Researchers gain insights on pulmonary fibrosis

DURHAM, N.C. -- By studying the genetics of the rarer familial form of pulmonary fibrosis, Duke University Medical Center researchers hope to gain broader insights into the more common forms of this devastating lung disease, which claims the lives of half its sufferers within five years.

In the largest U.S. study of families in which more than one member has been diagnosed with the disease, the researchers have determined that it appears to strike patients at a younger age (average age at diagnosis is 58), and that it predominantly affects Caucasians (92 percent).

The researchers believe that, like most diseases, the cause of pulmonary fibrosis will likely be a complex interplay between susceptibility genes and environmental factors, such as inhaled agents or dusts. While the researchers have yet to pinpoint a gene or genes for the disease, they say the key to unlocking the cause or causes will come from sophisticated analysis of large numbers of affected families.

To date, the researchers have complete genetic and clinical information on 125 affected members of 38 families; 68 more families are in various stages of analysis. The researchers are continuing to look for eligible participants.

The results of the team's study of the first 38 families were prepared for presentation Friday in a poster session during the International Congress of Human Genetics in Vienna, Austria.

Pulmonary fibrosis occurs when the thin layer of tissue around the lung's alveoli -- the tiny air sacs where gases are exchanged with the blood -- becomes damaged. The resulting scar tissue limits the lung's ability to take in oxygen and get rid of carbon dioxide. There are many forms of the disease, with the familial form estimated to make up 5 percent to 10 percent of all pulmonary fibrosis cases.

"This is the only ongoing program in the U.S. that is systematically studying the genetic basis of pulmonary fibrosis," said Duke pulmonologist Dr. David Schwartz, who leads a team of researchers from Duke, the National Jewish Medical Center in Denver and Vanderbilt University Medical Center in Nashville, in this National Institutes of Health-funded study.

"It is our belief that if we can understand the familial form of the disease, we can make great inroads in understanding why and how people get the other forms of this devastating disease," Schwartz said. "Once we get a better handle on the complex cascade of events that leads to the fibrosis, we should be able to devise appropriate interventions or determine when the actual disease process begins and stop it."

Other findings of the study include:

• Smoking was identified in 51 percent of cases;
• Exposure to environmental agents known to cause fibrosis, such as asbestos, silica or wood dust, was identified in 22 percent of cases; and
• Average age of diagnosis was 58 and average age of death was 61.

"In rare diseases like familial pulmonary fibrosis, it can be a real struggle to find patients," said Dr. Momen Wahidi, pulmonary fellow at Duke and first author of the current study. "We have found that our Web site (www.fpf.duke.edu), which describes the disease, has become a great recruiting tool for patients. We have been hearing from families all over the world."

Those families who agree to participate in the study can have all their tests conducted in their home towns. The results and samples are shipped back to Duke for further analysis.

"We have seen families where two members have the disease, as well as families where up to eight members are afflicted," Wahidi continued. "So there is wide variation in the disease, but in most cases the disease is fatal in a short period of time."

Treatment options for these patients are limited. There is no definitive treatment other than lung transplantation, according to Schwartz.

"This is such a challenging disease for us as clinicians to treat," Schwartz said. "Families who participate in this study are truly noble, because they know it is unlikely they personally will benefit from the research. We are indebted to them."

Note to editors: Dr. David Schwartz can be reached at (919) 668-0380 or [email protected].