TRANSCRIPT: I’m Aware That I’m Rare: Jeff Fineman, MD

Dr. Jeffrey Fineman is a pediatric critical care specialist, or intensivist, and the division chief of Critical Care at UCSF Benioff Children’s Hospital, San Francisco. He also is an associate investigator of the Cardiovascular Research Institute. His research has led to new therapies for pulmonary hypertension, including a drug called inhaled nitric oxide, which was approved by the U.S. Food and Drug Administration. Fineman's research has focused on diseases related to pulmonary circulation. In particular, he has been interested in the pathophysiology of pulmonary hypertension and heads a laboratory, funded by the National Institutes of Health, for these investigations.

My name's Jeff Fineman. I'm originally from New York, where I did most of my medical school training and then I moved out here to University of California, San Francisco where I trained in pediatric critical care medicine. I started my research career at the Cardiovascular Research Institute here. I do ICU for a living, predominantly cardiac ICU. I run the ICU here at UCSF Benioff Children's Hospital. I'm also now a Senior Investigator at the Cardiovascular Research Institute. I got started in the pulmonary hypertension world from a research perspective. Abe Rudolph, who was one of my mentors, originally, was really the first person to describe how blood goes through the lungs in the fetus and then how it changes dramatically at birth and started out with basic physiological studies and then got into pediatric pulmonary hypertensive disorders in the lab with particular focus on pulmonary vascular disease related to congenital heart disease because that's what I was taking care of in the ICU setting.

Then I met Ian Adatia, when he came to run this cardiac ICU at UCSF and I saw that he introduced me to outpatients, which I hadn't done in a very long time. When he left to go onto Edmonton, I started the pediatric pulmonary hypertension service, which is basically just kind of continuing what he did and then expanding it. We started that in 2012, so now I take care of pulmonary hypertension patients, not just in the ICU, but obviously in the outpatient setting and follow them. All of this, for me, really started from a research perspective. That's how I got involved in it.

The draw for me for research is, I see that understanding basic mechanisms is really where you could get target therapies. It can't be too far away from the bedside to keep me enthusiastic. I mentioned congenital heart disease because that's what I was taking care of in the kids and it was at a time, when there was a lot of morbidity and mortality related to perioperative pulmonary hypertension and congenital heart disease. It was a real significant problem. I was very, very fortunate that early on in my research days, I was interested in this role of this endothelial function or dysfunction in pulmonary hypertension and started studying something that we called EDRF or endothelium-derived relaxing factor, that turns out to be nitric oxide. Because of my work when Warren Zapol first started using it in animals, he called me and got me involved in the very first clinical trial of inhaled nitric oxide for newborns with pulmonary hypertension.

Very early on in my career I got to see a translation from the lab bench to the bedside, which was really exciting for me. I think that's what's kept me in the game in terms of trying to understand mechanisms of the disease so we can design better targeted therapies for the diversity of pulmonary vascular disease.

As you know, it's a rare disease. It's a spectrum of disease. Really, the way we're going to learn about things is trying to learn from every patient something. Really, the only way to do that is to collaborate and try to get together in a multi-centered way. I think the great paradigm for that is the cancer groups, where basically every patient is put into a protocol. From there you can see acute lymphoblastic leukemia, for example, in childhood is almost cured and it's because of those type of efforts. That's what we need to be doing in pediatrics. If you look at survival, obviously now compared to before we had these drugs, we're doing fantastic. I mean, it's great to have these different types of agents that we use, particularly for kids, where you can maybe give them a suspension, et cetera. I'm not minimizing what has advanced and it's really dramatically changed the playing field. There's some game changers here.

Having said that, and again not to minimize the advances we've made, I see us where maybe cancer was 30 or 40 years ago. You talk about adult versus pediatric, I would say the way we talk about pulmonary hypertension or pulmonary vascular disease, in general, it is such a spectrum of disease. It's like calling a 40-year-old woman with breast cancer and an 80-year-old man with prostate cancer as just the same, they both have cancer and we clearly know that they've very, very different diseases with different pathobiologies and require very different therapies.

I'd say we have a long, long way to go to learn about, even within just the classifications. What are the real mechanisms of disease related to congenital heart disease? What are the real mechanisms of the disease related to toxin-induced pulmonary hypertension? What are the mechanisms of the disease related to infections or idiopathic or idiopathic in a 10-year-old versus idiopathic in a 40-year-old? Really kind of get towards personalized medicine. If we can understand the differences and where the pathobiology lies, then instead of, this child's pulmonary hypertension's not too bad, we'll give them one drug, one of the classes, it's pretty bad, we'll give them two drugs, one from two different classes, or it's really bad, we'll give them three drugs, one from each class. I don't mean, again, to minimize. It's dramatically changed things, but I think we've still got a long way to go.

Then say, "Okay, this particular location at this age with this particular type of particular pulmonary vascular disease with this particular genotype. We start here and then if that doesn't work, we add this." That's where we need to be, but there's a whole other area. The smooth muscle cell, proliferation, et cetera. There's many other targets down the road, that I think we can get to where drugs can be designed that continue to change the face of this disease. Very exciting time, very exciting time.