Imagine that you have been waiting on a lung transplant list for several years. Finally, a donor pair of lungs the right size and appropriate blood type becomes available. However, your physician discovers these lungs have a mild bacterial infection and deems them unfit for transplant. You return to the waitlist, your chances of receiving a transplant growing ever slimmer. This scenario is all too common in the United States, where each year more than 3,500 people await a lung transplant. Most of them die waiting. Fortunately, a scientific breakthrough that harnesses the power of bacteria is likely to make lung transplantation a possibility for a much larger number of patients.
Bacteria and reperfusion
The single greatest setback to lung transplantation is the shortage of healthy donor lungs. This problem is compounded by the perception that lungs colonized by bacteria are unsuitable for transplant because they worsen a condition known as lung ischemia reperfusion injury (LIRI). This condition is caused by blood leaving part of the body (ischemia), followed by the blood’s return to that part of the body (reperfusion). During transplants, organs are first removed from a blood supply, then reconnected to it, making LIRI a significant concern.
While the underlying causes of this condition are incompletely understood, LIRI develops in 15-25 percent of lung transplant recipients. It is the leading cause of acute lung transplant recipient mortality and is associated with the development of airway complications, acute rejection and late graft failure. Researchers have always assumed that the presence of bacteria would exacerbate inflammation; therefore, increasing the likelihood a transplant patient would develop LIRI. To avoid this complication, hospitals typically discard all donor lungs with even a mild bacterial infection.
Harnessing the power of bacteria
Our new therapy is designed to use bacteria to create a protective effect for the donor lungs. We discovered that the biochemical receptor triggered in reperfusion can be "pre-fired" by exposure to bacteria prior to transplant surgery. The result is that the receptor becomes resistant to inflammatory activation during the surgical procedure, limiting the danger of reperfusion. Perfecting this technique will change the way we look at donor lungs, rendering bacteria-infected lungs suitable for transplant.
Who will benefit?
Potentially all lung transplant recipients would benefit from the knowledge gained in the proposed studies. This includes patients with cystic fibrosis, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), pulmonary hypertension, sarcoidosis and many other forms of advanced lung disease.