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Some 20 to 40 percent of extremely
premature infants suffer abnormal lung development that leads to
bronchopulmonary dysplasia (BPD). Little is known about how to predict whether BPD will develop, much less how to
prevent or treat it. Now, gene-
expression studies of these newborns' umbilical cords, published online by Genome Biology in October, provide an unexpected lead.
A team led by Isaac Kohane, MD, PhD, director of the Children's Hospital Informatics Program, and Jennifer Cohen, MD, a neonatology fellow at Children's Hospital Boston, obtained samples from the umbilical cords of 54 surviving infants born at less than 28 weeks' gestation and
analyzed the activity of the 30,000-odd genes for each infant. Twenty of the 54 infants developed BPD after birth; the other 34 did not.
"Of the infants who went on to have BPD, we were surprised and intrigued to find a difference in the chromatin
remodeling pathway, which is also
disrupted in adult chronic obstructive
pulmonary disease (COPD)," says Kohane, the study's senior author.
The chromatin remodeling pathway is responsible for the unwrapping of coiled strands of DNA, which enables a gene to be expressed. When it's disrupted, certain genes for inflammatory proteins get stuck "on," and the inflammation makes lung tissue degenerate and scar, says Kohane. (Although the lungs are uniquely
vulnerable, he speculates that other
tissues are also affected.)
Existing drugs-histone deacetylase inhibitors-already target this pathway, and are being developed as a treatment for COPD in adults. Doctors Kohane and Cohen hope that they can prevent or treat BPD, and perhaps avoid the need for premature infants to be on
ventilators for prolonged periods. They caution, however, that a larger study is needed to validate the genetic findings as a predictor of BPD.
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