John Granton, MD - phaware® interview 531

Dr. John Granton, a critical care and transplant physician at Toronto General Hospital, shares his journey in pulmonary hypertension and lung transplantation, detailing the groundbreaking advancements in transplant technology. He discusses the evolution of lung preservation methods, the challenges of chronic rejection, and the hope for longer-lasting transplants. With a passion for improving patient outcomes, Dr. Granton envisions a future where transplant becomes obsolete—replaced by treatments that cure underlying diseases.

My name is John Granton. I'm in Toronto. That's where I was born, just north of the city. I trained mainly in Canada, trained in London, Ontario and then went to McMaster and then University of Toronto and then University of British Columbia for a while and came back. I've been on staff there for about 30 years now at the Toronto General Hospital, primarily. I work as a critical care doc looking after sick patients who come in ill or after major surgery like transplant. I've also worked in the transplant space for many years as a transplant physician, but more commonly now as a critical care doc, looking after people after transplant. 

We started a pulmonary hypertension program in 1997. At the time, the head of transplant, Stephen Kestin, looked to me and I'd just come on staff. The paper on Flolan had just come out and he said, "We need somebody to do this." He said, "You like hemodynamics and stuff and you're a critical care doc. Why don't you do this?" I said, "Okay." I got some money together. We hired a nurse part-time, put a sign on the lawn and we've grown. We're a big program. Because of the resource, we serve a lot of different communities. We offer the range of critical care and transplant services in addition to pulmonary hypertension services as a major referral center. We also provide medical treatments, diagnostics, chronic thromboembolic pulmonary hypertension management, so major surgery.

I’m really here today to talk about the transplant aspect. Our program in Toronto is a big program. We transplant over 200 patients each year, so it makes us pretty much the largest program worldwide and a highly innovative program ,as well, doing a lot of really cool things, which ultimately will benefit patients by providing them with access to more lungs, so they have the opportunity to benefit from transplant, and also looking towards better outcomes for transplant.

One of the major things we're doing is looking at the role of when we get a lung from somebody who's died or a set of lungs from somebody who's died, we put them on this machine, which actually profuses it. We run a solution through it and we support it, kind of in an animated state, which allows us to check out the lung to make sure the lung's okay, functioning well, make sure there's no pneumonia. We can look into the lung with a small scope. We can take x-rays, CT scans. Our group's now modifying the lung, so you can actually treat the lung to make it better. You can make it perhaps more acceptable for the person, so they don't have to use as much immunosuppressants to suppress their immune system so they don't get infections and stuff, so they can tolerate the new lungs with their immune system better. Ultimately that will lead to better outcomes.

The major problem with transplant right now is that once you're committed to transplant, those lungs are yours. We know that in addition to the trouble with the drugs, those lungs will eventually fail because the body will continue to try to reject them. That's been the major limitation to transplant. Hopefully, with this kind of technology and availability and understanding of the biology and how things work, we're going to be able to manipulate those lungs so that they've got a much longer shelf life, if you will, and carry the patients through for a lot longer than it currently is. Usually, when we identify somebody, a set of lungs for a person, we call the person and we also call another person often as a backup, just in case something's going on. You can only have the lungs outside of a person's body for a period of time before it starts to deteriorate.

Having it on the system actually allows them to be animated for a longer period of time, so you can kind of coordinate things a little bit. Previously ,people had to live close to the hospital. They couldn't be more than a couple of hours drive, because they had to be available to go to the operating room real quick and you had to make decisions fairly quickly. Now, it puts us in the position where we can bring people in, they can drive from home a few hours away. When they're in the hospital, they kind of go in a waiting room and they sit there and hope that the lungs are going to be okay. Often, it's a dry run because the lungs don't turn out okay, because there's something wrong with them or they deteriorate. When you start to look at them, they're not performing well, so you don't want to put it in the person.

Even though that's discouraging for the person, it otherwise avoids them getting a set of lungs which may not have served them well. I think it also increases confidence that the lungs you're putting in are probably going to be good and you've improved them and they're looking better, and so you're much more confident in transplanting them into the person who's waiting. In the old days, you didn't have that confidence and so you turned away a lot of lungs that might've otherwise been pretty good, but also you may have put in some lungs which you wish you hadn't because things start to turn sour fairly quickly. Once they're in somebody, you can't look back.

Transplant used to be kind of an experimental therapy. Now, it's an established therapy. Treatments have improved and medications, particularly cyclosporine allowed transplant to occur successfully. Previously most grafts, kidneys, livers, lungs would fail very quickly. The advent of cyclosporine really allowed transplant to occur.

The problem with lungs is of all the organs, they tend to do the worst long-term. The reason for that is this ongoing rejection that can damage the lungs and cause them to not work properly and patients often have to go back on oxygen and other things like that and they start to feel short of breath and their quality of life, frankly, starts to deteriorate. If you look at things like survival, the average survival in many programs is about seven, maybe eight years for pulmonary hypertension. If you get through the initial phase, pulmonary hypertension patients who are transplanted do better than other reasons for being transplanted like COPD or interstitial lung disease, IPF. They still succumb eventually from this problem and we're trying to manipulate that, but we haven't found the secret recipe yet to prevent that from happening.

We're hoping that by conditioning the lungs early on, allowing better tolerance of the lungs will prevent that lungs standing kind of erosion of the lungs because of ongoing rejection or attempts at the body to try to get rid of those lungs, which can damage them. We haven't found that yet, and it really is the Achilles heel of lung transplantation, this chronic rejection. We do occasionally have to retransplant somebody. We never really go in saying, if these lungs don't work out, you're going to get retransplanted, because we don't know if that person would be eligible for another of lungs.

Generally, you go into transplant with the understanding that's probably your shot at it, with those sets of lungs. Occasionally, we can re-transplant people, but that's usually the exception as opposed to the rule. After transplant, because of the medications, you accumulate a lot of complications and you're also a bit older and you're also subject to the same kind of conditions that everybody else gets. Heart disease, kidney disease, liver disease, other things. Whereas you might've been a good transplant candidate at the time you got your first set of lungs, you may not be a good transplant candidate by the time you need a second set of lungs. So, you really have to hope that those lungs carry you through.

Even though we talk about the average survival being seven and a half, seven, eight years after transplant, but some people don't do well early on, but many patients do better than that. I still have some of my patients, I still run into the hallways 20 years after transplant. That's amazing. It's still too short. If you're a young person, 10 years is still a short period of time, so we'd like to be able to offer everybody a normal lifespan and look forward to that one day.

Secretly, I hope transplant goes out of business. That'd be fantastic, so that you could actually treat the underlying conditions and people would never need a transplant again. That is the ultimate. Transplant is really a failure of medical therapies to treat the underlying condition, whether it be heart disease, kidney disease, liver disease, whatever. Some of it is self-inflicted. We do recognize addictions that can cause lung disease and liver disease. Not so true for pulmonary arterial hypertension or people have pulmonary hypertension from other causes. Apart from those instances, but also treat people who have those addictions better, but also treat people with pulmonary arterial hypertension in particular with novel medications which might reverse the disease and at the very least prevent further progression of the disease so that people won't need transplant. That's kind of the holy grail is to get to that point. I don't think any of us would lose sleep if we never had to send our patients for transplant.

When you actually start talking about time though, when your life expectancy with the condition you have is worse than the life expectancy after transplant, and that's kind of the trade-off. You have to decide, okay, if average survival after transplant is seven and a half years, what's my average survival right now? If it's less than seven and a half years, then that's probably you're going to want to start thinking about transplant. Some conditions and the level of severity means that you're much higher risk of not surviving the next year or two. So, transplant becomes much more in the moment the conversation. It's a tough conversation because it's hard talking about the future and what that looks like and accepting your mortality and the timing of that. It's an upsetting conversation to have with people and it's upsetting for them and traumatic for them and their family to have those conversations. They thought about it.

There's another conversation though that I often find is a bit easier is that, “What's your quality of life like right now?” If we can't make that better through medication, we tried everything, at what point does your quality of life get so impaired and you're so unhappy with the way you're living and the things you can't do that you would be willing to risk your current situation for something better like transplant. I think having that quality of life conversation is a little easier sometimes than having the death conversation, because ultimately we accept that we're all going to die one day, but we hope we live well up until that point. That's the way I frame the conversation. It's much more around, “Let's talk about ways to improve your quality of life.” Transplant is a way of doing that.

It's hard to generalize, but I get a kick out of seeing patients after a successful transplant. I don't even recognize some of my patients ,because you saw them when they couldn't walk and they were carrying oxygen. I remember people with cystic fibrosis, they couldn't get along and they were coughing, a terrible quality of life. People with pulmonary hypertension really having to stop and pause and do things when you catch them walking from the waiting room or down the hall or wherever. Then, they're walking briskly to have their lung function done. Or I seem them out in the street somewhere and you just don't recognize them. They tap me on the shoulders. It's fantastic. As I said, some of the patients I've known for 10, now 20 years, you run into them and it's amazing. I get a real kick out of that.

To me, it's been transformative. Even those patients who I see who aren't doing well and maybe they're starting to get some rejection or their lung function's deteriorating, I ask them, “Was it worth it? Would you do it again?” They say, “Yeah, I would do it again. The years that I had were amazing. I was able to do things I could never do. I really got to enjoy my family. I traveled, I started riding, walking, hiking,” whatever they enjoy doing. That's really what it's all about, to get them back to that point where they want to be and live life. It's fun when they're able to do that.

My name is John Granton and I'm aware that my patients are rare.

Learn more about pulmonary hypertension trials at www.phaware.global/clinicaltrials. Engage for a cure: www.phaware.global/donate #phaware Share your story: [email protected] Like, Subscribe and Follow us: www.phawarepodcast.com. @UHN @teamphhope #phawareMD #PHILD #transplant @phacanada