Mehmet S. Copur, MD, FACP Medical Director

CHI Health St. Francis Cancer Treatment Center, Grand Island, NE

Professor, Department of Internal Medicine, Hematology/OncologyUNMC, Omaha, NE

CHI Health St. Francis Cancer Treatment Center

Founded in 1887, CHI Health St. Francis is a regional referral center with more than 100 physicians and 1,100 employees who work together to build a healthier community by delivering high-quality care – from maternity to cardiology to cancer – close to home.

The CHI Health St. Francis Cancer Treatment Center diagnoses and treats 500-700 new cancer patients from across the state each year. Our affiliation with the National Cancer Institute and UNMC Eppley Cancer Center allows us to offer the latest cancer treatments, and the percentage of our patients enrolled in clinical trials is among the nation’s highest.

The Cancer Treatment Center is a three-time winner of the Outstanding Achievement Award from the American College of Surgeons Commission on Cancer.

E-Cigarettes

Public Health Consequences

Cigarette smoking the most preventable cause of death in the United States- 480,000 deaths annually

15.1 % of the U.S. adult population=36.5 million adults smoke cigarettes (CDC-estimate)

Nicotine in inhaled tobacco smoke moves from the lungs into the bloodstream and to brain within seven to 10 seconds

Once there, nicotine triggers a number of chemical reactions that create temporary short-lived feelings of pleasure subsiding within minutes

As the nicotine level drops in the blood, smokers feel edgy and agitated—the start of nicotine withdrawal

Nicotine increases adrenaline which in turn heart rate, blood pressure, and restricts blood flow into the heart muscle

Nicotine also inhibits the release of insulin leading hyperglycemia

Nicotine activates the same reward pathways in the brain that other drugs of abuse such as cocaine or amphetamines do

The acute effects of nicotine wear off within minutes so smokers must continue dosing themselves frequently throughout the day to maintain the effects and to prevent withdrawal symptoms

Cigarette Smoking-Preventable Health Problem

Nicotine is one of the lesser harmful agents in a cigarette smoke butit is the addictive compound

Nicotine can influence many biological processes; can suppressimmune system which can be helpful for inflammatory bowel diseasebut harmful with other diseases by keeping immune system fromdoing necessary work

Nicotine is neuroprotective-it keeps cells from dying which may soundbeneficial but may promote certain forms of neoplastic growth

Effects vary from person to person and depend on the genetics for themost part but for sure most negative side effects result from long-term exposure

Nicotine-the Culprit

Nicotine-the Culprit

How Addictive is Nicotine By Henningfield Criteria

How Addictive is Nicotine?By Benowitz Criteria

An electronic cigarette or e-cigarette is a handheld electronicdevice that simulates the feeling of tobacco smoking

It works by heating a liquid to generate an aerosol, commonlycalled a "vapor" that the user inhales

Using e-cigarettes is sometimes called vaping.

The liquid in the e-cigarette, called e-liquid is usually madeof nicotine, propylene glycol, glycerine, and flavorings

Scientists are still working to understand more fully the healtheffects and harmful doses of e-cigarette contents when they areheated and turned into an aerosol, both for active users who inhalefrom a device and for those who are exposed to the aerosol second-hand

What is in E-cigarette Aerosol

The e-cigarette aerosol that users breathe from the deviceand exhale can contain harmful and potentially harmfulsubstances, including:

◦ Nicotine

◦ Ultrafine particles that can be inhaled deep into the lungs

◦ Flavoring such as diacetyl, a chemical linked to a serious lung disease

◦ Volatile organic compounds

◦ Cancer-causing chemicals

◦ Heavy metals such as nickel, tin, and lead

It is difficult to know what e-cigarette products contain

Some e-cigarettes marketed as containing zero percentnicotine have been found to contain nicotine

What is in E-cigarette Aerosol

2003 Headline: Invention of E-Cigarettes◦ The first person on record to have the idea for an electronic non-

tobacco option is Herbert A. Gilbert who filed for a patent in 1963,in an era when tobacco smoking was widely accepted and thehealth risks were less apparent

◦ Three pack-a-day smoker Hon Lik, a 52-year old Beijingpharmacist, created the first successful electronic cigarette afterhis father, another heavy smoker, died of lung cancer

◦ By 2007, e-cigarettes were marketed in Europe and in the UnitedStates by the manufacturer Ruyan as a way to safely stop smokingtobacco

Historical Perspective

In September 2008, the World Health Organization announcesthat marketers should immediately remove any claims that e-cigs are a "safe and effective smoking cessation aid" becausethere is no scientific evidence to confirm the product's safetyand efficacy

Soon after, a study funded by e-cigarette manufacturer Ruyandeclares the product to be 100 to 1,000 times less dangerousthan smoking tobacco, adding that when using their device,nicotine is "apparently not absorbed from the lung, but fromthe upper airways"

2008 Headline: WHO slams E-Cigarette Marketing

In July, an FDA news release discourages the use of e-cigarettes, saying they contain carcinogens and an ingredientused in anti-freeze, diethylene glycol

Vape supporters counter that diethylene glycol was found at avery low, non-toxic level of 1%, and that the carcinogens are atthe same levels as other FDA-approved nicotine cessationproducts, like patches and gum

Another concern arises as e-cigarettes are often marketed andsold to youngsters who, intrigued by the many flavors such aschocolate, bubble gum and mint, might easily adopt a smokinghabit as a result of trying the devices

By the end of the year, Amazon and Paypal restrict the sale ofe-cigs on their websites

2010 Headline: The Battle Heats Up

The Centers for Disease Control announces that e-cigarette useamong U.S. middle and high school students doubles between2011 and 2012, mirroring a similar increase in adult use

Most alarming for policy makers: CDC concerns that vapingamong adolescents may serve as a gateway to tobacco use

To measure nicotine delivery, United Kingdom Researchers test16 e-cigarettes with an automatic smoking machine and findwide variations in nicotine levels per puff, ranging from 0.5 to15.4 mg

In contrast, the typical level from a tobacco puff ranges onlyfrom 1.54 to 2.60 mg. The wide variation between e-cigarettebrands leads researchers to question how well they canfunction as a nicotine replacement device

2012 Headline: E-Cigarette Use Doubles in Adolescents

Several 2013 publications show minimal evidence that e-cigarettes help smokers quit-A cross-sectional study of1,836 tobacco smokers finds a significant association with e-cig use and "unsuccessful quitter" status but none with'quitter" status

Another study of callers to state tobacco quit lines finds e-cigarette users significantly less likely to be tobacco-freeseven months after they first try vaping compared withparticipants who never try e-cigarettes

A New Zealand Health Research Council Study of 657 smokersfinds e-cigarettes modestly effective in helping smokers quit

Researchers worry that e-cigarette use might distractsmokers from proven safe and effective methods for kickingtheir tobacco habit- "It's filter tipped, low tar, déjà vu all overagain: A Triumph of Wishful Thinking over Science."

2013 Headline: Do E-Cigs Really Help Smokers Quit?

The Centers for Disease Control releases data showing that the number ofcalls about nicotine E-liquids to poison centers rose from a scant one callper month in 2010 to 215 calls per month in 2014

More than half of the calls involved children under the age of 5 ingesting,inhaling or getting the substance in their eyes or on the skin

A study of over 75,000 Korean adolescents finds e-cigarette use to bestrongly associated with current and heavy traditional cigarette smoking

Data from the CDC find that the use of e-cigarettes among U.S. high schoolstudents grew from 4.5 % in 2013 to 13 % in 2014

In that same time period, use grew among middle-schoolers from 1 % to 4 %

A study comparing the use of e-cigarette inhaler to the barely used FDAapproved nicotine inhaler for smoking cessation finds the e-cig version aclear winner with users, providing more satisfaction and a better image

2014 Headline: Poison Center Calls Skyrocket

In 2014 more than half of reported exposures to e-cigarettes andliquid nicotine occurred in young children under the age of 6

Some children and toddlers who come in contact with e-cigarettedevices or liquid nicotine have become very ill; some even requiringER visits with nausea and vomiting being the most significantsymptoms

Adults should use care to protect their skin when handling theproducts, and they should be out of sight and out of the reach ofchildren

Additionally, those using these products should dispose of themproperly to prevent exposure to pets and children from the residueor liquid left in the container

2014 Headline: Poison Center Calls Skyrocket

In 2004, The US Centers for Disease Control and Prevention(CDC) reported several cases of bronchiolitis obliterans inworkers in a microwave popcorn plant in Missouri

Bronchiolitis obliterans is a serious and irreversible condition inwhich the tiny air sacs in the lungs become scarred

After investigation by the NIOSH (National Institute of OccupationSafety and Health), it was discovered that a flavoringagent, diacetyl, was used to give the popcorn a buttery taste

Inhalation of this flavoring likely contributed to the developmentof the illness

The disease that results often is associatedwith cough and shortness of breath, similar to that seen inpeople with chronic obstructive pulmonary disease (COPD)

This process is irreversible by current therapy.

What is, and What Causes Popcorn Lung?

It is not only microwave popcorn that containsdangerous chemical flavorings such as diacetyl

A study published in 2015 in the journalEnvironmental Health Perspectives showed thatharmful chemicals associated with "popcorn lung" arepresent in many types of flavored e-cigarettes,particularly those with flavors like fruit and candythat may appeal to young smokers

Of the 51 flavored e-cigarettes tested, flavoringchemicals were found in 47 and diacetyl specificallyin 39 samples

This suggests a potentially dangerous level ofexposure via e-cigarettes to chemicals that can causesevere lung damage

Do E-Cigarettes Cause Popcorn Lung?

The Centers for Disease Control releases data showing that the number ofcalls about nicotine E-liquids to poison centers rose from a scant one callper month in 2010 to 215 calls per month in 2014

More than half of the calls involved children under the age of 5 ingesting,inhaling or getting the substance in their eyes or on the skin

A study of over 75,000 Korean adolescents finds e-cigarette use to bestrongly associated with current and heavy traditional cigarette smoking

Data from the CDC find that the use of e-cigarettes among U.S. high schoolstudents grew from 4.5 % in 2013 to 13 % in 2014

In that same time period, use grew among middle-schoolers from 1 % to 4 %

A study comparing the use of e-cigarette inhaler to the barely used FDAapproved nicotine inhaler for smoking cessation finds the e-cig version aclear winner with users, providing more satisfaction and a better image

2014 Headline: Poison Center Calls Skyrocket

Devices similar to electronic cigarettes, have existed for years, but they were just not cool enough to catch on

Listed among the treatments used for helping smokers quit, nicotine inhalers were approved by the Food and Drug Administration (FDA) in 1997

The devices deliver nicotine to the mouth when the smoker puffs at the plastic mouthpiece that looks like an old-fashioned cigarette holder

These products have been around for over 15 years now, and physicians and consumers are not aware of them

Nicotine Inhalers

The nicotine inhaler is a form of nicotine replacement therapy (NRT) consists of a plasticcigarette-like tube that houses a replaceable nicotine cartridge and a mouthpiece

When a person draws on the mouthpiece nicotine is released and absorbed through themembranes in the mouth and throat with less than 5 percent of the inhaled nicotinereaching the respiratory tract

Of the 10 mg of nicotine in a cartridge, 4 mg can be inhaled and 2 mg absorbed into thebody, each cartridge lasts about 20 minutes and delivers approximately the sameamount of nicotine as one regular cigarette

Typically recommended amount for ex-smokers is to start with a minimum of 6 nicotinecartridges a day for 3 to 6 weeks up to 16 cartridges a day up to 12 weeks

After that, it should be tapered down with the help of doctor until weaned off of itcompletely

The nicotine inhaler is one of two types of nicotine replacement therapy that require adoctor's prescription(the other is nicotine nasal spray)

Nicotine Inhalers

A New England Journal of Medicine study sets off alarm bells byreporting that some e-cigarettes release formaldehyde, aprobable carcinogen, when heated by high-voltage batteries

A Cleveland Clinic clinical review restates ongoing concernsabout propylene glycol and the various food flavorings that arepart of e-juice-While considered safe to eat in food in smallquantities, researchers say PGs have not been studied when"inhaled deeply and repeatedly“

Another study looks at 51 of the nearly 7,000 e-cigarette flavorscurrently marketed to check for a flavoring chemical calleddiacetyl that has been shown to be associated with a diseasecalled popcorn lung

The study finds diacetyl at higher than laboratory normal levelsin 39 of the tested flavors-Researchers call for "urgent action" toevaluate the "potentially widespread exposure"

2015 Headline: Vaping Could be Dangerous, but perhaps a Quitting Aid

In late January, BMJ published a study that quizzed morethan 2,000 Hawaiian ninth- and 10th-graders about theire-cigarette and traditional cigarette use, then followed upa year later-Nearly all of the teens (98%) knew aboutvaping, and 68% considered e-cigarettes to be healthierthan smoking

They found that vapers were more than three times aslikely to have begun smoking cigarettes by the next yearcompared with "never smokers“

The study also found the effect of e-cigarettes wasindependent of other factors that encourage teens to pickup the habit, such as rebelliousness and lack of parentalsupport

While the study showed any level of vaping led to somecigarette use, it was the heavy vapers who were morelikely to become regular cigarette smokers

2016 Headline: Vaping a Gateway to Tobacco Use ... and No Better for Your Heart

Former smokers who replaced standard cigarettes with e-cigarettessubstantially reduced their intake of cancer-causing chemicals, accordingto a study published in Annals of Internal Medicine in February

Although it's clear that vaping is not a healthy behavior, many people arguethat it is at least better than smoking, Yet scientific evidence of how thesetwo behaviors compare has been sorely lacking

One study, published in Pediatrics showed teens using these flavoredversions were less likely to see tobacco smoking as dangerous, and thereforemore likely to take up cigarette smoking

The Food and Drug Administration recently announced that it will regulate alltobacco products, including e-cigarettes, cigars, hookah tobacco and pipetobacco, and will prohibit the sale to youths under the age of 18

But the regulations stopped short of regulating flavorings, which leaves thesealluring flavors on the market to entice kids to try e-cigarettes

2017 Headline: E-Cigarettes are Safer than Conventional Cigarettes

E-cigarette aerosol generally contains fewertoxic chemicals than the deadly mix of 7,000chemicals in smoke from regular cigarettes

However, e-cigarette aerosol is not harmless

It can contain harmful and potentially harmfulsubstances, including nicotine, heavy metalslike lead, volatile organic compounds, andcancer-causing agents

Are E-cigarettes less Harmful than Regular Cigarettes?

The U.S. Preventive Services Task Force, a group of healthexperts that makes recommendations about preventive healthcare, has concluded that evidence is insufficient to recommende-cigarettes for smoking cessation in adults, including pregnantwomen

To date, the few studies on the issue are mixed

A Cochrane Review found evidence from two randomizedcontrolled trials that e-cigarettes with nicotine can help smokersstop smoking compared with placebo (non-nicotine) e-cigarettes

However, there are some limitations to the existing research,including the small number of trials, small sample sizes, andwide margins of error around the estimates

A recent CDC study found that many adults are using e-cigarettes in an attempt to quit smoking yet most end upcontinuing to use both products known as “dual use”

Can E-cigarettes Help Adults Quit Smoking Cigarettes

In the United States, youth are more likely thanadults to use e-cigarettes

◦ In 2015, among adult e-cigarette users overall, 58.8%also were current regular cigarette smokers, 29.8% wereformer regular cigarette smokers, and 11.4% had neverbeen regular cigarette smokers

◦ In 2016, more than 2 million U.S. middle and highschool students used e-cigarettes in the past 30 days-4.3% of middle school students and 11.3% of high schoolstudents

◦ Among current e-cigarette users aged 18–24 years,40.0% had never been regular cigarette smokers

◦ In 2016, 3.2% of U.S. adults were current e-cigaretteusers

Who is Using E-cigarettes?

Brain Risks The part of the brain that's responsible for decision making and impulse control

is not yet fully developed during adolescence. Youth and young adults are alsouniquely at risk for long-term, long-lasting effects of exposing their developingbrains to nicotine including nicotine addiction, mood disorders, and permanentlowering of impulse control. Nicotine also changes the way synapses areformed, which can harm the parts of the brain that control attention andlearning.

Addiction Until about age 25, the brain is still growing. Each time a new memory is

created or a new skill is learned, stronger connections – or synapses – are builtbetween brain cells. Young people's brains build synapses faster than adultbrains. Because addiction is a form of learning, adolescents can get addictedmore easily than adults. The nicotine in e-cigarettes and other tobacco productscan also prime the adolescent brain for addiction to other drugs such ascocaine.

Behavior Risks E-cigarette use among youth and young adults is strongly linked to the use of

other tobacco products, such as regular cigarettes, cigars, hookah, andsmokeless tobacco

E-Cigarette Use Among Youth and Young Adults

Came out 2 years ago

Has already amassed nearly half of the e-cigarette market share

Every month the JUUL Labs produce 20 million products (devices and cartridges)

JUUL Device cost $34.99

Four-pack of pods costs $15.99

Nicotine in each pod=1 pack of cigarettes (200 puffs)

JUUL

JUUL devices heat up a cartridge containing oils to create vapor

Vapor quickly dissolves into the air

Small and sleek – tech inspired design that was inspired by a USB flash drive

Charges by plugging into laptop

How do JUULs work?

Glycerol – colorless, sweet liquid formed as a byproduct in soap manufacture-Used as an emollient and laxative and for making explosives and anti-freeze

Benzoic Acid – colorless crystalline solid. Combine with other acids to treat skin irritation and inflammation caused by burns, insect bites, fungal infections and eczema

Propylene Glycol – synthetic liquid substance that absorbs water- Used as an antifreeze, a solvent for food colors and flavors, and in the paint and plastic industry

Nicotine

Does not contain Diacetyl (which some e-cigarettes do).

Natural Oils

Extracts and Flavor

Ingredients in JUL Vapor

Majority of youth e-cigarette users think that the last time they used a product they vaped only the flavoring, not nicotine –According to University of Michigan 2016 Study

Nicotine is known to cause long-term impacts on brain development in youth

Centers for Disease Control and Prevention reported that 99% of e-cigarettes sold in the U.S. stores in 2015 contained nicotine

Flavoring to target youth – examples: Peach, Mango, Mint

Four times more likely to start smoking combustible tobacco –University of Pittsburgh Schools of Health Sciences (December, 2017)

Started August 23, 2017 – JUULvapor.com requires you to be 21 & Over to purchase

21 & Over only for online but can purchase JUUL device in a store at the states law for tobacco & nicotine products

JUUL uses a system at checkout that does a public records search to find age

If they can’t find information may be required to upload a picture of I.D.

Expert Committee of the National Academies of Sciences, Engineering, and Medicine

National Academies of Sciences, Engineering, and Medicine

Conclusive Evidence byNational Academies of Sciences, Engineering, and Medicine

Substantial Evidence byNational Academies of Sciences, Engineering, and Medicine

Exposure to nicotine and toxic substances There is conclusive evidence that exposure to nicotine from e-cigarettes

is highly variable and depends on the characteristics of the device andthe e-liquid, as well as on how the device is operated.

There is conclusive evidence that in addition to nicotine, most e-cigarettes contain and emit numerous potentially toxic substances.

There is substantial evidence that except for nicotine, exposure topotentially toxic substances from e-cigarettes (under typical conditionsof use) is significantly lower compared with conventional cigarettes.

There is substantial evidence that nicotine intake from e-cigarettesamong experienced adult e-cigarette users can be comparable to thatfrom conventional cigarettes.

National Academies of Sciences, Engineering, and MedicineConclusions Organized by Outcome

Dependence and abuse liability There is substantial evidence that e-cigarette use results in symptoms of

dependence on e-cigarettes.

There is moderate evidence that risk and severity of dependence is lower for e-cigarettes than for conventional cigarettes.

There is moderate evidence that variability in the characteristics of e-cigarette products (nicotine concentration, flavoring, device type, and brand) is an important determinant of the risk and severity of dependence on e-cigarettes.

Harm reduction There is conclusive evidence that completely substituting e-cigarettes for

conventional cigarettes reduces users’ exposure to many toxicants and carcinogens present in conventional cigarettes.

There is substantial evidence that completely switching from regular use of conventional cigarettes to e-cigarettes results in reduced short-term adverse health outcomes in several organ systems.

National Academies of Sciences, Engineering, and MedicineConclusions Organized by Outcome

Injuries and poisonings There is conclusive evidence that e-cigarettes can explode and cause burns

and projectile injuries. Such risk is significantly increased when batteries are of poor quality, stored improperly, or are being modified by users.

There is conclusive evidence that intentional or accidental exposure to e-liquids (from drinking, eye contact, or skin contact) can result in adverse health effects such as seizures, anoxic brain injury, vomiting, and lactic acidosis.

There is conclusive evidence that intentionally or accidentally drinking or injecting e-liquids can be fatal.

Respiratory effects There is no available evidence whether or not e-cigarettes cause respiratory

diseases in humans. There is moderate evidence or increased cough and wheeze in adolescents

who use e-cigarettes, and an increase in asthma exacerbations.

Reproductive and developmental effects There is no available evidence whether or not e-cigarettes affect pregnancy

outcomes. There is insufficient evidence whether or not maternal e-cigarette use

affects fetal development.

National Academies of Sciences, Engineering, and MedicineConclusions Organized by Outcome

Use by youth and young adults There is substantial evidence that e-cigarette use by youth and young

adults increases their risk of ever using conventional cigarettes.

Secondhand exposure There is conclusive evidence that e-cigarette use increases airborne

concentrations of particulate matter and nicotine in indoor environments compared with background levels.

There is moderate evidence that second-hand exposure to nicotine and particulates is lower from e-cigarettes compared with conventional cigarettes.

Cancer There is no available evidence whether or not e-cigarette use is

associated with intermediate cancer endpoints in humans. (An intermediate cancer endpoint is a precursor to the possible development of cancer; for example, polyps are lesions that are intermediate cancer endpoints for colon cancer.)

There is limited evidence from animal studies using intermediate biomarkers of cancer to support the hypothesis that long-term e-cigarette use could increase the risk of cancer.

National Academies of Sciences, Engineering, and MedicineConclusions Organized by Outcome

Scientific Summary:◦ Based on currently available evidence, using current generation e-cigarettes is less

harmful than smoking cigarettes, but the health effects of long-term use are not known

◦ As new evidence emerges, the ACS will promptly report these findings to policy makers,the public and clinicians

Clinical Recommendations:

◦ The ACS recommends that clinicians advise their patients to use FDA-approved cessationaids that have been proven to support successful quit attempts

◦ Many smokers choose to quit smoking without the assistance of a clinician and some optto use e-cigarettes to accomplish this goal

◦ The ACS recommends that clinicians support all attempts to quit the use of combustibletobacco and work with smokers to eventually stop using any tobacco product, includinge-cigarettes

◦ The ACS strongly discourages the concurrent (or “dual”) use of e-cigarettes andcombustible cigarettes

American Cancer Society Position StatementFebruary-2018

If you're a long-term cigarette smoker andhaven’t been able to cut back or stop smokingusing approved cessation methods, e-cigarettesand other vaping devices products appear to be asafer alternative than continuing cigarettesmoking, even if they do not help you reduceyour nicotine intake. However, if you do notsmoke or use other forms of tobacco or nicotine,steer clear of e-cigarettes and other vapingdevices. The potential risks to your long-termhealth outweigh any enjoyment in the moment.

What’s the bottom line?