Eric Austin, MD - phaware® interview 421

Jun 27, 2023

Eric Austin is the Director of the Vanderbilt Pediatric Pulmonary Hypertension Program at Vanderbilt University Medical Center’s Monroe Carell Jr. Children's Hospital. He is also a member of the adult program’s Vanderbilt Pulmonary Hypertension Clinical and Research Program, with whom he leads and/or participates in various translational research studies.

Dr. Austin discusses pulmonary hypertension associated with developmental lung disorder.

I'm Eric Austin. I'm a pediatric pulmonologist and pulmonary hypertension physician and scientist down at Vanderbilt University in Nashville, Tennessee. I've dealt with PH now actively since around 2006. I have been honored to work with patients and families, and providers taking care of children and some adults with pulmonary hypertension since that time. I direct the pulmonary hypertension program in Nashville, Tennessee at Vanderbilt University Med Center. I work closely with the adult team, doing studies of children and adults with pulmonary hypertension.

I've been honored to work intermittently with phaware, and I'm actually thrilled to just talk to you today about my experience with something that's near and dear to my heart, which is pulmonary hypertension associated with developmental lung disorder; so children who have problems with their lungs or their hearts related to issues usually around birth or shortly thereafter, or reasons that we don't totally understand that impact their development over time, and subsequently they may go on to or be discovered to have pulmonary hypertension.

You know may say, well, what is developmental lung disease and what is PH associated with developmental lung disease? It comes in a lot of different varieties. The most common varieties probably, from what we understand in terms of what associates with pulmonary hypertension, is people who are born preterm. Children are born prematurely or preterm every day, unfortunately. We know that those children come out of the gate from their delivery, from their mother's womb, and have varying degrees of problems with their bodies. One of the big things they struggle with is their lungs are underdeveloped. Depending on how prematurely you're born, or how many weeks you're born before you should be born, really helps to impact, unfortunately, the challenges that you have.

If you think of a "normal" pregnancy lasting from 37 to 40 weeks of the gestation for the baby, we are now, through the really unbelievable technologic and medical advances we've seen in obstetrics and gynecology as well as neonatal medicine, children are being born 21, 22, 23 weeks of age and being able to be delivered, but that's pushing nearly 20 weeks earlier than they should be. Of course, there are children who are in between there too, 25, 28, 29 weeks premature. But when those children are born premature, their preterm lungs are not developed completely. What that means is instead of spending extra time that they should have in the mother's womb developing and growing their airways and their lung blood vessels and their lung what we call lymphatics or drainage systems, they come out and they're born and those are not ready to participate in life requiring events typically like breathing. Those children require support, often through a breathing tube or through pressure through their face or their nose to help them breathe.

Not only do they then have preterm lungs that are not quite ready to function in the world, they also then have a lot of medical support that is wonderful because it keeps them alive, but that also can in and of itself cause damage to the very fragile lungs. The blood vessels of those lungs are underdeveloped and often inherently have high pressure in them relative to normal. They may have pulmonary hypertension simply because of their underdeveloped nature, or they may also get pulmonary hypertension because of the challenges of what we have to do to keep them alive.

You may say, "Well, when do we determine that they have pulmonary hypertension?" That determination can occur at lots of different points. It can be right from the get-go when they're delivered and they're really struggling with breathing and with blood pressure and with heart function, or it can also sometimes be detected later on. For example, we routinely now screen children around 36 weeks after they're conceived, we would say 36 weeks post-conceptual age or basically they're about two to four weeks short of their goal developmental time had they stayed in mother's womb, and we look at them by echocardiogram and we evaluate them clinically and we determine that they do or do not have pulmonary hypertension. That's one time we frequently detect it.

We also detect it among children who are in the neonatal units and struggling. One of the things, as you can imagine, if you have a child who's having low oxygen saturation or low oxygen counts in their blood or if they're having difficulty with breathing or with heart function, we get an echocardiogram oftentimes and we assess them through other means and we determine they have pulmonary hypertension.

What's also really interesting to me, and I think of concern, as we have this growing body of children who are entering childhood and adulthood formerly preterm, is that if you think about it, we've got about 100,000 babies that are born every year preterm. That means that about almost 3% of all live births are actually people who are born early. Well, thankfully many of those people do well when they're in the neonatal intensive care. They get discharged sometimes on oxygen, sometimes not, and they go on to have nice lives.

But we also know that from recent data, particularly studying adults, that those children may have what we call occult or hidden pulmonary hypertension or at least hidden vascular disease in their lungs that suggests that they have higher pressure than we realize. Sometimes that can manifest itself when they get sick as adults or if they get a bad viral infection during childhood in other ways. We know that there's a huge number of children who have preterm lung disease, or maybe just preterm lung condition that's not thought of as a disease, but if we stress them with activity or exercise or, god forbid, a bad infection, they may develop PH that was always there, we just didn't detect it before.

One of the things that we're really interested in the Pediatric Pulmonary Hypertension Network is thinking about children born preterm and their experience from birth to discharge from the neonatal intensive care unit. Then their experience from discharge from the neonatal intensive care unit to hopefully resolution of pulmonary hypertension and no longer needing to be followed by our PH programs. Many of our PH programs follow of multiple hundreds of children, and about 20% of those are actually former preterm infants. But as I mentioned, there's a whole group of other kids we never meet until they become sick. We're interested in studying those children and understanding why children are diagnosed at all sorts of different ages after preterm birth.

Efforts are going on to look at the children in our pulmonary hypertension clinics in the PPHNet, pulling together information about how early they were born, how long have they been treated, how long does their pulmonary hypertension last? Do they get better from their pulmonary hypertension, or do they actually continue to have it? Thankfully, the vast majority of children by about age four to seven have had quite improvement in their pulmonary hypertension to the point that many are actually off therapy.

Unlike an individual who's born who has, say, idiopathic or heritable or congenital heart disease, associated pulmonary arterial hypertension, children with preterm associated birth can actually have clinical resolution. It's just that they probably then always persist with a degree of PH that we just don't detect unless they get sick. Now, don't worry, most children don't ever have that present as children and adults, but we're interested in figuring out what is the risk to have it present and what is the resilience to keep it from ever presenting and being a problem. I've been fascinated by this concept and our Pediatric Pulmonary Hypertension Network is as well.

Another group of children who have developmental lung disorders are those children who were born with variations in their genetics. The common ones that you may have heard of before would be Trisomy 21, which is Down syndrome. There's three copies of the 21st chromosome for those children. The Down syndrome population of individuals has a heavy burden of PH. They too are well represented, unfortunately, in our PH programs. Those children can present with PH right after birth, whether they're premature or not, with what we call persistent pulmonary hypertension in the newborn that thankfully often does resolve, but not always. Or a child with Down syndrome could present with PH at a young childhood or mid-childhood age.

That occurs for a variety of reasons. One of them is because children with Down syndrome actually look like, at birth, they have lungs that are about that of a 32-week premature child. Those children who are born with Down syndrome, even if they're not preterm or premature, kind of have underdeveloped lungs similar to what you see with a modestly preterm child. Right after the get-go, their lung vasculature and lung airways are not as robustly formed as yours and mine. That's a risk factor for whenever they get sick or they have problems, that they could develop PH or have PH flare up.

They also can have PH if they have difficulties with sleep apnea. You may be familiar with the sleep disturbed breathing that many of us can have at any times in our life. Children with Down syndrome are more likely to have sleep apnea than the average individual, both because they have growth of their adenoids and their tonsils that's fairly impressive sometimes, or because their airways are more crowded than yours and mine just because of the way they're structurally made up.

Children with Down syndrome also are more likely to have pulmonary hypertension because they're more likely to have congenital heart disease. A child with Down syndrome is more likely to have an atrial septal defect or a ventricular septal defect, what we call a PDA, as well as some other structural heart disorders that associate with PH. They have underdeveloped lungs often. They have congeal heart disease often. They have obstructive sleep apnea. Or they may have other difficulties that can insult the lung. So our Down syndrome patients are not infrequently taken care of. That would be another class of child who has developmental lung disorders.

We also have children who have more profound developmental lung disorders. I should say that, if you think about it, the term developmental lung disorders to some extent explains these children. They have an abnormality of how they were developed in utero and that persists into their development, during their early childhood and beyond. Other children who would be represented, besides what we've already talked about, would be kids who have Trisomy 18 or Trisomy 13, which are two additional genetic syndromes, or children who have variations in how their lungs are born and developed from the get-go that are not associated with prematurity and not always even known genetically why it happens; where they have lung growth disorders, the lungs just don't grow as well as yours and mine. If you think about it, lungs that don't grow do so not just in the airways and in the little air sacs that transmit gases, but also in the lung blood vessels and the lung drainage vessels, called lymphatics, like we talked about earlier.

Our Pediatric Pulmonary Hypertension Network has really been interested in all types of developmental lung disorders and how we can better care for and support those children. As you know from other podcasts, I think Dr. Lew Romer recently spoke a podcast about clinical trials, we currently have a pediatric pulmonary hypertension PPHNet clinical trial going on, where we're trying to support children with medicines that are already in existence and use and trying to determine how many medicines to use when you first diagnose someone and how long to use those medications to help them. We have that going on, we have writing groups that are writing about these children in terms of clinical care guidelines and how we best take care of these types of children, and then we also have research studies that are ongoing to study the genetic and biologic markers in these children that may associate with outcome, onset of disease and the like.

If you think about having a child who's born prematurely or a child who has Down syndrome or a child who has some sort of other growth disorder in their lung, you may wonder, well, when do I think about pulmonary hypertension as a parent or a family member? Should I be constantly asking the doctors about this? Should I be thinking about it all the time? That's certainly a difficult thing to say across the board for every child, because of course every child is different. I don't mean that as a cop out to answer that question, but I mean it as a reality. But we do have certain ways we approach children.

For the child who has gone home from the hospital, has some sort of growth disorder of their lung that may be characterized, it may not, maybe they carry a label of they were born preterm or they carry a "label" that they have Trisomy 21 or Down syndrome. Or that they have some sort of other growth disorder of their lung, presumably, before those people go home from the hospital for the first time, they will have one or many echocardiograms under their belt and will have been assessed to see if they have pulmonary hypertension. If those have been felt to be normal over time, then you may ask, "Well, when would I ask for my child to be screened again?" There's a few guideposts that I like to think about.

Number one, if they're fairly young when they go home. For example, say they're four months old when they go home, and thankfully they got home, they're on a little bit of oxygen and things are going well, or they don't even need oxygen. Well, if that child gradually is able to come off of oxygen support or other breathing support, times when there are big changes in their medical management would probably be times that most PPHNet, or even other large PH centers or even non-large PH centers would say, "Well, why don't we get an echocardiogram? This is a point of change. Your child's been on oxygen, we're really thrilled they're coming off their oxygen. They're doing well, but why don't we just get an echocardiogram to make sure there's no evidence that there's strain on their heart? We'll have a clinical evaluation of course. If there's any question, we may do an electrocardiogram or some other studies as well, but let's just make sure things look okay."

Another time might be if, God forbid, the child has a bad illness, say they get influenza, the flu, and they get hospitalized. Commonly, if they're having difficulties with their breathing or with their gas exchange or they're struggling or you have a bad pneumonia on x-ray and on your clinical evaluation, we might get an echocardiogram to say, "Okay, what does it look like when this child's under stress?" By stress there, I mean illness stress. That would be another time.

But what if things go great? What if your child goes home, thankfully no oxygen, everybody's happy, it's hunky-dory, do I need to get an echocardiogram ever? Well, that's a tougher question, honestly. It depends on where you're followed and how your center likes to operate. It also depends on how the person is doing. If your child's growing and developing and exams with your pediatrician look terrific, I would say you don't necessarily need an automatic screening echocardiogram. If there's questions or concerns, it certainly is a good idea to go ahead and get one, or if new issues erupt. Like for example, I mentioned to you individuals who have Trisomy 21 or Down syndrome often have obstructive sleep apnea. Well, the truth is, so do the rest of us, it's not just isolated to a person who has a syndrome.

If you had a preterm child who went home and suddenly we found out they had bad sleep disorder breathing when they're four, they're snoring and choking and gasping, your pediatrician sends you for a sleep study and says, "Oh boy, they have obstructive sleep apnea." Well, that'll probably be fine and I bet we're going to handle that just fine. But it would not be inappropriate to say, "This is a child who had a lot of rough go early on. Why don't we get an echocardiogram as part of the sleep apnea workup and just make sure that the heart is not under from the sleep apnea?" To be clear, the echocardiogram is not because pulmonary hypertension causes sleep apnea. However, sleep apnea can cause or aggravate pulmonary hypertension. So I would get it during that time period.

Otherwise, I think I would do it if there were complaints from the family, like if the child did not seem to be performing like mom and dad or family thought; they weren't exercising as well as their brothers and sisters or their friends, they don't keep up at school, or if there's questions of "asthma" but they don't seem to respond to asthma therapy. Just keep that in the back of your mind, maybe we should repeat a question about whether they have pulmonary hypertension.

Well, I hope this was helpful to think about, people who have developmental lung disorders or really any sort of lung disorder that can be associated with or driving pulmonary hypertension. Certainly if you have questions or you're worried about your child and you think everything's going great but I just want to touch base, it's a great opportunity if you're not followed by a pulmonary hypertension center, which I hope you don't have to be, to just talk to your pediatrician and talk to your family doctor and just say, "Hey, can we have a discussion about that?" If there's questions or issues, of course, I'm sure your local PH center would be happy to help or phaware can put you in contact with people who'd be happy to help support you.

I think it's just important to realize that, thankfully, the vast majority of people don't have pulmonary hypertension. If you do, we do have options. We have care programs that can help support you and your family. I'm honored to talk today about that with you and certainly be happy to help in the future. PH is important. It's a challenging disease, but it also can be really well managed.

My name's Eric Austin, and I'm aware that I'm rare.

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