Background: The most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse. PS instillation therapy is dramatically effective for infant respiratory distress syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that the ineffectiveness of PS instillation for ARDS is due to insufficient delivery. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions.
Methods: Two types of 3D human airway model were prepared: One was from the trachea to lobular bronchi and the other was from a sub-segmental bronchus to respiratory bronchioles. Thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. Initially existing liquid layer was assumed to be replaced by instilled PS. Flow rate of instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving advective-diffusion equation.
Results: The driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure is given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS would not reach alveolar regions but move to and fro within the airway according to the change of ventilator pressure. On the other hand, the driving pressure from sub-segmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation.
Conclusions: The simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia even before ARDS. It will be also useful for preventing secondary lung fibrosis.