Modeling of lung function and mechanics

Bradford Smith

(Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, United States)

"Ventilator waveform analysis to diagnose and prevent ventilator-induced lung injury"

Acute respiratory distress syndrome (ARDS) is caused by diverse factors including sepsis, trauma, and COVID-19. The derangements of lung function associated with ARDS necessitate mechanical ventilation to sustain life. However, the mechanical ventilator can also cause additional ventilator-induced lung injury that leads to worse ARDS outcomes. Adjusting the mechanical ventilator to minimize VILI is a challenging task because the injurious forces are functions of the applied ventilation and the mechanical properties of the lung which, in turn, depend on injury severity and type. As such, the optimal ventilation settings for each patient are likely different, change with time, and are not readily discernable from clinical data. To address this challenge, our long-term goal is to develop a system to numerically identify and apply the optimally lung-protective ventilation for any particular patient. The first step is to develop and validate simulations that can accurately predict the response of the injured lung to changes in ventilator settings. We have developed a compartment model of the respiratory system that accounts for nonlinear tissue elastance, lung resistance, and the nonlinear dynamics of alveolar recruitment. The model parameters are identified by fitting to pressures and volumes measured in mechanically ventilated mice (the training data). The model predictions are compared to evaluation data collected in the same animal to show that this approach provides accurate predictions of the response of the injured lung to ventilator adjustments. The model outputs also provide an accurate assessment of lung injury severity when compared to gold-standard lung function assessments performed using flexiVent research ventilators.

Emily Heavner

(Colorado State University, United States)

"Estimation of airway resistance throughout the bronchial tree from mechanical ventilation output data"

We introduce a multi-compartment lung model based on resistance-capacitor circuits using an analogy between electric circuits and the human lungs. Multiple literature sources reveal a wide range of clinically used values for airway resistance, motivating an investigation to determine the role of airway resistance in the alveolar tree. The inverse problem of computing the vector of airway resistance values in the alveolar tree is studied using a linear least squares optimization approach. We compare the outputs of the model to real-world parameters collected from mechanical ventilation data of COVID-19 positive and negative patients.

Bela Suki

(Dept. Biomedical Engineering, Boston University, United States)

"Inflation instability in the lung: An analytical model of a thick-walled alveolus with wavy fibers under large deformations"

Inflation of hollow elastic structures can become unstable and exhibit a runaway phenomenon if the tension in their walls does not rise rapidly enough with increasing volume. Biological systems avoid such inflation instability for reasons that remain poorly understood. This is best exemplified by the lung, which inflates over its functional volume range without instability. The goal of this study was to determine how the constituents of lung parenchyma determine tissue stresses that protect alveoli from instability-related over-distension during inflation. We present an analytical model of a thick-walled alveolus composed of wavy elastic fibers, and investigate its pressure-volume behavior under large deformations. Using second harmonic generation imaging, we found that collagen waviness follows a beta distribution. Using this distribution to describe human pressure-volume curves, we estimated collagen and elastin effective stiffnesses to be 1247 and 18.3 kPa, respectively. Furthermore, we demonstrate that linearly elastic but wavy collagen fibers are sufficient to achieve inflation stability within the physiological pressure range if the alveolar thickness-to-radius ratio > 0.05. Our model thus identifies the constraints on alveolar geometry and collagen waviness required for inflation stability and provides a multiscale link between alveolar pressure and stresses on fibers in healthy and diseased lungs.

Vitor Mori

(University of Vermont, United States)

"Modelling the progression of Ventilation-Induced Lung Injury in Mice"

Mechanical ventilation is a crucial tool in the management of acute respiratory distress syndrome, yet it may itself also further damage the lung in a phenomenon known as ventilator-induced lung injury (VILI). We have previously shown in mice that volutrauma and atelectrauma act synergistically to cause VILI. We have also postulated that this synergy arises because of a rich-get-richer mechanism in which repetitive lung recruitment generates initial small holes in the blood-gas barrier which are then expanded by over-distension in a manner that favors large holes over small ones. In order to understand the causal link between this process and the derangements in lung mechanics associated with VILI, we developed a mathematical model that incorporates both atelectrauma and volutrauma to predict how the propensity of the lung to derecruit depends on the accumulation of plasma-derived fluid and proteins in the airspaces. We found that the model accurately predicts derecruitment in mice with experimentally induced VILI.