New insights into the mechanisms controlling the bronchial mucus balance

Karamaoun, Cyril; Sobac, Benjamin; Mauroy, Benjamin; Muylem, Alain Van; Haut, Benoı̂t

doi:10.1371/journal.pone.0199319

Cited by 36 publications

(63 citation statements)

References 59 publications

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“…However, the model must be able to qualitatively reproduce such data and, above all, to highlight interesting phenomena, in particular to shed new light on clinical data/experimental observations. In this sense, the model we are building here and the use we make of it is quite in line with many previous works (Van Muylem et al, 2003 ; Tawhai and Hunter, 2004 ; Kerckx et al, 2008 ; Warren et al, 2010 ; Florens et al, 2011a ; Karamaoun et al, 2018a , b ; Wells et al, 2018 ; Noel and Mauroy, 2019 ; Park et al, 2019 ).…”

Section: Introductionsupporting

confidence: 84%

“…A very known homogeneous description of the lung geometry is the seminal Weibel Type A model (Weibel, 1963 ). Such a representation is widely used for its simplicity, as it makes it possible not to consider all the airways individually in a given generation and therefore to greatly simplify the modeling (Weibel, 1963 ; Pedley et al, 1970a ; Paiva and Engel, 1981 ; Nowak et al, 2003 ; Jalal et al, 2016 ; Karamaoun, 2017 ; Karamaoun et al, 2018b ; Wells et al, 2018 ). However, in reality, the lungs present a structural heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

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Modeling of the Transport and Exchange of a Gas Species in Lungs With an Asymmetric Branching Pattern. Application to Nitric Oxide

et al. 2020

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Over the years, various studies have been dedicated to the mathematical modeling of gas transport and exchange in the lungs. Indeed, the access to the distal region of the lungs with direct measurements is limited and, therefore, models are valuable tools to interpret clinical data and to give more insights into the phenomena taking place in the deepest part of the lungs. In this work, a new computational model of the transport and exchange of a gas species in the human lungs is proposed. It includes (i) a method to generate a lung geometry characterized by an asymmetric branching pattern, based on the values of several parameters that have to be given by the model user, and a method to possibly alter this geometry to mimic lung diseases, (ii) the calculation of the gas flow distribution in this geometry during inspiration or expiration (taking into account the increased resistance to the flow in airways where the flow is non-established), (iii) the evaluation of the exchange fluxes of the gaseous species of interest between the tissues composing the lungs and the lumen, and (iv) the computation of the concentration profile of the exchanged species in the lumen of the tracheobronchial tree. Even if the model is developed in a general framework, a particular attention is given to nitric oxide, as it is not only a gas species of clinical interest, but also a gas species that is both produced in the walls of the airways and consumed within the alveolar region of the lungs. First, the model is presented. Then, several features of the model, applied to lung geometry, gas flow and NO exchange and transport, are discussed, compared to existing works and notably used to give new insights into experimental data available in the literature, regarding diseases, such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease.

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Section: Introductionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Modeling of the Transport and Exchange of a Gas Species in Lungs With an Asymmetric Branching Pattern. Application to Nitric Oxide

et al. 2020

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“…For instance, it is wellknown that inspiring cold and dry air when exercising can lead to a dehydration of the ASL, inducing cell shrinkage, release of inflammatory mediators, airway smooth muscle constriction and both physical and chemical activation of cough receptors (Banner et al, 1984;Kippelen and Anderson, 2013). Similar issues have been pointed out in several situations: when an invasive respiration is realized (intubation during an operation or tracheotomy) (Dery, 1973;Jackson, 1996;Rathgeber et al, 1996;Ryan et al, 2002), when taking care of a premature child (Jarreau, 2016), when ASL replenishment with water is impaired in cystic fibrosis (Karamaoun et al, 2018), when an asthmatic person is exercising or simply breathing in cold and dry air (Gilbert and Mcfadden, 1992;Mcfadden, 1992;Koskela, 2007;Cote et al, 2018;D'Amato et al, 2018).…”

Section: Introductionmentioning

confidence: 77%

Comprehensive Analysis of Heat and Water Exchanges in the Human Lungs

et al. 2021

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This work presents a new mathematical model of the heat and water exchanges in the human lungs (newborn to adult). This model is based on a local description of the water and energy transports in both the lumen and the surrounding tissues, and is presented in a comprehensive, dimensionless framework with explicitly stated assumptions and a strong physiological background. The model is first used to analyze and quantify the key phenomena and dimensionless numbers governing these heat and water exchanges and then it is applied to an adult in various situations (varying atmospheric conditions, exercising…). The results highlight several interesting physiological elements. They show that the bronchial region of the lungs is able to condition the air in all the considered situations even if, sometimes, for instance when exercising, distal generations have to be involved. The model also shows that these distal generations are super-conditioners. Moreover, the results quantify the key role of the submucosal glands in mucus hydration. They also show that, during expiration, a significant cooling of the air and condensation of water occur along the respiratory tract as the vascularization of the tissues surrounding the airways is not able to maintain these tissues at body temperature during inspiration. Due to the interaction between several phenomena, it appears that the ratio of the amount of water returned to the mucosa during expiration to the amount extracted during inspiration is almost independent of the breathing conditions (around 33%). The results also show that, in acute situations, such as suffering from a pathology with airway dysfunction, when being intubated or when exercising above an intensity threshold, the heat and water exchanges in the lungs may be critical regarding mucus hydration. In proximal generations, the evaporation may overwhelm the ability of the submucosal glands to replenish the airway surface liquid with water. In some situations, the cooling of the mucosa may be very important; it can even become colder than the inspired air, due to evaporative cooling. Finally, the results show that breathing cold air can significantly increase the exchanges between the lungs and the environment, which can be critical regarding disease transmission.

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“…To account for the core geometrical properties of the lung, we assume that the size of the branches in the conductive tree decreases from one generation to the next with a ratio 0 < h < 1 (Weibel, 1984; Mauroy et al, 2004; Karamaoun et al, 2018):…”

Section: Modeling Oxygen and Carbon Dioxide Transport In An Idealimentioning

confidence: 99%

Interplay Between Optimal Ventilation and Gas Transport in a Model of the Human Lung

Noël

Mauroy

2019

Front. Physiol.

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Ventilation is at the origin of a spending of energy coming from air circulation in the bronchial tree and from the mechanical resistance of the tissue to motion. Both amplitude and frequency of ventilation are submitted to a trade-off related to this energy, but they are also submitted to a constraint linked to the function of the lung: to transport enough oxygen and carbon dioxide in order to respect metabolism needs. We propose a model for oxygen and carbon dioxide transport in the lung that accounts for the core physical phenomena: lung's tree-like geometry, transport of gas by convection and diffusion, exchanges with blood and a sinusoidal ventilation. Then we optimize the power dissipated by the ventilation of our model relatively to ventilation amplitude and period under gas flow constraints. Our model is able to predict physiological ventilation properties and brings interesting insights on the robustness of different regimes. Hence, at rest, the power dissipated depends very little on the period near the optimal value. Whereas, at strong exercise any shift from the optimal has dramatic effect on the power. These results are fully coherent with the physiological observation and raises the question: how the control of ventilation could select for the optimal configuration? Also, interesting insights about pathologies affecting ventilation could be derived, and our model might give insights on therapeutical responses, with specific breathing strategies or for better driving mechanical ventilation.

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New insights into the mechanisms controlling the bronchial mucus balance

Cited by 36 publications

References 59 publications

Modeling of the Transport and Exchange of a Gas Species in Lungs With an Asymmetric Branching Pattern. Application to Nitric Oxide

Modeling of the Transport and Exchange of a Gas Species in Lungs With an Asymmetric Branching Pattern. Application to Nitric Oxide

Comprehensive Analysis of Heat and Water Exchanges in the Human Lungs

Interplay Between Optimal Ventilation and Gas Transport in a Model of the Human Lung

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