Researching Lung Collapse in Premature Babies

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In a study aimed at improving survival rates for prematurely born infants, scientists have pinpointed the gene that is vital for lung maturation in newborns and have also found that it is responsible for producing surfactant, which lines lung tissues and keeps the lungs from collapsing.

In a study posted online in the Proceedings of the National Academy of Sciences, investigators at Cincinnati Children’s Hospital Medical Center deleted a gene called Foxm1 in embryonic mice. The mice still went through the early stages of lung development, an observation that surprised the research team, but their lungs never reached complete maturity. The immature lungs also did not produce two crucial surfactant proteins, leading the mice to die from respiratory distress shortly after birth.

“Our findings demonstrate the Foxm1 gene’s central importance to lung maturation and surfactant production in mice,” said Vladimir Kalinichenko, a physician and researcher in the division of pulmonary biology at Cincinnati Children’s Hospital and the study’s lead investigator. “Ultimately, this information is important to newborn survival, as infants must breathe on their own at birth instead of getting oxygen from the mother’s umbilical cord blood.”

Respiratory distress syndrome is a common cause of death in prematurely born infants, and previous research — much of it pioneered at Cincinnati Children’s Hospital — has shown that the Fox genes (which control the transfer of genetic information to regulate proteins inside cells) are critical for the embryonic growth of lungs and other organs.

To study the role of the specific Foxm1 gene during the embryonic lung development period, investigators in the Cincinnati study generated transgenic mice and deleted the Foxm1 gene. Eliminating the gene did not affect the initial “budding and branching” or the growth of the lung. But it did inhibit anatomic and biochemical maturation of the lung, where air sacs did not fully form and surfactant production was significantly lessened.

The next step for the research team, Kalinichenko said in a release, is to find pharmacological compounds that can activate Foxm1. The compounds could be used to create new drugs to treat several different human diseases involving deficiencies of Foxm1. Pharmacological activation of Foxm1 in premature babies could even induce lung maturation and surfactant production, he said, helping fight respiratory distress syndrome.

In the study’s conclusion, Kalinichenko and his colleagues wrote: “Identifying critical regulators of lung maturation, such as Foxm1, may provide novel strategies for diagnosis, prevention and treatment of respiratory distress syndrome (RDS) in preterm infants.”

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