Phage Therapy in Lung Transplantation: Current Status and Future Possibilities

Abstract

Patients with chronic lung disease and lung transplantation have high rates of colonization and infection from multidrug-resistant (MDR) organisms. This article summarizes the current state of knowledge regarding phage therapy in the setting of lung transplantation. Phage therapy has been used in several lung transplant candidates and recipients on a compassionate use basis targeting mostly MDR gram-negative infections and atypical mycobacterial infections with demonstrated clinical safety. Phage biodistribution given intravenously or via nebulization has not been extensively studied, though preliminary data are presented. Phage interacts with both the innate and adaptive immune system; current literature demonstrates the development of serum neutralization in some cases of phage therapy, although the clinical impact seems variable. A summary of current clinical trials involving patients with chronic lung disease is presented, though none are specifically targeting lung transplant candidates or recipients. In addition to treatment of active infections, a variety of clinical scenarios may benefit from phage therapy, and well-designed clinical trials involving this vulnerable patient population are needed: pre- or peritransplantation use of phage in the setting of MDR organism colonization may lead to waitlisting of candidates currently declined by many centers, along with potential reduction of waitlist mortality rates and posttransplant infections; phage may be used for biofilm-related bronchial stent infections; and, finally, there is a possibility that phage use can affect allograft function and chronic rejection.