OBJECTIVES/GOALS: Asymmetries in lung pathophysiology can result in a maldistribution of gas between regions of the lungs which may generate dangerous pressures that are not observable by clinicians. Our study aims to demonstrate and quantify this through use of high-fidelity simulators to represent a range of commonly encountered clinical pathologies. METHODS/STUDY POPULATION: A benchtop study was performed with two high-fidelity breathing simulators, each representing one lung. This system allows for real-time monitoring of pressure and lung dynamics in a two-lung asymmetric injury model. One simulator was set to a fixed compliance and a resistance. A second simulator had a range of compliance and resistance values. Data were collected for 15 different test cases across a distribution of asymmetries. Each test case is run for 30 cycles. At the end of each ventilatory cycle, a short expiratory hold is performed, allowing pressure in the lung simulator, tubing, and ventilator circuit to equilibrate between cycles. RESULTS/ANTICIPATED RESULTS: Maldistribution of tidal volume was demonstrated when the compliance ratio between lung models (CL1/CL2) was 0.2 and the resistance ratio (RL1/RL2) was 10 with 23.9% (99% CI: 23.9-24.0%) of the gas volume distributed to lung 1 (103 mL L1 vs 327 mL in L2). Additionally, the injured lung when compared with the normal lung experienced higher peak pressures (12.8 cm H2O vs. 6.9 cm H2O, L1 and L2 respectively) and higher compartmentalized plateau pressures (11.5 cm H2O vs. 6.8 cm H2O, L1 and L2 respectively). DISCUSSION/SIGNIFICANCE: We demonstrate significant maldistribution of volume and pressures between two lungs in an asymmetric injury model. This study suggests significant impact of asymmetry in current lung-protective mechanical ventilation strategies and calls for better understanding of case-specific pathophysiologic changes affecting each of the two lungs.