For many years, researchers have tried to find ways to shrink the enlarged, overinflated lungs of advanced emphysema patients without resorting to high-risk surgery.
Now, implantable, one-way air valves are poised to become the first minimally invasive lung reduction option in the United States, based on results of an international clinical trial led by Temple University. The valves redirect air, shrinking diseased areas of the lungs and expanding healthier parts.
It's not a panacea. The Zephyr endobronchial valves, made by California-based Pulmonx, come with risks, are suitable only for a carefully selected subset of patients with severe emphysema, and don't work for all recipients.
But the pivotal trial showed that after a year, patients with valves had greater improvement in lung function, exercise capacity, breathlessness, and quality of life than a comparison group that relied on standard medical care — inhalers, steroids, and supplemental oxygen.
On Tuesday, the results were presented at a conference and published in the American Journal of Respiratory and Critical Care Medicine. The U.S. Food and Drug Administration is reviewing the data to decide on approval of the valve. It is already available in Europe, Australia, Asia and South America, and more than 12,000 patients have been treated, according to Pulmonx.
"I would emphasize, this is not for all patients; this is palliation," said study leader Gerard Criner, chair of thoracic medicine and surgery at Temple's Lewis Katz School of Medicine. "But we're talking about a couple hundred thousand patients" who might benefit in the U.S.
"We're very excited about the possibility of soon being able to offer this technology to U.S. patients," said Beran Rose, Pulmonx vice president of marketing. "The disease does progress, but [valve therapy] gives patients an opportunity to re-engage with life."
Emphysema is an incurable form of chronic obstructive pulmonary disease. It is usually caused by smoking and afflicts more than 3 million Americans. As tiny air sacs that absorb oxygen are destroyed, air gets trapped in diseased regions of the lung, gradually enlarging the organ. This hinders breathing – like being stuck on inhale – and leads to chronic coughing, excess mucus, frequent respiratory infections, and shortness of breath.
In advanced stages, many patients do not qualify for, or don't want the risks of, the last-resort treatments: a lung transplant or lung-reduction surgery to cut away diseased tissue. That's why Criner and other researchers have spent decades testing minimally invasive lung-shrinking techniques including coils, stents, injectable sealants, and one-way valves.
The challenges have proven to be huge, as Zephyr's history shows. Initially developed by another company, the pencil eraser-size device was rejected by the FDA in 2008 after an advisory panel concluded the benefits didn't outweigh the risks.
Pulmonx acquired the technology and added a pulmonary assessment system, called Chartis, to identify patients most likely to benefit and the best placement of valves.
It became clear, Criner said, that about 60 percent of patients compensate for emphysema by developing "collateral ventilation" that bypasses normal airways — just like many heart disease patients develop collateral blood flow. Chartis is used to screen out patients who have this end-run respiration. (Another company, Olympus, is also developing a one-way valve, called Spiration, that does not include a pulmonary assessment system.)
In suitable patients, two to eight Zephyr valves are strategically placed in airways using a bronchoscope – a tube with a light and small camera that is threaded through the mouth into the lung. The metal-and-mesh valves expand, seal the airways, and keep air from entering diseased parts of the lung so healthier regions can expand and function better.
In the pivotal trial, "benefits came from reduced lung volume," Criner said. "The volume fell by half a liter, so the patient could take a bigger breath."
At one year, almost half of the 128 ex-smokers who got valves had at least a 15 percent improvement in their lung function, measured by how much air they could force out in one second, compared with only 17 percent of the 62 patients with standard medical care. The valve group also showed improvements in a six-minute walking test and quality-of-life questionnaire.
Peter Terry, a pulmonologist and bioethicist at Johns Hopkins University, sees the prospect of FDA approval as "a moderately big deal for a very select group of patients."
"The question is whether or not the benefits are worth the risks," he said. "And that's a completely individual decision."
Stacy Nygaard, 57, an ex-smoker who lives in Millsboro, Del., knows both sides of the equation.
Two years ago, the former grocery store manager could no longer walk 10 feet without struggling for breath, and was considering lung-reduction surgery. She was happy to qualify for the valve study. But the first two valves gave her no relief, so Criner placed a third one.
Soon afterward, she suffered a life-threatening complication of the therapy, called pneumothorax. Basically, her stiff, untreated lung expanded too fast, ruptured, then collapsed. She said she spent 12 days in the hospital with a series of chest tubes while her reinflated lung healed.
Pneumothorax occurred in more than a quarter of valve patients within several days of their procedures, compared with none who received standard care. The complication led to a change in the treatment protocol, Criner said. Patients were monitored in the hospital for five days, rather than sending them home a day after valve placement. Two valve patients who went right home died of pneumothorax, and a third who suffered it in the hospital died 13 days after getting the valves.
While Nygaard's early recovery was rocky, she said she has no regrets. A month after treatment, she stopped feeling as if someone were sitting on her chest. Now, she works out with a therapist three times a week – treadmill, exercise bike, and weights – and has dropped 28 pounds.