Talking Tall Rounds®: Lung Transplantation

Podcast Transcript

Announcer:

Welcome to the Talking Tall Rounds Series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular &Thoracic Institute at Cleveland Clinic.

Kenneth McCurry, MD:

Well, good morning everyone. Thanks for being here. For those of you online, we're certainly happy to have you participate in our Tall Rounds this morning. For those of you, if you're not available, I guess you're not going to be online currently, but this will be available for future review as well, for those who have some power outages this morning. So what we're here to discuss today, we have a lot of esteemed members of our lung transplant program and there's a lot of new and innovative things going on in this field and we want to give you a little bit of a taste of sort of what's happening in the United States and a bit around the world, in particular, I think some novel and innovative things that we're doing here at the Cleveland Clinic.

Kenneth McCurry, MD:

Dr. Marie Budev is the Medical Director of our lung and heart lung transplant program and recently chaired the OPTN Thoracic Transplant Committee in the United States, which oversees allocation and policy development. So Marie?

Marie Budev, DO, MPH:

Hey, thank you Ken and welcome everyone, good morning and thank you for the opportunity to present. Over the next few minutes, I'm going to take you on a whirlwind tour of the change in the lung allocation in the United States and what this change means, what barriers have come up, what challenges, as well as opportunities for lung transplant programs across the country, including the Cleveland Clinic. I have no conflicts of interest to disclose in relation to this discussion. As Ken mentioned, I was the chair of the OPTN Lung Committee and this was responsible for the implementation of this allocation change. Our discussion aims are listed here, they're quite robust. So why don't we get started?

This is a timeline of the US allocation policies starting off from 1990 all the way up to the present allocation system to the far right of your screen. This new implementation of the allocation policy called continuous distribution was implemented on March 9th of 2023. But to understand why we had to change our allocation policy to get where we are today, you need to understand what the previous allocation policies had and also lacked. In 1990 when we had our first allocation policy, it really didn't include medical urgency. It was a parking lot. Patients went on the list no matter how sick they were and just waited for an organ transplant. Therefore, it resulted in a lot of mortality on the waiting list.

Subsequently, many of you are familiar with the Lung Allocation System or the LAS. At that time, medical urgency was incorporated and there was a great deal of emphasis put on medical urgency, so sick patients would be transplanted. However, it was highly impacted and hampered by geographic distribution, meaning geographic hard boundaries. So you would have a patient of low acuity within a geographic area and a patient with very high acuity or very high medical urgency, but the patient with low acuity would see an organ within that same geography first, and the patient that was sicker would not see that organ.

And subsequently you had high mortality rates and this came to a head in 2017 where there was a court ruling that led to the immediate removal of this geographic area. And I'll go into that in a little bit more detail now. So this lawsuit was filed by a family from New York. They had a patient that was a young woman who was waiting on the list and they filed a lawsuit against the Department of Health and Human Services to broaden geographic sharing. Basically in layman's terms, they wanted to get rid of that geographic hard boundary because they felt the allocation policy, at that time the LAS, resulted in the allocation of lungs by a candidate's place of residence and not by their medical urgency. So immediately after that court ruling went into effect, we ended up changing the allocation policy somewhat, a temporary change, where we changed that hard boundary, by changing it to a 250 nautical mile radius from the donor hospital where the donor organ was located.

That was just a temporary sort of stop. The transplant community recognized that we needed a new framework for allocation and subsequently, the OPTN adopted continuous distribution as the framework. And basically this is the geographic boundaries that are removed. It's a systematic removal of boundaries, basically a national allocation system. What it did, it operationalized using medical urgency and geographic feasibility, to make it efficient, to come up with an allocation policy. So continuous distribution was the new policy that was adopted for all solid organs. Heart is going through their selection of what we call attributes, and I'll go into that in one moment. Lungs were the first organ that were selected to implement and to use this framework. And again, the implementation took place in March of 2023. So the old system had geographic hard boundaries. The new system actually used a overall candidate score to rank candidates, and I'll go into that in more detail now.

So this score is called the Composite Allocation Score. It basically determines allocation priority. It's composed of five goals that you can see here in blue and there are attributes for each patient underneath these goals. And what does that mean? That means if you're talking about liver or kidney or you're talking about heart, you can have different attributes and different goals. This is adaptable to all organs out there. And again, lung was the first organ that underwent this implementation of the continuous distribution framework. At the same time as we were working on continuous distribution in this new allocation, OPOs were under a great deal of scrutiny. As you know, the NASEM report had come out, there were congressional hearings on OPO performance, and OPOs were tasked with increasing the number of organs that they were offering, getting more organs out there. So we had a storm happening.

We had a new allocation system with a borderless system that was national. We were getting offers from coast to coast and we had OPOs that had increased their activity. So that presents some really great opportunities for programs like ourselves, but it also created a lot of challenges that we are going to talk about over the next few lectures. So what did we learn from continuous distribution? The one-year implementation report just came out a few months ago. In essence, waiting list mortality rate decreased by 29%. That means less patients were dying on the waiting list or being removed for being too sick. The overall transplant rate increased by 16%, meaning we were doing more transplants. The number of lung donors per month increased, of overall 14% increase. This might have been due more to the OPO activity rather than the allocation system changing. But in terms of medical urgency and wait list mortality rate, the sickest patients, that was the highest rate of wait list removals. You would expect that with these very ill patients.

However, in terms of transplant rate, these sickest patients were getting transplanted the quickest. These patients, median time to transplant if they were really sick in the highest group, were getting transplanted quicker in a matter of days. If you looked at program size programs like ourselves, large programs that were doing more than four transplants per month, our transplant rates increased. But for programs that were smaller, doing less than two to four transplants or really small, doing less than two transplants per month, they were facing challenges with this new allocation system. Again, probably related to resources and some of the things that they're able to do, which you're going to hear about, what our group does very well.

There were some negative aspects to this allocation system going into effect. We were traveling much further. If you look at DCD donors and brain-dead donors, our median distance overall to travel had increased exponentially. Also, in addition, the efficiency in terms of getting organ offers out there and accepting organs. We were actually having an offer go out further in terms of number of centers that had to look at the offer before final acceptance, so that was weighing down the system and bogging down the system.

So just in summary, what have we learned since implementation? The benefits of the suppositives are great for a program like ours. There's no geographic boundaries limiting allocation, we're increasing the number of transplants, we're decreasing the number of patients that are on the wait list or being removed from the wait list for being too sick or dying on the wait list. But there are significant challenges that have been posed by this new system and this is what we're going to focus on in the next few lectures that you're going to hear.

We are traveling much more as I showed you. Our match run efficiency has gone down. We need to improve that. We have increased the cost, not just of travel, but we've increased the cost of using third party, like in the case that was illustrated by a previous speaker. We've also increased costs in terms of our donor coordinators, how many offers that they're seeing, what they're having to juggle. There are a lot of other costs that have gone into effect. So transplant and lung transplant has faced some significant increases financially. I'll stop here and then turn it over to the rest of the speakers and want to thank my team for all their support.

Kenneth McCurry, MD:

Thank you very much, Marie, that was outstanding. Great overview. Ken McCurry, I'm the Surgical Director of the program and I'm going to talk to you a little bit about today about sort of what we do here at the Cleveland Clinic to try to meet the need of our patients. As you've heard from Jason, we try to be very aggressive in terms of the patients that we offer transplantation to. As you've heard from Dr. Budev, the playing field in the United States is changing a little bit, but I think we're very unique in some regards in terms of how we approach utilization of what we would consider marginal organs, as well as utilization of ex vivo lung perfusion strategies to try to get our patients transplanted more quickly, to help them live a better life and a longer life.

So there's a lot of need for lung transplantation in the United States. So between 1980 and 2014, over 4 million patients died in the United States of some sort of chronic lung disease. A fraction of these patients get listed for lung transplantation. When I started in this field 27 odd years ago, too long to think about now, we were doing about 800 lung transplants in the United States. We currently do about 2,500 to 2,600, so we've tripled it over that period of time. But as you can see, there's still a great deal of need.

And although the changes in the current allocation system in the United States have decreased wait list mortality, even though we're still fairly restrictive, although we're pretty aggressive, if you look at the potential pool of patients that might benefit from transplant, we in the United States, list a fraction of those for transplant because of our restrictive listing policies. And part of that, has been because of the limitation in donors that have been available and still in the United States, despite some improvements that Dr. Budev articulated very well, there's about a 15 to 30% wait list mortality.

So part of this is due to sort of ideas that came when this field was evolving in the 1980s, and this was really led by Joel Cooper and Alec Patterson at Toronto and Alec Patterson ultimately at Washington University in the United States. But this idea of an ideal donor lung, and these are sort of the criteria that were accepted back in that period of time. The first successful lung transplant was done in the 1980s and through the late 1980s and early 1990s, this is really what we looked for and this is really a pristine donor. But this did hinder and it was necessary during that time to sort of optimize outcomes and develop the field, but it certainly hindered the number of organs that we could utilize and offer to patients.

Over the years, many programs across the world have contributed to this idea of expanding the criteria and utilizing what previously were considered marginal lungs. And that term marginal is really sort of a moving target. I think things that we certainly considered marginal 25 years ago now, we consider routine to use. We're very aggressive at our program and have contributed to some of this literature as well.

So much along the lines of what Jason said, we commonly utilize donors well into their 60s and some donors well into their 70s if other things look good. As Greg articulated, we'll sometimes travel long distance even for older donors. Smoking history, which used to be considered taboo, we realize that if we decline all donors with a smoking history, we'll offer this therapy to a lot fewer patients. So now we look for evidence of smoking related injury to the donor lungs, and if there is none, typically we'll utilize those lungs with very good outcomes. We and others have recently begun to use donors that are hepatitis C positive. That does result in transmission of hepatitis C to the recipient. But the therapies are very effective now at treating hepatitis C and this is a routine part of our program.

And then we routinely utilize organs with abnormal chest x-rays and CT scans as long as there's no infection, and this was really taboo in years past. And we've contributed significantly in this regard just demonstrating that in very high BMI donors, we normally see infiltrates and consolidation in the lower lobes, yet we're able to, if there's no infection, we're able to go to look at these lungs and ultimately transplant them and offer these to patients.

So despite all of this and this movement toward utilizing more marginal lungs, being more aggressive at our program and across the United States, we still unfortunately in the United States, utilize the minority of donor lungs that were potentially available. So of all donors that donate in Oregon, we currently across the United States, and there's significant variation region to region, we utilize only about 20% of those donors.

And a lot of donors are declined for the reasons I have listed here. So the lungs are edematous, perhaps there's infection or excessive ischemia time or perhaps the logistics and difficulty getting there, make it difficult to use those organs. So we and others in this technology was originally developed by Professor Stig Steen in Sweden, have begun to utilize a strategy called ex vivo lung perfusion. The idea behind this is that you can take lungs out, put them on a machine sort of schematically that I've shown on the right here, perfuse them with a solution that has a high concentration of albumin and dextran, so it has a very high oncotic pressure, potentially allows you to remove fluid from the lungs and to do other things to be able to treat these lungs while they're ex vivo, being perfused ex vivo, and we do this for about three to four hours and I'll show you our strategy.

And this has made a very positive impact on our program over the last six years or so. So EVLP as a reticulated perfusion of lungs, the way we see it, is it helps us to increase the donor pool. It does this by allowing us to assess questionable lungs, so lungs that we just don't know when they're in the donor whether they're transplantable or not, we can bring them back, put them on this machine, and we have the machine that I've shown on the right here, here at our institution, and we can assess them, we can take marginal lungs and assess those and potentially treat those. And I'll show you a couple of the ways that we do that. And then also allows us to address logistical issues. Although there are evolving strategies with regards to storage that may allow us to keep lungs outside the body for a longer period of time.

Sometimes we can use EVLP to sort of reset that and there's data that I mean by that, if we're approaching sort of the limits of cold ischemic time and we put lungs on the device, it sort of resets the lungs to tolerate a second longer ischemic time. So we've sometimes gone up to about 22 to 24 hours with the lungs outside the body with a period of just three to four hours of EVLP perfusion.

And then there's a lot of people including us, working on ways to actually modify lungs, and this is a bit futuristic, but to be able to use gene transfer, other technologies potentially to perfuse the lungs for several days, modify them genetically or pharmacologically or other sorts of things, to make them less resistant to rejection and to actually improve long-term outcomes. And there's a ton of work going on in this regard and it's really cool, the idea that we could have essentially rooms or warehouses full of lungs that we could modify for a particular recipient, personalize, and then ultimately transplant those days later.

So all of this helps us increase the pool of usable lungs and provides flexibility. So the way we see this is that some of these rejected lungs, we can evaluate with EVLP, determine whether they're transplantable or not and either accept or decline them. And this is really the way we sort of approach this at our institution or our program. If it's a standard donor, we go directly to lung transplant. If there's some question, marginal, something else, we go, we assess if we're able to do things at the donor hospital to make them better, we'll transplant them directly. If not, we'll bring them back, we'll put them on our EVLP machine and then make a determination after that utilizing those strategies and this has made a very positive impact on our program. We do about 40 to 45 of these a year. A lot of these lungs, the majority of these lungs would otherwise not be transplantable, yet we're able to use this technology to improve them, to contribute to our patients and their outcomes.

And when we transplant these lungs, the ones we do accept after EVLP, the outcomes are outstanding. As you can see, a 30-day survival of 98%, one year survival of 90%. This is actually much better than the International Society for Heart Lung Transplantation, 30-day and a 1-year survival. So marginal lungs transplanted into recipients, more options and better outcomes.

And we've contributed a lot to this literature here at the Clinic we have a lot of people working on this and have a laboratory based on this, but looking at ways to evaluate lungs on EVLP techniques with which to assess them and make determinations as to whether they're suitable. And then also therapies. So sometimes if the lungs are edematous, we'll do things as simple as proning them, so turning them upside down on the machine. And that actually has a very positive beneficial effect in terms of being able to mobilize the edema in the lungs and to reduce the inflammation.

So really truly an evolving field, and I'll just give you a quick video here of what the lungs look like on the device. So in this bubble that keeps them sterile and being perfused with the solution. And as you can see, we can actually ventilate them at the same time. So we could administer pharmacologic agents both via the trachea, as well as through the transfusion circuit and do other sorts of therapies like proning, as I discussed.

So all of this has contributed, as I stated, quite substantially to our program. And sorry, the numbers cut off on the bottom, but the most recent one on the right, 129 transplants was in 2023. So we're just one of a couple of few programs in the United States that have consistently been able to offer transplants to 100 or more recipients per year. And utilizing these approaches, we were able to transplant 129 patients last year, which was significantly by far the largest volume of lung transplants performed in the United States last year.

So I was formerly at the University of Pittsburgh quite a long time ago now, and Tom Starzl, who's widely regarded as sort of the father of liver transplantation, was their mentor of mine. And back in the '70s when he was developing liver transplantation, at one point, they were doing about 6 or 700 liver transplants per year at the University of Pittsburgh. And this Calvin and Hobbes cartoon strip was developed around that time. I wonder where we go when we die in Pittsburgh because they were doing so many liver transplants. So what we are striving to do here to offer this therapy, lung transplantation in more and more patients here in Cleveland, is we don't want people to die, but obviously things happen and when they do, hopefully you're an organ donor and your lungs potentially will come to Cleveland.

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