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Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure

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Systems Engineering Approach to Modeling and Analysis of Chronic Obstructive Pulmonary Disease.

Varghese Kurian¹, Navid Ghadipasha¹, Michelle Gee^1,2

¹Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States.

|June 19, 2023

Summary

This study models the cardiorespiratory system using engineering principles to understand chronic obstructive pulmonary disease (COPD). Increased airway resistance is identified as a key factor impacting the cardiorespiratory system in COPD patients.

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Area of Science:

Systems engineering
Cardiorespiratory physiology
Computational modeling

Background:

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by airflow limitation.
Understanding the complex mechanisms of COPD is crucial for effective management.
Existing models may not fully capture the integrated cardiorespiratory response.

Purpose of the Study:

To develop a systems engineering framework for modeling COPD.
To represent the cardiorespiratory system as an integrated biological control system.
To identify key physiological parameters that manifest COPD clinically.

Main Methods:

Modeled the cardiorespiratory system using four engineering control system components: sensor, controller, actuator, and process.
Integrated human anatomy and physiology to create mechanistic mathematical models.
Performed systematic analysis and multivariate analysis of the computational model.

Main Results:

Identified three physiological parameters critical for reproducing COPD manifestations: airway resistance, lung elastance, and pulmonary resistance.
Quantified changes in these parameters leading to a COPD-diagnostic systemic response.
Airway resistance changes were found to significantly impact the cardiorespiratory system.

Conclusions:

The developed systems engineering framework effectively models COPD mechanisms.
Increased airway resistance is a primary driver of cardiorespiratory dysfunction in COPD.
The pulmonary circuit is significantly stressed in COPD patients, particularly in hypoxic conditions.