Writing for the Washington Post, Lena Sun describes how CDC's "disease detectives" investigated an outbreak of vaping-linked illnesses—and explores what they're planning next.

The first cases of the vaping disease

The first cases of the previously unknown vaping-linked lung illness were reported in July among "previously healthy young" patients in Wisconsin and Illinois, Sun writes.

Originally, doctors assumed the cases were linked to e-cigarettes, "[b]ut the devices had been sold for more than a decade without reports of such a disease," Sun writes. "Why was this happening now?"

And the detectives faced several challenges right off the bat. Oftentimes, CDC's disease detectives have a "likely culprit, or at least a sense of how to approach the investigation." But in this case, the investigators had no "idea what might be making so many people so sick"—and, making it even worse, they had to consider thousands of possible culprits, including several hundred e-cigarette and vaping devices, and thousands of e-liquids that contained multiple ingredients, Sun writes.

Confounding things further, the disease also presented in different ways depending on the patient, according to Peter Briss, medical director of CDC's Center for Chronic Disease Prevention and Health Promotion. Some patients reported chest pain and shortness of breath while others reported nausea, vomiting, and a fever.

"The level of difficulty on this one is probably a 9 out of 10," said Jim Pirkle, director of the laboratory science division at CDC's National Center for Environmental Healthb. Pirkle, who has worked at CDC for nearly four decades, said he's encountered only two other investigations that posed more challenges: a mysterious syndrome tied to contaminated oil and finding a way to measure toxin dioxin levels in Vietnam War veterans exposed to Agent Orange. According to Pirkle, both of those investigations took several years to solve, while CDC has made great leaps in the vaping-linked illness case "in weeks."

Cracking the case

For months, researchers logged 14- and 15-hour days to determine what was behind the illness that afflicted so many previously healthy young patients.

When news of the first cases broke, the agency used a "scaled-down version" of a system that was originally used to track food-borne outbreaks to track data, according to Macarena Garcia, a chief data scientist for CDC—but when the illness first appeared in the Midwest this summer, CDC did not know the outbreak would eventually afflict over 2,000 patients within a few months.

As cases of the illness started to pop up all over the country, the scaled-down system struggled to keep up with new data. In addition to the sheer volume, the data was arriving in different formats from different states. For instance, some states asked patients "whether they vaped daily, weekly, or monthly. Others asked if they vaped two to three times a day, or more than 50 times a day," Sun writes. To keep up, Garcia's team had to create a separate system just for collecting data, which took several weeks, she said.

But in the fall, an analysis by FDA and the Wadsworth Center laboratory made the biggest discovery of the investigation so far. The analysis found vitamin E acetate was present in many of the products containing tetrahydrocannabinol (THC), which is the high inducing chemical found in marijuana.

The oil, which is used to dilute THC in "black-market" vape cartridges, doesn't usually cause harm to people who ingest it as a supplement, but when inhaled, it can interfere with lung function, according to research. But the researchers had to devote several more weeks of work to develop tests confirming that vitamin E acetate was a culprit—a test that involved more than 1,000 measurements, so as to ensure that the "methods were sensitive enough to detect a wide array of substances being investigated."

In November, a research team made a "remarkable" discovery: Vitamin E acetate was present in the lung fluid of 19 more patients with the illness. But what was even more remarkable, according to Pirkle, was that the scientists found no evidence that other chemicals or compounds were potential suspects, according to Sun.

But these results were not enough for CDC to make an official announcement. "[W]e needed to get results fast," Pirkle said. "We couldn't keep having people getting sick and dying."

A potential culprit

The team set out to gather more evidence so they could release a public recommendation based on their findings, but executing more lab tests proved to be another challenge.

The night before CDC started to analyze 10 more samples, the chemical analysis tool crashed—less than 12 hours away from the deadline.

At first, Pirkle thought his team was playing a joke on him when he heard the news. The researchers couldn't afford to lose the few samples they had. Some of them were so small that they only had a "dropper-and-a-half" of lung liquid, Sun writes.

But what Pirkle feared most was confirmed to be true. "No," they told him, "it really crashed."

But when technicians fixed the tool, the evidence was stronger than ever. Every sample came back positive for vitamin E acetate. Now, 29 out of 29 samples confirmed the presence of the oil.

Two days later, CDC's Principal Deputy Director Anne Schuchat announced that vitamin E acetate was a "strong culprit of concern" in the illness, adding that while the agency couldn't pinpoint vitamin E as the cause, an association was clear.

What happens now

The new findings gave CDC enough evidence to release official health warnings against using e-cigarette and vaping products that contain THC. But, because some sick patients still maintained that they only vaped nicotine products and others admitted to using multiple vaping products, CDC is still recommending that consumers avoid all vaping and e-cigarette products, Sun reports.

For now, the National Institute of Health is soliciting animal studies to figure out how vitamin E acetate may be causing the harm seen in patients' lungs. And the detectives, meanwhile, are trying to determine if the outbreak could have multiple causes. "It's possible the harmful thing doesn't even get produced until fluid is vaped," Pirkle said.

Over the last few months, researchers have been using 3-D printers to create custom parts for CDC's smoking machines, which are "puffing" vaping devices to test the aerosols that are released. The researchers hope to have results within about six weeks. "We'll be looking to see if we get anything unusual," Pirkle said. "It could be that only one of the products causes disease and the others did not. But we don’t know which one, so we still have to analyze all of them" (Sun, Washington Post, 11/25).