Role of Tidal Volume on Ventilator-Induced Lung Injury Under Heterogeneous Immunological Capabilities: A Mathematical Model Study

Mechanical ventilation, a lifesaving intervention for critically ill patients, can also cause ventilator-induced lung injury (VILI), which is related to its interplay with immune system. To explore this relationship, we established a model consisting of two subsystems: a lung immune response system (LIRS), elucidating the interactions between immune cells and epithelial cells within the pulmonary environment, and a tidal volume damage system (TVDS), quantifying alveolar epithelial damage by simulating the detrimental effects of mechanical ventilation across varying tidal volumes. The integrated framework presents a novel lens for examining the interplay between heterogeneous immunological capabilities and tidal volume. The model reveals distinct responses among the individuals with varying immune capacities when subjected to identical tidal volumes, manifesting in diverse outcomes for healthy epithelial cells (<i>eh</i>). Analysis of simulation results shows a weak correlation between initial immune cell variables and <i>eh</i>, and a stronger correlation between <i>eh</i> and baseline repair capacity. Furthermore, while the initial immune state of lung tissue moderately influences epithelial health, the heterogeneous and inherent immunological competence of the tissue plays a pivotal role in shaping the diverse patterns observed in the development and severity of VILI. This insight highlights the importance of tailoring therapeutic strategies to individual immunological profiles, thereby optimizing patient outcomes.