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Breathing easy: Synthetic lung surfactant could save lives, at low cost

What makes breathing possible is a thin coating of a soaplike film, or surfactant, that lowers the tension of the lung’s inner surface. Premature babies and adults with lung injuries are short on surfactant, and replacing it has been prohibitively pricey. That may be about to change.

Breathing is the first big challenge a newborn faces. That's not as easy as it sounds, I wrote in a news release about a study just published in Scientific Reports:

Imagine the force you’d need to blow up a balloon whose surface area nearly matched that of a tennis court. Imagine further that the balloon has a pocked, moist inner surface and is made of exquisitely delicate material. That balloon is your lungs, and every breath you take is a miracle. What makes it possible is a thin coating of a soaplike film, or surfactant, that lowers the tension of the lung’s inner surface, radically reducing the amount of force required to inhale. Without this surfactant, you couldn’t breathe.

Each year in the United States alone, 20,000-30,000 infants born too early to make their own surfactant get treated with a hugely expensive version derived from the lungs of cattle or pigs farmed for that purpose. The resulting product is so pricey it's available for babies only in rich countries.

(In recent years, a somewhat cheaper artificial substitute has become available, but it's still expensive and functionally inferior to the natural animal extract — so a nonstarter in any country where the natural version is covered by health insurance.)

A grown-up's lungs, meanwhile, are more than 20 times bigger than a baby’s, effectively pricing natural surfactant out of reach for life-threatening cases of acute lung injury even in the U.S., where 200,000 adults are affected annually. Acute lung injury can be caused severe lung infections, including bacterial and viral pneumonia; lung-collapsing impact from car accidents; water inhalation in near-drownings; or aspiration of foreign matter in drug overdoses.

Lung surfactant's miraculous capacity to ease breathing traces to a couple of special proteins in the mix whose structures uniquely enable them to cut surface tension, Stanford bioengineer Annelise Barron, PhD, the study's senior author, told me in an interview. Those same amazing structural properties, she said, also make these proteins tough to synthesize and purify and relatively unstable in solution, limiting shelf life and increasing price.

But an artificial surfactant Barron invented and has continued to develop over the last two decades could mean better, cheaper treatment. Barron's product replaces the natural version's finicky surface-tension-cutting proteins with a pair of synthetic protein mimics (called peptoids) that — while remarkably similar to the proteins they're filling in for — are extremely resistant to breakdown by heat or naturally occurring bodily enzymes called proteases. They're much less inclined to clump up (and stop working) than their natural counterparts. And they can be synthesized at one-quarter to one-third of the cost of getting the surfactant from animals.

Best of all, the study described in Scientific Reports showed, in a rat model, that Barron's peptoid-based artificial surfactant was actually superior to the animal-derived variety in oxygenating blood, which is our lungs' main purpose.

Plenty of rigorous preclinical tests, followed by carefully conducted clinical trials, lie ahead, Barron told me. But she intends to take her surfactant solution through whatever paces are needed to make it available at a reasonable price — reasonable enough so that, for the first time, clinical trials of a lung surfactant in adult cases of acute lung injury can become realistic.

"It would, finally, also be available to premature babies in developing countries like Bolivia, where my father was born,” Barron said.

Photo by geir tonnesson

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