More deaths reported among rising number of lung disease cases that could be due to vaping

US health officials announced Friday that they are now aware of at least 450 possible cases of severe lung disease that could be caused by vaping. These cases, which have occurred in 33 states and one jurisdiction, include some cases that are still under investigation by state health officials.

US Centers for Disease Control and Prevention officials on Friday revealed the third and fourth confirmed vaping related deaths in Minnesota and Indiana. Two deaths, one in Illinois and one in Oregon, had been previously reported.

Related article Michigan will be the first state to ban the sale of flavored vaping products

Minnesota health officials said the person who died there was over 65, had a history of underlying lung disease and passed away in August. The Minnesota patient had a “long and complicated hospitalization” that involved “a severe lung injury that progressed to include other conditions,” according to the statement. After the patient died, investigators linked the lung injury to “vaping illicit THC products.”

Another potential vaping-related death was reported in Los Angeles, according to an announcement by Los Angeles County Department of Public Health. The CDC has not confirmed if the LA death is part of the national trend. CNN has contacted to CDC for confirmation.

‘People should consider not using e-cigarette products’

The CDC, FDA and state health departments say they’re working together to figure out which products might have been used and to facilitate laboratory testing. Health officials say they haven’t found a definitive cause or a clear connection between cases, but some are zeroing in on potential clues.

The New York State Department of Health today announced new findings of its ongoing investigation into the vaping-associated pulmonary (lung-related) illnesses that have been reported across the state, including an updated case count and information regarding the testing being conducted at the Department's Wadsworth Center Laboratory.\r\r"The cases of pulmonary illnesses associated with vaping are continuing to rise across New York State and the country," said Health Commissioner Dr. Howard Zucker."We urge the public to be vigilant about any vaping products that they or any family members may be using and to immediately contact their health care provider if they develop any unusual symptoms. In general, vaping of unknown substances is dangerous, and we continue to explore all options to combat this public health issue."\r\rThe Department issued a health advisory in August, alerting health care providers of this emerging health threat and listing symptoms they should look for in patients. As of September 5, 2019, the Department has received 34 reports from New York State physicians of severe pulmonary illness among patients ranging from 15 to 46 years of age who were using at least one cannabis-containing vape product before they became ill. However, all patients reported recent use of various vape products.\r\rLaboratory test results showed very high levels of vitamin E acetate in nearly all cannabis-containing samples analyzed by the Wadsworth Center as part of this investigation. At least one vitamin E acetate containing vape product has been linked to each patient who submitted a product for testing. Vitamin E acetate is not an approved additive for New York State Medical Marijuana Program-authorized vape products and was not seen in the nicotine-based products that were tested.\r\rAs a result, vitamin E acetate is now a key focus of the Department's investigation of potential causes of vaping-associated pulmonary illnesses. Vitamin E acetate is a commonly availa

Related article Vitamin E chemical is 'key focus' in vaping illness investigation, health officials say

“We believe that a chemical exposure is likely associated with these illnesses,” Dr. Dana Meaney-Delman, CDC’s incident manager for the response to the outbreak, told reporters Friday.

“At this time, no one device, product or substance has been linked to all cases,” she added, “and continued investigation is needed to better understand if a true relationship exists between any specific product or substance and the illnesses we are observing in patients.”

The CDC and various state health departments have reported widespread use of products containing THC, or tetrahydrocannabinol, the psychoactive substance in cannabis.

On Thursday, New York health officials said their investigation had found “very high levels” of the chemical vitamin E acetate in nearly all cannabis-containing vaping products that were analyzed. The chemical is now “a key focus” of the department’s investigation into the illnesses.

Related article FDA warns companies to stop illegally marketing vape products

Mitch Zeller, the director of the FDA’s Center for Tobacco Products, told reporters that “no one substance or compound, including vitamin E acetate, has been identified in all of the samples tested.” The agency has so far received more than 120 samples showing a “mix of results,” he said.

“It’s important to emphasize that identifying any compounds that are present in the samples will ultimately just turn out to be one piece of the puzzle that will not necessarily answer questions about causality,” cautioned Zeller, who encouraged anyone who has had unexpected health or product issues from vaping to notify the FDA through its online safety reporting portal.

Doctors also think it’s possible that mixing a variety of ingredients in vapes could result in the creation of new toxic agents.

Meaney-Delman warned users Friday not to buy e-cigarette products off the street or modify them in any way. She added the primary way to prevent these illnesses is to not vape at all.

“Most importantly, while this investigation is ongoing, people should consider not using e-cigarette products,” she said.

New reports emerge

In a preliminary report published Friday in the New England Journal of Medicine, health officials from Illinois and Wisconsin gave a breakdown of the first 53 cases in their states: 83% were male, with a median age of 19, and 94% had been hospitalized. More than half landed in the ICU, and roughly a third needed intubation and mechanical support to breathe.

Related article Cases of lung disease possibly linked to vaping continue to rise. This teen was given a 'second chance'

Despite the patients being “generally young and healthy,” nearly all experienced respiratory symptoms like shortness of breath, 81% had gastrointestinal symptoms, and all had general symptoms such as fever, fatigue or weight loss.

The majority, 84%, had used products containing THC, though “a wide variety of products and devices was reported,” said the authors.

In another report published in the same journal, doctors said they found different imaging patterns on lung scans — which could suggest “different mechanisms of injury.”

One of these patterns was lipoid pneumonia, which was the focus of yet another report published Friday regarding the “outbreak” in North Carolina.

“It can occur when either oils or lipid-containing substances enter the lungs,” explained one of the authors of that report, Dr. Daniel Fox, a pulmonary and critical care physician at WakeMed Health and Hospitals in North Carolina. “It is a rare diagnosis.”

According to his report, one possible explanation for why five patients developed lipoid pneumonia was that aerosolized oils deposited in their airways, causing local inflammation that impaired their lung function. Case reports from previous years have linked vaping to lipoid pneumonia, as well.

Meaney-Delman cautioned that it’s unclear whether these lipids came from e-cigarettes, somewhere inside the body or some other source. “It’s too early to know” whether such findings, also described by doctors at University of Utah Health Friday, will provide a key clue to the investigation, she said.

Experts say the prevalence of lung disease potentially attributable to vaping could be much larger, as doctors may not pick up on some of the milder cases.

“These cases may be some of the most severe, and the full spectrum of illness may be broader,” she said.

Call for e-cigarette regulation

After news of additional deaths spread on Friday, US Senate Democratic Whip Dick Durbin called on FDA Acting Commissioner Dr. Ned Sharpless to act on regulating e-cigarettes and flavors in the next 10 days. Durbin said he would call for Sharpless’ resignation if he did not take action.

Related article Study finds e-cig flavors can damage cardiovascular cells

“As Acting Commissioner of the FDA, you alone have the power to stop this vaping epidemic, which has now reached the point where children and young adults are getting sick and dying,” Durbin said in a statement. “If you continue to refuse to do your job — which is to protect the public health — then it is time to allow someone else to take the helm.”

CNN has reached out to the FDA for a response.

This week, Michigan Gov. Gretchen Whitmer announced the state would ban the sale of flavored e-cigarettes in brick-and-mortar stores and online sales. The ban gives sellers 30 days to comply and lasts six months, though the governor can decide to renew it.

Citing these products’ appeal to kids, Whitmer also ordered the Michigan Department of Health and Human Services to “ban misleading marketing of vaping products, including the use of terms like ‘clean,’ ‘safe,’ and ‘healthy’ that perpetuate beliefs that these products are harmless,” the announcement said.

SAN FRANCISCO, CA - MAY 05: E-cigarettes are displayed at Gone With the Smoke Vapor Lounge on May 5, 2016 in San Francisco, California. The U.S. Food and Drug Administration announced new federal regulations on electronic cigarettes that will be the same as traditional tobacco cigarettes and chewing tobacco. (Photo by Justin Sullivan/Getty Images)

Related article Lawmaker asks FDA to crack down on Juul's 'fraudulent' medical claims

Flavors are at the center of the regulatory debate on e-cigarettes: Some say they’re an important tool in getting adults to switch from combustible cigarettes, while others want to ban them entirely because they appeal to kids and minimize how harmful and addictive vapes are perceived to be.

In June, San Francisco’s board of supervisors unanimously voted to make the city the first in the US to effectively ban e-cigarette sales. The ordinance it passed said “no person shall sell or distribute an electronic cigarette to a person in San Francisco” unless that product has undergone premarket review by the US Food and Drug Administration. To date, none have.

CNN’s Jacqueline Howard and Jamie Gumbrecht contributed to this report.