I'm Aware That I'm Rare: Roberta Keller, MD (Part 1)
Dr. Roberta Keller is a neonatologist, an expert in caring for critically ill newborns, particularly those with congenital lung or heart disease. She is director of the USCF Benioff Children’s Hospital Extracorporeal Membrane Oxygenation (ECMO) program, or artificial lung, for newborns. Her research addresses lung and heart disorders affecting newborns, such as congenital diaphragmatic hernia and patent ductus arteriosus. In this episode Dr. Keller discusses Pediatric Pulmonary Hypertension Guidelines.
I’m Dr. Roberta Keller. I work at the University of California San Francisco, the Benioff Children’s Hospital. And my specialty is neonatology, which is newborn intensive care. And my area of focus is newborn lung disease and pulmonary vascular disease and lung disease leading to chronic problems with pulmonary hypertension.
So the guidelines on pediatric hypertension, which we worked on together as a group, were published in the fall of 2015, and really represented a great amount of work, part of a large number of people, to help really consolidate information that is out there, evaluation and treatment of the various forms of pulmonary hypertension that we see in children. So children have a number of diverse underlying conditions which can predispose them to pulmonary hypertension. I mentioned newborns with lung disease for instance, which are unique compared to what we see in the adult population, adult patients. So, we felt that was important to break those areas down more specifically to help practitioners think about children with pulmonary hypertension related to their underlying etiology of their disorder.
Also, we know that the evidence base and the data that are out there for the types of treatments we have for pulmonary hypertension, the data are much more limited in children than they are in adults. Most of the studies have been done in adults, and the gold standard for evidence-based medicine is the randomized control trial in the literature. And we have very few of those in pediatric pulmonary hypertension. And part of it is the complication of having the diverse etiologies, part of it is the complication of how you assess for response to therapy. For instance, in the adult literature the studies are done using a six minute walk test as a primary outcome in many instances, but babies don’t walk. And so we need to think about other ways to assess whether or not they’re responding to therapy. So, there are real limitations in the literature that make it difficult to select appropriate therapies, appropriate doses for children with pulmonary hypertension. And our hope in creating these guidelines was to provide some guidance for people out in the community as to how to approach therapeutic decision in children with pulmonary hypertension.
Many of our tools for assessing children with chronic illnesses are relatively crude. We bring them into our hospital or a clinic, we do a number of assessments, and we make some recommendations. And then they go out for a month or three months or six months based on those recommendations. There might be some follow-up phone calls. And then they come back and we do the same thing all over again. And I feel like with the technological tools we have available we can really get a lot more information about what’s happening with children as they live their lives every day. And not just at those moments in time. So, I think something for a child who’s learned how to do a six minute walk test, to be able to do that in the course of your regular life and do it on a more frequent basis, I think that would be incredibly valuable. I can think about all sorts of other ways that I would love to measure sort of physiologically what’s going on as children kind of live their lives, and understand better what their needs are in much more of a live feedback environment than we have now.
In the groups we work with I’ve been very fortunate to work with a group of people who helped put together the guidelines. We have another group, the Pediatric Pulmonary Hypertension Network, which is made up of just some centers of pediatric practitioners where we talk about this all this time and think about this all the time and how do we design and develop and fund trials to get people the information that they need. And I think that’s the real challenge. So the information people need, they need to know what is safe in terms of dosing and side effects for medication, what is effective. So again we have diverse etiologies, and there might be some drugs that are more effective in some populations than others. And the how do we assess outcomes in a standardized way that will help people feel comfortable that that information is information they could apply to their patient in front of them that they’re thinking about treating? And so I think those are the challenges we have.
The approach we are currently taking is trying to gather all of our information together in a registry. And so we can pull out some of those groups and see what some of the effects are of the medications and see if we can understand who’s responding and who’s not responding to certain classes of medications. The medications work by different mechanisms, and so with different etiologies of pulmonary hypertension it may be that one mechanism is much more important than the other.
And then on top of that there’ needed to be very individual differences as we see in any patient population related to undergoing genetics and other things that are going to take a little more work than just a registry to help us pull out. So we also are working on collecting biospecimens and hopefully being able to do some more advanced genomics approaches to trying to understand, again, what are some of the factors that might predict who can respond to one class of medication versus the other. So I think it’s understanding dose, by looking at what we’re giving, and pharmacodynamic studies that are out there and that we can do, looking at adverse effects, which are collected in trials but probably even better collected in broader populations of patients because you can have adverse effects even if you didn’t qualify for a trial. And then really trying to understand those subsets of patients that can respond to different classes of medications, again, to help inform people as to how to start the treatment.
Most of the published literature that we’re making decisions on are groups of 20 to 40 patients are considered to be a lot. Many of them are case series where we have information pooled from two or three centers, with 15 to 30 patients. So the numbers are much smaller.
So I think PPHNet, the Pediatric Pulmonary Hypertension Network is something that really has come out of the efforts of Steve Abman at Colorado Children’s Hospital. And a really huge effort on his part which has just kind of pulled the group together and kept the group together. And I think it’s a really, really valuable group to benefit children with pulmonary hypertension. Pulmonary hypertension’s not a common disease regardless. Pulmonary hypertension in children is even less common. And by bringing together these major centers from across North America we’re really able to share our experience and our patient populations to continue to learn, pool our knowledge, and continue to learn and continue to benefit children both within and outside our centers by bringing together our relatively small groups of these different patient populations to learn a lot more.
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