PERSISTENT PULMONARY HYPERTENSION IS A LIFE-THREATENING CONDITION in newborns that tightens the arteries carrying oxygen from the lungs, causing the baby’s skin to turn blue. Although this condition affects nearly 4,000 infants each year in the United States, the underlying causes remain largely unknown. Treating them with nitric oxide gas for an average of four to five days, however, reliably provides lasting relief.

Warren Zapol, an anesthesiologist at Massachusetts General Hospital (MGH), has spent the past two decades investigating the applications of nitric oxide for treating pulmonary hypertension and other conditions. This work led his team to engineer a device that synthesizes nitric oxide from ambient air.

What’s so important about nitric oxide?
Scientists had invented drugs back in the 1980s that helped by dilating blood vessels in the lungs, but the drugs also dilated and expanded blood vessels throughout the body, causing a drop in blood pressure that was capable of stopping the heart.

But in 1987, it came out that nitric oxide [NO], a gas made naturally in the body, could dilate blood vessels. And I just wondered, if you breathe in NO gas, could it selectively diffuse into the lungs and dilate the lung’s blood vessels?

So we took little baby lambs that were similar in weight and anatomy to newborn babies and artificially constricted the circulation in their lungs. Our results showed that a little bit of NO dilated lung blood vessels and increased the circulation to their lungs but did not dilate the rest of their body’s vessels, which was the goal. And it happened with minimal side effects.

Then our team of doctors tried it in 1990 with newborn blue babies here at MGH. The babies just turned pink before our eyes. And over time, they remained pink.

And what’s new about how you produce it?
Not long after these studies, I read that NASA had sent a plane through a lightning bolt to capture gas. And guess what? The lightning bolt was full of nitric oxide.

It turns out that as lightning goes through the atmosphere, it grabs nitrogen and oxygen and sticks the molecules together to form nitric oxide. But what you need is a spark called a plasma discharge.

The original device I made was about the size of my desk. But we got to work figuring out how to make a nitric oxide device portable and more efficient—a current version is handheld—and as free of byproducts as possible.

Have you tested this new portable device?
We gave mice this gas to breathe for 30 days, and then analyzed their lungs and found nothing abnormal. We are currently in the process of testing the device in a group of human patients to show that it performs comparably to a conventional nitrogen tank.

If it passes approval, this portable device has tremendous potential, and not just for persistent pulmonary hypertension in newborns. It can be useful for lung disease, situations where the right ventricle is not pumping a sufficient amount of blood to the lungs and chronic pulmonary hypertension in adults. With an iPhone-size device that can make nitric oxide on demand, patients will be able to travel without being held back by bulky nitrogen tanks.

And making nitric oxide to order is cheaper?
In the United States, the nitric oxide market is a monopoly with $360 million in sales each year. Here at MGH, it can cost $14,000 to treat a baby for five days. But there is no reason it has to be this expensive. You can do this whole job with an oxygen concentrator and a NO generator.

There are, we hope, implications for the whole world. Blue babies are everywhere. I went to China and India and there was no nitric oxide whatsoever. With a technology that is this effective and with so few side effects, it is only a matter of time before we can make it available worldwide.