Cystic Fibrosis – Pediacast 218

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Dr Karen McCoy joins Dr Mike Patrick in the Pediacast Studio to discuss cystic fibrosis. As many as 1 in 25 caucasians are carriers of this disorder, which results in severe life-long problems. We discuss the cause of CF along with its symptoms, diagnosis, treatment, complications, current research, and the long-term outlook for those with the disease.

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  • Cystic Fibrosis

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Announcer 1: This is PediaCast.

(Music)

Announcer 2: Welcome to PediaCast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike!

Dr. Mike Patrick: Hello, everyone and welcome once again to PediaCast, a pediatric podcast for moms and dads. This is Dr. Mike coming to you from the campus of Nationwide Children's Hospital in Columbus, Ohio. I'd like to welcome everyone to the program. It is July 11th 2012. This is PediaCast 218, 2-1-8 and we're calling this one Cystic Fibrosis.

Ah. It's hot. It is definitely summer and I know there's a heat wave throughout the United States and with recent storms there are lots of people without power and so I just want to say a friendly reminder, just make sure that your kids get lots of fluids. You definitely want to avoid dehydration and heat exhaustion and heat stroke and those kinds of things. So just make sure you find a cool spot and keep yourself well hydrated, that's my community service message for you.

01:24

Before we get to our topic today, I also want to remind you about a couple of upcoming conferences that I want to remind you about. The Autism Speaks National Conference for Families and Professionals is coming to Columbus August 3rd and 4th at the Hilton Columbus at Easton. You still have time to register. In fact, early bird registration has been extended to July 20th 2012 and remember there are separate tracks for healthcare professionals and families, so a promise is to be a great educational opportunity for clinicians and for moms and dads. You can find out more information at the conference website and we'll put that link in the Show Notes for you over at pediacast.org.

Another upcoming national conference to let you know about, this one is called A Healthy You and 22q and it's coming to the campus of Nationwide Children's September 22nd 2012 here in Columbus, Ohio. So what is 22q? I'm so glad you asked. Unfortunately, the answer is a long one and we are covering cystic fibrosis today not 22q so we don't have time to get into the details, but Dr. Richard Kirschner will be back in the PediaCast studio soon to talk about 22q, so stay tune for that in the coming weeks.

In the meantime, if you have a child with 22q or you know a family who does; this conference will definitely be of interest to you. It's a day-long conference, funded in part with support from the Dempster Foundation and its target audience is parents, caregivers and patients affected by 22q. The conference will cover general medical concerns, genetics and educational strategies.

There'll also be an opportunity for conference goers to participate in live chat rooms with local and national 22q experts and the chats will be broadcast live on the internet so families around the world can join in. You can expect separate sessions designed for school age and Pre-K children and speakers include experts in Allergy, Behavioral-Developmental Pediatrics, Cardiology, Education, Endocrinology, Genetics, Psychiatry, Reconstructive and Plastic Surgery, and Speech and Language Therapy.

So, definitely a wide range of topics, they're going to have light refreshments and lunch included. And again the date is September 22nd 2012 here on the campus of Nationwide Children's Hospital in Columbus, Ohio. If you like more information about the conference and to register be sure to find the links in the Show Notes at pediacast.org.

03:51

All right. Let's move on to cystic fibrosis. This is another one of those diseases that most people have heard about. If you mention cystic fibrosis it's just one of those, you've kind of got it in the back of your head, hey, yeah, that's not something I've never heard, it's something that I know is out there. But unless you have a close relative with the disease or you're a medical professional, you might not know any of the details about cystic fibrosis. And it's an important disease because it's quite prominent, especially in Caucasians of Northern European descent. And in fact, in the United States it's estimated that as many as 1 in every 25 Caucasians may be carriers of the disease.

So what is cystic fibrosis? What parts of the body does it affect? What symptoms does it cause? How do you diagnose it? How do you treat it? Can it be prevented? Is there a cure? And if there's not a cure, what is the long-term outlook for kids who have cystic fibrosis?

To help me answer these questions and many more, we have a fantastic studio guest lined up for you today, Dr. Karen McCoy, MD, is back. She is the chief of Pulmonary Medicine here at Nationwide Children's and I think we could say that she is now a frequent visitor of the program. We need to get Dr. McCoy a punch card. You get like one free visit to the PediaCast studio once you've come like five times. It's free. What am I even talking about? I don't know.

05:18

All right. We're going to get to Dr. McCoy shortly. First, I want to remind you that if there's a topic that you'd like us to talk about, if you have a question, you want to point us to a news item, really, any communication that you would like to do with PediaCast it's an easy thing, just head over to pediacast.org and click on the Contact link. You can also email pediacast@gmail.com or call the voice line at 347-404-KIDS. That's 347-404-K-I-D-S.

Also, I want to remind you the information presented in every episode of the program is for general educational purposes only. We do not diagnose medical conditions or formulate treatment plans for specific individuals. So if you have a concern about your child's health, make sure you call your doctor and arrange a face-to-face interview and hands-on physical examination. Also, your use of this audio program is subject to the PediaCast Terms of Use Agreement, which you can find at pediacast.org.

All right. So let's turn our attention to Dr. Karen McCoy. She is the chief of Pulmonary Medicine for Nationwide Children's Hospital and a professor of pediatrics at the Ohio State University College of Medicine. She also serves as the director of the Pediatric Cystic Fibrosis Program at Nationwide Children's and as a principal investigator with the Cystic Fibrosis Translational Therapeutic Development Program.

Dr. McCoy is no stranger to our program, in fact, she last visited PediaCast in the fall to talk about asthma. This time we have cystic fibrosis on the agenda so it's with a warm welcome back that we say hello to Dr. Karen McCoy.

06:50

Dr. Karen McCoy: Thanks for having me, Dr. Mike.

Dr. Mike Patrick: So, let's start with just a quick definition of cystic fibrosis. I know there's a lot to talk about in terms of the disease, but sort of just a nutshell, what is cystic fibrosis?

Dr. Karen McCoy: Well, the term cystic fibrosis is really no longer useful. What really stemmed from a very long ago pathologic diagnosis and it referred to the pancreas and so the cysts that were formed there and the scarring, meaning the fibrosis part, is how this was originally described and that's what the disease was named. But our concerns about cystic fibrosis go far beyond the pancreas. In fact, involve every epithelial organ in the body, which means everything from the respiratory tract, the elementary canal, the GI tract to the skin, the reproductive tract, the liver, the pancreas, etc. So many, many organs are affected by the changes that take place in cystic fibrosis.

Dr. Mike Patrick: Right. Since it's the pulmonologist who takes care of cystic fibrosis I would assume that the biggest concern is with the lungs.

Dr. Karen McCoy: Yes. About 90% of the mortality earlier than expected for our population results from the things that happened in the lungs.

08:04

Dr. Mike Patrick: So it's a lung disease, but it affects more body systems than just that and we'll get to exactly why that is in just a minute. So who does this disease affect? In the introduction I mentioned that it's most common in Caucasians and there's that figure out there like 1 in 25 is a carrier. Is this something that only affects Caucasians or can it affect other races as well?

Dr. Karen McCoy: Not at all. In fact, it's known to be seen in all races, but there are, as you noticed, a lot of differences between the races. Among Caucasians, the live birth rate is about 1 in 2,500 babies born and that's about a tenth so often in the African-American population and then much less common among Asians. But as I said, it does occur in all different races.

Dr. Mike Patrick: Yes. Possible. But in Caucasians it's about 1 in every 2,500 live births. So it's a common disorder. This is also has a genetic basis to it too, doesn't it?

Dr. Karen McCoy: Yes, it does. It's inherited from each parent what we call a recessive disorder and if you get it you get it from each of the parent's donating one affected gene. Of course, the parents are clinically normal, but putting the two genes together makes the child have the disease.

09:26

Dr. Mike Patrick: Great. So, our listeners have to think back to high school biology and remember the Punnett square and so you have if both parents are carriers then you have a 25% chance of having a child with the disease, 50% chance that your child will be a carrier and 25% chance that they won't be a carrier at all, even though mom and dad were carriers.

Dr. Karen McCoy: Absolutely.

Dr. Mike Patrick: So you got to kind of draw the blocks and I'm sure there are parents out there who are rolling their eyes and thinking I don't want to go back to that.

[Laughter]

So now that we know that there's a genetic basis to it, can you kind of walk us through how you get from having the abnormal gene to having a disease?

Dr. Karen McCoy: Well, again, if you have two copies of the gene in a child who's born, they have cystic fibrosis from the time of conception. You don't get cystic fibrosis, you are born with it. In times past, before about 2006, what we looked for was clinical markers of the disease that prompted us to do what's called a sweat chloride test to make the full diagnosis. Since late in 2006 we like some other states have adopted a pre-robust newborn screening program, so that the majority of patients nowadays are picked up, at birth really, at the time when they had that blood spot test done and then within about two to four weeks their pediatrician and their regional cystic fibrosis center are made aware that they have an abnormal test. The abnormal test then may result in testing to find out that they don't have cystic fibrosis, they were picked up because they have one copy of the gene, which might have some importance to the family as they go on having children.

Dr. Mike Patrick: Sure.

Dr. Karen McCoy: But that child will be totally normal then or we confirm our genetic testing with a sweat chloride test again and then make the diagnosis and get quickly on to treatment because our usual, back in clinical diagnosis days before 2006, was that we found a sick child often where the parents had been saying there's something wrong, they keep getting sick, they keep getting infected, they're not growing, were the common things.

And usually with a lot of angst because they know something's wrong and they would actually be quite damaged in the pulmonary system by the time we ever made the diagnosis. Nowadays, we get perfectly normal set of lungs in the newborn screen to fine kids, which gives us an opportunity to initiate and they can stay ahead of it.

12:08

Dr. Mike Patrick: Great. When you have the abnormal gene, we've talked on this show before that genes code for proteins, as one of the functions, and so this is kind of an abnormal protein, so you have a gene that's abnormal that leads to a protein that's abnormal. Can you talk a little bit about what protein is abnormal or what the function is in the cell and then how that leads to disease?

Dr. Karen McCoy: OK. So, yeah, now we know about 2,000 genes that can create a diagnosis of cystic fibrosis. So that's a lot to keep track of and there's always the potential for another one, we're discovering still. But what happens when the gene then turns on the cellular machinery to make a protein, the protein that comes out, in this case, is called the cystic fibrosis transmembrane regulator, which is a mouthful and we call it CFTR at home.

[Laughter]

Dr. Mike Patrick: Yeah.

Dr. Karen McCoy: So, this is a massive protein. It actually is responsible for getting out of the protein-making machinery and up to the cell surface where it inserts itself and then it's in charge of a very, very important cellular function, which is to take a lot of charge of the way salt and water move across that membrane. It's really critical and so when it does its job in a defective way as an abnormal CFTR would do, what happens is we end up not being able to get chloride ions through the gate or the membrane into the outside of the cell.

And as a result of not getting the chloride out, of course sodium likes to stay where the chloride is to balance electrically, and of course where salt goes water would go, but it doesn't. So on the surface of the cells we have a very dehydrated environment and that leads to a mucous that doesn't work for us, it works against us. Most of us have our mucous, especially in the respiratory system, pick up bacteria and particles of dust and this and that and they get them out and you eventually either swallow or spit them out.

In the case of people with cystic fibrosis, everything breaks down and just turns into a sludge and traps the bacteria and of course they multiply and pretty soon you have a reborn infection.

14:43

Dr. Mike Patrick: Yeah. Yeah. So I want to just kind of sum that up again, certainly there are a lot of parents who aren't necessarily science-minded out there. So we have the gene, it's making a protein that's not quite normal; that protein goes to the cell surface; the job of that protein is to move chloride back and forth across or in one direction or another across the cell membrane. And normally what would happen is chloride would go out, sodium would follow it, water would follow it and then you'd get a mucous that's nice and thin and slippery that's sort of the normal thing. But if the protein that moves the chloride is not working, then chloride can't go across the cell membrane, then sodium doesn't follow, water doesn't follow and so the mucous that gets made is kind of thick, I mean it doesn't have a good water component to it.

Dr. Karen McCoy: That's right.

Dr. Mike Patrick: So rather than being a lubricant, it actually clogs things up.

Dr. Karen McCoy: More like glue.

Dr. Mike Patrick: Yeah. And then that's an issue in the respiratory tract and then in the GI tract. So, let's kind of move to that point then. So what do we see? Let's take sort of each of the major body systems one at a time. In the respiratory system, if you have this thicker mucous that's not doing the job it's supposed to do and clogging things up, what sort of symptoms then does that create in the respiratory tree?

15:58

Dr. Karen McCoy: Well, it creates the need to cough and the need to move mucous a different way so there's lot of coughing, often wheezing, sometimes difficulty breathing when the infection would flare up in particular or it gets pretty far advanced. And so common respiratory symptoms, but in a pattern that is too frequent, too often requiring antibiotics that of sort thing. It just continues to repeat itself.

Dr. Mike Patrick: Sure. Wheezing, shortness of breath kind of stuff, exercise intolerance, kind of like you would see with asthma.

Dr. Karen McCoy: Tired. Yes. All those things.

Dr. Mike Patrick: Nasal polyps? Is that more in an older population?

Dr. Karen McCoy: Come on. I actually found a small child, a two-year old, with a large amount of polyps recently, but that's more rare. Mostly, it tends to occur in later childhood or in adolescence and then all through life after that.

17:00

Dr. Mike Patrick: Sure. So, let's move in to the GI tract and we talked when cystic fibrosis back like in the 1930s when it was first described, the reason it was called cystic fibrosis was because of cysts and scarring in the pancreas. So what's happening there?

Dr. Karen McCoy: So you may remember that the pancreas is a two-fold sort of organ. It has a duct system called the exocrine pancreas and has a secretory type of system, which is the endocrine pancreas. So the first thing that happens is the ducts, part of that epithelial apparatus, are affected by the malfunction of the CFTR and so instead of secreting nice liquid secretions into those ducts so that they can then empty into the intestine and help aid with digestion, the enzymes that are supposed to start that process in the gut are trapped in those ducts and instead of digesting what we eat, they digest the pancreas. So it's damaged severely at a very early age from that scarring. Later on in life we see and find that that scarring actually leads more to diabetic types of issues and that kind of thing.

Dr. Mike Patrick: Sure. And the pancreas is making digestive enzymes as one of its roles and so if you can't break fluid apart and digest it then that's going to lead to issues with nutrition and growth…

18:30

Dr. Karen McCoy: Malabsorption, unusual bowel movements and loss of energy in molecules.

Dr. Mike Patrick: Right. Yeah. Some of these questions, as I was kind of coming up with these, I kind of think back to my training when there wasn't the newborn screen and so you did want to pick these kids up clinically and then test them for cystic fibrosis. What kind of stools are we talking about usually?

Dr. Karen McCoy: Bulky, often described as greasy and fatty and may be described as floating in the toilet because it's lighter than the water.

Dr. Mike Patrick: Yeah. Because if you don't have the digestive enzymes to break down fats so those are going to end up in the stools so you get that greasy.

Dr. Karen McCoy: Along with all your nutrition.

Dr. Mike Patrick: Right. Right. And that's why they don't grow well when they…

Dr. Karen McCoy: Right.

Dr. Mike Patrick: Right. Exactly. What about in the GU tract in males, so there's some talk about infertility in males that have cystic fibrosis, what's happening there?

Dr. Karen McCoy: Well, again, we get back to the epithelial cells in small ducts that are involved in the male reproductive tract and in fact this sometimes becomes an issue even while the child is still developing in utero so that those ducts have sludgy extra heavy mucous that blocks them and then they scar and some of the structures, the vas deferens for example, cannot form at all because of probably very important messaging types of things that don't happen as they should.

20:09

Dr. Mike Patrick: Right. Sure.

Dr. Karen McCoy: And so most males with cystic fibrosis, not all, are infertile and it's not to say that they don't have sperm, they do, they also have normal sexual function, but their sperm cannot get to where they need to be to fertilize an egg. So they turn up if they don't know what's going on they turn up having chagrin about the fact that they can't be a father. In fact, it is possible to extract the sperm, which are normal, and do in vitro or other types of fertilization with those sperms because they function normally, they just can't get to where they need be.

Dr. Mike Patrick: Right. Now, of course they would have an increase risk then of their offspring having cystic fibrosis as well so that's something else for them to consider.

Dr. Karen McCoy: Right. Yes.

Dr. Mike Patrick: Although if it was fertilized with a person who wasn't a carrier then the baby would just be a carrier.

Dr. Karen McCoy: Exactly.

Dr. Mike Patrick: Yeah. Again, back to those Punnett squares.

Dr. Karen McCoy: Yes.

[Laughter]

Dr. Mike Patrick: OK. So we have this set of symptoms and when we kind of walk through disease here on PediaCast we talk about the differential diagnosis, so what other disease could cause this same set of symptoms? And this is kind of a unique set when you look at pulmonary and GI together. So you're seeing frequent lung infections and wheezing, respiratory problems in combination with a kid being malnourished and having stool problems and digestive problems and those things.

Dr. Karen McCoy: Right. And that's of course the full blown thing. A full blown syndrome, we'd often don't get all of those which is why you do need to keep in mind a reasonable differential diagnosis.

22:00

Dr. Mike Patrick: Sure. And kids can have more than one disease too. So you could have a kid with asthma who also has a GI disorder and so that's another place. So what are some of the other diseases just to sort of name a few that could sort of masquerade as a…

Dr. Karen McCoy: Well, since we've talked about things that can be very non-specific symptoms and also occur in kids who are perfectly normal and would just get a fair number of respiratory infections triggered by viruses over the course of a year or two, that has to be kept in mind. Common things that we often say is it this, is it that, or the other, would be things like asthma and maybe allergic rhinitis with some sinus problems, so that would be the top of your list of differentials and actually of course what people think about first.

Dr. Mike Patrick: Right. Yeah. Because it's so common.

Dr. Karen McCoy: It's often that you see somebody diagnosed with that and then it's so not, it's so not, it's so not and finally you get to the real diagnosis.

Dr. Mike Patrick: Right.

Dr. Karen McCoy: Other things would be immunodeficiencies where children either treated for something else or because they are born with some little chink out of their immune armor, would come up with repeated infections and show up in very much the same set of symptoms. There's a disorder you know about called Primary Ciliary Dyskinesia (PCD) where symptoms, again, respiratory symptoms start really early in life and a lot respiratory infections can affect the appetite without the GI tract being completely involved, so those are some of the really common ones that we see.

23:45

Dr. Mike Patrick: Now, my next question was once you have that differential diagnosis and so you're thinking about you have a set of symptoms, you've developed the differential diagnosis, screw traditional medical training, so then you have to kind of weed down well which is it, is it cystic fibrosis or is there something else. So, the newborn screen of course has really surged, as you mentioned changed how a lot of kids with cystic fibrosis get diagnosed, but let's say we're in a state where they don't test for cystic fibrosis or it didn't get done, I suppose you could have a false negative on the newborn screen.

Dr. Karen McCoy: Absolutely. I mean, everything from could they mix up the sample to it just was a bad test. But the other thing you have to keep in mind is that a small number of children with cystic fibrosis would never trigger the test because their pancreases work from the beginning and so they don't actually trip the wire of the IRT or immunoreactive trypsinogen that is the signal that says do the genetic test. So they would be missed and I think one of the reasons why pediatricians need to be even more suspicious and aware of this than ever. Those were the ones who would be getting missed longer before because they didn't have the classic GI nutrition as well as pulmonary respiratory things.

Dr. Mike Patrick: Yeah. I think too with they're being such a strong family history component to this since it's a genetic-based disease, families should know their family history and communicate that with their pediatricians, hey, I've got an aunt or an uncle with cystic fibrosis or a cousin or…

Dr. Karen McCoy: Yeah. You'd think. But I have to tell you that the majority of the times when I've made the diagnosis clinically over the course of my career so far, when I say have you ever had anybody in your family diagnosed with cystic fibrosis or to have this kind of symptom complex, most of the time it's we had no clue. So it really is a surprise to most families.

Dr. Mike Patrick: Yeah. So, let's say a doctor then does have a clinical suspicion for cystic fibrosis even in the light of a negative newborn screening test, you talked about sweat chloride as being sort of the next step in the diagnosis and I suspect that this is kind of the reverse of what we are talking about with the mucous, so in normal sweat production that the chloride would normally be taken out of the sweat, but because that protein is not working that normally moves chloride ions then you're going to have more chlorine in the sweat.

26:22

Dr. Karen McCoy: Right. You do. You'd have more salt in the sweat and you're going to actually lose a lot of sweat and electrolytes that way so that's another clinical threat to these patients.

Dr. Mike Patrick: Sure. And so if you do the sweat chloride then, do you make the diagnosis based on that or do you go on into genetic testing once you have a positive sweat chloride?

Dr. Karen McCoy: Well, it's interesting. The sweat chloride test is a powerful test. It will make a definitive diagnosis of CF in most cases, but nowadays we want the genetics and we'll talk more about that I guess in a minute. We want to know what the genes are to inform the family and for a lot of reasons, but the sweat test is non-invasive, it's quick, you'll have your results by the next day at the latest and if properly done, it either sways you completely away from that and move on to other considerations, reassure a family.

And you'd never want to do a couple of things, you'd never want to just sort of I'm going to do this test and not explain and that needs to be delicately done. It's a very complex issue and people would go on the Internet and get all kinds of crazy ideas and you also want to be sure that people are done at the right time. I really discourage testing in the hospital because people are usually in the hospital because they're sick, may not have the right hydration, maybe they're in PO for test and we get an awful lot of Q&S tests, which then have to be repeated and so it's important to kind of get input as to what's the best way to do this.

28:02

Dr. Mike Patrick: Yeah. I suspect that there are some moms and dads listening right now who are thinking how in the world do you collect sweat.

[Laughter]

Dr. Karen McCoy: OK. So there is an agent called pilocarpine, which induces sweating and it's actually placed on the skin, on the forearm, then the skin is completely cleansed of all surface salt, that doesn't contaminate anything. And then a little watch band type of thing with the micro capillaric tube system is tightly applied and then for about 30 minutes the stimulated sweat is then collected in that tube.

Dr. Mike Patrick: Yeah. Very interesting. I suspect that there are sweat chloride results that you can get that are negative and then there are ones that are definitely positive. Do you get some in grey zone then too or you still even after the sweat chloride test you're not quite sure?

Dr. Karen McCoy: Sure, we actually do get some in the grey zone and we always say did something go wrong with the test, but this is not a definitive answer so we'll then repeat those tests. The grey zone is a little bit movable because it's somewhat age dependent and so we have to have that knowledge as we look at those tests. But they are above 60 collections then they actually are pretty definitively abnormal and most of them come in at about 90 or 100.

Dr. Mike Patrick: Some and then those cases there's no question…

Dr. Karen McCoy: There's no question.

Dr. Mike Patrick: Unless they had salt on the surface.

Dr. Karen McCoy: Right, interesting.

Dr. Mike Patrick: They had the French fries before they came over for the test. So if you do have to move on in the genetic testing, you talked about all the different mutations that can then lead to that abnormal protein because the protein can be abnormal in many number of ways, whether it be physically abnormal or maybe abnormal in a way that it metabolizes energy so it can't work correctly so there are lots of different ones and if you're doing genetic testing there's not just one test, you have to search for each of those mutations. Is that right?

30:15

Dr. Karen McCoy: Well, generally, if we know anything else about the family then that's obviously a leg up. If we had a newborn screen that showed us one gene, but then we couldn't find the other one then we at least know which one we have and that can limit our testing to other things. But then in the worst case scenario, if you send the blood sample and you say look for them all and that takes a little while, just a downside.

Dr. Mike Patrick: Yeah. And probably pretty expensive too.

Dr. Karen McCoy: Cost a little bit.

Dr. Mike Patrick: Little bit.

Dr. Karen McCoy: Yeah.

Dr. Mike Patrick: So, let's say now we're at the point where we're pretty sure a kid does have cystic fibrosis. Are there other studies, whether lab tests, X-rays, I mean what other kind of workup then do you do once you're at that point where you think this is the diagnosis?

Dr. Karen McCoy: So we've made the diagnosis of CF and then we kind of want to know where we're starting from. So ideally, we would like some imaging of the chest to see what damage is already there; we'd like lung functions, of course; we'd like to do a pretty complete nutritional panel to make sure that they're not needy in terms of certain specific vitamins that tend to be affected by the lack of enzymes from the pancreas. And then we do things to say, hey, is your liver OK, how are your kidneys working? Because those things are going to be impacted by treatment.

Dr. Mike Patrick: Sure. So you get a kind of a baseline function of those organs.

Dr. Karen McCoy: Uh-huh. Yeah.

Dr. Mike Patrick: So then what do we do to treat cystic fibrosis?

Dr. Karen McCoy: Well, there are two complicated, but really simple mainstays of therapy for cystic fibrosis. The first addresses nutrition to make sure that all of the fat soluble vitamins and just the general nutritional health, we'd like these kids to be at the 50th percentile for BMI or weight for length and not below that. And also those specific things that might be missing we attend to.

Dr. Mike Patrick: Sure

32:19

Dr. Karen McCoy: And it's interesting to notice that the strongest correlation between survival and good lung function for people with cystic fibrosis is nutrition.

Dr. Mike Patrick: You really want their immune system to be able to be top-notch working great and of course it needs substrate for the immune system to work, so you really want that.

Dr. Karen McCoy: Absolutely. Right. So the other is taking care of those lungs. We want those boys to last as long as possible and it really is a matter of trying to figure out all the different ways that we can aid the problem that they have with clearing mucous. And daily clearance several times a day is one of the biggest things that we do for cystic fibrosis. Yes, we periodically treat with antibiotics and sort of clean up the system, but we really feel like getting the mucous a way out that gets around the basic problem in cystic fibrosis lung infections is the best way to go.

Dr. Mike Patrick: And how do you do that? How do you get the mucous out?

33:24

Dr. Karen McCoy: Well, we start with, in the very young child, we teach the parents how to pat on their chest and basically do chest drainage appropriate to each lung lobe. And I do that a couple of times a day and we start it very young because if they've grown up with it it's sort of like they accept it. Try teaching that to a two-year old and they're against everything. And so we start them out that way and then when their chests get to a big enough size, which is if they're growing well usually by their second birthday if not before. Then we can use the thing called the therapy vest or one of those automated vest that encircles the thorax and upper abdomen and has little percussors to take the place of parents at all of the lung lobes.

Dr. Mike Patrick: Sure.

Dr. Karen McCoy: So then we shake it up and then they've got to clear it.

Dr. Mike Patrick: So in terms of the chest physical therapy you are really hitting the chest to try to vibrate to loosen up that mucous mechanically from the outside.

Dr. Karen McCoy: Exactly. Uh-huh.

Dr. Mike Patrick: Is that pretty well tolerated?

Dr. Karen McCoy: Very well tolerated.

Dr. Mike Patrick: I mean, kids don't get bruises or have any, you know hitting them hard.

34:35

Dr. Karen McCoy: No. No. I mean, it's a good whack, but it's amazing that kids actually ask for harder.

Dr. Mike Patrick: Because they feel it's going to help clear that mucous up.

Dr. Karen McCoy: Exactly.

Dr. Mike Patrick: Yeah. Let's kind of move in to sort of what complications you can see with cystic fibrosis because then I guess that extends how the rest of the treatment goes.

Dr. Karen McCoy: Well, complications come in a lot of jars for cystic fibrosis, I mean, complications of the disease are paramount because if we don't take good care of those lungs then you'd lose lung functions deadly over the course of your lifetime. And then lifetime will be significantly shorter than the usual U.S. citizen.

Dr. Mike Patrick: Right.

Dr. Karen McCoy: And that, as I said, is about 90 plus percent of the time is what shortens life for people with cystic fibrosis. We treat that infection and sometimes you have to treat it very aggressively with pretty strong antibiotics. So one type of complication would be that we use medicines that can have their own toxicities and we have to be very surveillant for that.

Dr. Mike Patrick: Right. How often would you say kids with cystic fibrosis sort of on average need to be on antibiotics.

Dr. Karen McCoy: There's not a formula for that. I mean, really if people are able to clear well and have some luck then sometimes it's years. On the other hand, you get a virus and your bacterial lung infection flares up, then you may have two or three in a winter time.

Dr. Mike Patrick: Sure. What about bronchodilators, like you would treat asthma with Albuterol that sort of thing, is there a rule in that when treating cystic fibrosis?

36:24

Dr. Karen McCoy: It's used. We use it pretty consistently. Again, if you try to wait until somebody is five years old and they started to have symptoms and you try to introduce a lot of new therapies, it's not taken very well.

Dr. Mike Patrick: Yeah.

Dr. Karen McCoy: So we start them off really early in life feeling like at the very least that may help their cilia work.

Dr. Mike Patrick: Sure. And increase the diameter of the airways so that if there is mucous clogging it up it's less of an issue because you're relaxing the smooth muscles in the airways.

Dr. Karen McCoy: That's the hope. Yeah.

Dr. Mike Patrick: Yeah. What about steroids?

Dr. Karen McCoy: Steroids do have a use in cystic fibrosis, sometimes we get a particular problem such as allergic bronchopulmonary aspergillosis where the airways are actually inflamed and allergic to a common fungus and they're a specific therapy for that. And then in some situations, they do have asthma and it needs to be treated in the standard way you treat asthma with corticosteroids. Inhaled corticosteroids for cystic fibrosis per say, not so much. But the people who have CF and asthma, this has been proven, will benefit by those.

Dr. Mike Patrick: Sure. And of course, steroids, especially when taken by mouth or through an IV, do also decrease your immune system's ability to fight infections so then you might be at an increase risk for pneumonia if you do those too much. So, kind of a double edged sword.

37:52

Dr. Karen McCoy: It is.

Dr. Mike Patrick: Yeah. What about on the GI front? What kind of complications can you see there with cystic fibrosis?

Dr. Karen McCoy: Well, I've already mentioned the long-term outcome of pancreatic scarring might be to develop CF-related diabetes so that's something that we kind of expect in the second decade of life. And so we screen kids starting at about 10 years of age for glucose tolerance because you can get behind it, the 8-ball, nutritionally so fast if that starts to be operational.

Dr. Mike Patrick: Right. And that affects your immune system as well then if you have uncontrolled diabetes.

Dr. Karen McCoy: Absolutely. Another issue is that the liver's another one of those epithelial organs has duct and that sort of thing and if they are clogged up you get a sort of a hepatitis and in a small number of people with cystic fibrosis you can actually develop cirrhosis. So, we're pretty surveillant about the liver.

Dr. Mike Patrick: Sure.

Dr. Karen McCoy: The intestinal tract itself is technically normal, but because one of the unsung heroes of the pancreatic function is that the pancreas puts a lot of water in the intestine which does not happen for people with cystic fibrosis. So they can actually easily develop dehydration in the intestines and turn that into serious constipation or even a bowel blockage.

Dr. Mike Patrick: Right. And that's one of the things, we would do, we didn't mention, but with babies sometimes they present that way with the bowel obstruction and then ends up being cystic fibrosis, that's the issue.

Dr. Karen McCoy: Correct.

39:29

Dr. Mike Patrick: I also want to go back to the lungs real quick. What about lung transplant?

Dr. Karen McCoy: Well, I think it's a good idea if you're the right candidate and have gotten to the in-stage of your lung disease. We know that there are a steadily increase in number of lung transplants that are performed for cystic fibrosis. They tend to be the more successful lung transplants compared to other disease processes such as pulmonary fibrosis or COPD and things like that in the standard adult patient.

Dr. Mike Patrick: Right.

Dr. Karen McCoy: So, we definitely planned for that and have some criteria for when we start talking with people about maybe we should do this a priority before it becomes a critical issue and some people then say, you know it's not for me. They may have a variety of reasons for that and we respect that. If they are interested and the right kind of candidate, in other words they've done their basic therapy so we know that they would take the medications that are absolutely essential to support the transplant then we move ahead and get them prepared.

Dr. Mike Patrick: Sure. And this would be both lungs. We couldn't just transplant one.

40:43

Dr. Karen McCoy: Generally, that's what's taught. There've been a few little experimentations with single lung transplants in CF, but you tend to think well there's this bag of infection on this side and then there's just one over here that were immuno-suppresing to keep and that really sets you up for having infection move in to the new lung.

Dr. Mike Patrick: Sure. Is there any way to, when you have a kid with cystic fibrosis and you're thinking about lung transplant, I would imagine that there are certain centers, they have more experience doing that. And we've been doing those here at Nationwide Children's, correct?

Dr. Karen McCoy: Yes. We have been doing them and it's always a very patient specific decision because there are times when we're considering more than one transplant. We may have a person who has cirrhosis and has lung failure and they may need those two organs in which case you have to pick the best center for the particular application and so we do that. And then fight with insurance and things like that.

Dr. Mike Patrick: Yeah. Yeah. Yeah. Because it may not always be in the insurance company's local area.

Dr. Karen McCoy: Right.

Dr. Mike Patrick: Or they may just deny it because they want to deny it.

Dr. Karen McCoy: I've had it denied because they think it's experimental which definitely is not.

42:00

Dr. Mike Patrick: All right. So what is the long-term outlook for kids with cystic fibrosis in terms of quality of life and life expectancy? What can folks plan for?

Dr. Karen McCoy: Well, with good care we have seen a steady incline or increase in the projected meeting survival which is now just under 40 years of age for the whole population. We have patients that are in their mid-60s that we follow at Nationwide.

Dr. Mike Patrick: Wow!

Dr. Karen McCoy: I'd say that in most centers, combined adult pediatric centers right now, it's almost even Steven for how many pediatric under 18 patients you have and those that are above 18.

Dr. Mike Patrick: And back in the 1950s, most of these kids died before grade school, really. I mean it was pretty universal that kid would die from it. And I remember when I was training back in the early 90s the trend at that point was kind of into the 20s. We've made quite a bit of progress with life expectancy.

43:12

Dr. Karen McCoy: And there have been a lot of things that have supported that. You mentioned one of my activities is director of this translational center and I think the Cystic Fibrosis Foundation has done absolutely superb and model-worthy job of marshalling their resources, having centers that are set up to do research so that you can compare what happens at one place to another and actually derive information from the date. And I think that that has been a critical part of saying we've got this new candidate drug, see what it does in people. And having really, really compelling studies that are done very, very quickly by this group. So that's extremely neat.

Dr. Mike Patrick: Yeah. Absolutely. And then in terms of sort of quality of life, these are kids who are going to see their pulmonologist a lot. I mean, they're like your kids.

[Laughter]

Dr. Karen McCoy: Yeah.

Dr. Mike Patrick: Frequent doctor visits and it's going to impact pretty much every level of their life. With the Cystic Fibrosis Center here at Nationwide Children's I suspect then that educational, social work, behavioral, I mean that all is an important component to treating cystic fibrosis as well as just the medical part.

44:30

Dr. Karen McCoy: Another area where cystic fibrosis has really seen the vision up ahead is that we've been practicing this multidisciplinary model of care for many, many years. And now I see other disease processes starting to emulate that and it's really made a lot of difference. But yeah, it is a life differing type of thing which we hope that people, as much as humanly possible, take in stride, make the best of it and stay healthy because we are right now on the cuss with finding some almost curative therapies. We have one recently FDA approved drug which is about 5% of the CF population actually changes everything. They get their appetite back, their lung function goes up. They have less need for therapy and believe it or not, their sweat tests normalized.

Dr. Mike Patrick: Wow!

Dr. Karen McCoy: So it's like a pill that's taken in and goes all over the body and makes those CFTRs behave better.

Dr. Mike Patrick: And of course whether you respond to that particular drug or not depends on what exact mutation and what abnormal protein that you have.

Dr. Karen McCoy: Exactly.

45:42

Dr. Mike Patrick: What about a genetic cure? Is there a way to change the genetic code?

Dr. Karen McCoy: We keep trying. I think that it was 1999 when the gene, delta-F508, that the most common one was discovered by scientists that worth being supported by the CF Foundation and I think one of the fears that all of us had at that point was, hey, what if they just work on that and it doesn't turn out to be. Well it hasn't really panned out, it's not a totally moot point at this time, but it really hasn't yet born any fruit to speak of. So again, I have to give credit that the leadership at the CF Foundation was able to say, let's diversify; let's look at every line of therapy, whether it's nutritional, antibiotic, genetic, etc. and that's where we've gotten to this actually genetic style therapies.

One of the most exciting things for me is that 88% to 90% of the CF population carries at least one delta-F598 gene. It's that 90% of people with CF. And we currently are working on two drugs that might do that same thing to the CFTR or that they already one thus for its genetic target.

Dr. Mike Patrick: Wow! That's amazing.

47:12

Dr. Karen McCoy: So that would just effectively put me out of business and it's a business that I would gladly say I'd rather have them cured.

Dr. Mike Patrick: Yeah. Absolutely. Absolutely. The cystic fibrosis program here in Nationwide Children's is a nationally ranked program and folks who would want, maybe things aren't happening, some more complicated child or they want a second opinion or they just want to come and see you, is that possible?

Dr. Karen McCoy: Oh yeah. Yes. We take parent referrals for cystic fibrosis. We never tried to get between a child and their pediatrician or their specialist, but if parents decide that they would like to come get a second opinion, I think all of us in the CF world are very comfortable having our patients go and say, is the grass greener, can I learn something different; is it just a better personality match for me?

Dr. Mike Patrick: Right. And we'll have links in the Show Notes so people know how to contact the Cystic Fibrosis Program here at Nationwide Children's if parents are interested in doing that. We'll also put a link to the Cystic Fibrosis Foundation as you mentioned they've done a lot of great work and with parents aren't familiar with them we'll put a link in the Show Notes to their site as well.

All right. Well I really appreciate you stopping by and taking the time to talk about cystic fibrosis today. I really appreciate it.

Dr. Karen McCoy: Glad to be here.

48:39

Dr. Mike Patrick: I want to thank Dr. Karen McCoy. Also thank you, all the listeners out there for taking time out of your day to make PediaCast a part of it. I just want to remind you that iTunes reviews are helpful as our links on your webpages and mentions in your blogs, on Facebook and your tweets and on Google+. Be sure to join our community by liking PediaCast on Facebook. You can also follow us on Twitter and hang out with us over on Google+.

Be sure to swing by the Show Notes at pediacast.org to add your comments on today's show. And of course we also appreciate you telling your family, friends and neighbors about PediaCast. Don't forget to tell your doctor about the show next time you're in for a sick office visit or well child check-up. Just let them know, hey, we found this great evidence-based podcast from Nationwide Children's and you should tell all the other patients about it.

We also have posters that you can download and hang up. You can find them under the Resources tab at pediacast.org. Once again, if there's a topic that you'd like us to talk about or you have a comment for the program, just head over to pediacast.org and click on the Contact link. You can also email pediacast@gmail.com or call the voice line at 347-404-KIDS. That's 347-404-K-I-D-S.

And until next time, this is Dr. Mike saying stay safe, stay healthy and stay involved with your kids. So long everybody.

[Music]

Announcer 2: This program is a production of Nationwide Children's. Thanks for listening. We'll see you next time on PediaCast.

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