Penn State Researcher Works To Understand Lung Disease In Newborns

January 31, 2000

?HERSHEY, PA--A new study at Penn State's College of Medicine is underway to better understand the molecular dynamics and genetic defects involved with the human fetal disease, pulmonary hypoplasia and associated congenital diaphragmatic hernia (CDH).

"It is known that herbicides are present in the environment and may cause certain defects in humans. Our mouse model of pulmonary hypoplasia and CDH, which mimics the human condition, is designed by using a herbicide, nitrofen * (2, 4-dichlorophenyl-p-nitrophenyl ether)," explains Mala R. Chinoy, Ph.D., associate professor of surgery. "We have observed and published that the fetal exposure to nitrofen during a specific period of pregnancy results in congenital cardiopulmonary (heart and lung) malformations in our model".

very critical time during pregnancy. This malformation or abnormal development of lung results in respiratory distress and affects the survival of the babies born with this defect. Respiratory failure as a manifestation of inadequate lung development is the most important reason for morbidity and mortality in newborns today. Pulmonary hypoplasia (small, insufficient lungs), which results in respiratory distress, is one form of abnormal lung development, which occurs in about 1 in 2,500 newborns and is frequently seen as cystic fibrosis. Up to one third of full-term newborns who die within their first week of life suffer from pulmonary hypoplasia. Chinoy has also recently identified several genes that have a possible role in influencing the growth and development of lungs in newborns.

Chinoy received a three-year grant for $214,500 for this project and other similar research from the American Heart Association. She has also received funding from the American Lung Association for her research.

Chinoy explains further that this project is focused on the development of the pulmonary vasculature, its significance for lung growth and the development of the air-breathing units (alveoli). "Using our animal model, we will examine the differences between the blood vessel network (vasculature) of normal and hypoplastic lungs. Proper development of the blood vessel network in the lungs is important as it plays a very crucial role in the air exchange in the lungs," says Chinoy. "In newborns with pulmonary hypoplasia and CDH, pulmonary hypertension (elevated blood pressure in lungs) is responsible for respiratory failure and subsequent cardiac failure. We propose to study the interaction and specific role of vasculature with the process of normal lung development. We will examine and identify the differentially expressed genes and proteins, which may be responsible for regulation of normal development of lungs."

Chinoy's research associates on the project are Robert Cilley, M.D., associate professor of surgery, Steven Zgleszewski, M.D., anesthesia resident, and Zandra Cheng, M.D., surgery resident.

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