Thermo‐physical properties of synthetic mucus for the study of airway clearance

Lafforgue, Olivier; Bouguerra, Nizar; Poncet, Sébastien; Seyssiecq, Isabelle; Favier, Julien; Elkoun, Saïd

doi:10.1002/jbm.a.36161

Cited by 18 publications

(23 citation statements)

References 42 publications

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“…The implementation of a non Newtonian rheological behavior for the mucus based on the experiments of Lafforgue et al ( 2017 );…”

Section: Discussionmentioning

confidence: 99%

“…Its depth varies between 5 and 100 μm depending on the position in the bronchial tree (Widdicombe and Widdicombe, 1995 ). One of the main difficulties met for its characterization is the huge variability of its rheological properties (Lafforgue et al, 2017 ). It can indeed vary by several orders of magnitude during the same day within a particular person (Kirkham et al, 2002 ).…”

Section: Introductionmentioning

confidence: 99%

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Transport and Mixing Induced by Beating Cilia in Human Airways

et al. 2018

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The fluid transport and mixing induced by beating cilia, present in the bronchial airways, are studied using a coupled lattice Boltzmann—Immersed Boundary solver. This solver allows the simulation of both single and multi-component fluid flows around moving solid boundaries. The cilia are modeled by a set of Lagrangian points, and Immersed Boundary forces are computed onto these points in order to ensure the no-slip velocity conditions between the cilia and the fluids. The cilia are immersed in a two-layer environment: the periciliary layer (PCL) and the mucus above it. The motion of the cilia is prescribed, as well as the phase lag between two cilia in order to obtain a typical collective motion of cilia, known as metachronal waves. The results obtained from a parametric study show that antiplectic metachronal waves are the most efficient regarding the fluid transport. A specific value of phase lag, which generates the larger mucus transport, is identified. The mixing is studied using several populations of tracers initially seeded into the pericilary liquid, in the mucus just above the PCL-mucus interface, and in the mucus far away from the interface. We observe that each zone exhibits different chaotic mixing properties. The larger mixing is obtained in the PCL layer where only a few beating cycles of the cilia are required to obtain a full mixing, while above the interface, the mixing is weaker and takes more time. Almost no mixing is observed within the mucus, and almost all the tracers do not penetrate the PCL layer. Lyapunov exponents are also computed for specific locations to assess how the mixing is performed locally. Two time scales are introduced to allow a comparison between mixing induced by fluid advection and by molecular diffusion. These results are relevant in the context of respiratory flows to investigate the transport of drugs for patients suffering from chronic respiratory diseases.

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“…The implementation of a non Newtonian rheological behavior for the mucus based on the experiments of Lafforgue et al ( 2017 );…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transport and Mixing Induced by Beating Cilia in Human Airways

et al. 2018

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“…Mucus simulants solutions 0.5 to 2 wt % in Actigum were prepared as described in Ref. and were found to mimic accurately the main thermophysical properties of bronchial mucus in the case of different pathologies as shown by the recent work of Lafforgue et al…”

Section: Methodsmentioning

confidence: 99%

Rheological properties of synthetic mucus for airway clearance

Lafforgue

Seyssiecq

Poncet

et al. 2017

J Biomedical Materials Res

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In this work, a complete rheological characterization of bronchial mucus simulants based on the composition proposed by Zahm et al. (Eur Respir J 1991; 4:311-315) is presented. Dynamic small amplitude oscillatory shear (SAOS) experiments, steady state (SS) flow measurements and three intervals thixotropy tests (3ITT), are carried out to investigate the global rheological complexities of simulants (viscoelasticity, viscoplasticity, shear-thinning, and thixotropy) as a function of scleroglucan concentrations (0.5-2 wt %) and under temperatures of 20 and 37°C. SAOS measurements show that the limit of the linear viscoelastic range as well as the elasticity both increase with increasing sclerogucan concentrations. Depending on the sollicitation frequency, the 0.5 wt % gel response is either liquid-like or solid-like, whereas more concentrated gels show a solid-like response over the whole frequency range. The temperature dependence of gels response is negligible in the 20-37°C range. The Herschel-Bulkley (HB) model is chosen to fit the SS flow curve of simulants. The evolution of HB parameters versus polymer concentration show that both shear-thinning and viscoplasticity increase with increasing concentrations. 3ITTs allow calculation of recovery thixotropic times after shearings at 100 or 1.6 s . Empiric correlations are proposed to quantify the effect of polymer concentration on rheological parameters of mucus simulants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 386-396, 2018.

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“…Some devices have been developed to take advantage of the exhalation phase and the shearthinning and thixotropic properties of mucus to enhance the propulsion of mucus from the airways of CF and COPD subjects. Example, the device Simeox R imposes a succession of very short negative pressure pulses of increasing intensity during exhalation, reducing the mucus viscosity and enhancing its simultaneous propulsion from the peripheral pulmonary zone to the central airways, and then coughed or spit out by the patient [65][66][67].…”

Section: Discussionmentioning

confidence: 99%

Airway Pressure Gradient May Decrease the Beating Amplitude of Cilia

George

Pidaparti

2019

Front. Phys.

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Motile cilia reside on the surface of the epithelial layer of the lungs and facilitates the clearance of mucus in the airways. Bordering the epithelial layer and surrounding cilia is the periciliary liquid (PCL) that lubricates the epithelial layer. In the present work, we propose a novel approach to study how changes in biomechanics affect the physiological functioning of cilia in healthy subjects and in patients with CF, COPD, and primary ciliary dyskinesia (PCD). In particular, we investigate the response of cilia to different local pressure gradient during gaseous exchange. We hypothesize that the airway pressure gradient that occur during inhalation and exhalation may displace mucus and PCL and exert pressure on cilia. Therefore, cilia must be able to withstand the forces created by the airway pressure gradient, otherwise the magnitude of its efficient strokes and its rate of mucociliary clearance would decrease. We develop a computational model of the airways to quantify the effect of airway pressure gradient on cilia dynamics. In the model, cilia are represented as elastic solids, PCL and mucus is represented as fluids with different viscosities. The simulation results show that in diseases such as PCD, where there exist changes in ciliary structure, the airway pressure gradient may affect the propulsive stroke of cilia and decrease the rate of mucociliary clearance. Simulation results predict that the average stress experienced by cilia varies exponentially with the number of cilia shed from CF and COPD airways.

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Thermo‐physical properties of synthetic mucus for the study of airway clearance

Cited by 18 publications

References 42 publications

Transport and Mixing Induced by Beating Cilia in Human Airways

Transport and Mixing Induced by Beating Cilia in Human Airways

Rheological properties of synthetic mucus for airway clearance

Airway Pressure Gradient May Decrease the Beating Amplitude of Cilia

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