commercial light . There is currently a pilot study of the commercial product ongoing at UofL and there are plans for a large , multicenter trial of 20,000 patients and a goal of getting FDA approval .
Dr . van Berkel began to wonder , though , if we could identify cancer , could we also identify other benign conditions like pneumonia ? They began testing with a porcine model , starting with pigs with lung sizes similar to humans . Starting with healthy pigs , they put them to sleep then do a bronchoscopy and a washing of the lungs and inoculate them with Staph . On days 3 and 6 , they put them to sleep again and do another bronchoscopy and another bronchoalveolar lavage . On day 9 , they do the same thing and a necropsy and take the lungs . They ’ ve found that as time progresses , more and more bacteria grow , and pneumonia develops . They started collecting breath from the pigs to see if they could detect any markers , which they found they could . While this is still in preliminary phases , they are seeing good results . They are now collecting the breath of patients in the ICU before their operations and immediately post-operatively and tracking them throughout their hospital stay every couple of days . The hope is that this can be used for transplant rejection monitoring in the future .
The next big question on the horizon for Dr . van Berkel is how to increase the lung donor pool . While there are many ideal donor characteristics ( ABO compatible , age < 55 , clear chest X-ray , etc .), variance from these guidelines is common and 56 % of the time , at least one criterion is not met . Because of this , lungs are only procured from 15-20 % of cadaveric donors . Often , whatever it is that turns someone into an organ donor can damage the lungs and make them unsuitable for transplant . This can happen because of a variety of reasons such as a pulmonary contusion , aspiration with associated pneumonia or fluid overload .
This led to the idea of ex-vivo lung perfusion ( EVLP ). First reported in 2006 , they were taking lungs that were marginal and would hook them up to a heart-lung machine with one canula going into the pulmonary artery and one coming out of the pulmonary vein , circulating through a hyperosmolar fluid to help draw off effusion and then the lungs were hooked up to ventilator . They monitored for oxygenation , vascular resistance and wet / dry weight . The first report from a study in Canada took 23 rejected donor lungs and after four hours of perfusion , oxygenation improved , and they transplanted those lungs . In comparison to standard lung transplants done at the same time , they found that they did well and had identical 30-day and one-year survival rates and , interestingly , had less primary graft dysfunction in the EVLP group . This led to a flurry of activity and an FDA trial in the U . S . which led to the approval of EVLP within lung transplant .
Dr . van Berkel wants to look at how they can use this technology to clear out pneumonia in a short time . In the pig experiment described before , they took the infected lungs and put them on the machine and found that the lungs would not be considered for transplantation . They are also using low-dose radiation therapy , which
has some positive effects . It does do some minor DNA damage but not enough to lead to cell death and leads to anti-stress and apoptotic pathways . It also helps with hermetic processes ( having just enough of something , not too much or too little ) which stimulate cell functioning and cell signaling . There is some evidence that you can develop an adaptive response , developing better resistance to stressors .
Over the next few years , they are planning to take the infected pig lungs to the Brown Cancer Center and put them on the XRT machine for low-dose radiation . They are going to try that and a higher sterilizing dose to see if they can kill the bacteria without killing the lungs themselves . Once radiated , they can bring them back and put them on the ex-vivo rig and see how they perform . If successful , they will potentially treat pigs in-vivo and see if they can treat the pneumonia that way . Also , they will examine if the lungs treated for pneumonia can be transplanted back into pigs and have them work well .
Dr . van Berkel and his team will have many moving pieces and hurdles to overcome in the future with their research , that ’ s for certain . However , with the progress made already , it seems promising . When things get challenging , just remember … breathe in , breathe out .
Kathryn Vance is the Communication Specialist at the Greater Louisville Medical Society .
October 2023 25