ASSOCIATE PROFESSOR HUICHUAN LAI MS’90 PhD’94 began exploring the link between nutrition and cystic fibrosis in 1994, when she spent a year working in UW-Madison’s pediatric pulmonary center. A registered dietitian trained in biostatistics, she has spent much of her career scouring epidemiological data for trends that explain how diet affects the health and longevity of children with the genetic disorder. Her work led the national Cystic Fibrosis Foundation in 2005 to rewrite its nutritional guidelines, a move that is contributing to a heartening trend toward better nutrition and increased life expectancy among CF patients.
What causes cystic fibrosis?
The basic defect is in the gene that encodes a transport protein for chloride. It affects almost all organs in the body, but the clinical manifestation is primarily in the lungs and in the digestive system. The classic presentation for undiagnosed CF is failure to thrive, meaning that kids don’t grow as they normally would. Because of the problem in the digestive system, they can’t absorb fat, and fat contains a lot of energy. The lung involvement does not manifest until a little bit later in life, and most patients end up dying from respiratory complications.
What can doctors do?
Because the lung disease is what causes mortality, the treatment now is really focused on that part of it. But there are many anecdotal observations, small studies, that show that if patients preserve good nutritional status the lung disease will progress more slowly. Over the last 10 years more and more emphasis has been placed on treating malnutrition, with the hope that you can slow down lung disease. And nutrition treatments have lengthened survival dramatically. The median age of survival is beyond 40 now. Three decades ago it used to be less than 10.
How is nutritional status measured in these patients?
It’s important to define optimal nutritional status in CF patients because nutrition has such a big impact on lung disease, quality of life and survival, and that’s what my research focuses on.
So the Cystic Fibrosis Foundation publishes clinical practice guidelines—the first one was done in 1992, and then it was updated in 2002 and again in 2005. The guidelines traditionally have been based on how close a patient’s weight is to an ideal standard. So when a patient comes to the clinic, doctors will try to calculate the patient’s ideal weight, and then they will take their actual weight as a percentage of ideal weight. If the result is above 90 percent, they say, “That’s fine. Let’s keep watching.” If it’s below 90 percent, they do something about it. One of my major contributions to the field is that I proved this percentage of ideal body weight guideline is faulty. It’s only correct for children of average stature.
What was wrong with it?
At the extremes (of height), the ideal body weights are wrong. If the patient is short, for instance, the ideal weight is underestimated. So when you do the calculation for a short child, a doctor is more likely to think a child is fine, when in fact he is too thin.
How did you figure this out?
I didn’t just discover it. I was motivated by questions coming from the clinic. I work with dietitians and pulmonologists a lot, and this question was brought by a dietitian who was using this index in the clinic. She had calculated the ideal weight for a child who was particularly short, and it just didn’t seem right to her. She said, “This child is not supposed to be at this weight. It would be too low.”
I also heard about problems with tall patients, where the dietitian would say, “I can’t increase his weight to that level, I think it’s way too high. Why is that the standard?” It’s not only frustrating. It doesn’t make sense to them.
So these comments motivated me to look into whether there was anything wrong with the definition of this parameter. That is how I got started.
What happened after you found the flaw?
When I first presented it at the annual CFF meeting, people were really skeptical because that parameter had been used for decades. I was trying to prove my point, but explaining my statistical methods to the clinical community was really difficult because my proof involved really complex mathematics. Some of them got it and believed it, but some of them really didn’t. After this, I realized I needed to give practical examples, specific patient examples, to help convince people.
Eventually, the CFF convened a consensus committee to revise the guideline. I was on that committee. So we dropped that (faulty) parameter in 2005, and CF centers started using the new guideline, which is based on body mass index, after that.
What are some of the outcomes of adopting this new guideline?
There are 115 Cystic Fibrosis Centers around the nation, and each year the CFF publishes annual reports where they rank CF centers in terms of key parameters. In these reports they calculate the percentage of patients that are in nutritional failure, and so clinics do their best to improve patients’ nutritional status so that they won’t be counted as nutritional failures. After the CFF adopted the new guideline, one-third of the centers ended up changing their rankings on this parameter. Originally the UW’s Cystic Fibrosis Center was in the middle, but with the new guideline we moved to the top quartile, something that affirms the benefits of the newborn screening for CF that we do here.
More recently, I’ve been working on the CFF’s height parameter in the guidelines. I came up with a new method that is more accurate. It’s a little bit more complicated than the original CFF method, but it’s simple enough for use in the clinic. It’ll be interesting to see if this parameter gets adopted what kind of impact it will have on rankings.
Does the CFF ever see you as a troublemaker, looking for problems with their guidelines the way you do?
Sometimes they do, I think. But it’s important to work within the system because the CFF facilitates so much in terms of translating research into care. If an individual researcher is promoting their findings to the clinical community, it is not very effective in my experience. It’s better when the CFF acts as a liaison to get the word out and uses research findings to update clinical guidelines.
What’s next for you? Another guideline to debunk?
We are developing a separate set of nutritional status parameters for adolescents. Right now, the child guidelines are supposed to cover them, but adolescent growth is so different from pre-adolescent because they go through growth spurts, where they’ll grow four centimeters a year for two years in a row. So the classical growth charts do not apply during that time. This is also the period when patient lung function declines the most, and there has got to be some relationship between nutrition, growth and lung function that is unique to this period. That’s what I’m working on now.