Thanks in large part to a dying patient's generosity, researchers have for the first time begun to analyze the progression of idiopathic pulmonary fibrosis (IPF), a degenerative illness distinguished by lung inflammation, scarring and diminished breathing capacity that typically leads to death within about five years of diagnosis.
The project, involving the examination of lung tissue recovered shortly after death in a process called warm autopsy, is described by University of Pittsburgh School of Medicine researchers in the June issue of PLoS Medicine, an online journal of the Public Library of Science.
"Up until now, what we have been able to do has been limited by the lack of availability of lung tissue for study," said Naftali Kaminski, M.D., director of the Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease in the division of pulmonary, allergy and critical care medicine at the University of Pittsburgh School of Medicine and senior author of the PLoS essay, "Lessons from Our Patients: Development of a Warm Autopsy Program."
Warm autopsy - a practice involving retrieval of organs within six hours of death - has been in use for more than 25 years, chiefly in the study of Alzheimer's disease and multiple sclerosis. However, the University of Pittsburgh's program, which began at the suggestion of an IPF patient, is among the first to use the technique for lung disease research. "Obtaining such prompt access to the organs will, we hope, allow us to approximate disease conditions in a living patient," said Kathleen Oare Lindell, R.N., clinical nurse specialist at the Simmons Center and the essay's first author. "The goal is to learn as much as we can about how IPF works."
Some 5 million people worldwide and 200,000 in the United States are affected by pulmonary fibrosis. Some known causes of pulmonary fibrosis include occupational and environmental exposure to asbestos, metal dust, farming chemicals and mold, an inflammatory disease called sarcoidosis, radiation, drug reactions, autoimmune disorders and possibly a genetic predisposition, according to the American Lung Association. By far, most cases are considered to be idiopathic, or of unknown origin. Treatment options include corticosteroids and supplemental oxygen. There is no cure, although long-term benefit is possible with lung transplantation. According to the United Network for Organ Sharing, slightly fewer than 1,200 lung transplants were done in the U.S. in 2004 for all causes, including IPF. As of the same year, more than 3,500 people were still waiting for donor lungs to become available.
"Why a patient with IPF dies is not completely understood," said Dr. Kaminski. "We have funding from the National Institutes of Health to do some reverse engineering on IPF using genomics in order to better understand the disease mechanisms - to look at all the genes expressed and track them as the disease progresses."
Since 2003, Dr. Kaminski and his colleagues have examined donated lungs from 12 patients, beginning with tissue from a retired firefighter who suggested the idea after participating in support group sessions. "We had never had patients wanting to donate their lungs before and had not even discussed the possibility," said Ms. Lindell, adding that research into the proposal revealed there were no such programs in the country for lung disease.
"The tissue that is available from lungs is rare and primarily from cancer patients," explained Dr. Kaminski. "Most IPF patients will have one biopsy for diagnostic purposes, and because of surgical risks and their fragile health, some may not get a biopsy at all."
But thanks to warm autopsy donors, tissue studied soon after death can be compared to tissue collected at biopsy - usually years earlier. Preliminary analysis has revealed some promising paths for further research.
"With IPF, many areas of the lung look normal, while others are scarred," said Dr. Kaminski. "Using these donated lungs, we can retrieve tissue from multiple locations within the organ and see how they compare."
Collagen- and connective tissue-making cells in lungs affected by IPF begin to look and act more like muscle cells, he continued. These cells, called fibroblasts, in essence become supercharged, secreting more connective tissue proteins and fibers than normal and becoming more resistant to killing, in a way similar to cancer cells.
"Looking at the genes as if they are molecules in a computer program, you can see where in IPF, the program is distinct and very different from normal," said Dr. Kaminski. "With this new direction of research, we will be trying to reverse the process."
The warm autopsy program also has a bonus of strengthening connections between patients, their family members and the health professionals who care for them, said Ms. Lindell. "This program is one example of how a patient can make a difference and initiate something that will help others. It conveys a message that the team respects patients' wishes and allows them to contribute, even in their last days."