Are e-cigs safe?

Results of an animal study at CU suggest that the nicotine devices may be just as toxic to skin and lungs as tobacco cigarettes
January 27th, 2017
Samples of skin flap tissue from the CU study. The dark outlined areas at the top of each are dead tissue. The sample on the right is from a rat exposed to e-cigarette vapor; on the left is a sample from a rat exposed to tobacco smoke.
Samples of skin flap tissue from the CU study. The dark outlined areas at the top of each are dead tissue. The sample on the right is from a rat exposed to e-cigarette vapor; on the left is a sample from a rat exposed to tobacco smoke.

One day a few years ago, Frederic Deleyiannis, MD, was walking through the pre-operative area at Children’s Hospital Colorado when he encountered an unusual sight. A patient awaiting check-in for surgery was puffing on an electronic cigarette.

Smoking is anathema to Deleyiannis, a plastic and reconstructive surgeon with the CU School of Medicine who practices at Children’s Colorado and University of Colorado Hospital. He specializes in skin flap surgery, which involves harvesting tissue from one part of the body to repair damaged areas in another. It is well established that the nicotine and the particulate matter in tobacco cigarettes constricts blood vessels, increases blood clotting and slows wound healing.

“Tobacco can cause part of the flap to die,” Deleyiannis said. “We tell our patients to stop using it at least a month before flap surgery.”

Electronic cigarettes (e-cigarettes) deliver nicotine dissolved in a liquid by heating it and converting it into a vapor that smokers inhale. The liquid includes glycerol and propylene glycol and often one of a host of flavorings. Despite a recent warning from the U.S. Surgeon General, the devices have long been billed in some quarters as a safer alternative to their tobacco counterparts. Deleyiannis’s chance encounter in pre-op caused him to think about that.

“I realized that nobody can answer the question of what is going to happen to patients who smoke e-cigarettes,” he said. Nor was there much information about the devices he or other providers could use to make decisions about the risks of performing surgery or the probable outcomes.

Cutting through the haze

The questions remain open for debate, but Deleyiannis and School of Medicine colleagues have nudged science closer to an answer. In a study of rats undergoing flap surgery, they showed that exposure to e-cigarette vapor was at least as harmful to tissue healing as exposure to tobacco smoke. Healing was best for rats exposed only to room air.

The study, which was funded by a CU Department of Surgery grant, has been accepted for publication by the Annals of Plastic Surgery. Aline Rau, MD, the research resident devoted to the study, presented the findings at the May 2016 meeting of the Plastic Surgery Research Council meeting in New York City.

Previous studies have looked at the effects of e-cigarette vapor on cells, Deleyiannis said. But the CU work is the first he’s aware of conducted on living animals with the aim of examining the effects of e-cigarettes on skin flap survival.

Among Deleyiannis’s collaborators were Eric Schmidt, MD, and Laima Taraseviciene-Stewart, PhD, of CU’s Division of Pulmonary Sciences and Critical Care Medicine. Preliminary data from the study suggest that e-cigarette vapor may also increase the risk of emphysema, or breakdown of the tiny air sacs in the lungs, just as tobacco smoke does.

As principal investigator for a 2009 study that looked at the effects of second-hand tobacco smoke on rats, Taraseviciene-Stewart laid the groundwork for Deleyiannis’s work. The study included groups of rats exposed for two and four months, respectively, to mainstream and sidestream smoke – similar to sitting in a bar or casino and breathing in smoke exhaled by puffers and being exposed to smoke from the burning ends of cigarettes. The rats had severe lung damage and evidence of an inflammatory response linked to tissue destruction.

“They showed the same disease progression as we see in humans who smoke,” Taraseviciene-Stewart said.

Waiting to inhale

The vaporfrom e-cigarette is pumped into this smoking chamber, which houses the study animals (who are not in this photo).
The vapor from e-cigarette is pumped into this smoking chamber, which houses the study animals (who are not in this photo).

To put the rats in a consistently hazy environment for that study, Taraseviciene-Stewart and her colleagues used a smoking machine developed by Teague Enterprises that contains a microprocessor that delivers measured amounts of cigarette smoke to animals in chambers. When Deleyiannis came up with the idea for the e-cigarette study, he contacted Tarseviciene-Stewart, hoping he could use the Teague machine to study the effects of electronically generated vapor on rats.

There was a catch, however: The machine wasn’t equipped to handle an e-cigarette, which is larger in diameter than a tobacco cigarette. Undeterred, the researchers used a portion of the Department of Surgery grant to buy a Teague machine customized to accommodate an e-cigarette. It pumped vapor to the rats four hours a day, five days a week for four weeks.

In addition to showing the toxic effects of vapor on skin flap healing, the e-cigarette study essentially duplicated the pulmonary results of the 2009 tobacco investigation, Taraseviciene-Stewart said.

The customized smoking machine used in the study. A glowing e-cigarette on the left is being “inhaled” by the machine.
The customized smoking machine used in the study. A glowing e-cigarette on the left is being “inhaled” by the machine.

“We saw the same pathology in the cells of the lungs in rats exposed to e-cigarette vapor as we had seen with tobacco smoke in the previous study,” she said. “There is no question.”

Her assertion will be a tough sell to many, however. “There has been an explosion in e-cigarette use,” Deleyiannis said.

Market muscle

The National Center for Health Statistics, for example, estimated that in 2015 nearly 9 million adults used e-cigarettes daily or on some days and some 30 million had tried it. In 2015, 16 percent of high school students used e-cigarettes, up from just 1.5 percent four years before, according to the Centers for Disease Control and Prevention.

Ivan Rodriguez, MD, a professional research assistant with the CU School of Medicine, prepares an e-cigarette for the smoking machine.
Ivan Rodriguez, MD, a professional research assistant with the CU School of Medicine, prepares an e-cigarette for the smoking machine.

In Deleyiannis’s view, the growth is a tribute to marketing, sometimes with the support of health care providers. Most notably, a 2015 report from Public Health England – an agency of the United Kingdom’s Department of Health – touted e-cigarettes as an effective aid to smoking cessation and estimated that the devices are “around 95% less harmful to health than smoking.”

With restrictions on tobacco smoking in public places firmly in place around the country, e-cigarettes offer an attractive alternative. That’s reflected in the hundreds of brands, models of delivery devices and flavors now available. For Deleyiannis and Taraseviciene-Stewart, this last is especially problematic.

They point out that while researchers don’t yet fully understand what effect, if any, inhaling the flavorings has on the body, there are thousands of them on the market, with no testing requirements. Early studies have, in fact, shown flavorings to add to an e-cigerette’s health risk.

“When you add the flavorings, you are adding different compounds to the e-cigarettes, and they are unregulated,” Tarseviciene-Stewart said.

There is more work to be done. Deleyiannis is now designing a study to determine if stopping vaping can reverse the effects of damage to skin flap tissue and lung air sacs – and if so how long the cessation period must be. If nothing else, he said, the research suggests the safety of e-cigarettes deserves the same scrutiny that was applied to regular cigarettes many years ago.

“Our studies will affect how we counsel our patients,” Deleyiannis said. “There may be a health benefit to using e-cigarettes instead of tobacco, but no one yet knows the true risk.”

About the author

Tyler Smith is a freelance writer based in metro Denver.