Phenotype- and patient-specific modelling in asthma: Bronchial thermoplasty and uncertainty quantification

Donovan, Graham M.; Langton, David; Noble, Peter B.

doi:10.1016/j.jtbi.2020.110337

Cited by 11 publications

(8 citation statements)

References 49 publications

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“…7,10,41 The model studied here is also implemented using lumped parameters, but unlike the previous ones, its R, I, and C are nonlinear parameters, with values controlled by flow, inlet and pleural pressures according to the empirical tube-law (2), so their values follow also the lung volume. Another group of publications assumed static 48,49,58 or quasi-static 4,14,16,17 conditions, in particular a constant flow. On the contrary, this model is fully dynamic with the accumulation and release of air in the flexible bronchi and alveoli, T A B L E 1 Performance measures of the algebraic approximation: the root relative square errors of simulated pressure P ao (δP), flow Q ao (δQ) and volume V t (δV) signals, and the index of simulation time reduction (R t ), for spontaneous breathing (SB), mechanical ventilation (OVW), and forced expiration (FE) with different speeds of expiratory muscle activation (10, 20, taking into account the inertia of the lung, chest, and air.…”

Section: Discussionmentioning

confidence: 99%

“…27 The second type of simplifications was based on the assumption of rigid walls of the airways, 13,32,33,35,47,48,[51][52][53][54][55] analyzing the system for a single lung volume or constant flow. 10,19,21,53,55,58 Among these approaches, the quasi-3D model using plenty of wires to simplify fluid dynamics simulations, 56 has proved particularly successful. 12,36,57 In other cases, the wave-speed limitation was omitted when including FL by dissipative pressure loss in flexible airways.…”

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confidence: 99%

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Algebraic approximation of the distributed model for the pressure drop in the respiratory airways

Polak

2022

Numer Methods Biomed Eng

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The complexity of the human respiratory system causes that one of the main methods of analyzing the dynamic pulmonary phenomena and interpreting experimental results are simulations of its computational models. Among the most compound elements of these models, apart from the bronchial tree structure, is the phenomenon of flow limitation in flexible bronchi, which causes them to collapse with increasing flow, thus their properties, such as resistance, compliance and inertance, are highly nonlinear and time‐varying. Commonly, this phenomenon is ignored, or a distributed model for the airway pressure drop is applied, simulated with a modified numerical solver of this differential equation (ODE). The disadvantages of this solution are the problems with taking into account the inherent singularity of the model and the long computation time due to iterative nature of the ODE procedure. The aim of the work was to derive an algebraic approximation of this distributed model, suitable for implementation in continuous dynamic models, to validate it by comparing the results of simulations with the respiratory system model including approximate and original (ODE solver) numerical procedures, as well as to evaluate possible acceleration of calculations. All simulations, including spontaneous breathing, mechanical ventilation with the optimal ventilatory waveform and forced expiration, proved that algebraic approximation yielded results negligibly differing from the ODE solution, and shortened the computation time by an order. The proposed approach is an attractive alternative in the case of computer implementations of pulmonary models, where simulations of flows and pressures in the complex respiratory system are of primary importance.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Algebraic approximation of the distributed model for the pressure drop in the respiratory airways

Polak

2022

Numer Methods Biomed Eng

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“…Computational experimentation is an emerging tool that is increasingly being leveraged to elucidate complex structure-function relationships in a number of biological systems such as the lungs 1,2 , placenta [3][4][5] , tumors 6,7 and others [8][9][10][11] . This in silico approach overcomes challenges of conventional experiments, allowing for novel measurements to be made or experimental interventions to be actioned, both of which would otherwise be difficult, if not impossible to achieve conventionally.…”

Section: Mainmentioning

confidence: 99%

“…(1) in rats is used to investigate mechanisms of placental impairment during late pregnancy compared to control rat pregnancies. Umbilical artery flow measurements (from Bappoo et al 13 ) are taken in utero using High Frequency Doppler Ultrasound imaging (2) to define model inputs for in silico computational fluid dynamics (CFD) simulations.…”

Section: Mainmentioning

confidence: 99%

Anin vitro, in uteroandin silicoframework of oxygen diffusion in intricate vascular networks of the placenta

Bappoo¹,

Kelsey²,

Tongpob³

et al. 2021

Preprint

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The placenta is a temporary and complex organ critical for fetal development through its subtle but convoluted harmonization of endocrine, vascular, haemodynamic and exchange adaptations. Yet, due to experimental, technological and ethical constraints, this unique organ remains poorly understood. In silico tools are emerging as a powerful means to overcome these challenges and have the potential to actualize novel breakthroughs. Here, we present an interdisciplinary framework combining in vitro experiments used to develop an elegant and scalable in silico model of oxygen diffusion. We then use in utero imaging of placental perfusion and oxygenation in both control and growth-restricted rodent placentas for validation of our in silico model. Our framework revealed the structure-function relationship in the feto-placental vasculature; oxygen diffusion is impaired in growth-restricted placentas, due to the diminished arborization of growth-restricted feto-placental vasculature and the lack of decelerated flow for adequate oxygen diffusion and exchange. We highlight the mechanisms of impairment in a rat model of growth restriction, underpinned by placental vascular impairment. Our framework reports and validates the prediction of blood flow deceleration impairment in growth restricted placentas with the placenta’s oxygen transfer capability being significantly impaired, both globally and locally.

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“…Tissue remodeling in the airways is the result of epithelial cell derangement, goblet cell hyperplasia, increased airway smooth muscle cells, thickening of the basal membrane, increased neovascularization in the sub-epithelial cell layers, and increased deposition of various extracellular matrix components [1]. It is currently unknown if specific structural changes characterize asthma pheno-and endo-types [2,3]. Moreover, none of the drugs used for asthma therapy show any reducing effect on airway wall remodeling [4].…”

Section: Introductionmentioning

confidence: 99%

Airway Wall Remodeling in Childhood Asthma—A Personalized Perspective from Cell Type-Specific Biology

Fang

Roth

2021

JPM

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Airway wall remodeling is a pathology occurring in chronic inflammatory lung diseases including asthma, chronic obstructive pulmonary disease, and fibrosis. In 2017, the American Thoracic Society released a research statement highlighting the gaps in knowledge and understanding of airway wall remodeling. The four major challenges addressed in this statement were: (i) the lack of consensus to define “airway wall remodeling” in different diseases, (ii) methodologic limitations and inappropriate models, (iii) the lack of anti-remodeling therapies, and (iv) the difficulty to define endpoints and outcomes in relevant studies. This review focuses on the importance of cell-cell interaction, especially the bronchial epithelium, in asthma-associated airway wall remodeling. The pathology of “airway wall remodeling” summarizes all structural changes of the airway wall without differentiating between different pheno- or endo-types of asthma. Indicators of airway wall remodeling have been reported in childhood asthma in the absence of any sign of inflammation; thus, the initiation event remains unknown. Recent studies have implied that the interaction between the epithelium with immune cells and sub-epithelial mesenchymal cells is modified in asthma by a yet unknown epigenetic mechanism during early childhood.

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Phenotype- and patient-specific modelling in asthma: Bronchial thermoplasty and uncertainty quantification

Cited by 11 publications

References 49 publications

Algebraic approximation of the distributed model for the pressure drop in the respiratory airways

Algebraic approximation of the distributed model for the pressure drop in the respiratory airways

Anin vitro, in uteroandin silicoframework of oxygen diffusion in intricate vascular networks of the placenta

Airway Wall Remodeling in Childhood Asthma—A Personalized Perspective from Cell Type-Specific Biology

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