New School of Medicine research could help physicians more quickly determine which infants will improve and which will worsen so that necessary therapy can be started as early as possible. The work is being supported by two grants totaling $4.6 million from the National Heart, Lung, and Blood Institute.

F. Sessions Cole, M.D.

One of the most serious forms of respiratory distress in infants results from a lack of pulmonary surfactant, a substance produced by the lungs that keeps them inflated during exhalation. Without enough surfactant, the lungs lose their elasticity, breathing becomes difficult and the baby may die. In 1993, researchers at the medical school discovered the gene for surfactant protein B (SP-B), a key component of this lethal disease.

F. Sessions Cole, M.D., the Park J. White M.D. Professor of Pediatrics, and his colleagues will use a five-year, $3.6 million grant to look for genetic variations in the SP-B gene in approximately 50,000 children on four continents. The research will help determine how frequently this illness occurs and how each mutation contributes to respiratory distress.

"We hope to identify one or more genetic variants that may one day be used to screen fetuses or screen prospective parents to find out whether one or both of them carry mutations that might increase the risk of respiratory distress," Cole said.

The researchers will analyze DNA samples from 20,000 infants born in Missouri in one year. Blood spots taken from each baby's heel at birth will be processed for the SP-B gene by the University's Genome Sequencing Center. For any found to have mutations in the gene for SP-B, medical charts and death certificates will be studied to determine the symptoms, progression of illness and, in some, age at death.

Similar genetic analysis on populations of children in Oslo, Norway; Seoul, South Korea; and Cape Town, South Africa, will allow investigators to estimate the frequency of SP-B mutations in different ethnic groups and geographic areas.

Aaron Hamvas, M.D.

"This is the first attempt to do genetic risk assessment for respiratory distress," said Cole, also professor of cell biology and physiology and vice chair of the Department of Pediatrics. "Historically, being born prematurely has been the principal way to determine whether or not an infant will have respiratory distress.

"If a baby must breathe fast for a genetic reason during the first few days of life, that condition will not improve with time, and that has important implications for prognosis and treatment."

The second research effort, funded by a $1 million grant, is led by Aaron Hamvas, M.D., associate professor of pediatrics. He, too, will investigate pulmonary surfactant deficiency but from a different perspective.

Hamvas' research compares babies with normal lungs to those with abnormal lungs in an effort to find differences in surfactant pro-duction. He will study three groups: premature infants, infants under 1 year old awaiting lung transplantation because of lung disease and infants under 6 months old with normal lungs who are on mechanical ventilation for other reasons.

By measuring fluid production from each baby's windpipe, or trachea, Hamvas aims to determine how surfactant is produced and used differently in the body of a baby with lung disease than in one with normal lungs.