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New test promises quicker, more accurate evaluation for cystic fibrosis patients
Date:10/23/2008

s' FEV1 does improve when inflammation is reduced, but not all patients' FEV1 improves significantly, and changes can take weeks to months to show up. It can be prohibitively expensive to conduct phase 2 or phase 3 trials of medications long enough to detect the changes in FEV1.

National Jewish researchers thought white blood cells circulating in the blood might be a good source of biomarkers for a more sensitive and accurate test. White blood cells are the predominant cell type at sites of tissue destruction in CF patients' lungs. As they circulate through the lungs in the blood they encounter the inflammatory environment and alter their gene expression as a result. By measuring mRNA, scientists can identify which genes are being expressed and how strongly.

The researchers evaluated 18 CF patients who were suffering severe exacerbations of their disease. They withdrew blood before and after two weeks of intravenous antibiotic therapy. The severe exacerbation and antibiotic therapy served as a condensed model of illness and response to therapy; in these cases antibiotic therapy is usually successful, and patients' clinical symptoms and FEV1 both improve rapidly.

Using microarray gene analysis of the blood samples, the researchers identified 10 genes that differed significantly in their expression before and after therapy. Using real-time polymerase chain reaction and additional statistical tools, the researchers identified three of those genes that most accurately correlated with a positive therapeutic response: CD36, CD64 and ADAM9. CD36 and CD64 are genes associated with cells' absorption of foreign organisms and cellular debris. ADAM9 is associated with tissue destruction that allows inflammatory cells to move through tissue. This process is also believed to contribute to permanent tissue destruction.

"The expression of these genes correlated with FEV1, other inflammatory markers, and various clinical factors," said co-author Dr. Jerry Nick, A
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Contact: William Allstetter
allstetterw@njc.org
303-398-1002
National Jewish Medical and Research Center
Source:Eurekalert

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