I’m Aware That I’m Rare: Rajan Saggar, MD (463)

phaware global association®
9 min readApr 8, 2024

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the phaware® interview

Dr. Rajan Saggar, a pulmonologist at the University of California in Los Angeles, discusses the complications of pulmonary hypertension in various lung diseases. He explains that pulmonary hypertension can either be its own disease or can complicate other conditions such as heart disease or lung tissue diseases like emphysema or fibrosis. Dr. Saggar mentions a recent FDA-approved medication for pulmonary hypertension complicating lung tissue diseases, and ongoing research to develop more treatments.

My name is Rajan Saggar. I’m a pulmonologist. I work out of the University of California in Los Angeles, where I actually did my training. I also span the advanced lung disease area of medicine, so I’m also heavily active in the transplant world, as well. I co-direct the program at UCLA with Dr. Richard Channick. I’ve been there now since the early 2000s, so it’s been a good ride.

One of the topics we will address today would be specifically pulmonary hypertension complicating various types of lung disease. I get to see the natural history of those types of diseases as well as just regular PAH. All the different kinds of pulmonary hypertension, all groups and how some of those patients unfortunately do progress over time. Some of these unfortunate patients regardless of all the medications we try to use or get on board, eventually need a lung transplant. I have a perspective, which I think is a little bit different from others.

As all of us know with this pulmonary hypertension business, high blood pressure in the lung is a final common pathway for a lot of different diseases. It either comes by itself as its own disease or it can complicate other types of diseases. So, for instance, it can complicate heart disease. In other words, where the pulmonary hypertension is a consequence of the heart disease. Then, what we’re talking about here is pulmonary hypertension complicating an underlying lung disease.

Pulmonary hypertension is a lung disease. It involves the blood vessels, but it can actually be the consequence or it can complicate what we call parenchymal lung disease. The parenchyma means the actual lung tissue itself. So if you have a lung tissue problem, that lung tissue problem sometimes can be complicated by pulmonary hypertension. The lung tissue problems that we’re talking about, generally speaking, most common one is emphysema, or sometimes we call it COPD. Chronic obstructive pulmonary disease comes in many flavors, but emphysema is one type of COPD. It turns out that pulmonary hypertension can complicate the course of patients who have COPD or emphysema. Not all patients who have COPD or emphysema develop pulmonary hypertension. There’s a select group that develop it, and we’re always trying to figure out who is more predisposed compared to others.

Another kind of lung disease of the lung tissue, if you will, are diseases that scar the lung. The word in medicine for scarring is we call it fibrosis. That’s a fancy word for scarring. Then sometimes, you may hear the term interstitial lung disease. Interstitium is one part of the lung where you tend to develop this scarring process or fibrosis. Interstitial lung disease and fibrosis are on a spectrum. It’s a type of lung tissue disease. Just like the COPD emphysema type of lung tissue disease, this particular type, the interstitial lung disease fibrosis lung tissue problem can also be complicated by pulmonary hypertension.

It turns out that for years we’ve tried to use different medications to try to treat that type of pulmonary hypertension, specifically complicating the lung tissue diseases. In our attempts have failed several times over; however, there is a recent arrival of a medication that we also use in regular pulmonary hypertension, where you don’t have a lung tissue problem, where we were able to use the same medicine. Luckily, it actually did work in patients who specifically have this lung tissue problem, this interstitial lung disease or fibrosis or scarring of the lung complicated by pulmonary hypertension.

We used a pulmonary hypertension medication to try to work on the pulmonary hypertension complicating this lung tissue problem. Now, that’s FDA approved. It’s the first medication that’s now approved in this particular type of pulmonary hypertension, which is cool. At this point now, since there’s one medication that’s hit the market specifically for this fibrosis, scarring of the lung disease complicated by pulmonary hypertension, there’s a lot of interest by other companies in drug development who are trying to look into other ways or other pathways to help folks with the pulmonary hypertension piece complicating this scarring of the lung disease. What’s interesting is some of the medications may actually work on not just the pulmonary hypertension part, but you might get a twofer. In other words, the medication actually helps with preventing progression of the scarring. There’s some thoughts that there’s certain medications that might be able to hit both problems, because the patients we’re talking about here have two lung problems. They have a scarring of the lung problem and they have a high blood pressure in the lung problem.

It would be ideal to have a medication that either reverses or helps to improve or doesn’t allow progression of the scarring, as well as helps the pulmonary hypertension piece, the high blood pressure piece, which would be really great for patients. Right now, the medication that’s approved that I mentioned earlier, the one single medication we have is inhaled. There’s a big push to use something that’s inhaled, so it has direct delivery to the lung. A lot of companies are interested in looking at this not just from a new medication standpoint, but using something that’s inhaled, which the medical community feels may be the best way to deliver such a medication even though some of these medications can be given orally or through the veins or a lot of different ways to give medications as one might predict. But for lung diseases involving the actual lung tissue, the inhalational route seems to have gained a lot of momentum, and that’s where the field’s going.

The scarring of the lung diseases are considered to be an orphan lung disease. The idea is you have less than 200,000 cases in the US at any given time, the definition of an orphan lung disease. Then, you’re talking about that disease being complicated by the high blood pressure or pulmonary hypertension, which affects a fraction of those patients. But what’s interesting is some of the work that’s been looked at in terms of following patients with the scarring disease to see if they develop pulmonary hypertension, if they don’t have it on the initial evaluation, the overwhelming majority will go on to develop some degree of the high blood pressure problem.

Then, the question is, does it matter how high your blood pressure is before one of these medications can actually help you? In other words, a lot of people will have a mild variety, but then even a smaller group will have more of the moderate severe variety. That’s where we’ve seen most of the medications work for the high blood pressure piece complicating the scarring. But now, there’s a push to see, well, maybe if we treat these patients earlier, even when they have a mild problem. Or, for instance, if they just have scarring, we just mentioned earlier maybe a medication can prevent both. So if someone just has scarring and no high blood pressure and you use one of these medicines, maybe you could prevent the development of the high blood pressure problems. None of this is in stone. It’s all evolving. We’re looking and thinking out of the box with all this stuff.

I’ve always said the patients who we see who have lung tissue diseases, particularly when it’s progressive, and even if it’s not, pulmonary hypertension patients too, high blood pressure patients, when you combine the two, the double whammy I call it, where you have two lung diseases, generally speaking, are patients with advanced lung disease, they’re just a special group of patients in the sense that they’re more than happy to sort of give to the scientific endeavor.

They understand that they have diseases that don’t have obvious cures. They are interested, obviously, in helping themselves, but also in helping move the scientific community forward. You can imagine to do any of these studies, you need willing patients. You need patients who are willing to put themselves into a study where they might not get an active medication. It’s disconcerting when you think about it. If you’re going to enter a clinical study, and remember a lot of these studies we do in medicine, they’re so-called blinded. The doctors don’t know what the patient’s getting and the patients don’t know what they’re getting. But we all know that they could be getting one of two things. One thing could be the active drug that’s being studied, where we’re trying to get some experience and some data so that we can prove that something works or doesn’t work. But the other arm of the study is where they’re getting not the real drug. They’re getting some what we call placebo, which they’re going to get for some amount of time.

You have to be a special person to enroll in a study and to want to put yourself on the line, so to say. Now granted, there’s not a lot out there as it were, but still some people feel very uncomfortable with the concept. But the studies are designed in a way such that if someone has a worsening of their status while they’re in the study, of course, we don’t know if they’re getting the active drug or placebo, but while they’re in the study, the studies are designed, and folks should know this, such that if they are to progress and meet criteria for progression or worsening, and those are preset criteria. They’re usually pretty forgiving in the sense that we will pull them out of this study, and then they can go into what’s called an open label extension, where they would get the active drug regardless of what they were getting to begin with because no one knows.

We would assume that they’re not necessarily getting the drug. They may have been getting the drug, but the point is after that point that they got worsening of their condition, everyone would get the drug. They would continue to be followed as part of what they call an open label extension to the main study. My only point in all this is that we as the medical community in this setting want to move the field forward. We can’t do that without patients who are willing to enroll in such studies.

I want to give props to the patients. The majority of the patients we deal with are more than willing to help. They’re really moving the needle to help folks in the future and hopefully help themselves, but it’s a selfless act. I think at the end of the day, we just want the listeners to know, we’re very much committed to trying to prevent and decrease the need for lung transplantation from any lung disease. There’s so many different ones that can progress and eventually require a lung transplant, because when we have no medical options, then we take the surgical option, which is the last thing we want to do.

No one actually says, “Oh, I wish I could have a lung transplant,” obviously, but at the end of the day, it is some light at the end of the tunnel. Having said that, our job and goal all the time is to get medical options to, number one, help people, improve people, et cetera, get people better, having full lives and getting back to their lives, knowing that they have a chronic disease. Of course, a cure would be amazing, but even just to slow down the process or keep what you got in terms of your lung function would be amazing. But what we also really want to do is really minimize the folks who need a lung transplant or hopefully obliterate it.

As we sit here today, unfortunately, lung transplant still remains the last option. That whole process of transitioning to we have no medical therapy, we need to commit to a lung transplant, that’s a whole other discussion and a very difficult one for patients, because it’s scary. It’s really scary. Our job is to help people not miss the boat and basically realize that their options may be dwindling sometimes. Some of these patients have to go to lung transplant. But our overall overarching goal is to decrease the number of transplants. Actually, that’s what’s happened as the pulmonary hypertension, high blood pressure medications in the lung have rolled out over the years, the need for lung transplant, for pulmonary hypertension, the pure disease of high blood pressure in the lung has gone down. That’s a nice thing to see.

My name is Rajan Saggar, and I’m aware my patients are rare.

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phaware global association®

Are You #phaware? Pulmonary hypertension (PH) is a rare, life-threatening disease affecting the arteries of the lungs. www.phaware.global