Dynamic Therapy for Pulmonary Fibrin Accumulation

Abstract Pulmonary fibrin accumulation is caused by aberrant cascade interactions that promote fibrin protein deposits in the lung. Fibrin buildup stiffens the lungs, decreases gas exchange, and impairs lung function. Unregulated fibrin accumulation can devolve into irreversible scarring, called fibrosis, and ultimately lung failure. Diseases with pulmonary fibrin accumulation such as acute respiratory distress syndrome (ARDS) have no known cure. Supportive care that is open-loop and nonpersonalized is the only treatment option. Here, we propose closing the loop for ARDS with a feedback treatment regimen of a novel protein therapeutic, activated protein C (APC). We show the observability, controllability, and feedback linearizability of a single-input, single-output control-affine nonlinear system that captures the simplified dynamics of pulmonary fibrin accumulation during virally-induced ARDS. We then apply our developed input-state feedback linearizing APC controller to our simplified system and demonstrate the return of a diseased patient to a healthy reference.