RT Journal Article SR Electronic T1 Expanding Clinical Phage Microbiology: Simulating Phage Inhalation for Respiratory Tract Infections JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.14.448272 DO 10.1101/2021.06.14.448272 A1 Shira Ben Porat A1 Daniel Gelman A1 Ortal Yerushalmy A1 Sivan Alkalay-Oren A1 Shunit Coppenhagen-Glazer A1 Malena Cohen-Cymberknoh A1 Eitan Kerem A1 Israel Amirav A1 Ran Nir-Paz A1 Ronen Hazan YR 2021 UL http://biorxiv.org/content/early/2021/06/14/2021.06.14.448272.abstract AB Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in-vitro model to evaluate phage inhalation.Eight phages, most of which target CF-common pathogens, were aerosolized and administered to a real-scale CTâ–¡derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebulizer and the tracheal level of the model were determined and compared to the loaded amount.Phage inhalation resulted in a diverse range of titer reduction, primarily associated with the nebulization process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.Take-Home Message Phage therapy can be used against infectious diseases if personally tailored. Using a 3D airways model, we show that phage delivery by inhalation to the respiratory tract is unpredictable and also requires a precise evaluation.Competing Interest StatementThe authors have declared no competing interest.