A secondary function of the respiratory system of the mammals is, during inspiration, to heat the air to body temperature and to saturate it with water before it reaches the alveoli. Relying on a ...mathematical model, we propose a comprehensive analysis of this function, considering all the terrestrial mammals (spanning six orders of magnitude of the body mass, M) and focusing on the sole contribution of the lungs to this air conditioning. The results highlight significant differences between the small and the large mammals, as well as between rest and effort, regarding the spatial distribution of heat and water exchanges in the lungs, and also in terms of regime of mass transfer taking place in the lumen of the airways. Interestingly, the results show that the mammalian lungs appear to be designed just right to fully condition the air at maximal effort (and clearly over-designed at rest, except for the smallest mammals): all generations of the bronchial region of the lungs are mobilized for this purpose, with calculated values of the local evaporation rate of water from the bronchial mucosa that can be very close to the maximal ability of the serous cells to replenish this mucosa with water. For mammals with a mass above a certain threshold (Formula: see text kg at rest and Formula: see text g at maximal effort), it appears that the maximal value of this evaporation rate scales as Formula: see text at rest and Formula: see text at maximal effort and that around 40% (at rest) or 50% (at maximal effort) of the water/heat extracted from the lungs during inspiration is returned to the bronchial mucosa during expiration, independently of the mass, due to a subtle coupling between different phenomena. This last result implies that, above these thresholds, the amounts of water and heat extracted from the lungs by the ventilation scale with the mass such as the ventilation rate does (i.e. as Formula: see text at rest and Formula: see text at maximal effort). Finally, it is worth to mention that these amounts appear to remain limited, but not negligible, when compared to relevant global quantities, even at maximal effort (4-6%).
In this work, we aim to analyze and compare the mechanisms controlling the volume of mucus in the bronchial region of the lungs of a healthy human adult, at rest and in usual atmospheric conditions. ...This analysis is based on a balance equation for the mucus in an airway, completed by a computational tool aiming at characterizing the evaporation, during respiration, of the water contained in the bronchial mucus. An idealized representation of the lungs, based on Weibel's morphometric model, is used. The results indicate that the mechanisms controlling the volume of mucus in an airway depend on the localization of the airway in the bronchial region of the lungs. In the proximal generations, the volume of mucus in an airway is mainly controlled by the evaporation of the water it contains and the replenishment, with water, of the mucus layer by epithelial cells or the submucosal glands. Nevertheless, cilia beating in this part of the bronchial region remains of fundamental importance to transport the mucus and hence to eliminate dust and pathogens trapped in it. On the other hand, in the distal generations of the bronchial region, the volume of mucus in an airway is mainly controlled by the mucociliary transport and by the absorption of liquid by the epithelium. This absorption is a consequence of the mucus displacement by the cilia along generations with an interface between the epithelium and the airway surface layer of decreasing area. The numerical results obtained are in good agreement with previously published experimental data, thus validating our approach. We also briefly discuss how our results can improve the understanding and, possibly, the treatment of pulmonary diseases.
Though considered as an inflammation marker, exhaled nitric oxide (F
NO) was shown to be sensitive to airway caliber changes to such an extent that it might be considered as a marker of them. It is ...thus important to understand how these changes and their localization mechanically affect the total NO flux penetrating the airway lumen (JawNO), and hence F
NO, independently from any inflammatory status change. In this work, a new model was used. It simulates NO production, consumption and diffusion inside the airway epithelium, NO excretion from the epithelial wall into the airway lumen and, finally, its axial transport by diffusion and convection in the airway lumen. This model may also consider the possible presence of a fluid layer coating the epithelial wall. Simulations were performed. They show the great sensitivity of JawNO to peripheral airways caliber changes. Moreover, F
NO shows distinct behaviors depending on the location of the caliber change. Considering a bronchodilation, absence of F
NO change was associated with dilation of central airways, F
NO increase with dilation down to pre-acinar small airways, and F
NO decrease with intra-acinar dilation due to the amplification of the back-diffusion flux. The presence of a fluid layer was also shown to play a significant role in F
NO changes. Altogether, the present work theoretically supports that specific F
NO changes in acute situations are linked to specifically located airway caliber changes in the lung periphery. This opens the way for a new role for F
NO as a functional marker of peripheral airway caliber change.
In healthy subjects, at low minute ventilation (V̇e) during physical exercise, the water content and temperature of the airways are well regulated. However, with the increase in V̇e, the bronchial ...mucosa becomes dehydrated and epithelial damage occurs. Our goal was to demonstrate the correspondence between the ventilatory threshold inducing epithelial damage, measured experimentally, and the dehydration threshold, estimated numerically. In 16 healthy adults, we assessed epithelial damage before and following a 30-min continuous cycling exercise at 70% of maximal work rate, by measuring the variation pre- to postexercise of serum club cell protein (cc16/cr). Blood samples were collected at rest, just at the end of the standardized 10-min warm-up, and immediately, 30 min and 60 min postexercise. Mean V̇e during exercise was kept for analysis. Airway water and heat losses were estimated using a computational model adapted to the experimental conditions and were compared with a literature-based threshold of bronchial dehydration. Eleven participants exceeded the threshold for bronchial dehydration during exercise (
) and five did not (
). Compared with post warm-up, the increase in cc16/cr postexercise was significant (mean increase ± SE: 0.48 ± 0.08 ng·L
only in
but not in
(mean difference ± SE: 0.10 ± 0.04 ng·L
). This corresponds to an increase of 101 ± 32% range: 16%-367% in
(mean ± SE). Our findings suggest that the use of a computational model may be helpful to estimate an individual dehydration threshold of the airways that is associated with epithelial damage during physical exercise.
Using a computational model for heat and water transfers in the bronchi, we identified a threshold in ventilation during exercise above which airway dehydration is thought to occur. When this threshold was exceeded, epithelial damage was found. This threshold might therefore represent the ventilation upper limit during exercise in susceptible individuals. Our results might help to prevent maladaptation to chronic exercise such as exercise-induced bronchoconstriction or asthma.
In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial ...activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might provide an interesting way to characterize the extent of BC in unhealthy patients.
A model of optimal control of ventilation has recently been developed for humans. This model highlights the importance of the localization of the transition between a convective and a diffusive ...transport of respiratory gas. This localization determines how ventilation should be controlled in order to minimize its energetic cost at any metabolic regime. We generalized this model to any mammal, based on the core morphometric characteristics shared by all mammalian lungs and on their allometric scaling from the literature. Since the main energetic costs of ventilation are related to convective transport, we prove that, for all mammals, the localization of the shift from a convective transport to a diffusive transport plays a critical role on keeping this cost low while fulfilling the lung function. Our model predicts for the first time the localization of this transition in order to minimize the energetic cost of ventilation, depending on mammal mass and metabolic regime. From this optimal localization, we are able to predict allometric scaling laws for both tidal volumes and breathing rates, at any metabolic rate. We ran our model for the three common metabolic rates -- basal, field and maximal -- and showed that our predictions reproduce accurately experimental data available in the literature. Our analysis supports the hypothesis that mammals allometric scaling laws of tidal volumes and breathing rates at a given metabolic rate are driven by a few core geometrical characteristics shared by mammalian lungs and by the physical processes of respiratory gas transport.
The challenges of the Haitian democratic construction present a unique perspective on an institutional model that has garnered extensive attention in the contemporary human rights discourse and ...developed into a strategic priority for the United Nations, that of national human rights institution (NHRI). A preliminary examination of how the NHRI movement came to be and the normative framework it spurred reveals the attachment of international stakeholders to a singular standard for structuring and assessing NHRIs, one in which context and domestic effectivity are at best secondary considerations. How well this standard translates in Haiti is informed by the peculiar account of the establishment and functioning of the Haitian Office de la Protection du Citoyen as a status “A” accredited NHRI. Partly building on fieldwork in Haiti, this thesis examines the discrepancy that seems to exist between the OPC’s international recognition as a NHRI and its ability to effectively function in that capacity in the trying Haitian human rights environment.
The mucus on the bronchial wall forms a thin layer of non-Newtonian fluid. One of the roles of mucus is to protect the lungs by capturing inhaled pollutants. It is transported by mucocilliary ...clearance toward the tracheo-pharyngeal bifurcation, where it is eliminated. Due to the corrugation of its interface with air, the mucus layer is subject to surface tension forces that interact with its rheology. It is still not clear whether these forces can affect mucus displacement and, if they can, under what conditions and how this displacement can occur. In this work, we model the mucus as a thin Bingham fluid layer located on the wall of idealized, multi-scaled airway bifurcations. We analyze the resulting physical system using lubrication theory and 3D simulations. The theoretical analysis allows us to characterize the nonlinear behavior of the system and determine the geometric conditions under which the Bingham fluid can be moved by surface tension. 3D simulations are then used to quantify the effects in idealized airway bifurcations on a range of scales corresponding to those of bronchial bifurcations. Our results suggest that surface tension effects can displace overly thick mucus layers in airway bifurcations, a typical situation in obstructive lung pathologies (asthma, BPCO, cystic fobrosis, etc.). Moreover, our results indicate that this movement can disrupt mucociliary clearance and the homogeneity of the layer thickness, thus increasing the risk of lung infection.
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