sampling photometric monitor was used to detect the concentration of fully respirable (<4.25µm) particles produced. The use of water and non-water-cooled equipment and 2 different types of face mask (standard surgical and FFP3) were compared. An 8-stage Marple Personal Cascade Impactor modelled the deposition of the particulates in relation to the human respiratory tree. Qualitative analysis of these particulates was performed using scanning electron microscopy and energy dispersive x-ray spectroscopy. Motorised odontoplasty created aerosolised particulates that could reach all levels of the human respiratory tree. These particulates were composed mostly of calcium and phosphate, although traces of metals were found. The concentration of fully respirable particulates exceeded the recommended exposure limits set by the Health and Safety Executive. The use of an FFP-3 face mask significantly reduced the level of inhaled particulates. This was a simulated experiment. It does not take into account the variety of environments in which routine treatment takes place. There are possible health risks in performing a large amount of routine motorised dentistry due to inhalation of aerosolised particulates. The use of an adequate face mask lowers exposure levels to within acceptable limits and, therefore, should be worn.

Implementation of a Fractional-Order Electronically Reconfigurable Lung Impedance Emulator of the Human Respiratory Tree

The fractional-order lung impedance model of the human respiratory tree is implemented in this paper, using Operational Transconductance Amplifiers. The employment of such active element offers electronic adjustment of the impedance characteristics in terms of both elements values and orders. As the MOS transistors in OTAs are biased in the weak inversion region, the power dissipation and the dc bias voltage of operation are also minimized. In addition, the partial fraction expansion tool has been utilized, in order to achieve reduction of the spread of the required time-constants and scaling factors. The performance of the proposed scheme has been evaluated, at post-layout level, using MOS transistors models provided by the 0.35 μ m Austria Mikro Systeme technology CMOS process, and the Cadence IC design suite.

Penetration of inhaled aerosols in the bronchial tree

It has long been recognized that the pattern of particle deposition in the respiratory tree affects how far aerosols penetrate into the deeper zones of the arterial tree, and hence contribute to either their pathogenic potential or therapeutic benefit. In this paper, we introduce an anatomically-inspired model of the human respiratory tree featuring the generations 0–7 in the Weibel model of respiratory tree (i.e., the conducting zone). This model is used to study experimentally the dynamics of inhaled aerosol particles (0.5–20µm aerodynamic diameter), in terms of the penetration fraction of particles (i.e., the fraction of inflowing particles that leave the flow system) during typical breathing patterns. Our study underline important modifications in the penetration patterns for coarse particles compared to fine particles. Our experiments suggest a significant decrease of particle penetration for large-sized particles and higher respiratory frequencies. Dimensionless numbers are also introduced to further understand the particle penetration into the respiratory tree. A decline is seen in the penetration fraction with decreasing Reynolds number and increasing Stokes number. A simple conceptual framework is presented to provide additional insights into the findings obtained.

Microbiological assessment of aerosol generated during debond of fixed orthodontic appliances.

The aims of this study were to describe bacterial load and diversity of the aerosol created during enamel cleanup after the removal of fixed orthodontic appliances and to assess the effect of a preprocedural mouth rinse. The study involved the sampling of ambient air adjacent to the patient's mouth during adhesive removal using a slow-speed handpiece and a spiral fluted tungsten carbide bur without water irrigation. Sampling was carried out during enamel cleanup with or without a preprocedural mouth rinse of either sterile water or chlorhexidine. Airborne particles were collected using a viable inertial impactor simulating the human respiratory tree. The bacteria collected were analyzed using both culture and molecular techniques. Bacteria produced during debond and enamel cleanup can reach all levels of the respiratory tree. The use of a preprocedural mouth rinse, either sterile water or chlorhexidine, increased the numbers and diversity of the bacteria in the air. When using a slow-speed handpiece and a spiral fluted tungsten carbide bur for enamel cleanup after orthodontic treatment, the bacterial load and diversity of the aerosol produced are lower when a preprocedural mouth rinse is not used.

A 2-adic approach of the human respiratory tree

We propose here a general framework to address the question of trace operators on a dyadic tree. This work is motivated by the modeling of the human bronchial tree which, thanks to its regularity, can be extrapolated in a natural way to an infinite resistive tree. The space of pressure fields at bifurcation nodes of this infinite tree can be endowed with a Sobolev space structure, with a semi-norm which measures the instantaneous rate of dissipated energy. We aim at describing the behaviour of finite energy pressure fields near the end.The core of the present approach is an identification ofthe set of ends with the ring $\ZZ$2 of 2-adic integers. Sobolev spaces over $\ZZ$2 can be defined in a very natural way by means of Fourier transform, which allows us to establish precised trace theorems which are formally quite similar to those in standard Sobolev spaces, with a Sobolev regularity which depends on the growth rate of resistances, i.e. on geometrical properties of the tree. Furthermore, we exhibit an explicit expression of the 'ventilation operator'', which maps pressure fields at the end of the tree onto fluxes, in the form of a convolution by a Riesz kernel based on the 2-adic distance.

Viscoelasticity and fractal structure in a model of human lungs

This paper provides a model of the human respiratory system by taking into account the fractal structure of the airways and the viscoelastic properties of the tissue. The self-similarity of airway distribution is admitted up to the 24th generation. Due to periodic breathing which results in sinusoidal excitation of the respiratory system, an electrical equivalent model is developed. The periodic current in this electrical network, that preserves the geometry of the human respiratory tree, is equivalent to the oscillatory air-flow. The model is expressed by Navier–Stokes equations under cylindrical symmetry, linked with an equation responsible for the motion of viscoelastic tissue of airway walls. By use of both electro-mechanical analogies, the total impedance of the respiratory system is determined and compared to the measured data in the clinical range of 4–48 Hz, as well as in the low-frequency range of 0.1–5 Hz. We propose also a lumped model of fractional orders, which is able to capture frequency-dependent variations in both clinical as well as in the low-frequency ranges. The models proposed in this paper can be further used to determine the effects of disease on the lung morphology.

Mechanical Properties of the Respiratory System Derived From Morphologic Insight

This paper aims to provide the mechanical parameters of the respiratory airways (resistance, inertance, and compliance) from morphological insight, in order to facilitate the correlations of fractional-order models with pathologic changes. The approach consists of taking into account wall thickness, inner radius, tube length, and tissue structure for each airway level to combine them into a set of equations for modeling the pressure drop, flow, wall elasticity, and air velocity (axial and radial). Effects of pulmonary disease affecting the inner radius and elastic modulus of bronchial tree are discussed. A brief comparison with the circulatory system, which poses similarities with the respiratory system, is also given. The derived mechanical parameters can serve as elements in a transmission line equivalent, whose structure preserves the geometry of the human respiratory tree. The mechanical parameters derived in this paper offer the possibility to evaluate input impedance by altering the morphological parameters in relation to the pulmonary disease. In this way, we obtain a simple, yet accurate, model to simulate and understand specific effects in respiratory diseases; e.g., airway remodeling. The final scope of the research is to relate the variations in airway structure with disease to the values of fractional-order model parameters.

Constructal theory and flow architectures in living systems

We apply Constructal theory to the study of the flow structure of the human respiratory tree. We show that the flow architecture that would per form oxygenation of the blood and removal of carbon dioxide best, i. e. with lowest resistance, would be composed of a channel system with 23 bifurcation with a diffusive zone (alveolus) at the end. As this tree matches the human respiratory tree we conclude that nature has optimized it in time. Two constructal relation ships also emerge: (1) the length l, de fined by the ratio of the square of the airway diameter to its length, is constant for all individuals of the same species, and (2) the length ? is related to the volume of the space al located to the respiratory process, to the length of the respiratory tree and to the area of the alveoli, and determines univocally the branching level of the respiratory tree.

Predicting the efficacy of antimicrobial agents in respiratory infections--is tissue concentration a valid measure?

Despite methodological and interpretive problems associated with studies of antibiotic concentrations in tissues, it is important to confirm the presence of a drug in significant concentrations in tissues and fluids at a particular site. For antibiotics used in the treatment of community-acquired respiratory infections, tissue distribution at sites of potential infection in the respiratory tree has been related to clinical outcome. Measurement of antibiotic concentrations achieved in lung parenchyma epithelial lining fluid, bronchial mucosa or bronchial secretions has indicated significant levels for beta-lactams and macrolides. Many respiratory infections are caused by obligate or facultative intracellular pathogens, which may be eradicated as a result of intracellular penetration and accumulation of macrolides, as shown in several models of phagocytic cells, and of intracellular antibacterial activities. For bacterial infections located in extracellular pulmonary sites, a knowledge of achievable concentrations of beta-lactam and of macrolides should be of value. For bacteria multiplying in alveolar macrophages the high concentrations of the new macrolides that can be achieved in extravascular and intracellular fluids should have clinical relevance, as shown in this review. Moreover with newer macrolides one may expect a better patient compliance due to prolonged persistence of drug in tissues and cells which results in shorter duration of treatment and once-daily dose administration. Finally, for some sites of infection and particularly in the human respiratory tree, there is a clear relationship between local concentrations and clinical efficacy.