In Silico Modeling of Pulmonary Surfactant Dynamics From Alveolus to Whole Lung

Surfactants play a crucial role in maintaining lung mechanics by reducing alveolar surface tension and preventing alveolar collapse. Deficiencies or alterations in surfactant properties can lead to significant changes in lung mechanics and impairments in lung function. However, understanding how changes in surfactant concentration and properties impact lung function at the organ level remains challenging. In this study, we integrated a previously published model of alveolar surfactant dynamics [Otis et al., 1994, "Dynamic Surface Tension of Surfactant TA: Experiments and Theory," J. Appl. Physiol. (1985), 77(6), pp. 2681-2688] into a computational model that links acinar mechanics with ventilation of the full conducting airway tree. This approach allowed us to explore the regional and global effects of surfactants on lung function under different ventilation conditions. Simulations mimicking saline filled, lavaged, and air-filled lungs demonstrated the well-known effect of surfactant on reducing surface tension at the air-liquid interface and establishing the hysteresis observed during inhalation and exhalation. Increased hysteresis was observed during ventilation with higher tidal volumes, while increasing breathing frequency led to increased heterogeneity in surfactant distribution and acinar compliance. These findings demonstrate that reductions in surfactant concentration impair alveolar expansion and ventilation efficiency, influencing lung function under varying mechanical ventilation strategies. By integrating surfactant dynamics with acinar mechanics, this computational model has the potential to predict how surfactant depletion, as seen in neonatal respiratory distress syndrome and acute lung injury, leads to alveolar instability and ventilation heterogeneity. The framework provides a tool to assess surfactant-related lung dysfunction and optimize mechanical ventilation strategies to improve alveolar recruitment and gas exchange in patients with surfactant deficiencies.