Speaker 1Hello everyone and welcome to another episode of Poem Peeps. We've had a lot of fun episodes recently including our Chess 2023 preview. It was a great chess conference. We had a meeting one-on-one with Hannah Wunsch discussing her book Autumn Ghost and recently Firth was able to partner with ATS Breathe where he provided some high-yield tips on tricks and teaching in the ICU. So Firth, I'm really excited to be coming back to an episode on a core pulmonary topic of lung transplant. So excited to hear what you think about the episode today and what are you looking forward to the most?
Speaker 2Yeah, Christina, I'm pumped to be back. I also love these episodes that I think people are always asking about. You're a pulmonary fellow, you're a resident, you don't know that much about this really key concept that comes up for lots of our patients and comes up both in the outpatient and the inpatient setting. I think lung transplant is fascinating. I almost became a lung transplant pulmonologist or for Megan, respirologist if I was practicing in Canada and I think this is something that really every pulmonary fellow for sure but even residents should have a good understanding of because lung transplant is such an increasingly available and successful option for our patients with end-stage lung disease. So I'm really excited to dive in and scratch the surface at least with this introductory episode.
Speaker 1Yeah, couldn't agree more. And Firth, I feel like people's ears probably went up when you're like, can we still have the potential to get Firth to do transplant? Like it's never too late. Maybe after today we'll get you switched and then Hannah and Megan could try to get you both to their
Speaker 2respective institutions. Yeah, the never too late and broad interest has probably been my downfall throughout my medical career. But hey, let's keep our interests broad all the time. I love it.
Speaker 1For sure. So excited today to be joined by two faculty experts on lung transplant and end-stage lung disease. First, we have Dr. Hannah Manum, who's an associate professor of medicine at UVA Health. Hannah joined faculty at UVA in 2016 and she has expertise in ILD as well as lung transplant. Hannah, it's so great to have you joining us today.
Speaker 3Hello from Virginia and thanks so much for having me here today. Megan, great to see you again virtually. I'm so honored to be a part of this podcast and excited to share some insights with you all today on lung transplant.
Speaker 2Yeah, the pleasure is all ours for having you. Thanks for being here. We're also joined today by Dr. Megan Aversa. Megan is an assistant professor of medicine at the University of Toronto with an expertise involved in patients with end-stage lung disease and lung transplant. Megan also personally taught me most of what I know about lung transplant and I feel extremely privileged that she's here because she's a great educator, a great transplant physician. I'm excited for her to join us today. Thanks for having me. Thank you. Thanks for coming on the show.
Speaker 3Hi, guys. Thanks so much for having me.
Speaker 2Before we dive in, just our standard disclaimer. As a reminder, this podcast is not meant for specific medical advice. The views we express today do not reflect the opinions or policies of our respective employers. We're going to talk about some case vignettes and anything that we talk about is HIPAA compliant with details changed to protect the privacy of our patients. So to start things off, I know many listening today are on the primary teams caring for patients with end-stage lung disease. They may be doing general medicine and have patients who are seeing a consulting pulmonary physician. They may also be a pulmonary consult fellow or attending who's treating patients with these end-stage lung disease and needs having a framework for approaching them. So to do that, we want to have a case vignette that we're discussing to frame our questions and delve in further to the topic. So for this case, we have a 58-year-old man with idiopathic pulmonary fibrosis who's on an antifibrotic agent. For the last three months, he's had progressive lung function decline that we've seen on pulmonary function tests. He's also had exertional dyspnea, a progressive dry cough, and severe fatigue. He recently completed an eight-week course of pulmonary rehab, but he shares that unfortunately, his functional decline has continued and it's now impacting his activities of daily living, and he's requiring more supplemental oxygen at rest and with exercise. So the primary team is now consulting pulmonary for consideration of an inpatient lung transplant evaluation as he's come in and requiring more oxygen and admission.
Speaker 1Ber, if I remember getting these consults as a first-year pulmonary fellow, and we all know today that lung transplant is a really broad topic, but we're hoping to provide some clarity and hear from Hannah and Megan today on a few key teaching points, a few being including the primary indication for a lung transplant, patient eligibility and selection, as well as some risk and complications associated with lung transplant. So we're going to go ahead and get started. And to also discuss any methods that we can to minimize these during the evaluation process. Ber, if I don't know about you, but I definitely think we need a second episode as I'm thinking through things to discuss some post-transplant management complications of immunosuppression, probably some ECMO and transplant as a bridge. So I know we have some things to also look forward to. And Hannah, before we get into some specific questions that I just mentioned, I'm wondering if you can share some recent data on the number of in recent years and the most common disease indications warranting a transplant.
Speaker 3Sure, Christina. We recognize the data lags behind a little bit, but there's been a gradual increase really worldwide over the past three decades in lung transplant. And based on the most recent ISHLT registry, although lung transplant has been growing, it still remains somewhat of an orphan disease. Approximately 4,500 lung transplants are done a year worldwide, and a little over half of those have consistently been done in North America. So that's a lot of data. So I'm wondering if you can share some data on the number of transplants that have been done in North America. While that number is growing, single lung transplants remain pretty steady at approximately 750 per year. And the growth has really been in double lung transplants over the past three or four years. Not only is the number growing, but the indications are broadening. And specifically with interstitial lung disease, there's been a steady rise in number of transplants for interstitial lung disease. As of 2009, worldwide, it surpassed COPD as the number one indication. And it actually makes up almost half, about half of the total number of transplants for interstitial lung disease. About 40% of all the transplants done, 32% of those are for IPF alone. This ILD increase in trend is really mostly driven by North America, and COPD does come in a close second as the indication for lung transplant. While cystic fibrosis and bronchiectasis are third, it's quite a lower percentage. And really that trend has actually been declining in the past five years, and that's most likely secondary to improvements in drugs and CFTR, modulators and development. When we think about lung transplant as a whole, though, certainly over the past five years, lung transplant candidates have been evolving. We know that they're sicker, their score at the time of listing is higher. 21%, which is like a shocking number, are hospitalized at the time of their transplant. More patients have antibodies that make them have a harder match. And age is one of the more dramatic ones. As you can imagine, as ILD goes up in number, so does age. And so currently, the average age of lung transplant patients is 57 years old, with about 35% being greater than 65. And just to give some perspective there, the older ISHLT guidelines for lung transplant indications, greater than 65 was actually a contraindication to lung transplant. And now it's making up 35% of the population. Some of this trend, I do think, you know, was reinforced with the COVID pandemic. COVID really changed the paradigm for how we think about lung transplant a little bit. And so, you know, I think it's really important that we think about lung transplant for a little bit. And in October of 2020, UNOS added two more indications to lung transplant, including COVID-19 related ARDS and COVID-19 related pulmonary fibrosis. And when you look at that data, basically in 2021, those two diagnoses of COVID was made up about 10% of lung transplants, which actually made it third most common indication for lung transplant in 2021, which is pretty huge. Two thirds of those were really COVID-19 ARDS, and only one third were really pulmonary fibrosis. Of course, that number is going to be ever changing, especially with vaccines coming into play. The incidence of COVID-related ARDS was down significantly. But I think it's still a little early to see where COVID pulmonary fibrosis is going to fall into indications for lung transplant and how this will affect the overall lung volume moving forward.
Speaker 2Yeah, it's so interesting how the world evolved during the COVID pandemic and then now is normalizing back. But the lasting impact and changes are going to be something for us to continue to adapt to. And the age thing you mentioned is really remarkable, especially when we think about end-stage lung disease. Outside of things like cystic fibrosis, so many of our patients are in this older age range. So the increasing prevalence really is going to impact our care and evaluation, I think. This gradual increase in the number of transplants performed worldwide and the big bolus with COVID, I think also just gives more experience and more comfort and overall maybe hopefully can have a positive impact on the health of our patients. So I think it's going to be a positive impact for all our patients. Bringing the discussion back from the general to our case presentation. So we now have a middle-aged man with IPF and progressive symptoms, despite the best treatments that we have for IPF right now with antifibrotics, long-term oxygen support and pulmonary rehab. And so certainly we're thinking about transplant. Megan, I'd love if you could share with us a bit more about the appropriate timing for a transplant evaluation referral. I feel like this is a huge topic and that often it's too late when people get sent. And so I'm I'd love for our listeners to know when they should start thinking about this earlier on for their patients with progressive lung disease.
Speaker 4Sure. I first just want to highlight that the ICHLT consensus document for the selection of lung transplant candidates was just updated in 2021, and it's available on the ICHLT website, and it really provides a nice guideline for pulmonologists who are considering referring a patient for lung transplant assessment. Generally, based on this guideline, the rule of thumb for all patients with any type of chronic end-stage lung disease is to consider a lung transplant if there is a high, meaning more than 50% risk of death from the lung disease within the next two years. But of course, the big prognostic markers differ based on the underlying lung disease, so the consensus document also outlines disease-specific recommendations that I highly recommend reading, but I'll go over the big four, the COPD, ILD, CF, and PH briefly. For patients with COPD, we typically say they should be referred when the BODE index is in the range of five to six, and there are additional factors present that tend to increase mortality, like frequent exacerbations, really low, FEV1 in the range of 20 to 25%, or a rapidly increasing BODE. We should also be referring any time we have a patient with COPD who is clinically deteriorating or has an unacceptably low quality of life despite maximal medical therapy. For ILD, this is typically a much more rapidly progressive disease, so we say patients should typically be referred earlier. For IPF in particular, we would like patients to be referred at the time of diagnosis, but for any type of pulmonary fibrosis, it's best to refer if the FEC is likely to be referred at the time of diagnosis. If the FEC is likely to be referred at the time of diagnosis, we would like to see a patient with a FEC of less than 80% or declining by 10% in two years, or the DLCO is less than 40% or declining by 15% in two years if there's any radiographic progression or a need for supplemental oxygen. Cystic fibrosis, CF, is something we're seeing less and less of come to transplant, but we would certainly like to see anyone with an FEV1 less than 30%, even 40% if there's a reduced walk distance, hypercapnia, hypoxemia, PH, or frequent exacerbations, or really anyone who's rapidly declining. And lastly, for pulmonary hypertension, we should be seeing patients with a reveal score of 8, significant RV dysfunction or progressive disease on therapy, anyone needing IV prostacyclin therapy, and certainly those with PVOD, PCH, scleroderma, pulmonary artery aneurysms in particular should be referred early as they can really progress quite quickly.
Speaker 2I think that the DLCO decline that you mentioned is really a reminder for everyone, like the importance of having routine follow-up with your patients with advanced disease and making sure that you get things like PFT, six-minute walk, and thinking about their progression. I feel like a lot of times, especially with residents and sometimes even fellows, as I'm discussing, they don't see the utility of these long trends we're doing and there are these fluctuations, but really if you're seeing a steady decline that you think is reproducible, this should be your first signal that you should send someone for a little bit more of an evaluation. So it's always just a good reminder for everybody.
Speaker 1Thanks, Firth. And thanks, Michael. Thanks, Megan, for providing that framework and being an adult CF provider, I definitely have seen in our own institution with the advancements of CFTR modulators, still the number of decreasing lung transplant outcomes, but I still do have patients who are adult who have end-stage disease, so less than 30%, as you mentioned, who are needing to be evaluated. But the question always comes up, what is the timing? So I appreciate you telling us a little bit more information about that and we'll definitely provide the link for the ISA, sorry, we'll definitely provide the link for the ISA. Yes, HLT 2021 guidelines that you mentioned. It does feel that this patient is definitely appropriate for the reasons that you said, Megan, and I know that the process itself and evaluation involves various people from the transplant group and different multidisciplines, and this can really occur in multiple stages. Hannah, so I'm wondering if you would just mind walking us through, what does that evaluation process entail for those that may be hearing about it for the first time?
Speaker 3Sure. So it definitely is broken into phases, and it's a lot of different phases. So it's a lot of different phases, and it's a lot of different phases. So it's a lot of different phases. So the timing of those phases is ever-changing depending on the severity of the lung disease. The first step is obviously a referral, and usually that referral comes from the primary pulmonologist. However, patients can also self-refer as well, and sometimes we do get that in patients who are in a pulmonary rehab or in the community who've heard about lung transplant from someone else. Most centers start with insurance authorization to ensure that the workup, which can be quite extensive and expensive, is going to be covered. And for most centers, this isn't a huge barrier. Sometimes it determines where that patient will be sent for lung transplant, especially if there's multiple centers around them, but usually it can be done within days. When the patient comes, I would say the first part of the evaluation process is the initial visit and evaluation by the physician. And when the patient comes for that visit, the real job of the lung transplant physician at that time is to confirm the underlying diagnosis, make sure that we're working with what we think we are, and also to make sure that we've exhausted other treatment options. For example, pulmonary hypertension, making sure that they really are maxed out on IV therapy, and there's not more treatments that could be offered. In some patients, for example, in COPD, we have to think about other potential therapies that aren't medication related. For example, lung volume reduction or bronchoscopic valve reduction surgery. And if we think that there could be other treatment options available, obviously coordinating those processes within your institution and with other physicians is really important. And a lot of times we see patients where they're still going to need a lung transplant, but they're still going to need a transplant, but maybe by going up on their cell set for their scleroderma or putting a valve in might help bridge them for the timing of their transplant. And so looking at those other treatment options while also doing the lung transplant evaluation in parallel can be helpful. The second part of that initial visit is really to assess their end-stage lung disease severity for the timing of workup. Timings of workup varies dramatically between institution and at our center, we can work up somebody in literally 48 hours if we need to. We've gotten that sophisticated in the inpatient workup. However, with someone with stable COPD, who's maybe a little bit early for transplant, that workup may drag on for up to three months. Some centers have someone come and stay and do the workup all in the five-day period, while other centers will schedule things within weeks to a month timeframe. But we tend to set that timeline at the first visit when we recognize how sick the patient is and how quickly we really need to make a decision. And so that's a big part of the workup. Obviously, the optimal and most common evaluation will then involve outpatient pre-scheduled testing and appointments that, like I said, can take place in weeks to a month, depending on how the center is organized. Education is a key part of that visit, but education continues along the evaluation. And the second large part of the evaluation process after they get through the initial visit and the assessment of the physician is really the diagnostic steps. Ultimately, we want to find patients who are going to have the greatest and longest benefit, greatest being, I think, the first priority. Secondarily, probably the longest benefit with new lungs. And in order to do that, we need to identify risk factors, both medical ones, but also psychosocial ones as well. So patients undergo a large variety of testing that does vary within center to center, but there's a lot of consistency across the board. So all centers are going to do a large plethora of blood work, cardiac testing with an echo left and right heart cath. Almost all centers will do some form of GI testing that kind of varies across the board, depending on the underlying lung disease. Lots of imaging, including abdominal imaging to look at the liver, VQ scans, DEXA scans, 24-hour urine to evaluate the renal function. So as you can see, a lot of it's not very invasive, but does involve lots of different imaging modalities, I would say. And the second part of this diagnostic workup phase involves meeting people from the multiple centers. So we're going to do a large multidisciplinary team. So much of lung transplant success revolves around not only their medical comorbidities, but all the other really almost more important things sometimes. And so meeting social work, finance, nutrition, pharmacy, physical therapy, at most centers, some kind of neuropsychological evaluation, and then potentially other consult services like transplant ID, endocrine, depending on other comorbidities the patients have, really make up a large part of this. And centers are pretty savvy at organizing things. So we're going to do a large part of this in a way that really optimizes the efficiency for the patient and for themselves as well. Part three of the evaluation phase, I would argue, is follow-up appointments. So most centers see the patient at least twice before really determining candidacy. And a lot of that is important because then, as Megan was saying, you get to see the evolution of the disease. You have multiple PFTs in a row to really see where this patient's falling in regards to transplant. We do ask that all patients are up-to-date on their healthcare maintenance and up-to-date on their medical vaccines, most centers per the CDC guidelines. And so those are things that are happening on the sideline as the rest of the workup's going on. And then the last part of the evaluation process is the selection committee, where basically patients will then get an answer from the team on, are they a candidate? Are they not a candidate? Or a lot of times what happens is you are a candidate if and when, and they get a to-do list per se of things they need to do. For example, complete your hep B vaccine or lose five more pounds. And the important part of that selection committee also involves timing of listing, where people will discuss, are you too early? And can we can wait a while, even though you're a candidate, which ideally would be the best place to be for the patient? Or is it time to list now? Sorry, it's a lot, but it is a lot.
Speaker 2It's a lot, right? It's a lot for the patient to have, and they need the education that's going. It's a lot for us to consider. I wanted to do a follow-up question for you, just about one aspect of it. It's amazing that your center can do things in as short as 48 hours and select patients. We're going to talk in a minute about the selection. committees and what that involves. But do you, is that reserved for specific patients? Like are patients of a specific pre-screening based on their age and severity of illness? Or I always feel like we get these questions, a patient who's very sick, can they be urgently worked up for transplant? But then it's always a tough question of if they're too sick to even undergo that rapid
Speaker 3evaluation. Yeah, that's a great question. First of all, that is definitely an exception to the rule and not the way we want to be working up a patient. But like you said, there are select patient population that are perhaps acute exacerbation, IPF, otherwise healthy prior to, especially if they've already met the transplant team before, and maybe have already started their workup, where there are some unique situations at individual centers where patients get admitted and then either complete their workup or even undergo their entire workup in the hospital. Of course, in order to do that, the patient, there's a big selection by as of who you're admitting to the hospital. And you're trying to find patients who haven't, quote unquote, lost their window for a transplant. So when someone walks in who is considerably overweight with a BMI greater than 40, who's in a wheelchair and hasn't done pulmonary rehab and is on 12 liters of oxygen, obviously, unfortunately for that patient, we're probably not going to be able to get these things accomplished and get them to be a great transplant candidate in the short period of time that they have with their lung disease. However, especially if it's a young patient who has a rapidly progressive disease and we feel like the outpatient workup may take too long and their disease is outpacing them, sometimes admitting them to the hospital to get their workup done in a rapid fashion is the right thing to do. But you certainly have to be very select about who you're going to be doing that for and making sure that you otherwise think they're a good candidate from all the other factors before you would do those kind of workups. And some of those patients end up leaving the hospital and going home. did. They don't necessarily live in the hospital until their transplant, but we want to ultimately have lung transplant as a door of opportunity and not a absolute have to happen kind of situation. And so if we can get people on the list as quickly as possible, when we see that their lung disease is rapidly declining, that then helps them with keeping their rehab and all the other important factors for transplant up to par.
Speaker 2Yeah, absolutely. I feel like everybody's had one or two of those patients that are like the young patients who are just moving very quickly. And then sometimes they get a transplant, but sometimes they even just go home and are very well plugged in. Thanks for reviewing that. Megan, I want to talk a little bit more about the evaluation process. We talked about the selection committee and the multiple disciplines that are involved. So can you give us a little bit more insight about what the selection committee, when they're meeting, what they're focusing on to discuss the eligibility and what kind of criteria they're using or risk factors they're considering?
Speaker 4So at our lung transplant assessment meeting, we're going to be talking about the selection committee. And we're going to be really our entire team is present. We have our thoracic surgeons, our pulmonologists, we call you respirologists in Canada, our social work team, our physiotherapists, our anesthesiologists, our dietician, and our nurse coordinators. And one member of the team presents the patient's history and all of the testing that is typically done as part of the transplant assessment that Hannah was outlining, the PFTs, the chest imaging, the left and right heart caths, the echo, the MIBI, the bone marrow density test, the blood work, the GI testing, if it's done. Our physiotherapist then reports on the candidate's six-minute walk test and other markers of their physical strength. Our dietician reports on the BMI and any nutritional concerns that might be present. And our social worker discusses the adequacy of the overall support plan after transplant. It's really a time for us all to review the candidate together and discuss their trajectory of disease, medical comorbidity, surgical risk, physical strength, nutrition, and social support, as that all really pertains to their transplant candidacy. And their overall readiness for listing.
Speaker 2Yeah, there's a lot that goes into it. And I feel like a process that sometimes patients have a little bit of trouble understanding too of all the things, but hopefully we can talk them through the different aspects that they're looking at. I think one thing that comes up is sometimes someone is considered not an appropriate candidate after that initial selection review, but it's not because it's something that is an absolute contraindication. Like it's not because they're 85 years old or something like that. Do you often have patients who have something like this and then can be reevaluated at a future time point? And how do you set them up for that?
Speaker 4Absolutely. This does sometimes happen. Sometimes we do review a patient, for example, someone with ILD who does appear to be an appropriate candidate for transplant, but is quite functional, fairly stable, really a slow progressor. We would likely say in that instance, this candidate is too early for transplant right now, but when the time comes would be a candidate if nothing else changes or arises medically later on. We tend to follow these patients along with the referring pulmonologist and list them for transplant when they are sicker. Also, we can review a patient, for example, someone with COPD who seems like an appropriate candidate also, poor quality of life and poor exercise capacity, but who has not yet participated in pulmonary rehab. And not only do we want to make sure that our candidates are pursuing transplant only after maximizing every other possible avenue to improve their condition, but we really want them to go into transplant in the best possible physical conditioning, as this is going to benefit them hugely. In terms of their recovery and post-op complications. So we may say for someone with a poor six-minute walk test, let's get them into pulmonary rehab, reassess after that, because it may improve their quality of life sufficiently, or at least their physical conditioning will have improved such that they are then a much stronger candidate for transplant.
Speaker 1Thanks so much, Megan, for sharing. And kind of, I think words you had used earlier is how to conceptualize it as listing, no listing, or potentially deferring based on circumstances. But definitely there are certain patient populations that could be re-evaluated at a later point. I know that you brought up some risk factors already that were important to think about, but one thing that I've encountered before is really more around the infectious disease realm. And so being a CF physician can be a contraindication at certain institutions and that can be institution specific and probably thoracic surgery specific as well. But Hannah, I'm wondering if you could share us a little bit more about, are there certain infectious risk factors such as B. sepatia, NTM, hepatitis, or HIV, that we need to consider differently as patients are being evaluated? Sure. I think this is hugely important, especially
Speaker 3in the CF population, because we know a lot of these infections are very common. While we do, the International Society for Heart and Lung Transplant does have some guidelines. They're very vague. And so it really does then become a center-dependent issue. Referring back to the guidelines Megan already talked about, November 2021, ISHLT guidelines, active TB, and HIV, with a detectable viral load are still what we would call absolute contraindications in thinking about infections. And then there's a broader class of mycobacterium abscesses, Burkholderia, Sinosapacia, or Gladioli, and then Lomentospora prolificans, which I know and formerly known as Scutosporium that most people are familiar with. Those along with active hep B and C with positive viral loads and or fibrosis, those are considered high or substantially increased risk. So this particular group is a little bit challenging, and it's very center-dependent. Almost all those patients are going to be seen by transplant ID. And most societies also emphasize that there should be thoughtful consideration about whether or not these should be transplant patients, but also whether or not they should be referred to high-volume centers that do these types of infection, simply because it's such a small population and certain centers have done groups of cohorts of mycobacteria. So in the future, we really know whether we're harming or helping patients with these particular infections. That being said, a lot of centers have evolved in the way they're looking at hepatitis C and HIV specifically. So most centers will take on patients with hepatitis C with a negative viral load, assuming they don't have any AIDS-defining illness, and also that they've followed with their infectious disease doctors and demonstrated adherence to therapy. There's a whole host of other types of infections that make us nervous, but we don't necessarily exclude from transplant. But anytime, I would say, someone has a chronic or smoldering lung infection, such as aspergillus, any kind of atypical mycobacterium or history of multi-drug-resistant organism, bacteria, such as Pseudomonas. At least at our center, we get transplant ID involved pretty early on. First of all, to make sure that pre-transplant, we're ensuring that they have the infection under control prior to listing. A lot of, for example, with mycobacterium obsessus, a lot of centers are going to want at least the culture to be positive close to the time of listing and probably treat through transplant. We know there's pretty good data that if you have one of these kind of really resistant bugs prior to transplant, that the same thing is going to pop up early post-transplant as well. So making sure they're at least under good control prior and even equally as important, I think, that the patient can tolerate the treatment. Because as we know, a lot of these treatments can be really hard on the body and patients can't tolerate them. But transplant ID also then knows the patient prior to going into transplant. And so we have a preset plan for what we're going to give these patients perioperatively and immediately post-transplant from an infectious disease treatment course to hopefully help mitigate the risk of reinfection after transplant and then have close follow-up with transplant ID afterwards as well.
Speaker 2Thanks, Anna. It's always really helpful. And it's just so interesting to think about all the different factors that go into this and all the people who can help play a role and the different experiences of centers. If you've done this multiple times, you may have a better protocol or a better tolerance for some issues that other centers can't. So it's always great to think about the global transplant population of patients and centers that are doing this. We've had a great discussion about what is involved in referring a patient for candidacy, what's involved in the evaluation and the selection process. But I think there's also this question about the timing of transplant. So timing of referral is really important, and I'm glad we discussed that. But I'd also like to talk about when you're seeing a patient, when you think is the appropriate time. Megan, you mentioned you want them to be in the best physical shape possible, but I know you also don't want to do it too early and subject them to the risks of transplant before it's necessary. Could you talk to us about when you think about listing your patient for lung transplant once they've gone through this evaluation and are determined to be a candidate?
Speaker 4Sure, absolutely. Again, I. Highly recommend reviewing the IHLC consensus statements. Very helpful. It goes over a lot of the specifics in terms of how we as transplant providers think about timing of listing, which can be very tricky. For patients with COPD, we're likely to list when the BODE index is in the range of 10, the FUV very low, under 20%. There's at least moderate pH, chronic hypercapnia, or really severe exacerbations. For patients with ILD, we're likely to list when they're. Demonstrating progression, a decline in FEC or DLCO, or their six-minute walk distance. They are hypoxemic, or again, if they have mounted secondary pulmonary hypertension or being hospitalized for complications or exacerbations. Patients with CF are likely to be listed when the FUV1 is below 25%, or those who are rapidly declining or frequently hospitalized. Again, if they have mounted pulmonary hypertension or, again, are chronically hypoxemic or hypercapnic. And lastly, for patients with pulmonary hypertension, primary pulmonary hypertension, we often list them when the Reveal score is above 10 on IV therapy. They are progressively hypoxemic, or they're having renal or liver dysfunction as a result of the pH.
Speaker 2That's great. Thanks, Megan. We will definitely post a list of the ICHLT guide consensus statements. As a pH provider, I'm always bad if you have pH. It sounds like that's always an indication to be thinking about this. But I really like reviewing those and really thinking about conceptually that they're supposed to be used as a prognostic. That's a fantastic risk factor of saying, "Look, these are the patients that we know, they're on therapy. They still have these risk scores, are really going to decline over a period of 12 to 36 months. And so we have to start thinking about a more sustainable therapy for them."
Speaker 1That's awesome. Yeah, Megan, as Firf said, that was a great way to conceptualize things. And I know when I was doing fellowship training, once a patient was listed, they were given a long allocation score. And if I remember correctly, that was determined by two big variables, the first one being risk of one-year weightless mortality. And then the second one was likelihood of one-year post-transplant survival. But I know this last year in March of 2023, this was changed to what's called a gas or composite allocation score. Hannah, I'm wondering if you could share the reasoning behind this change and what variables are included now in this score.
Speaker 3Sure. This could maybe be a whole podcast, but I don't know that I'd be the one to be doing it if it were. This is a big topic. And obviously, we talked about how COVID's kind of changed our lives. It's changed the way we look at transplant. And this has been another big change in the past two years. As you mentioned, the lung allocation was basically based on candidate groupings. So we took identical blood types, and we took 250 nautical miles from the donor hospital. And then we used, as you said, the two factors of weightless survival, post-transplant survival at one year. And it's important to note in there that when we looked at those two factors, that it was weighted as a two-to-one ratio. So the weightless survival was weighted twice as much. So it was the sickness before transplant had a higher weight to it. And as of March 2023, we did change to this composite allocation, which really uses a continuous distribution. So it's no longer these large candidate groupings. And the goal was really to improve organ matching. So I think the reasoning behind this was to try to still prioritize sick candidates, but also to look at improving long-term survival. So one of the big changes that came out of the CAS was that, you know, we had a lot of people who were sick. And so I think one of the big changes that came out of the CAS was that when we look at medical urgency, we do still look at the mortality one year without a transplant, weightless mortality. But when we look at likelihood of survival post-transplant, instead of looking at it at one year, as they did in the LAS, it's now being looked at greater than five years in the CAS system. And they're being weighted equally. So that's been a huge change to try to look at improving long-term survival. I think one of the other big reasons and goals of the CAS was to help provide more equity. So to increase transplant operations. So to increase transplant opportunities for patients who may be medically harder to match. To increase transplant opportunities for patients with distinct characteristics, mainly the pediatric population. And then also to promote efficiency and management of organ placement as far as geographical variation. So the way that it really changed, you still have a score that goes up to 100, just like the LAS. But there's, instead of these two factors, we now have basically five components. And half of the score is still made. And half of the score is still made up of those two things that were from the LAS. So the medical urgency, meaning the weightless mortality at one year without a transplant. However, now that carries equal weight to the likelihood of survival. And that survival went from one year to five years in the new CAS. So you can get 50 points just from those two factors alone. But then the next step would be looking at other recipient variables, which would give you up to 15 points. And this is trying to look at patients who may be, harder to match. One, height discrepancy. So height matching, blood type matching, recognizing that certain blood types are more common than others. Sensitization or basically immune system matching based on antibodies, which is a huge one. There's a lot of patients, especially females with autoimmune lung disease are highly sensitized. And so it's harder for them to find a match with their antibodies. And so trying to give point up to 15 points for these variations in patients and patient factors. And then another thing they look at up to 25 points. So a lot of patients with autoimmune lung disease are highly sensitized. And so a large chunk of the points is based on candidate biology. So maybe mainly pediatric patients. So patients that are less than 18 years old, you can get quite a lot of points for that. And then also a prior living donor, which is a kind of an odd one. But if you think about it, for example, if you gave one of your kidneys when you were 25 to your brother, and now you have ILD and need a lung transplant, the fact that you gave your kidney and you were a donor already, you get points for that. And then lastly, up to 10 points. So approximately 13 points. So approximately 13% of the scoring pie is trying to look at donor variables and basically trying to help promote efficiency with organ placement. So looking at proximity and also travel distance from the organ hospital. So 10 of those points patients are getting almost at the time of the organ match itself. It's not been going on very long. There have been already some data shown and some changes made even based on the three-month monitoring. For example, this summer, based on the three-month monitoring, they did see that the number of patients with O blood type had gone down despite the overall number of transplants actually going up by 16% actually. So with that, they've actually already done some scoring changes with how we look at blood type and how we're giving scores to O versus AB versus A and B. And some of the other data we've seen is that it looks like it could be doing some of the goals we've talked about. So it's increased the number of lung transplants by 16%. It's decreased the weightless death and removal. It has. It has increased, interestingly, the median distance between donor hospital and transplant center. And also, there's been an increase in the number of exception scores quite dramatically from 38 to 120, which basically means if you have a patient and you feel like their score isn't reflective of how sick they are, you can put in an exception. There's already exceptions preset for pulmonary hypertension, but you can also write in your own exception. And so it's interesting to me, anyway, that the number of exceptions has dramatically gone up. Now, a lot of these. But I think that shows reflection of some of the other data that have come out of this already, which is that the number of transplants for patients greater than 65 has actually gone down, which you could imagine looking at a longer-term survival than a shorter-term survival. And while the rest of the age groups, the number of transplants have actually gone up. And so I think that when you look at the patients who were removed for weightless because of death or because they were too old, or because they were too sick, those patients were ones that had really high medical urgency scores, which are not weighted the same anymore as the lung allocation score was. And that might also reflect why there's been more exceptions put in, because there's these patients in the hospital that potentially are on ECMO or are being bridged to transplant. And while their medical urgency score is very high, some of they might not be getting points for all these other scores. And so they don't get to the top of the list as quickly per se as they did with the LAS score. We have to be cautious. All this data is very early. And you also have to think about every center knew this was coming. So perhaps there's some clinical practice changes that also could have occurred with the change in the scoring system. I think that there's definitely going to be more to come. And it's being tracked very closely with the medical directors across the country. The data is being tracked very carefully and will most likely evolve as we go.
Speaker 2Thanks for going over that, Hannah. I think this process is such an interesting aspect of medicine. I think it's very important. interesting for both people in medicine to think about, but also the general public about the equity of how we use this very limited resource. And so it's amazing to know that people are always evaluating and adjusting the system to try to improve that equity on multiple different scales. On that note, I know, Megan, that one of your passions is thinking about the equitable distribution of resources for people who may not be in the easiest immune matching for their organ. I was hoping you could talk to us a little bit more about that.
Speaker 4Definitely on the topic of health equity and lung transplant, a group that is significantly disadvantaged when it comes to access to transplant is that highly sensitized patient group, patients who have mounted anti-HLA antibodies, usually from prior pregnancies, prior transfusions, or prior transplants. Because of the very common practice of trying to avoid a positive cross-match at the time of transplant, which means avoiding using donor lungs that will have any of the antigens that would be targets for the anti-HLA antibodies that are circulating in the recipient, we really limit the potential of those antibodies. And so we're trying to avoid those antibodies. And so we're donor pool for candidates with a lot of anti-HLA antibodies. And as a result, they are much less likely to get a transplant and much more likely to die on the wait list. Our program in Toronto has done a lot of work to show that with appropriate perioperative desensitization, our regimen includes perioperative plasmapheresis, IVIG, and thymoglobulin, we are able to perform cross-match positive lung transplants safely. And these recipients end up doing just as well as patients who have had a cross-match negative transplant at our center. I think it's really important to work to mitigate the wait list disadvantage for our highly sensitized candidates and using a perioperative desensitization strategy such as ours is one effective way to do that.
Speaker 2That's fantastic. It's always centers like Toronto that have such a high volume and are doing advanced things like this. Thank you again for reviewing Megan. I think as a final question, before we take away some learning points from this episode, which has been fantastic, is just what patients can expect. After they get a lung transplant, I think a lot of providers don't even know what to tell them. So if you guys don't mind sharing what you tell patients in terms of the expected prognosis and survival and their course after lung transplant, once they've gone through this referral process. A loaded one.
Speaker 3I won't give you my whole spiel. Sometimes when I give it in clinic, patients are like, I hope you've recorded that. And you could just play that instead of repeating it every single time you see a patient, but it's really variable depending on the diagnosis, depending on the age. Depending on the comorbidities. However, when you look at overall survival, the overall survival, the 50% survival at five years, it's about six, six and a half. Is that what you would say, Megan, based on all the data out there? And so six and a half years, sorry, I should note that. Now that greatly varies. If you look at patients with CF, you're young, or you look at patients older than 65, it's worse than that. If you look at patients just with ILD, you're alone, it's about five and a half. When you look at, um, survival past one year and you look at overall survival, it's about five and a half years, 50%, five and a half years survival. So it's not great. Although it has gotten better, even in my time as a lung transplant pulmonologist. And the way I look at that with patients is I honestly, I give that data to them, but I try not to focus on the survival alone, because I think that for a lot of the patients, especially in this, in the COPD population, depending on how you time their transplant, they're not necessarily getting a lot of life years after transplanting. So I think it's a good idea to look at that. Because we know that patients with COPD can live for a long time with just a really debilitated lifestyle. And so I try to focus more about what the patient goals are for transplant and what they're looking to get out of it and focus more on quality of life and really try to give them an understanding of what that life might look like, because as we know, quality of life can be different for everybody. And a lot of times when I tell people, so within five and a half years, 50% of people are dead. They look at me like, oh, I'm going to die. I'm going to die. I'm crazy. Why would I do this? But then you have to remind them that we would only give you a transplant, right? If we thought that your survival was much less than that. And when I talk to them about quality of life, I try to give them the overall picture that even though we're curing their underlying lung disease, hopefully it's still a huge investment in the healthcare team. And that it's still a lot of visits, more blood work, probably than ever, more meds than ever, more PFTs than ever. So while you're otherwise, healthy from a lung perspective, hopefully that it really involves the trust and the team to really be a patient for life. And I usually, if someone's had kids, I usually relate it to hopefully after the first year, it's more like a well baby check-in and not a something's wrong all the time, but it's a different change of culture to be a healthy patient. You have to come to the doctor a lot. And that's the outlook they have to have. I also expressed to them that complications can definitely happen within the, especially within the first year. And that within the first three to six months that lung transplants really a full-time job and go over, of course, all the different types of complications and potentially side effects of medications that they might have, but also try to give them a layer of comfort that one of the beauties of lung transplant is it's such a multidisciplinary practice that it's not just the physician, but it's the nutritionist, the physical therapist, the neuropsychologist, all of which are going to be able to help troubleshoot things that arise after transplant to hopefully make their quality of life the best it can be. I don't know, Megan, if you want to comment too, if I said anything out of.
Speaker 4I'm smiling because I think our spiels are virtually identical. I have a very similar spiel. I quote a lot of averages, average ICU stay, average hospital stay, average life expectancy. But I really remind patients that I'm referring to averages. There are bell curves on either side of that. And we have to leave room for the unpredictability of the transplant course afterwards. And certainly complications that can arise that we don't foresee as the team. If we are listing somebody for lung transplant, that means to the best of our knowledge with the data that we have on the patient. And in our experience, we really feel this patient has a good chance of surviving, doing well after the transplant, walking out the door. And I think that's a really important part of the process. Enjoying a good quality of life afterwards. And obviously that's the goal, but sometimes we have to understand that post-op complications can arise. I talk a lot about the same post-op complications that Hannah has outlined. And I do remind them that by and large, we achieve a very good and impressive increase in their quality of life after transplant, certainly compared to life with end stage lung disease. But that comes with many other things that do take away from our quality of life, side effects, renal complications, certainly having frequent medical visits and spending a lot of time at the hospital with doctors, simple things like nausea, vomiting, diarrhea, appetite changes from the medications, and then bigger things like the malignancy risk and infection risk after transplant on the immunosuppression. But all in all, even with those things factored in, we often do achieve a very impressive improvement in quality of life and patients are by and large happy after transplant.
Speaker 3And I would just say too that, I think that, you know, while we need to make sure that their other organs are intact to get them through the medical complications, this is where I think lung transplant can evolve because so much of what makes someone a successful candidate or recipient, I should say, of a lung transplant, it's more than just how their heart and liver works, but it's a lot to do with their frailty, their motivation for wanting to condition and rehab post-transplant. And also something that I don't think we can account for objectively, which is just their fight and their spirit in the game. I usually have patients make a small list of things that they're hoping to achieve after transplant for goals. There's a lot of ethics and a lot of opinion about transplanting these older patients and patients in their seventies. And while I won't go into my whole opinion about it today, I do think that there are some patients that it doesn't really matter per se their age, even someone who's 71, if they have a long list of things they're trying to accomplish in their life and they're super motivated and have great support and pretty good mental health, you really see just fascinating changes and patients coming back to you saying that even if they don't live as long as you hoped, even if they're only living three years after their transplant, you could argue donor equity and donor allocation all day, but the patient themselves, even if they only have a short time after transplant, most of the time, that population will say that they're so grateful and that they really lived more in those three years than they've lived in the five before it or something like that. So I think that trying to get a feel for patients of what they're looking to achieve and what they're looking for their life to be like, I think really helps us as the physician get an understanding of if we think they'll be successful after a transplant.
Speaker 1Thanks so much, Hannah and Megan. And I feel, Hannah, you did say that was a loaded question to end our episode today, but I think you just, you both just gave a great preview to what we're going to be going next. I think of this episode as lung transplant 101, and I can already see lung transplant 102 and 103. I think that was a really great end to it. I think that was a really great end to it today. And I learned so much today. I know Firth and I always end the show with one takeaway point that we want listeners to remember. I think mine's very brief, but concise, but really when Megan, you were saying, when should we refer someone for lung transplant evaluation? When I heard you say someone with ILD, specifically IPF, that should really start occurring at the time of diagnosis. Firth, what about you?
Speaker 2Yeah, so much that I learned, but I love that the lung allocation score has been updated to this composite allocation score that includes your risk of one-year mortality, your five-year survival, other recipient variables that are of note, your prior donor status, and then some interesting things about the donor geographic considerations. That's my learning point for the
Speaker 3day. My take-home point for lung transplant with this particular topic that we discussed today would be early referral. And mainly because even ILD, yes, at time of diagnosis, but I would say in general, early referral is always better. We can educate patients to feel more mentally prepared when it is time for them to get listed. And we have a lot more time to work on their modifiable risk factors, like their weight, their conditioning, their social support that makes the patient the best candidate they can be, which usually leads to a more successful transplant. And I always tell patients the best place you can be is knowing you're a lung transplant candidate, but being too early to be listed. And that can only happen if people are referring earlier on.
Speaker 2Fantastic. Megan, any takeaway point for people?
Speaker 4I agree with that wholeheartedly. And I think it's important to be able to be a good patient. And I think it's important to be a good patient.
Speaker 2This was a great hour. Thank you guys so much for your time and for coming on the show. Thank you all for listening. This episode was written, edited, and produced by myself and Cristina Ventimaior. And we will see you for the next episode.
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