Acute respiratory distress syndrome (ARDS) and infant respiratory distress syndrome (IRDS) are pulmonary diseases with a mortality rate of âˆ¼40% and 75,000 deaths annually in the United States. Mechanical ventilation restores airway patency and gas transport but leads to ventilator-induced lung injury. Surfactant replacement therapy alleviates these effects in IRDS, but is ineffective due to surfactant delivery difficulties and deactivation by vascular proteins leaking into the airspace in ARDS. Here, we demonstrated that surfactant function can be substantially improved (up to 50%) in situ in an in vitro pulmonary airway model using unconventional flows that incorporate a short-term retraction of the air-liquid interface, leading to a net decrease in cellular damage. This research may provide a starting point for developing novel ventilation waveforms to improve surfactant function in edematous airways.