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Mathematical modeling of ventilator-induced lung inflammation
Sarah Minucci1, Rebecca L Heise2, Michael S Valentine2
1Department of Mathematics & Applied Mathematics, Virginia Commonwealth University, Richmond, VA, USA.
Journal of Theoretical Biology
|April 30, 2021
Summary
Mechanical ventilation can cause lung injury. This study models the immune response to ventilation-induced lung injury (VILI), identifying epithelial repair and macrophage activation as key factors for better outcomes.
Area of Science:
- Pulmonary Medicine
- Computational Biology
- Immunology
Background:
- Mechanical ventilation is crucial for respiratory failure but can cause lung injury.
- Damage to the pulmonary epithelium triggers immune responses, involving macrophages with diverse phenotypes.
- Understanding these complex interactions is vital for improving patient outcomes.
Purpose of the Study:
- To develop a mathematical model simulating the immune response to ventilation-induced lung injury (VILI).
- To investigate the influence of macrophage phenotypes on VILI and post-ventilation recovery.
- To identify key parameters and potential intervention strategies for mitigating VILI.
Main Methods:
- Developed a mathematical model of immune system and lung damage interactions, incorporating macrophage phenotypes.
- Utilized Latin hypercube sampling to generate parameter sets and simulate VILI.
- Employed random forest decision trees and eFAST for parameter sensitivity analysis.
Main Results:
- Identified parameters and transient properties related to epithelial repair and M1 macrophage activation as critical.
- Demonstrated that baseline immune state and lung health significantly impact VILI outcomes.
- Hypothesized and tested intervention strategies to modulate the response to ventilation.
Conclusions:
- Epithelial repair and M1 macrophage activation are crucial for managing ventilation-induced lung injury.
- Mathematical modeling provides insights into immune dynamics and potential therapeutic targets.
- This approach can guide the development of targeted interventions to improve VILI outcomes.
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