Health officials are still scrambling to pinpoint the cause of an outbreak of lung illnesses in people who vape — and the wide geographic spread of cases and the vast vape market are making that investigation more challenging.

There have been 380 confirmed and probable cases of the severe breathing illnesses among people who vape, according to the Centers for Disease Control and Prevention. Six people have died due to the illnesses, which have cropped up in 36 states and the U.S. Virgin Islands.

Those numbers, released late last week, marked a decrease from the 450 cases reported the week prior, when officials were also counting “possible cases” that were still under investigation in their tallies.The CDC says the number of cases is likely to climb as they classify more cases, a thorough process that involves reviewing a patient’s medical records and interviewing their health care providers.

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But health officials still haven’t identified why vapers —  the majority of cases are in young men — are developing severe cases of pneumonia. Health officials across the country are still hunting for a cause, running tests on samples from products patients used and scouring for common threads between cases.

Here are five key questions about the outbreak.

Is a specific product or substance to blame?

The majority of people who developed the respiratory illness said they had vaped tetrahydrocannabinol, or THC, the main active ingredient in marijuana. Other patients have reported vaping THC and nicotine together, while a small share said they only vaped nicotine. But health officials acknowledge that some patients might be reluctant to disclose THC use, given that the marijuana remains illegal in many states.

The FDA has been working with local and state health officials to collect and test samples of the vaping products sickened patients used. At this point, health officials haven’t been able to nail down a specific culprit, whether that’s a common type of e-cigarette, brand, or substance.

“Trying to tease out which of those things it is is really kind of challenging,” said Dr. Dana Meaney-Delman of the CDC’s lung injury response program.

And the vast vape market only makes things more complicated. There’s a wide range of devices — and a plethora of products vaped with those devices. Some of them aren’t clearly labeled. People purchase vaping products online, in retail stores, and on the street.

“That complicates our ability to specifically identify any single product or a substance at this time,” said Brian King, the deputy director of research translation in the CDC’s Office on Smoking and Health.

The fact that health officials haven’t been able to narrow their search has made testing the samples more difficult. Because health officials don’t know what they’re looking for, they can’t narrow their search.

“You’re taking a very broad approach to try to identify any chemical constituent, and that takes a lot longer than if you know you’re looking for a particular chemical,” said Dr. Jon Meiman, the chief medical officer of the Wisconsin health department.

Do these cases represent only one illness?

Health officials still aren’t sure whether they’re grappling with one syndrome or a handful of different illnesses. While many of the cases bear striking similarities, patients have reported a range of symptoms, from nausea and vomiting to fever and fatigue. Some experienced symptoms for weeks, while others were ill for just a few days. Many have developed acute respiratory distress syndrome, a condition that occurs when fluid accumulates in the lungs and makes it difficult for oxygen to circulate as needed.

“We’re dealing with an illness that is still not well-characterized. You’ve probably seen a lot of different descriptions in news reports, and that’s because people present with lots of different clinical presentations,” said Meiman.

In August, the CDC set a definition of what constitutes a case: vape use in the past three months, scans that show spots on the lungs; no sign of pulmonary infection; and no evidence to support other diagnoses. The newest case counts — the 380 confirmed and probable cases announced on Sept. 12 — were the first national data to use that definition.

Is this issue new — or just now being recognized?

Better understanding the range of symptoms will also help health officials answer another key question: Why is this issue just now surfacing?

E-cigarettes aren’t new — they’ve been sold in the U.S. for years and are increasingly popular among young people. But reports of vaping-related illnesses have proliferated this year. State health officials in Illinois and Wisconsin tracked 53 cases and traced the earliest signs of illness — often, coughing, chest pain, and trouble breathing — to April. Health officials in Illinois reported the first known death due to vaping-related illness on Aug. 23.

But it isn’t known whether the 380 confirmed and probable cases represent an issue that’s just now cropping up — or whether they represent a health risk that is just now being recognized. Meaney-Delman of the CDC said it isn’t clear whether there has been a range of vaping-related illnesses that have been going on for longer, with the most serious cases only now coming to light.

“We don’t know if this is the tip of the iceberg, and we’re seeing those who are most severely ill,” she said.

But others believe the cases signal a new issue.

“Clearly for a couple of years you’ve seen people come to [the emergency room] with vaping- related issues, but they’re released and sent home. This is new. The severe injury, lung injury, ending up in ICU is new,” said Richard Danila, the deputy state epidemiologist for Minnesota.

Does the way people use e-cigarettes complicate the task of homing in on what’s causing the lung damage?

A huge part of the complexity of figuring out what is causing this lung damage is the fact that people who use e-cigarettes may vape a variety of products, either sequentially — something now and something else later — or in combination. Some buy pre-mixed products and some concoct their own.

When disease detectives — epidemiologists — set out to determine what is the cause of an outbreak of illness, they typically conduct what is called a case control study. They compare people with the illness (cases) to people similar to the cases but who didn’t get sick (the controls).

If there was a foodborne outbreak linked to a particular restaurant chain, investigators would interview people who ate at restaurants in the chain — some cases and some controls — to try to determine what the people who got ill ate that the others did not.

If the people who got sick went to the salad bar but the people who didn’t skipped it, then investigators start looking at what was in the salad bars. If some people who didn’t get sick went to the salad bar but didn’t eat tomatoes, then you might start to look at where the tomatoes came from.

Trying to set up a case control study of vaping, though, requires some careful planning. Meaney-Delman said that because the investigation hasn’t yet homed in on a suspect, choosing the controls is a challenge.

Think about it: Do you compare sick vapers to people who vaped but didn’t get sick? Or people who vaped THC to people who did not?  Or people who vaped THC in combination with nicotine to people who only vaped THC? Or people who vaped THC using the latest generation of devices — which heat the fluids used to very high temperatures — to people who used older devices? The mind boggles.

“At this point, given that we haven’t narrowed it down entirely to one product it would … have to be broad,” Meaney-Delman said. “People who didn’t get sick but who used … these vaping products. And ideally we would be able to narrow that down and have controls specific to a particular behavior or a particular substance. But because of where we are at the moment with our data, it’s harder to establish the controls.”

How much does it complicate matters that THC appears to be front and center here?

Quite a bit.

For starters, some of the patients may not be eager to tell public health officials they were vaping THC, especially in states where it is illegal. Some of the cases are teens who are legal minors; when they are interviewed, a parent probably has to be in the room. That too could impact their willingness to be completely forthcoming, said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy and Minnesota’s former state epidemiologist.

When public health officials investigate food related outbreaks, they try to do what’s called a trace back — find the contaminated food item and follow it back to its source. At the end of the day, they can sometimes tell what farm tainted lettuce or berries came from.

But when a substance is illegal, those kinds of efforts can hit a dead-end, Danila said.

“Here it may be like …. ‘I got it from a friend,’ ‘I got it from a drug dealer,’ ‘I got it on the street,” he said. “We can’t do a trace back because we get as far as the drug dealer and that’s it. You’re not getting any further, right?’’

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  • My position is that you need a case-control study if you are doing an outbreak investigation. If you don’t have the numbers, it’s very hard to defend a ban. This doesn’t even happen with food outbreak investigations until they are done with the case-control study. That’s what this article is about. WHI showed us that HRT gives you heart attacks, but women still take it if they want. It’s too late in the US healthcare system to even care about profits. HRT probably sells, too. We just have to try the least of evils. If that doctor thinks it’s unsafe, maybe he’s right, and he is welcome to do a case-control study. Until then, like the HRT women, I’d prefer not to be paternalized.

    • Read THE GREAT BORD FLU HOAX by D. Joseph Mercola, the same CDC, FDA and Big Pharma bums rush modus operandi to ban cannabis products, proven in thousands of published and vetted nih.gov endocannabinoid studies, to block blood glucose uptake via the P53 chromosome to radicalized, metastisized cells, lesions or tumors, that starve and dissolve them non evasively, with no pyschosctive intracontradiction. This attempted bs in vapes is about protecting big tobacco big pharma and big booze revenues.

    • Monika,
      We certainly would have more evidence with a randomized study. In the absence of that, one has to balance the risks. Charlie Baker decided that it’s more important to avoid having people get sick and die than to worry about businesses losing profits. You seem to be arguing that it’s more important to make sure that businesses do not lose profits than to worry about people getting sick.

  • Bruce, please don’t troll me. I have been to Toronto and used a vaporizer there. The Volcano is an air vaporizer that uses heat and not oil. I actually have an expensive Pax hand vaporizor because I did not like the Volcano, and I do not like the Pax. I used it when I first moved here and before they started selling oil vape at my dispensary. I am not lazy, I grind and smoke my own cannabis flower and it is hurting my lungs. The oil vaporizer is the issue. Pax and Volcano are air vaporizers. There was some belief that illegal vendors were including Vitamin E oil in some of the oil vaporizers. The good news is that the court is weighing in on the issue in Massachusetts. Please have some compassion.

  • Commenters – Bruce is correct, in that I cannot purchase my vaping products anymore. I can purchase the ingredients, take them home, and put them together myself. His point actually supports my point about how this is not the “public health way” to do a ban. In my case, the ban makes no sense because I can put together the same products with the same ingredients bought from the same place. (This is prohibitively challenging for me so I have opted to smoke rather than watch YouTube videos, buy equipment, and try to figure out how to DIY vape without hurting myself.)

  • Thank you for this article. It’s challenging, but I feel something sinister is going on because I am not seeing any case control studies, and I’m seeing lots more cases than we get with food outbreaks. It’s hard to choose controls, so you just get several sets of them and use them all and look at the differences. The control sets you suggest are great ideas. I feel that the CDC is falling down on the job and I’m disgusted because I’m an epidemiologist. Already there is a vaping ban in Massachusetts and I cannot vape medical marijuana, even though I’m a registered patient using our dispensaries. I can’t believe anyone is making policy without a single case-control study. I can’t believe the publications from the CDC that don’t include the source of the vaping products (legal, illegal, dispensary, etc.). It seems like all we’ve learned about public health and policy has been thrown out the window. I’m embarrassed and disgusted with our public health in the US.

    • Monika, you are mistaken. The vaping ban applies to vaping of THC or nicotine using e-cigarettes. People are allowed to purchase marijuana, and they are able to take it home and vape it.

      I agree that the CDC has not handled things well. They were slow to release information on what people with the illness had been vaping. They have not yet indicated whether those people who said that they only vaped nicotine were in a state in which marijuana and THC are illegal, which would call their statements into question. At least we know that everyone with the illness reported vaping THC, CBD, and/or nicotine, and none of them reported vaping marijuana.

  • people that vape are constantly vaping. when you smoke a cigarette or a joint, you smoke one at a time, maybe two, then you have an oxygen break for a while in between. youre not 100 back to back constantly all day long. vaping makes it too easy to overdose. id bet the people affected are super heavy users. puffing out clouds all day long and never stopping. i see people that never put them down! they are just as bad as phones in that they never put them down. tasting and smelling so good make it easy to not think about just how much they are imbibing, its like vitamins that taste like candy. its really easy to overdo it.

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