Big problems for small lungs  pg. 6

The study, sponsored by the Vermont Oxford Network, a NICU quality and information sharing organization, suggests that other factors besides mechanical ventilation are driving new BPD.

According to Vanderbilt neonatologist Lance Prince, M.D., Ph.D., infection may play a role.

Lance Prince, M.D., Ph.D.
Photo by Joe Howell

“We have made great strides in understanding the mechanisms involved in inflammation,” says Prince, an assistant professor of Pediatrics. “At the same time, we have a lot more knowledge of normal fetal development. In this work with new BPD, we are trying to find the intersection of the two.”

Prince began by examining the lungs of babies who died from BPD.

“Lung development of the babies who had been exposed to infection was months behind. We were looking at lungs that appeared to be remodeled with large, dilated or boggy air sacs,” he says. “But in a premature baby not exposed to inflammation, lungs still continue to develop outside the womb.”

Using a mouse model, Prince has identified some of the chemical changes that occur when lungs are exposed to infection before they fully develop.

In a 2006 study, he exposed fetal mouse lungs at the equivalent of 27 weeks of human gestation to endotoxin released by the common bacterium E. coli. The alveoli, the tiny air sacs in the lungs, stopped developing, and levels of FGF10, a chemical known to be important to normal lung development, dropped precipitously.

The latest in microscopic video imaging techniques showed for the first time how normal cells lay down the structure of the innermost airways, and then what happens to them if FGF10 goes away in the face of infection. Prince says that without the crucial chemical the cells responsible for alveolar construction appear to “wander aimlessly.”

Prince teamed up with Vanderbilt’s Tim Blackwell, M.D., Rudolph H. Kampmeier Professor of Medicine and chief of the Division of Allergy, Pulmonary and Critical Care, for the next phase of his work: honing in on the pathway involved.

Blackwell had developed a way to borrow nature’s florescence and luminescence -- from jellyfish and fireflies -- to illuminate activation of a common inflammatory pathway involved in adult chronic lung disease.

When this technology was applied to Prince’s fetal mouse lung model, the researchers observed macrophage cells involved in the fetal mouse’s inflammatory response glowing “like a firefly” as FGF10 levels dropped.

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