Researchers Profile Gene Activity In Acutely Ill Idiopathic Pulmonary Fibrosis Patients

Main Category: Respiratory / Asthma
Also Included In: Genetics
Article Date: 15 Jul 2009 - 0:00 PDT

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New research may help doctors pinpoint when patients with idiopathic pulmonary fibrosis (IPF) are becoming dangerously ill. The findings may also point the way to interventions that could sustain the lives of IPF patients until life-saving transplants could be performed.

"Nearly 600 genes were differentially expressed between IPF patients who had accelerated disease and those who were stable" said lead author Kazuhisa Konishi, M.D., of the University of Pittsburgh School of Medicine.

The results were published in the July 15 issue of the American Journal of Respiratory and Critical Care Medicine

For most IPF patients, the lung-scarring disease progresses gradually and lung function slowly deteriorates. But for unknown reasons, some IPF patients experience rapid declines that cause diffuse damage of the lung alveoli, the tiny sacs where the exchange of oxygen and carbon dioxide occurs.

"Approximately ten percent of patients develop an acute phase that in most cases is lethal," said senior author Naftali Kaminski, M.D., associate professor of medicine, computational biology and pathology and the director of the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases at the University of Pittsburgh School of Medicine and the University of Pittsburgh's School of Medicine. "There has been very little understanding of the molecular basis of this syndrome, but because of the dedication of our patients and their families, we are getting closer to some answers."

To better understand the molecular mechanisms of exacerbation, the researchers compared the gene activity profile of the lungs of eight IPF patients who were having an exacerbation when they died with those of 23 stable IPF patients and 15 people with healthy lungs.

Dr. Kaminski and collaborator, Dong Soon Kim, M.D., of the Asan Medical Center and the University of Ulsan in Seoul, South Korea, found that levels of a protein called alpha-defensin were particularly high in the blood of patients undergoing an exacerbation. If the findings are verified with more research, which is underway, the proteins could be the first biomarker blood tests that doctors could track to identify patients at risk for sudden deterioration of lung function.

"This work opens an important window into the mystery of why patients with lung fibrosis suddenly decompensate and how to identify these patients for more aggressive therapies," said Mark T. Gladwin, M.D., chief of the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh's School of Medicine. "Our current research efforts in the division focus on the development of novel therapeutics that will target the molecular pathways identified by our basic science laboratories."

There was no evidence that infection or inflammation was the cause of disease acceleration, Dr. Kaminski noted. Instead, there were indications that the cells of the alveolar epithelium, which is the tissue that covers the surface of the air sacs, were rapidly dying.

"That could mean that drugs that are used to protect the epithelium in other illnesses, such as cancer, might help IPF patients survive an exacerbation," said study co-author Kevin Gibson, M.D., associate professor in the Division of Pulmonary, Allergy and Critical Care Medicine at Pitt's School of Medicine. "If we can keep them alive, there's a chance they could get a life-saving lung transplant."

Source
American Thoracic Society

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