Nearly two dozen people in the Midwest were hospitalized with severe respiratory problems, and doctors are not sure why any type of equipment used them. Also, doctors do not know where they bought the devices or e-liquids.
Some patients said they had used e-cigarette devices to inhale nicotine as well as THC, the psychoactive ingredient in marijuana.
"We know that there are certain features that are common to these cases, but we have not been able to pinpoint exactly which aspect of the vapor habit or product or solvent or oil is causing the injury." Minnesota Medical Director, Emily Chapman, a pediatric healthcare system headquartered in Minneapolis.
Four of the cases were reported in Minnesota, twelve in Wisconsin and six in Illinois.
Chapman told NBC News that all four children admitted in Children's Minnesota had arrived at what doctors originally thought was a serious respiratory infection, such as pneumonia.
But instead of getting better, they got worse.
"They have significant breathing difficulties and increasing lung complaints," said Chapman. "They finally needed our ICU and, in some cases, help with breathing."
Physicians in Illinois and Wisconsin faced the same situations.
"All patients stated to quench before their hospitalization, but we do not know all the products they have used," said Andrea Palm of the Wisconsin Department of Health opposite WGBA, the NBC News subsidiary in Green Bay, Wisconsin.
You literally do not know what you breathe into your body.
One such patient, Dylan Nelson, 26, of Burlington, Wisconsin, fell ill after receiving a few hits from a new vape cartridge. The next morning he went to the hospital, and his symptoms worsened progressively throughout the day.
At dusk, his lungs filled with fluid and the doctors had to put him into a medically induced coma. He has since been released from hospital and is recovering slowly.
His brother, Patrick DeGrave, said that Nelson did not buy his vape cartridge in a reputable store.
"People will buy them in the states where it's legal and they'll bring them back to states like Wisconsin where it's not legal," DeGrave said.
"You do not know if you're buying something from a middle-aged man who picked it up from a pharmacy or if you buy it from someone who manipulated it and made his own mix," he said.
"You literally do not know what you breathe into your body."
It is unclear whether there was any kind of contamination of equipment or e-liquids that led to the clusters of cases, including Nelson's. The brand, thanks to Vapes, which he bought, was discontinued a few years ago, but the packaging still floats around.
"Could it be that these particular patients smoked something together? Definitely possible. It's also possible that clusters will become obvious as doctors, and we'll start looking for more things," Dr. Christy Sadreameli, pediatric pulmonary physician at the Johns Hopkins Hospital in Baltimore and volunteer spokeswoman for the American Lung Association.
Sadreameli also pointed out e-cigarettes are harmful to the growing body of teenagers, regardless of their source.
The juvenile lungs are not fully developed, potentially making them more susceptible to chemicals contained in e-cigarettes.
"The aerosol is heavy metals and ultrafine toxic particles that penetrate deep into the lungs," said Sadreameli.
Because the Food and Drug Administration does not require manufacturers of e-cigarettes to list all of their ingredients According to product labels, scientists have taken the equipment to the lab to find out the ingredients.
A recent study by Yale University identified chemicals called acetals in some juul-e-cigarette fluids. According to the researchers, these chemicals could be particularly irritating to the lungs and cause damage when inhaled.
"These incidents raise serious concerns and underline why the FDA should review e-cigarettes and determine their health effects before they are approved the market," the campaign for tobacco-free children wrote in a statement to NBC News.
The Wisconsin Department of Health has turned to the Centers for Disease Control and Prevention to coordinate investigations with states.