Interview with Dr. Dennis Nielson and Martha Richards: Advances in Cystic Fibrosis Care

Dennis Nielson

Photos by Tom Seawell.

Audio Interview

Hear an interview with Dr. Dennis Nielson, a pulmonologist and director of the UCSF Pediatric Cystic Fibrosis Center and nurse practitioner Martha Richards talk about the latest advances in cystic fibrosis. You can also view a video about three young patients living with CF.

Understanding Cystic Fibrosis

Interview Transcript

Andrew Schorr:

What is the latest in the treatment and research for cystic fibrosis (CF)? We'll hear more coming up next on Patient Power.

Hello and welcome to Patient Power sponsored by UCSF Medical Center. I'm Andrew Schorr.

Cystic fibrosis is certainly a life-threatening, life-shortening condition, but we've made tremendous progress in this genetic disease. Now to help us understand more about it is the Director of the UCSF Cystic Fibrosis Center, Dr. Dennis Nielson. Dr. Nielson, I understand that your center is one of the really oldest in the country, and happily now you have adult patients, many of them, as well as children. People are living longer. Tell us about the center and how we're making progress in cystic fibrosis.

Dr. Nielson:

Well, thank you for having me on the show. Cystic fibrosis has changed dramatically over the years, not the basic disease but the outcomes, the treatments, and everything is much, much better than it used to be. We follow close to a couple of hundred patients here at UCSF. Half of our patients now areare over the age of 18, so we consider half of our surviving patients as adults.

Not only are they living longer but they're living better. Their lung function, their nutritional state, everything about them has improved over the years.

Andrew Schorr:

Help us understand. Cystic fibrosis, as I said, is genetic, so newborn screening can identify it. And then what are the symptoms that develop?

Dr. Nielson:

Well, prenatal testing and newborn screening both have been used to identify it. Even though it's not mandated by law, these days I think most women actually choose to be screened for genetic disorders during pregnancy. That will allow one to identify moms who are carriers of some of the common CF mutations, that actually has been a source of identification. And if a pregnant woman comes up positive then oftentimes there's screening of her partner, and if you have an at-risk couple then the baby is screened, and we routinely now, not frequently, but routinely once or twice a year we'll actually see a woman during pregnancy to talk about her CF baby and what to expect.

The newborn screening in California is required by law, so all babies are screened for it now. It's part of the newborn screening where after your baby is born they come in and they prick the baby's heel and they collect some blood spots on a little card, then they send that off to the state to screen for a lot of different disorders, but cystic fibrosis is on that list.

Now we're seeing routinely a number of babies every year that are suspected of being at risk for cystic fibrosis. The way the screen works in California, if you have a positive screen then there's about a one-in-four chance that your child has CF. And a screen is a screen. It isn't a diagnostic test. It tells you that there's risk. There are some of the screens that are positive in a way that we're quite sure when the family comes in that the baby has classic cystic fibrosis, but for every baby that we see that is in that category we see almost three babies who have something else, whether it's some risk for problems, but not for classic cystic fibrosis. This is an area that's presented us with some new challenges and some new opportunities to prevent disease, actually.

Andrew Schorr:

And help us understand the disease. When it is cystic fibrosis, as it develops what's happening? I understand it deals with thick mucus in the lungs and infection, and these were conditions that used to cause an early demise, but as you were saying now people are living much longer.

Dr. Nielson:

Well, the paradigm of sticky mucus still holds in cystic fibrosis. We understand a lot more about what that means and the other implications of that. But basically what happens is mucus in the lungs and secretions in the pancreas tend to be deficient in water and salt, and that makes them sticky, and this tends to then lead to plugging of the airways. It's the lung disease that really is the life-threatening, life-shortening problem.

The pancreas is an organ that secretes insulin, but it also secretes enzymes into the intestinal tract, and it's there where the pancreatic ducts become plugged because of these thick, sticky secretions, and then the pancreatic enzymes, the digestive enzymes aren't delivered appropriately to the intestine so that in the old days before newborn screening most of our babies presented with poor growth. And that is a problem that we can treat. We've been able to treat it for years by just giving enzymes in the form of a pill or little micro granules with every feeding for the babies, and that corrects that problem.

The lung problems have been much more difficult because you do get mucus plugging of airways. You also get a secondary infection that is related to CF, and we're still trying to sort out exactly how it's related. But it does lead to chronic lung infections that gradually eat away at the airways in the chest and that causes a type of chronic bronchitis, what we call bronchiectasis, which just means that the supporting tissues around the airways are gradually destroyed, and you get these lungs that are trapping air, that are full of infected secretions, and that then untreated leads to a very early death.

Living Longer and Better with Cystic Fibrosis

Andrew Schorr:

All right. You used the word "untreated," but in recent years you have treatments, and even in the last year you have a treatment for the underlying disease that's helping a lot of people. Help us understand where we are now and what's enabling people to live longer and live better.

Dr. Nielson:

Well, before this most recent development what's happened over the years when survival has gone from 18 years median survival in 1980 to 38 years in the last few years, what's happened has been basically a better understanding of the disease process and how one can impact it with aggressive medical care. Up until this recent breakthrough therapy, what we've been confined to is using lots and lots of antibiotics, doing things to try to loosen up the mucus, which includes things like inhaling very salty solutions from a nebulizer, inhaling antibiotics, inhaling an enzyme that breaks down DNA from dead bacteria and from white cells in the lungs that are part of the mucus in CF, doing a lot of manipulations to try to move the mucus out of the lungs, what we call chest physiotherapy. For that we have a lot of different devices that have been developed over the years like the high-frequency vibrating vests, a number of other things.

All of those things have resulted in small steps adding up to a very large change in survival over the last 30 years, so this has been a fantastic thing to see happen once you look back. So that's really the sort of the past.

What we've seen this year is that for a small group of CF patients there's a drug that has been tested and approved that actually changes and improves the function of the CF protein. The CF protein is a chloride channel in cell membranes in the lungs. It's in the upper membrane of the lining tissue of the lung, and what happens in CF, this channel is either absent or not very functional. And we've discovered a drug — when I say "we" I mean the world, and people who have worked very hard in this area have discovered a drug that's now approved, that if you can get the channel into the cell membrane you can actually turn it on and make it function more normally.

That turns out to be very useful in about five percent of CF patients, and it's actually in many ways a transformative therapy. We saw in the clinical trials that the risk of hospitalization went way down in patients who were taking the drug. One of the diagnostic tests called the sweat test, measures chloride concentration in sweat that became nearly normal in many of the patients who are on this drug.

Andrew Schorr:

And the drug is called Kalydeco (ivacaftor), I understand

.

Dr. Nielson:

Yes. The brand name is Kalydeco (ivacaftor), and it's the only one of its kind currently on the market or in the world. But it changed the sweat test, which — people in general or rarely die of the complications of CF that affect the sweat glands, but it's a physiologic change that is reflected in the lungs and in other parts of the body, and the impact of actually improving the CF channel function has had very dramatic impact so far on these patients.

Expanding the Benefits of Drug Therapy to More Patients

Andrew Schorr:

Doctor, people who are not in the genetic category, who are treated by that drug are saying, well, you said at the outset it helps a small group of patients. What about everybody else? Where are we now with research, and I know your center is a research center. Where are we now in trying to expand the benefits with that drug or other drugs to more patients?

Dr. Nielson:

Well, people are making progress, and there are some other drugs in clinical trials that may have some benefit. At this point I don't know how effective they will be. One hopes that they will be very effective; however, looking at the initial clinical results I don't think they're going to be as dramatic as Kalydeco (ivacaftor) in this one small group. Kalydeco (ivacaftor) works on proteins that actually make it into the cell protein, and it appears to be specific to the CF protein, but it doesn't seem to care much about which mutation you have. All of the studies done, bench studies, if you can get that protein into the cell membrane this drug will turn it on. It will force it to spend more time open, and by forcing it to spend more time open then the salt and water move more normally across the cell membrane.

The problem for the most common mutations in CF is that the protein just isn't there. It doesn't make it into the cell membrane, and that's been a much more difficult challenge, trying to find a drug that will sort of chaperone that protein through the cell and allow it to be inserted into the cell membrane, and that's been much harder to find a compound that does that efficiently.

Andrew Schorr:

But work goes on at centers such as yours, and if someone is a patient, there may be a clinical trial at some point where you discuss with the family or the patient themselves participating in such research, right?

Dr. Nielson:

Absolutely. There are two trials going on now with combinations or two general groups with two different what we call correctors, the drugs that move the protein through the cell, combined with Kalydeco (ivacaftor) that would then turn on whatever makes it through the cell. And that's where the next breakthrough will come is when we find a corrector that will increase the amount of the protein in the cell membrane enough that then this drug Kalydeco (ivacaftor), or whatever other drugs like it come in the future, will allow them to do their job and actually turn it on.

There are some in our field who feel like we might actually need a third drug, that you might actually have to correct the protein production in two different parts of the intracellular manufacture of these proteins to actually efficiently increase the amount of protein that makes it into the cell membrane.

Cystic Fibrosis Research Centers

Andrew Schorr:

Dr. Nielson, we'll talk to your nurse practitioner in just a minute, Martha Richards, but I wanted to get your perspective. You obviously are the Director of the UCSF Cystic Fibrosis Center and have worked for years, with a very vibrant, skilled team. What do you think makes your center special, if you will, and if a family is affected by CF that at least if they're in your area it would be a wise choice?

Dr. Nielson:

Well, I would say we have a very dedicated team. We have people who have a lot of experience with cystic fibrosis, and we all feel very engaged with our patients and their families. I know that at all CF centers around the country people are engaged. They care about their patients or they wouldn't do this because the financial rewards are really not great. The biggest rewards that we have are the interactions and the things that we see happen with our patients.

I mean, if we look back over the years and see this transformation in outcomes where CF used to be something that was greatly feared when you first made the diagnosis, and now we think of it more in terms of a chronic illness rather than a fatal disease, it's a very different perspective. We get to know our patients very well. We know them as people. We try to treat whole families. We've worked very hard to make sure that our clinical outcomes are as good as they can possibly be. We've made progress in that over the year, so we're very proud of what we do here and the improvements that we've seen in our work and the work nationally. There are many good CF centers around, but certainly we feel like we're one of them, and we certainly have a long, long history in the world of cystic fibrosis care.

Andrew Schorr:

Yes, you do. Dr. Nielson, one other question for you. People who are affected by this condition use someone like yourself, a renowned expert, as sort of a barometer of how things are going. From what you've seen recently and your sense of where things are headed, what would you say to them to give families hope?

Dr. Nielson:

Well, these days most of our patients come in through the newborn screening program, and part of those first talks, discussions that we have with them in addition to educating them about CF and CF care, we also talk about the fact that their expectation should be that their child will make it to high school, graduate, go to college, that they'll fall in love, that their life in most ways will be pretty much the way it would have been without the cystic fibrosis, and that we have this thing that we call CF that we need to work on together, and that we're there to help them and support them through that, but that they shouldn't give up those other dreams. If they thought their son or daughter was going to be a future president or athlete — we have a number of excellent athletes among our kids in CF — those dreams don't have to go away, and that they're all part of routine living with CF now.

CF care is a lot of work. You can spend hours every day taking care of yourself, but with the tools that we have now and with the tools that we expect to have in the future, the expectation should be that their lives in most ways should be what they were going to be before they had this diagnosis.

Andrew Schorr:

Dr. Dennis Nielson, Director of the UCSF Cystic Fibrosis Center in San Francisco, I want to thank you for your devotion to patients and families, and thank you for being with us today.

Dr. Nielson:

Well, thank you, and it's my pleasure.

Cystic Fibrosis Help and Support

Martha Richards

Andrew Schorr:

Also joining us today is Martha Richards. Martha is nurse practitioner at the UCSF Cystic Fibrosis Center, primarily works with children and parents.

Martha, the doctor has explained about the disease and the treatments and the research, but it's still a heavy load for a family to deal with or even someone who is dealing with it as a young adult or an adult. How do you work with patients and families at the center to support them so that they can have the highest possible quality of life?

Martha Richards:

Well, my role is really the Pediatrics CF Center Coordinator, so I make sure that they get the lab tests that they need and coordinate those kinds of things so that they stay on track with different tests and so on that they need.

But the other thing that I focus on — two major things, I would say. One is support of parents of the young children when they are diagnosed and throughout their child's life, really, until they graduate on to the adult program. I help provide a lot of support for the parents. The parents, even when their children are doing very well, their lung function is excellent and they're healthy and their weight is good and they're active, parents still are anxious and they're worried, as any parent would be, and so I provide a lot of support for them and am available to talk with them and help them work through different fears or concerns that they have about their child's future and their child's health.

And the other big part of it is education, the education of the parents and other adults in the child's life but also education of the children. And we believe that if children understand about their disease and what the medications do and why we're doing them, that they actually will be more invested in actually doing the treatments that they need to do, and then when they get to be adults they'll be ready to take on their own care when they go to college, when their parents aren't around anymore.

And we actually have developed in our center a developmental approach so that we start at age eight and every couple of years we have a different set of goals for them, questions for them to answer, things for them to learn, and it proceeds in a developmental way and actually goes all the way up to age 21. We're hoping that by the time they're 18 to 21 they're really ready to take on their own medical care and that they understand why and therefore will be just way more invested in doing their own treatments and keeping themselves healthy.

As you know, it's hard for young people, especially adolescents to do all these things they need to do. They want to have a social life, they want to be in sports, and they need to spend a fair amount of time every day taking care of their health, it takes a lot of education and support.

Andrew Schorr:

A key devotion of yours at the center and some of your colleagues is to help…

Martha Richards:

Right. Mine and my colleagues. We have a dietician. We have a social worker. We have a respiratory therapist. All these people do their part in teaching and talking to patients and their families.

Andrew Schorr:

Martha, you are very devoted to helping parents and children understand that there can be a future with CF.

Martha Richards:

Right. And of course they have a future. I mean, when I started, which was a little over 20 years ago, working with children with CF we didn't have the medications and treatments we have available now. Things started coming in the 90s, I would say. By the end of the 90s we had an inhaled antibiotic, which was revolutionary. We had medications that would help loosen the mucus. We had better ways of helping children clear the mucus out of their lungs. All these things have come along, and when I first began our patients, our children — we had patients who died every year. Now it's rare, extremely rare for a child to die of CF. Our patients, they all graduate up to the adult center, and they go on to have careers and active lives.

Andrew Schorr:

Just to sum up then for perhaps new parents listening or new patients, you feel hopeful for them, positive for them?

Martha Richards:

I feel more hopeful than I've ever felt, and I think that's partly because of this new drug, the Kalydeco (ivacaftor), because now the research is really focusing on targeting the gene and trying to fix what's wrong with it, and that's amazing. That's a really terrific avenue of research. But I also feel hopeful, now we say when our babies come in and they are diagnosed, basically you have a healthy, normal child who happens to have cystic fibrosis. There are things we need to do. We're very aggressive, and we want the parents to be because that's how we get healthy kids and healthy adults. But we expect them to have basically normal lives. That's what we want for them and that's what we expect for them.

Andrew Schorr:

Nurse Practitioner Martha Richards from the UCSF Cystic Fibrosis Center, thank you so much for all you do and your devotion to patients.

Martha Richards:

Thank you so much for having us.

Andrew Schorr:

I'm Andrew Schorr. Thank you for joining us. And remember, knowledge can be the best medicine of all.

 

Reviewed by health care specialists at UCSF Benioff Children's Hospital.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.

Related Information

UCSF Clinics & Centers

Cystic Fibrosis Center
1825 Fourth St., Sixth Floor
San Francisco, CA 94158
Appointments: (415) 353-7337
Office: (415) 476-2072
Fax: (415) 476-9278