PROJECT SUMMARY/ABSTRACT A large number of patients with infectious respiratory diseases such as COVID-19, influenza, and SARS require respiratory support. Noninvasive Positive Pressure Ventilation (NPPV) via a mask is an appropriate treatment for many patients that can lead to better outcomes than intubation. Additionally, the equipment used for NPPV (such as CPAP machines) is widely available, making NPPV well suited for responding to outbreaks and pandemics. Unfortunately, NPPV masks increase the risk of disease transmission by spreading contaminated aerosols leaking from the mask seal. This exposes health care workers and other patients to increased risk and can hamper efforts to contain outbreaks of infectious diseases. The objective of this program is to develop an innovative NPPV patient interface that greatly reduces the leakage of contaminated aerosols through the mask seal. The two key innovations are a purged dual seal and a mask integrated vacuum ejector. The dual seal captures contaminated leakage across the primary mask seal and integrated ejector provides the purge flow required by the dual seal. All the contaminated flow is then passed through to a viral filter before exhausting to the room. Our device is a cost effective drop in replacement for existing masks that integrates easily with NPPV equipment used in hospitals. In a prior program and Phase I, we developed and tested initial PDS mask prototypes. We demonstrated far better sealing performance than a leading commercial mask in laboratory and human subject testing. In the proposed Phase II program we will refine and productize our mask design, extensively test the performance, publicize the results, and prepare for regulatory clearance and commercialization. This will enable our innovative leak-prevention mask technology to be widely deployed in critical care settings—benefiting patients and protecting health care workers.