MEDICINE / RESPIRATORY DISTRESS SYNDROME : Success of Synthetic Lung Substance Cited

Scientists here have developed an artificial lung substance that in animal tests prevented respiratory distress syndrome--a significant killer of adults and premature babies, according to a study published today in a scientific journal.

Researchers have labored for years to develop a synthetic form of the substance, called surfactant. Each year about 39,000 premature babies are born without surfactant and develop respiratory distress syndrome, an inability to keep air sacs open in the lungs. The disorder also affects about 150,000 adults a year.

In healthy people, surfactant is secreted by lung cells, coating the inner lining of the lung and preventing it from collapsing when exhaling. Several other artificial versions have been developed in attempts to prevent the syndrome, but with varying success.

Scientists hope that this latest version developed by scientists at Scripps Research Institute might be the most effective, acting most like the human substance it mimics.

“This may come as close as you are going to get without actually being human surfactant--this may well be the best,” said Dr. Louis Gluck, professor of pediatrics and director of newborn medicine at UC Irvine.

Pending federal approval, the new drug will be tested on premature babies early next year, said Dr. Charles Cochrane of Scripps’s department of immunology and an author of the report in the journal Science. The drug was used on 18 prematurely delivered rhesus monkeys and scores of rabbits.

The monkeys, born 80% mature, were grey and ashen, laboring to breathe until they were given the drug. Within six hours, they became pink and were breathing easily, the Scripps doctors said.

The syndrome kills one-quarter of the infants and about half the adults it strikes, according to the American Lung Assn.; the victims’ lungs become inflamed and cease producing surfactant.

Just before birth, babies develop the ability to produce surfactant, which is composed of proteins and fatty substances called lipids. But those born prematurely may not be able to produce the substance and are unable to expand their lungs. This means they receive too little oxygen and cannot empty the carbon dioxide from their lungs.

These infants are dubbed “$100,000 babies” because of the costs associated with placing them on respirators and keeping them alive, Cochrane said. This--in some cases combined with the administration of existing surfactants-- maintains the infants until their lungs are mature enough to function on their own.

In adults, the syndrome is triggered by such factors as injury, surgery or diseases that inflame the lungs and stop surfactant activity.

One currently available surfactant is made from cow lungs--but some humans develop harmful allergic reactions to it. Because it takes five cow lungs to produce one dose, it is expensive, said Susan Revak of Scripps’ department of immunology and an author of the study.

The other existing surfactant is called Exosurf. While this drug is also synthetic, it lacks proteins--a factor that scientists believe may make it less effective than the new one developed at Scripps, Cochrane said.

Studying surfactants for four years, Cochrane and Revak determined that one protein, called Surfactant Protein-B, played a key role in keeping air sacs open in the lungs. Next, the Scripps team set to work creating a synthetic version of the components of surfactant, including this protein.

“The protein holds everything together like reinforcing concrete with steel barriers,” he said. The drug is administered to the lungs in a tube through the trachea.

Other experts voiced cautious optimism and agreed that the protein could make the drug a more effective treatment.

“It certainly would be considered by most of us as a real advantage that should help improve babies--it probably would be something with advantages over what we now have,” said Dr. Ron Ariagno, professor of pediatrics at Stanford University.