A quasi‐3D wire approach to model pulmonary airflow in human airways

Abstract

The models used for modeling the airflow in the human airways are either 0-dimensional compartmental or full 3-dimensional (3D) computational fluid dynamics (CFD) models. In the former, airways are treated as compartments, and the computations are performed with several assumptions, thereby generating a low-fidelity solution. The CFD method displays extremely high fidelity since the solution is obtained by solving the conservation equations in a physiologically consistent geometry. However, CFD models (1) require millions of degrees of freedom to accurately describe the geometry and to reduce the discretization errors, (2) have convergence problems, and (3) require several days to simulate a few breathing cycles. In this paper, we present a novel, fast-running, and robust quasi-3D wire model for modeling the airflow in the human lung airway. The wire mesh is obtained by contracting the high-fidelity lung airway surface mesh to a system of connected wires, with well-defined radii. The conservation equations are then solved in each wire. These wire meshes have around O(1000) degrees of freedom and hence are 3000 to 25 000 times faster than their CFD counterparts. The 3D spatial nature is also preserved since these wires are contracted out of the actual lung STL surface. The pressure readings between the 2 approaches showed minor difference (maximum error = 15%). In general, this formulation is fast and robust, allows geometric changes, and delivers high-fidelity solutions. Hence, this approach has great potential for more complicated problems including modeling of constricted/diseased lung sections and for calibrating the lung flow resistances through parameter inversion.

Leukotriene B4 indicates lung injury and on-going inflammatory changes after severe trauma in a porcine long-term model

“…ARDS often remain non-specific and subsequently under-diagnosed or under-treated due to the lack of knowledge concerning the pathophysiology of lung injury, pulmonary complications and repair mechanisms. Kannan et al have performed very high fidelity 2D and 3D simulations for accurately and efficiently predicting and quantifying local and global injuries (caused by trauma, hemorrhages, blasts) for organs like the brain and the lung [7,8]. They were able to noninvasively "numerically penetrating" the tissues, and reconstruct the optical properties the presence of water, oxygenated and de-oxygenated blood [7,8].…”

“…Kannan et al have performed very high fidelity 2D and 3D simulations for accurately and efficiently predicting and quantifying local and global injuries (caused by trauma, hemorrhages, blasts) for organs like the brain and the lung [7,8]. They were able to noninvasively "numerically penetrating" the tissues, and reconstruct the optical properties the presence of water, oxygenated and de-oxygenated blood [7,8]. These numerical noninvasive measurements are then used to predict the extent and severity of the organ hemorrhage/injury.…”

Administration of JTE013 abrogates experimental asthma by regulating proinflammatory cytokine production from bronchial epithelial cells

“…However, Kannan et al have revealed that the deposition of particle substance to airway and lung depends on many factors including the property of the particle, anatomical geometry of the airway, and respiratory pattern [46, 47]. And it may be possible to obtain more analysis from the computational Euler-Langrangian particle delivery approach of Kannan et al [47].…”

In Silico Methods for Development of Generic Drug–Device Combination Orally Inhaled Drug Products

“…The Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research at the FDA has funded two grants related to the in silico modeling of OIDPs prior to fiscal year 2018 using funds obtained from the Generic Drug User Fee Amendments regulatory science program . In 2014, a grant titled “A Predictive Multiscale Computational Tool for Simulation of Lung Absorption and Pharmacokinetics and Optimization of Pulmonary Drug Delivery” was awarded to CFD Research Corporation for the development of an integrated CFD‐PBPK lung model, which has been previously described in this article . The key gap that this grant addressed is the lack of PBPK models for OIDPs that take full advantage of CFD for its ability to both predict deposition and to capture the effects of mucociliary clearance.…”

“…Another area of potential improvement for lung PBPK models is mucociliary clearance methodology, where most models use a compartmental approach. Kannan and colleagues have addressed this issue in part by developing a Q3D methodology that is capable of local absorption prediction with much greater precision . A Generic Drug User Fee Amendments–funded continuation of this work has recently been announced by the OGD, which will involve the expansion of the Q3D model to include respiratory airways and the application of the Q3D methodology to other lung geometries…”