Lung Transplant: Breathing in a Better Life
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Lung Transplant A-Z: From Referring a Patient to the Impact of COVID-19. Together Dr. Raed Dweik, Chair of the Respiratory Institute, and Dr. Marie Budev, Director of the Lung Transplant Program, tackle the huge subject of lung transplant, covering a range of topics that includes when the right time to refer a patient is and what the contraindications are for transplant. They discuss the Lung Allocation Score, lung transplant survival rate and how long it takes to get a patient ready for transplant. Dr. Budev also talks about new ways in which the donor lung pool is being expanded and the impact of COVID-19 on lung transplant patients.
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Lung Transplant: Breathing in a Better Life
Podcast Transcript
Announcer:
Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular, and Thoracic Institute at Cleveland Clinic. Cleveland Clinic patients benefit from a multidisciplinary approach to care. This podcast is brought to you in conjunction with Cleveland Clinic's Respiratory Institute.
Raed Dweik, MD:
Hello and welcome to this episode of the Respiratory Exchange Podcast. I'm your host Raed Dweik, chairman of the Respiratory Institute at Cleveland Clinic. My guest today is Dr. Marie Budev, who's the director of our lung transplant program. Welcome, Marie.
Marie Budev, DO, MPH:
Thank you, Dr. Dweik, and welcome to the audience.
Raed Dweik, MD:
Yeah, our goal today is to really talk about lung transplant. I know it's a big area and there are a lot of topics we can cover, but we're going to do a high level and hopefully, I know there's a lot of interest in this area. Maybe we'll have some follow up podcasts. But let's focus on the basics and the high level discussion about lung transplant. And Marie, can start maybe by telling us who is qualified for a lung transplant and what diseases do we usually transplant for?
Marie Budev, DO, MPH:
Great question. I'll start with the latter first. So, the number one disease worldwide for which we transplant is chronic obstructive lung disease or emphysema. If you look in the United States and North America, the number one disease reason why for which we transplant is pulmonary fibrosis. But other diseases where we consider transplantation as a therapeutic option when medical and surgical therapies have failed, include cystic fibrosis, bronchiectasis due to non-CF reasons, sarcoidosis and pulmonary vascular diseases such as pulmonary hypertension. But there are also some other diseases that may not be as popular or common, but please, I would refer you to the International Society for Heart Lung Transplant website, as well as their guidance document on the recipient selection criteria that was published in 2021 for some of the disease states that may be less common that we transplant for.
Raed Dweik, MD:
Me as a non-lung transplant physician, and I know those physicians listening to us in the audience today, the question always in my mind is when is the right time to refer somebody for transplant? I don't want to be too late, but also I don't want to send them to you too early. How do I balance that?
Marie Budev, DO, MPH:
I think most of us would say, as transplant physicians, and this is a great question because it's a moving target, refer early. Refer always early, and get to know your local transplant center and their referral pattern and how quickly they transplant patients. And the third thing is, this document I just talked about a few minutes ago, the 2021 ISHLT recipient guideline document, Laurie Leard is the lead author, L-E-A-R-D. This actually provides you with some referral guidelines in terms of time points and sort of cutoffs in terms of physiology. It's very easy to kind of list a bunch of things that you should say, they have to have this FEV1, they have to have this walk distance, they have to have this oxygen requirement, but sometimes that doesn't capture your patient. It's really putting a lot of things together.
But I would tell you, as referring providers, please call us. Call me, email me, text me. I'll be more than happy to go over your patient with you and let you know if this is the time we should be seeing a patient. It takes a long time to get a patient ready for transplant, both mentally, psychologically, financially, and from their support system and to go through the testing. And so you want to allow for a lot of time for patients to get adjusted to all these different things and the idea that they are going on a transplant list and the stress that goes along with that. But this takes early referral, and so referring them early is always a good thing. I would tell you it's never a bad thing. It may set some expectations or let some patients down that they're not in the window for a transplant, but I think, as they learn more and more about transplant, they'll probably appreciate being referred early.
Raed Dweik, MD:
Yeah. I heard you often refer to this transplant window. What do you mean when you say transplant window?
Marie Budev, DO, MPH:
Great question. So, transplant window refers to the optimal time that a patient should be placed on the list and have a reasonable period of time to get used to the idea of being transplanted. This is a patient that's not too well for a transplant and that they're just coming back and going through the testing and they're just kind of hanging out, wondering when am I ever going to get on the list? And when they're too late or outside of the window, that's when a patient is too sick and that a transplant may not be as successful.
Raed Dweik, MD:
So, as a referring physician, I shouldn't worry about the specifics with that just refer often, refer early, I think is what you're telling.
Marie Budev, DO, MPH:
Yeah, I think so. I think let us worry as transplant physicians about the window. But I think for a referring doctor, make it easy on yourself and make it easy on your patients. Refer them early. That'll give them time to get used to these various aspects that we're going to discuss.
Raed Dweik, MD:
Are there any particular reasons, barriers, comorbidities that I just should not even bother sending somebody for transplant, I know upfront they won't be a candidate?
Marie Budev, DO, MPH:
Right. These are what we call absolute contraindications and this absolute contraindication list, it's gotten smaller as the years have gone on, but there are some things that have never changed. Patients that are actively using any substances, whether it be alcohol or narcotics, would not be considered for a transplant. That includes a chronic use of narcotics for pain management. We really try to stay away from these patients because of the increased incidence of delirium after transplantation. Patients that are actively smoking or using nicotine products, including vaping, these patients we need to be careful about considering for transplantation. BMIs that are over the BMI of 34, these are patients that have a higher incidence of graft failure after transplant, so we suggest these patients have their BMI come down, and then we're happy to see them when their BMIs are around 34 or lower. Patients have to have adequate social support in general and they should be free of any psychological or psychiatric illnesses that would lead to non-compliance. We know depression, anxiety are very common in this chronic lung disease population, and that's something we can deal with and help them deal with, with our transplant psychiatrist's assistance. But someone that is actively psychotic or you know has a history of pure non-compliance, they're not going to do well with transplantation. The stress of transplant surgery, as well as the obligation to take 12 to 14 drugs a day, is very burdensome for this sort of patient. So, these sort of patients should not be considered for transplant. But if it is someone that has a psychiatric issue and it can be controlled and they have adequate support, this is a patient we don't want to discourage from being referred, but we'll have to work on them with different angles and support.
Raed Dweik, MD:
Yeah, thank you. Another tricky area as you know as an ICU physician, I hear that also from our families but also from outside physicians who want to send patients and who are critically ill. Either they are in severe RDS, they're on a ventilator, sometimes even on ECMO, and they think they should send them for lung transplant because the family pressure for to salvage them, this the last ditch effort kind of thing. Is that the right way to do it?
Marie Budev, DO, MPH:
It's always very appealing to think that would work, but rarely ever is transplantation a salvage therapy. The patient that we use as a salvage therapy is a younger patient, someone that's already well known to transplant or the transplant center, and someone that knows what they're getting into before they got very ill. That means the obligation to taking the medications, the follow-up, understanding they're the steward for this very precious resource and gift. So, very rarely in an ICU setting is transplantation a salvage therapy or an option.
Raed Dweik, MD:
It's a good point. I think the patient needs to participate in the decision making if they are not that ill. Sometimes they may not be, but you don't want to wake up and realize you have a new set of lungs and have not participated in the decision making.
Marie Budev, DO, MPH:
Yeah. A few years ago, there was a center that was transplanting for ARDS, and there were several patients that they had transplanted that were not aware that they were going to get a transplant and one of them happened to be a nurse, and was extremely upset at waking up and finding out she had been transplanted. So, we hear of these stories out there, and we've looked at this as salvage therapy, and we found over time the best thing is to have the patient's participation and an understanding of what they're getting into, because the family also needs to understand if the patient will want this in the first place or not.
Raed Dweik, MD:
So, as a referring physician, I figure out, okay, I want to send the patient early, I have patient who is deteriorating or asking about lung transplant, and I send them to you. What should I tell them to expect when they come to a transplant center?
Marie Budev, DO, MPH:
That's a great question. So, the transplant center first visit is usually a three day visit. It includes a myriad of tests that are performed to start off, so we get information about where the patient is in the timeline in terms of listing and how quickly we have to go through the evaluation, whether it just needs a few weeks or whether this patient has a few months. So, that's what that first meeting focuses on in terms of the testing. But the other part of that meeting is a lot of information and patients really need to come with a loved one. And stress to your patients, come with a group, ask questions, have questions written down before you come. They will get binders for both the caregiver and the patient themselves so that they will be having written material that they can reference. They'll also be directed to several websites. They'll be asked to participate and go back to pulmonary rehab. But it is a very busy, intense sort of three days for patients. It can be overwhelming, but I think to advise your patients, tell them to come with an open mind, tell them to come with a notebook, tell them to come with a loved one so they can hear everything that's being said.
Raed Dweik, MD:
Great advice. Thank you for sharing that. We've hearing patients sometimes get one lungs or two lungs. Is that something decided by the patient, by you, by the referring physician? How is that decision made?
Marie Budev, DO, MPH:
The determination to receive a double lung or a single lung is based on several factors. Age is probably the biggest consideration. An older patient, we want less anesthesia, less OR time, quicker recovery. So, someone over the age of 70, we may be considering a single lung, and these patients could do very well. It's important to stress to the patients, if you're getting a single lung, you didn't get short changed. Actually, you're going to have an excellent quality of life, you'll recover quicker, and you'll be off oxygen in almost 99% of cases. A double lung is usually reserved for patients that are younger. Also, for patients that may have pulmonary hypertension or suppurative lung diseases.
Raed Dweik, MD:
Separate of single or double lung, how do we decide where to put somebody on the lung transplant list up or down? Is that something that we can control or is it a system for doing that?
Marie Budev, DO, MPH:
So, there's a system by which we allocate organs and how we place them on the list. So, patients go through a significant amount of testing, as I mentioned earlier. And some of the variables that calculate a score, called a lung allocation score, are taken from these tests that have been done. This is objective data, it is not subjective. And this lung allocation score runs from 0 to 100. And if a patient is very, very sick, like in the ICU with an ECMO, a patient may have a score around 80 to 90, and these are patients that are placed at the top of the list because the allocation systems favors patients who are the sickest. We're trying to allocate organs to the most appropriate patients who are the sickest and whose lives could be saved. This allocation system is generally fair.
Marie Budev, DO, MPH:
In the past the allocation system was just a list. You were put on a list and you had to accrue time. We no longer do that. It's really based on a dynamic flow of physiological parameters that do change and place patients at different portions of the list. This allocation system will be changing in the future, taking into attributes that may disadvantage certain patients and place them and take them into account, and place them at a fairer point on the list. And that's going to be a composite allocation score and Dr. Maryam Valapour will be discussing this in a separate podcast in the future, so look out for that. But right now, the way we are currently placing patients on the list is a very objective process that's done through a lung allocation score and a calculation.
Raed Dweik, MD:
And of course, having this lung allocation score is just a reflection of the scarcity of organs. If everybody could get an organ, we don't need an allocation score, I guess. The reality is not everybody who needs an organ gets one. So, other ways we are doing, at the Clinic or nationally, to improve this donor pool?
Marie Budev, DO, MPH:
Yeah, the donor pool is what holds us back. We could be transplanting everybody and not have any end-stage lung disease out there, but unfortunately we don't have enough donors. So, one message from this podcast is please talk to your families and your patients' families and patients about signing up to be organ donors. We could hopefully put a little dent into this organ need. But patients are still dying on the waiting list while awaiting organs. And we're looking at ways to expand the donor pool and this is through looking at physiological parameters that we can change. We no longer use the term marginal donors, or everybody is a standard donor. They may just have some different things about them that could make them a better donor, but we don't use these marginal terms. We throw away less organs than we used to in the past, so we're getting better. Some of the means by which we're doing this is, number one, using hepatitis C positive organs. As you know, hepatitis C is a curable disease now with the DAA acting agents, and also many of these individuals that do have hepatitis C are viable donors. They're younger, they have great organ function and now that hep C can be cured, these are a new pool of donors that we're using. Also, ex vivo lung perfusion, which is a device by which you can recondition or refurbish lungs, just to put it simply, it's where we can take the lungs out of the donor body and look at the physiological parameters to ensure they're still functional or improve their function if they're placed on a device called ex vivo. We have data from both Europe and North America that shows excellent outcomes with the use of ex vivo lung profusion, and it's about 25% of our practice here at the Cleveland Clinic. We use about 25% of lungs that come off of ex vivo and transplant them.
Raed Dweik, MD:
Wow. That's like transplant ICU, I guess. Resuscitation of the lungs to get them ready to be put in the right person.
Marie Budev, DO, MPH:
Absolutely.
Raed Dweik, MD:
So, that's amazing, the advancement in science. So, let's say one goes through all of these and they get allocated along. Can you tell us a little bit about the surgery and the hospital stay? How long would a patient be expected to be in the hospital following a lung transplant?
Marie Budev, DO, MPH:
This is a great question, because this is the first question your patients are going to ask you after you tell them you're referring them for a transplant. So, the average lung transplant surgery for a single lung is about four hours. Pretty uncomplicated usually, if it's a single lung. Double lung transplant is about eight hours. After a patient is done with the surgery, they return to the ICU, they'll have chest tubes in, they'll be intubated. Once we know the graft or the organ is working well, we take out the endotracheal tube and these patients are in the ICU for about two days. After they do well in the ICU and they're eating and walking around a little bit, we transfer them to a step down floor and patients spend about two weeks on the step down floor where they learn about their medications, their new lifestyle. We look for side effects and complications from the surgery itself and from the medications.
Marie Budev, DO, MPH:
Once we know patients are doing well and they're able to take their medications and understand their medications, and this is why education is so important and that patients have the support system available. Patients are discharged to a local area, usually the hotel that's on campus, or to our transplant house. They'll stay there for about six to eight weeks and they're seen in our outpatient clinic on a weekly basis to ensure they're continuing to progress. And then once we feel they're stable, they're allowed to return home. When patients are waiting for a transplantation, the one advantage we have at the Cleveland Clinic that many other programs do not offer is that we allow patients to stay at home. We believe patients heal better and stay healthier while they're on the waiting list if they're at home and surrounded by the things that they love. So, we allow patients within a thousand miles of the Cleveland Clinic to stay at home as they're waiting for a lung transplant. And when the time comes and a donor is available, we'll actually transport that patient in if they live more than or greater than five hours away from the Clinic.
Raed Dweik, MD:
Wow, that's a great benefit. I think that's wonderful. I think always better to be at home in your own surroundings than be in a strange place. Something we didn't touch upon yet, but I think this is a good time, is the lung transplant survival. I know we are trying to balance how long can I survive with the disease, how long are you going to survive with the transplant? Tell us more about what to expect, how long to live after somebody gets a transplant.
Marie Budev, DO, MPH:
So, I think most of you know, as referring providers, when you're looking at end-stage lung disease, it's very hard to say how long the patient will survive. And so that's what you want to balance with lung transplant survival, and I think that's what you're alluding to. The average survival for a lung transplant patient for all-comers, irrespective of age, any other comorbidities is about 7.3 years, according to the most recent International Society for Heart Lung Transplant 2019 registry data. But if you're starting to look at populations or subpopulations that are older, someone that's older than the age of 70, you're looking at a survival between three to four years. Younger patients, you're looking for a longer term survival. The longest survival we've had at the Cleveland Clinic in a patient has been 24 years and this individual had cystic fibrosis, was transplanted in their early twenties, subsequently ended up needing a kidney transplant after their lung transplant due to the damage caused to the kidneys over time from the immunosuppressive drugs that they took.
Marie Budev, DO, MPH:
So, the lifespan, when you're looking at it, can be short or it can be long. What's important to talk to your patients about is what their expectations are. For certain patients that are on 10 liters of oxygen, can't do anything and even taking a shower during the day is a major ordeal, a survival of five years is a lifetime. But in a patient that's on no oxygen, that has a depressed FEV1 or is limited in terms of quality of life, a five to seven year survival is a very limited amount of time. So, it's really something we talk about candidly with patients, the reality and the expectations. Transplantation is something that there is a little bit of gamble. It's not definitive that you're going to meet that seven year mark. Again, a lot of things can happen, unlike heart and kidney and liver transplantation, lungs are more vulnerable to certain complications. And so that survival may not be reached. So, it's very important to have this sort of open conversation that's very transparent with patients and set their expectations. Again, it's going to depend on the patient and what they're willing to accept as a survival and with the complications that could occur.
Raed Dweik, MD:
So, you're really balancing their expected survival with their disease, their expected survival with their lung transplant, and the quality of life with either one as you make a decision, combined with the patient and the family is to make. Is that about right?
Marie Budev, DO, MPH:
That's very well put.
Raed Dweik, MD:
Yeah. One thing I want to ask you about also, you mentioned that patients requiring a kidney transplant after having a lung transplant made me think about the multiple organ transplants. I know you've sometimes done more than a heart-lung, kidney-lung. How do we decide those and is there anything special about approaching these types of transplant?
Marie Budev, DO, MPH:
We're very fortunate at the Cleveland Clinic. We have such a strong transplant center and community that we are able to deal and offer to our patients, heart-lungs, combined transplants, liver-lungs, and in the future lung-kidneys. And we're able to do this for many disease states. Cystic fibrosis, for example, Alpha-1. Sometimes different diseases that are not associated with each other, short telomeres, for example. But these multi-organ transplants offer a unique opportunity for patients that they cannot have at many other centers. So, if you feel that your patient may have some kidney disease or may have liver disease and you don't think they'd be a transplant candidate, I'd ask you to give me a call, because in many cases we can actually look at these patients for dual organ transplant, which can be done simultaneously or staged. For example, if you have a patient that has chronic kidney disease, what we can do is look at them for their lung transplant and then we can say, we'll stage their kidney transplant after transplantation. So, there are many different options and some of the paradigms that you had heard of in the past, those have now become defunct and are old fashioned and we're able to look forward and offer patients many other opportunities.
Raed Dweik, MD:
That's wonderful. Science keeps advancing and medicine keeps advancing, which is great to benefit our patients. I want to shift gears a little bit here and talk about COVID. First, how has COVID affected our lung transplant recipients?
Marie Budev, DO, MPH:
So, our lung transplant recipients are highly immunosuppressed, probably more than any other solid organ. And again, as I said, they're always exposed to the environment in the air. Many of our lung transplants recipients ended up being significantly immunosuppressed and not having an immune response to the three doses of the vaccines, and subsequently became infected with COVID. We've had about a 25% mortality rate in our population that has acquired COVID. We've had a large number of patients that did well and did not get really affected by COVID, maybe had cold-like symptoms, constitutional symptoms. But then we had a small fraction that ended up in the ICU and subsequently dying of lung failure.
Raed Dweik, MD:
Yeah, that's a very terrible disease that affected everybody, including our lung transplant population. The other side of this is, do we transplant patients with COVID? COVID really is, the lung is a major target, and they get severe lung disease. What about transplanting those with COVID lung disease?
Marie Budev, DO, MPH:
As physicians out there are dealing with COVID and the worst cases of COVID, people are desperate, and lung transplantation is only offered to a select number of patients that have COVID-induced lung injury. And it is an option, but again, only in a select group of patients and these are patients that are awake, participating in pulmonary rehab, patients that can consent to the transplant procedure. This is not reserved for patients in the acute phase of COVID ARDS or COVID fibrosis. You have to know that your patient has irreversible lung injury, and these are patients that have been on ECMO for several months. I'll tell you, in the cases that we have transplanted at the Cleveland Clinic, we've had seven cases, and the majority of these patients have been on ECMO or mechanical ventilation for at least a few months before it's been determined that they have non-resolving lung injury. And then these patients have all been ambulatory, interactive with physical therapy, with excellent nutrition and single organ failure who got transplanted. And thankfully, these patients are doing well, but it was a long course that it took for these patients to get listed and subsequently recover from the transplant. Months, many times, after the transplant, before they left the hospital.
Raed Dweik, MD:
Well, thank you, Marie. This has been really very informative session. Thank you so much for sharing your expertise with us. Anything you'd like to wrap up with before we close?
Marie Budev, DO, MPH:
I'd like to just end with please call us if you have any questions. And the key takeaway is early referral. So, please call me if you have any questions or get in touch with our program.
Raed Dweik, MD:
Thank you so much, Marie, and thank you to our listeners for joining us for this podcast. Again, this is your host Raed Dweik, Chairman of the Respiratory Institute at Cleveland Clinic, and my guest today was Dr. Marie Budev who's the Director of our lung transplant program. Thank you, Marie.
Marie Budev, DO, MPH:
Thank you.
Raed Dweik, MD:
Thank you.
Announcer:
Thank you for listening. We hope you enjoyed the podcast. We welcome your comments and feedback. Please contact us at heart@ccf.org. Like what you heard? Subscribe wherever you get your podcasts or listen at clevelandclinic.org/cardiacconsultpodcast. For more episodes from the Respiratory Institute, please listen to the Respiratory Exchange Podcast.
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Cardiac Consult
A Cleveland Clinic podcast exploring heart, vascular and thoracic topics of interest to healthcare providers: medical and surgical treatments, diagnostic testing, medical conditions, and research, technology and practice issues.