research on vaping 2022

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Wednesday, October 26, 2022

NIH-funded studies show damaging effects of vaping, smoking on blood vessels

Combining e-cigarettes with regular cigarettes may increase health risks.

Long-term use of electronic cigarettes, or vaping products, can significantly impair the function of the body’s blood vessels, increasing the risk for cardiovascular disease. Additionally, the use of both e-cigarettes and regular cigarettes may cause an even greater risk than the use of either of these products alone. These findings come from two new studies supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH).  

The findings, which appear today in the journal  Arteriosclerosis, Thrombosis, and Vascular Biology , add to growing evidence that long-term use of e-cigarettes can harm a person’s health. Researchers have known for years that tobacco smoking can cause damage to blood vessels. However, the effects of e-cigarettes on cardiovascular health have been poorly understood. The two new studies – one on humans, the other on rats – aimed to change that.

“In our human study, we found that chronic e-cigarettes users had impaired blood vessel function, which may put them at increased risk for heart disease,” said Matthew L. Springer, Ph.D., a professor of medicine in the Division of Cardiology at the University of California in San Francisco, and leader of both studies. “It indicates that chronic users of e-cigarettes may experience a risk of vascular disease similar to that of chronic smokers.” 

In this first study, Springer and his colleagues collected blood samples from a group of 120 volunteers that included those with long-term e-cigarette use, long-term cigarette smoking, and those who didn't use. The researchers defined long-term e-cigarette use as more than five times/week for more than three months and defined long-term cigarette use as smoking more than five cigarettes per day.

They then exposed each of the blood samples to cultured human blood vessel (endothelial) cells in the laboratory and measured the release of nitric oxide, a chemical marker used to evaluate proper functioning of endothelial cells. They also tested cell permeability, the ability of molecules to pass through a layer of cells to the other side. Too much permeability makes vessels leaky, which impairs function and increases the risk for cardiovascular disease.

The researchers found that blood from participants who used e-cigarettes and those who smoked caused a significantly greater decrease in nitric oxide production by the blood vessel cells than the blood of nonusers. Notably, the researchers found that blood from those who used e-cigarettes also caused more permeability in the blood vessel cells than the blood from both those who smoked cigarettes and nonusers. Blood from those that used e-cigarettes also caused a greater release of hydrogen peroxide by the blood vessel cells than the blood of the nonusers. Each of these three factors can contribute to impairment of blood vessel function in people who use e-cigarettes, the researchers said.

In addition, Springer and his team discovered that e-cigarettes had harmful cardiovascular effects in ways that were different from those caused by tobacco smoke. Specifically, they found that blood from people who smoked cigarettes had higher levels of certain circulating biomarkers of cardiovascular risks, and the blood people who used e-cigarettes had elevated levels of other circulating biomarkers of cardiovascular risks.

“These findings suggest that using the two products together, as many people do, could increase their health risks compared to using them individually,” Springer said.  “We had not expected to see that.”

In the second study, the researchers tried to find out if there were specific components of cigarette smoke or e-cigarette vapor that were responsible for blood vessel damage. In studies using rats, they exposed the animals to various substances found in tobacco smoke or e-cigarettes. These included nicotine, menthol (a cigarette additive), the gases acrolein and acetaldehyde (two chemicals found in both tobacco smoke and e-cigarette vapors), and inert carbon nanoparticles to represent the particle-like nature of smoke and e-cigarette vapor.

Using special arterial flow measurements, the researchers demonstrated that blood vessel damage does not appear to be caused by a specific component of cigarette smoke or e-cigarette vapor. Instead, they said, it appears to be caused by airway irritation that triggers biological signals in the vagus nerve that somehow leads to blood vessel damage, possibly through an inflammatory process. The vagus is a long nerve extending from the brain that connects the airway to the rest of the nervous system and plays a key role in heart rate, breathing, and other functions. The researchers showed that detaching the nerve in rats prevented blood vessel damage caused by tobacco smoke, demonstrating its key role in this process. 

“We were surprised to find that there was not a single component that you could remove to stop the damaging effect of smoke or vapors on the blood vessels,” Springer said. “As long as there’s an irritant in the airway, blood vessel function may be impaired.”   

The finding has implications for efforts to regulate tobacco products and e-cigarettes, as it underscores how difficult it is to pinpoint any one ingredient in them that is responsible for blood vessel damage. “What I like to tell people is this: Just breathe clean air and avoid using these products,” Springer said.

Lisa Postow, Ph.D., an NHLBI program officer in NHLBI’s Division of Lung Diseases, agreed that the study results “provide further evidence that exposure to e-cigarettes could lead to harmful cardiovascular health effects.” She added that more data is needed to fully understand the health effects of e-cigarettes. The NIH and others are continuing to explore this area.

Research reported in the e-cigarette study was funded by NHLBI grants U54HL147127, P50HL120163, and R01HL120062 and the U.S. Food and Drug Administration Center for Tobacco Products (FDA CTP); and grant P50CA180890 from the National Cancer Institute at the NIH and FDA CTP. Research reported in the cigarette smoke/-vagal nerve study was supported by NHLBI grants R01HL120062 and U54HL147127 and FDA CTP and grant P50CA180890 from the National Cancer Institute at the NIH and FDA CTP. For additional funding details, please see the full journal articles.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit www.nhlbi.nih.gov .   

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .

NIH…Turning Discovery Into Health ®

Chronic e-cigarette use impairs endothelial function on the physiological and cellular levels. Arteriosclerosis, Thrombosis, and Vascular Biology. DOI: 10.1161/ATVBAHA.121.317749

Impairment of Endothelial Function by Cigarette Smoke is not Caused by a Specific Smoke Constituent, but by Vagal Input from the Airway. Arteriosclerosis, Thrombosis, and Vascular Biology. DOI: 10.1161/ATVBAHA.122.318051

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Studies show that about 9 percent of the population and nearly 28 percent of high school students are e-cigarette users.

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Restricted airways, scarred lung tissue found among vapers

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Small study looks at chronic e-cigarette users, seeing partial improvement once they stop

Chronic use of e-cigarettes, commonly known as vaping, can result in small airway obstruction and asthma-like symptoms, according to researchers at Harvard-affiliated Massachusetts General Hospital.

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In the first study to microscopically evaluate the pulmonary tissue of e-cigarette users for chronic disease, the team found in a small sample of patients fibrosis and damage in the small airways, similar to the chemical inhalation damage to the lungs typically seen in soldiers returning from overseas conflicts who had inhaled mustard or similar types of noxious gases. The study was published in  New England Journal of Medicine Evidence .

“All four individuals we studied had injury localized to the same anatomic location within the lung, manifesting as small airway-centered fibrosis with constrictive bronchiolitis, which was attributed to vaping after thorough clinical evaluations excluded other possible causes,” says lead author Lida Hariri, an associate professor of pathology at Harvard Medical School and a pathologist and physician investigator at MGH. “We also observed that when patients ceased vaping, they had a partial reversal of the condition over one to four years, though not complete due to residual scarring in the lung tissue.”

A huge increase in vaping, particularly among young adults and adolescents, has occurred in the United States, with studies showing about 9 percent of the population and nearly 28 percent of high school students are e-cigarette users. Unlike cigarette smoking, however, the long-term health risks of chronic vaping are largely unknown.

In order to determine the underlying pathophysiology of vaping-related symptoms, the MGH team examined a cohort of four patients, each with a three- to eight-year history of e-cigarette use and chronic lung disease. All patients underwent detailed clinical evaluation, including pulmonary function tests, high resolution chest imaging, and surgical lung biopsy. Constrictive bronchiolitis, or narrowing of the small airways due to fibrosis within the bronchiolar wall, was observed in each patient. So was significant overexpression of MUC5AC, a gel-forming protein in the mucus layer of the airway that has been seen in airway cell and sputum samples of individuals who vape. In addition, three of the four patients had evidence of mild emphysema consistent with their former combustible cigarette smoking history, though researchers concluded this was distinct from the findings of constrictive bronchiolitis seen in the patient cohort.

Because the same type of lung damage was observed in all patients, as well as partial improvement in symptoms after e-cigarette usage was stopped, researchers concluded that vaping was the most likely cause after thorough evaluation and exclusion of other possible causes. “Our investigation shows that chronic pathological abnormalities can occur in vaping exposure,” says senior author David Christiani, a professor of medicine at HMS and a physician investigator at Mass General Research Institute. “Physicians need to be informed by scientific evidence when advising patients about the potential harm of long-term vaping, and this work adds to a growing body of toxicological evidence that nicotine vaping exposures can harm the lung.”

A hopeful sign from the study was that three of the four patients showed improvements in their pulmonary function tests and high-resolution computed tomography (HRCT) chest imaging after they ceased vaping. “While there is growing evidence to show that vaping is a risky behavior with potential long-term health consequences for users,” says Hariri, “our research also suggests that quitting can be beneficial and help to reverse some of the disease.”

The study was funded by the National Institutes of Health.

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Electronic cigarettes and health outcomes: umbrella and systematic review of the global evidence

Affiliation.

• 1 National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT.
• PMID: 36939271
• PMCID: PMC10952413
• DOI: 10.5694/mja2.51890

Objective: To review and synthesise the global evidence regarding the health effects of electronic cigarettes (e-cigarettes, vapes).

Study design: Umbrella review (based on major independent reviews, including the 2018 United States National Academies of Sciences, Engineering, and Medicine [NASEM] report) and top-up systematic review of published, peer-reviewed studies in humans examining the relationship of e-cigarette use to health outcomes published since the NASEM report.

Data sources: Umbrella review: eight major independent reviews published 2017-2021. Systematic review: PubMed, MEDLINE, Scopus, Web of Science, the Cochrane Library, and PsycINFO (articles published July 2017 - July 2020 and not included in NASEM review).

Data synthesis: Four hundred eligible publications were included in our synthesis: 112 from the NASEM review, 189 from our top-up review search, and 99 further publications cited by other reviews. There is conclusive evidence linking e-cigarette use with poisoning, immediate inhalation toxicity (including seizures), and e-cigarette or vaping product use-associated lung injury (EVALI; largely but not exclusively for e-liquids containing tetrahydrocannabinol and vitamin E acetate), as well as for malfunctioning devices causing injuries and burns. Environmental effects include waste, fires, and generation of indoor airborne particulate matter (substantial to conclusive evidence). There is substantial evidence that nicotine e-cigarettes can cause dependence or addiction in non-smokers, and strong evidence that young non-smokers who use e-cigarettes are more likely than non-users to initiate smoking and to become regular smokers. There is limited evidence that freebase nicotine e-cigarettes used with clinical support are efficacious aids for smoking cessation. Evidence regarding effects on other clinical outcomes, including cardiovascular disease, cancer, development, and mental and reproductive health, is insufficient or unavailable.

Conclusion: E-cigarettes can be harmful to health, particularly for non-smokers and children, adolescents, and young adults. Their effects on many important health outcomes are uncertain. E-cigarettes may be beneficial for smokers who use them to completely and promptly quit smoking, but they are not currently approved smoking cessation aids. Better quality evidence is needed regarding the health impact of e-cigarette use, their safety and efficacy for smoking cessation, and effective regulation.

Registration: Systematic review: PROSPERO, CRD42020200673 (prospective).

Keywords: Electronic cigarettes; Public health; Systematic review.

© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.

Publication types

• Systematic Review
• Research Support, Non-U.S. Gov't
• Electronic Nicotine Delivery Systems*
• Prospective Studies
• Smoking Cessation*
• Young Adult

Grants and funding

• National Health and Medical Research Council