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George B. Mallory Jr., MD - phaware® interview 348

Nov 10, 2020

George B. Mallory, MD is a pediatric pulmonologist at Texas Children's Hospital. In 2001, he joined the Baylor College of Medicine pediatric faculty and founded the TCH Lung Transplant Program. 

In this episode, Dr. Mallory reflects on his 40 years of clinical practice and how the treatment of pulmonary hypertension has profoundly changed over the years.

My name is George Mallory, MD I'm a Professor of Pediatrics at the Baylor College of Medicine in Houston, Texas. I was the medical director of the Pulmonary Hypertension Program at Texas Children's Hospital until turning it over to a younger colleague three years ago. I now have the title of Medical Director Emeritus, and I will be retiring from clinical practice next year, but will continue to be involved at the hospital in teaching and mentoring. Pulmonary hypertension is one of my passions.

I will take the listeners back to an early part of my career. I remember in the 1980s at one of the international pulmonary meetings, being attracted to a lecture on pulmonary hypertension, which was a condition that I didn't know very much about. It was very interesting. Back in the 1980s, there were no approved medications for pulmonary hypertension. So, it was felt to be a very uncommon, serious, and life-threatening disease, largely in adult women, but was known to occasionally occur in childhood.

As we moved into the 1990s, I became involved with pediatric lung transplantation. At that time, children and teenagers with pulmonary hypertension were being referred to our program in St. Louis. When the diagnosis occurred, again in the absence of treatment, with a natural history that suggested that it was a progressive and terminal condition.

In the 1990s, the first FDA-approved therapy came into being. It was epoprostenol, which was known as Flolan, its trade name. It required, and continues to require, 24-hour-a-day infusion into a blood vessel of a very potent medication. It really changed things quite a bit. It also led to greater interest on the part of both cardiologists and pulmonologists in the adult arena and in the pediatric arena. One of the truths that emerged in the 1990s was that infants and children seem to have a more malignant form of pulmonary hypertension, with a faster progression to death than adults.

So, we did have the occasion to meet a number of these children. Many of them came to lung transplantation, and many of them were cured of their pulmonary hypertension. To date, lung transplant is the only cure for pulmonary hypertension. It's important for listeners to note that lung transplantation, despite its cure of pulmonary hypertension, introduces some new healthcare variables related to lung donor allograft rejection and enhanced chance of infection, that doesn't make it the best option for every patient and family.

After 2000, quite a number of medications became available. I've been at Texas Children's Hospital now for 19 years, and it has become my responsibility to oversee and be involved in hundreds of infants, children, and adolescents with pulmonary hypertension. One of my concerns shared by the families of many of these patients is that many physicians in the United States, and I would say around the world, are not familiar with the many faces of pulmonary hypertension. Many families are disappointed and sometimes angry that their sick children sometimes wait until the disease has advanced before a diagnosis is made and referral to a specialty center, where the complicated choices of medications can be made.

So, I think it's appropriate to indicate to the listeners that pulmonary hypertension can present in a very slow and non-specific way. In newborns, it's most common to be seen with very dramatic symptoms. This is quite unusual, but very important, to make a timely diagnosis and referral for selected infants.

In older children, the non-specific nature of the symptoms may be lower activity, poor color, breathing difficulty, particularly with viral infections, not very often with many more specific symptoms. The physical examination in children and adolescents is also quite subtle. There may be an increased second heart sound, sometimes a new heart murmur. Sometimes the palpation of the anterior chest wall leads to a very prominent cardiac impulse. It's called a right ventricular heave. And very commonly in the school-age child and the adolescent is decreased exercise tolerance with complaints of breathlessness.

More often than not, pediatricians, emergency room physicians, will suspect that the patient has asthma. If the child has associated congenital heart disease, the cardiologist may not appreciate that there is an increasing level of pulmonary hypertension that may not fit the child's underlying diagnosis, whether that's a repaired or an un-repaired congenital heart defect.

So, the most important thing is it needs to be on a list that all physicians keep in their mind. Frankly, as parents become more and more sophisticated, get online, they need to ask the difficult questions. "There's something wrong with my child. It may not be evident to you. Could we consider some additional testing or a referral to a specialist?"

In Houston, unlike in many other pediatric centers in the country, it is the pediatric pulmonologist who dominates the pulmonary hypertension center. So, cardiologists actually refer patients to group. In other centers, the pediatric cardiologists may be the dominant members of the group. But since this disease is in the lung, but has its greatest impact on the heart, it's actually an ideal situation for a cardiologist and a pulmonologist to collaborate.

So, diagnosis is often delayed. Sometimes physicians who are not familiar with the current medications and their impact on the natural history of the disease, it is our job in the Pulmonary Hypertension Center to educate families. We have many good educational tools these days. And let them know what the current state of therapeutics might be, that at least a trial of medications would be important.

Every family is different. Some families, and we're often talking about the parents, are not ready to listen at the very beginning of what may be a journey, but we try to listen to them, talk to the children, help them understand what has been going on in their body. Then, my personal approach is to be cautiously optimistic that with the medications we now have available, we'll be able to improve the child's health and may lead to a near normal life for some months or years to come.

We now appreciate that there are so many different faces, as I mentioned before, of pulmonary hypertension. There are some very young children who will actually have forms of pulmonary hypertension that may prove and regress during the early years of life. There are other patients who have forms of pulmonary hypertension that are inevitably going to get worse and for whom medication may not be helpful. Some older patients we're just not certain, but we hope that there will be stabilization of the condition for many years to come.

I would say most general pediatricians in the United States probably do not have firsthand experience seeing children with pulmonary hypertension, but it is not so rare that they shouldn't be able to access easily available information. Hopefully, if questions arise, also access via our multiple forms of communication, experts who can answer their questions and encourage referral, if appropriate.

I also want the listeners to know that with this disease, we're starting to develop a national network of specialists who go to common meetings, who know each other, who can refer patients when families move. My estimate right now is there are no more than 20 to 25 or 30 formal pediatric pulmonary hypertension programs in children's hospitals around the country.

The Pulmonary Hypertension Association has a certification system. I don't believe more than a dozen pediatric centers have been certified. What that means is there are more than 100 children's hospitals where there likely is a pediatric cardiologist or pulmonologist who has been designated a person who can be called in when such a diagnosis is made. I think that can be really helpful in terms of confirming the diagnosis, which is most commonly made by echocardiography. The findings on echocardiogram are sometimes very obvious, and it's very easy to make the diagnosis. At other times, it may be subtle enough it can be missed.

The therapeutics today with more than 16 separate FDA-approved medications is complex enough that we who do this for a living really believe that virtually all infants, children, and adolescents with pulmonary hypertension should be referred to specialized PH centers.

We enjoy sharing care with our colleagues in other cities in Texas. Oklahoma and Louisiana are other common locations of our patients. So we take care of a fairly broad expanse of patients, and communication is so very important.

The other aspect of PH care that I think is somewhat unique and very important is that the medications are quite expensive. So the majority of these 16-plus medications are available by mouth. Some of them are available both as tablets as an oral suspension for babies or, in the case of bosentan, in a dispersible tablet, which is meant to dissolve easily in water. Special requirements are required for a physician to enroll in prescribing programs for bosentan, ambrisentan, macitentan, and that particular group of medications, partly related to the teratogenic potential of those medicines.

Pulmonary hypertension therapy is not something that a physician should dabble in, and parents need to ask the tough questions, as well. I would tell you, at least 50% of the time that we get patients referred from even our most frequent referring physicians, the doses of the medication they're taking are either too high or too low. It really concerns me, because the recommended dosing is pretty standard now. There are enough review articles and guidelines written. It's not that the medications have horrible side effects. It's really important that you give it regularly, the family gives it regularly, and the physician prescribes it in the right dose. If the patient doesn't do well, you don't know if this was a true treatment failure, which might lead to surgical options or even referral for a lung transplant, or whether it was related to the wrong dose.

I see in the next 10 years, a slow, gradual penetration of expertise, information, trained physicians beyond the larger centers with formal pulmonary hypertension programs to other children's hospitals. There are many pediatric programs that exist in smaller cities that may not have a freestanding children's hospital, where parents bring their children with lung disease or congenital heart disease and expect good care.

So, I think this topic is very timely. It will continue to be important for people to know about, both physicians and families. There is a significant genetic component in what we think now is a minority of the patients we take care of, but we are ever expanding the genetic mutations that have been associated with pulmonary hypertension. When that occurs, there are two important corollaries. One is, it may run in families. So, additional testing of other family members, or genetic counseling of young adults about their plans to have families, will move forward. We’re just now getting into the era where some of the genetic mutations are giving us clues as to how this often terrible disease does its dirty work. Moving backwards from the genetic mutation can sometimes lead to new avenues for therapy.

This has been dramatically shown in cystic fibrosis, where some of our most impressive therapies have been introduced based on their ability to impact the abnormal protein, which we only know about because we've figured out that genetic mutation.

I would say within five to 10 years, we're going to have some new classes of medications that may even more dramatically change the natural history of pulmonary hypertension, based on the basic science work leading from genetic mutations. I find that exciting.

Even as I anticipate retirement from clinical practice, I hope to continue to be involved and reading and writing and teaching and mentoring. This story is a fascinating one. It's changed profoundly during my almost 40 years of clinical practice.

My name is Dr. George Mallory, and I realize that my patients are rare, unique, precious, and deserve the very best in diagnosis and treatment.

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