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Salk breathes new life into fight against primary killer of premature infants

Ron Evans and Liming Pei

Ron Evans and Liming Pei

Respiratory Distress Syndrome (RDS) affects about 1 percent of infants born in the United States and is the leading cause of death among premature babies. It occurs because the infants' lungs are not yet fully developed at birth and lack a slippery substance called surfactant, which is crucial for the newborn lung to inflate with air. To encourage the lungs to develop faster, doctors treat many expecting mothers and premature infants with anti-inflammatory glucocorticoids, steroid drugs that speed maturation of surfactant-producing cells, known as type 2 pneumocytes.

In some cases, however, infants fail to respond to the steroid treatment and die from the respiratory syndrome, which suggests that some other biological mechanism might be at work. To explain this, researchers in the lab of Ronald Evans turned their attention to another type of cell lining the lungs, type 1 pneumocytes, ultra-thin flat cells that allow air exchange between the bloodstream and the lung's interior. They developed a strain of mice in which they disrupted the ability of type 1 pneumocytes to respond normally to thyroid hormone, which prevented the cells from maturing.

Unlike type 2 pneumocytes, which mature rapidly in infants given steroid hormones, the type 1 cells failed to respond to steroid treatment, and the mice died due to their lungs' inability to function. However, mice treated with the medications propylthiouracil or methimazole, normally given to people with thyroid disease, recovered from the disorder, and their type 1 cells matured normally.

"This might explain why some infants don't respond to steroid treatment, which only targets the type 2 pneumocytes," Evans says. "There may be an entirely different underlying problem than what the doctor is treating."

The genetic makeup of mice and humans is very similar, so the researchers are optimistic that their findings, which were published in Nature Medicine, will eventually lead to new treatments for infants with RDS. "These mechanisms could also play a role in healing lung tissues," says Liming Pei, a postdoctoral research associate who led the project. "They might help older children and adults who have suffered lung damage from flu, asthma, emphysema or other types of respiratory disorders."