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Researchers creating the most advanced 3D human lung to test e-cigs

Lung

The University of Colorado Anschutz Medical Campus announced the funding of $3.4 million by the U.S. Food and Drug Administration (FDA) to create the most advanced living mimicry of a human lung to identify toxicity and cancer-causing potential of emerging tobacco products.

Kambez Benam's lab team at the CU Anschutz Medical Campus
Kambez Benam’s lab team at the CU Anschutz Medical Campus

To study the effects of a human smoker, the research team led by Kambez H. Benam, DPhil, assistant professor at the CU School of Medicine, will create the first-in-kind multi-cellular three-dimensional (3D) living structure of a human lung containing cells that naturally line our conducting airways. This includes the physiological scaffold – also known as extracellular matrix, on top of which the airway lining sits, the soldiers of our immune defense – also known as leukocytes, and the matrix-embedded stromal cells that are critical for development and resolution of organ injury.

This microengineered human lung will allow a better understanding of the harm of e-cigarettes and hookah by evaluating the impact on genes, proteins, pathways, and cell/organ function. In the past, laboratory animals have been widely used to assess the effects of conventional cigarette smoke and more recently e-cigarette vapors; however, translation of findings to human has been challenging.

Kambez Benam, DPhil, assistant professor at the CU School of Medicine
Kambez Benam, DPhil, assistant professor at the CU School of Medicine

“Providing the next generation of a human lung model to compare the toxicity of emerging products, particularly hookah and e-cigarettes, will help identify dangerous and carcinogenic formulations,” said Dr. Benam. “This study has an unprecedented potential to advance the available toolkits for FDA to better protect and promote public health concerns around tobacco products.”

Tobacco-related products such as e-cigarettes and hookah are drastically gaining popularity; but, the biological impact of their emissions on the human lung is not well characterized.

This project adds unique capabilities to Dr. Benam’s work on recently developed technological platforms, namely ‘Small Airway-on-a-Chip’ and ‘Breathing-Smoking Human Lung-on-a-Chip’ published in Nature Methods and Cell Systems.

With the passage of the Family Smoking Prevention and Tobacco Control Act in June 2009, the FDA acquired the authority to regulate the manufacturing, marketing, and distribution of tobacco products in order to protect public health. As of 2016, FDA finalized a rule extending its regulatory authority to cover all tobacco products, including waterpipe tobacco.

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Gov. Hickenlooper signs executive order recognizing Vape-Free November

Gov. John Hickenlooper joined leading health organizations, including the University of Colorado Cancer Center and Children’s Hospital Colorado, in calling for a reduced tobacco use and vaping among youth — an urgent issue given a recent report that Colorado leads the nation in teen vaping.

In a press conference at Children’s Hospital Colorado on Nov. 2, Hickenlooper signed both a proclamation recognizing “Vape-Free November” in Colorado and an executive order that takes steps to curb vaping. Also speaking were Amy Sass, MD, associate professor of pediatrics-adolescent medicine in the CU School of Medicine and a Children’s Hospital Colorado physician; and Tista Ghosh, MD, interim chief medical officer for the Colorado Department of Public Health and Environment (CDPHE).

Youth vaping graphic
This graphic shows the rate of e-cigarette use among youth in Colorado counties in 2017.

The health leaders called the youth use of vapor products, known as vape or e-cigarettes, an “epidemic of nicotine addiction,” leaving teens at risk for long-lasting effects of exposing their developing brains to nicotine. The risks include nicotine addiction, mood disorders and decreased impulse control.

Sass said she sees firsthand evidence of vaping among her youth patients, and notes that even children in elementary school are reporting experimenting with vaping. She said misconceptions abound that vaping products are not as harmful as cigarette smoking.

One in four teens vape

“The aerosols in many of these electronic nicotine devices are equally harmful, both to the user and bystanders who are exposed to the vapors,” she said. “These are pollutants and can contain harmful chemicals including carcinogens and heavy metals.”

TOBACCO PREVENTION BLUEPRINT

The executive order also makes suggestions for the Legislature to consider, including:

  • Raise the minimum sales age for tobacco and e-cigarette products to 21. Coloradans must be 21 to buy alcohol or marijuana, but only 18 to purchase tobacco and vaping products.
  • Prohibit the sale of flavored tobacco and vaping products in Colorado.
  • Require all retailers of tobacco products, e-cigarettes and vaping products to be licensed.
  • Extend the excise tax on tobacco products to e-cigarettes, vaping devices and liquids.

Sass said it’s important for health care providers, as well as parents, to talk with youth and their families about the health risks of vaping. Colorado has made great strides in curbing cigarette use in Colorado, she said, and “it’s going to take a similar multifaceted approach to address the issue of vaping.”

Ghosh said more than one in four of Colorado high school students use vaping products and almost half have experimented with them. “When our kids experiment with vaping, they think they are just using flavored water,” she said. “What they don’t realize is that almost all vapor products sold in convenience stores contain nicotine.”

Risky behavior

Studies indicate that vaping might be an indicator for other high-risk behaviors, Ghosh said. “Teens in Colorado who vape are more likely to binge drink, use marijuana, use prescription pain not prescribed to them, and engage in other risky behavior,” she said.

Hickenlooper said the nation-leading rate of teen vaping is not a distinction Colorado wants to have. “I think it would be foolhardy and irresponsible if we didn’t address this … Like so many challenges we’re trying to address with a holistic approach, we need to educated family members, friends and make sure policy makers and the whole community understands what this means.”

Immediate actions

The executive order:

  • Directs the Department of Revenue to double its compliance checks of tobacco and e-cigarette retailers to ensure they are not selling to underage persons.
  • Extends the current prohibition on smoking in state buildings to e-cigarettes and vaping. It also extends prohibitions on smoking and vaping to the grounds of state buildings, not just the buildings themselves.
  • Directs CDPHE to issue a health advisory on e-cigarettes and vaping.
  • Directs CDPHE to investigate the association between vaping and other risky behavior and identify programs to prevent those behaviors.

Hickenlooper said, “We want to say with one voice: Put down the pods; trash the pens; and live a little.”

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Top global expert on air pollution and tobacco control takes reins of ColoradoSPH

The newest dean on campus has a lot to boast about. A recent invitation to the Vatican. An award presented by a king. But after 40 years in a career that landed him many top-level posts and prominent international recognition, the dean of the Colorado School of Public Health (ColoradoSPH) remains straight-forward and modest.

Unless the conversation turns to grandchildren, of course.

Distinguished Professor Jonathan Samet, MD, MS, who took over his new desk on the University of Colorado Anschutz Medical Campus before making his pontifical stop, came from the Keck School of Medicine at the University of Southern California, where he was chair of the Department of Preventive Medicine.

Considered a top global expert on air pollution and tobacco control, Samet’s accolades include a National Academy of Medicine election, a National Cancer Advisory Board appointment, two Surgeon General’s Medallions and the Prince Mahidol Award for Global Health presented by the King of Thailand.

Samet recently sat down with CU Anschutz Today to discuss his career highlights and outlook for the ColoradoSPH.

Jonathan Samet in front of painting of Pope Francis at the Vatican
Jonathan Samet, the new dean of the Colorado School of Public Health, relaxes during a workshop break at the Vatican.

Today: How did you earn an invitation to such an exclusive Vatican event?

Samet: For decades, I have focused on air pollution and air quality, and I’ve been involved in many related issues. I chaired the Environmental Protection Agency’s Clean Air Scientific Advisory Committee, and I’ve been involved with the World Health Organization and the Surgeon General’s office and written extensively on this issue.

Today: At the Vatican, you spoke on the disease burden of air pollution. Tell us about your message.

Samet: Outdoor air pollution causes 5 million premature deaths a year. Then there are a billion and a half people or so who are exposed to smoke indoors from biomass fuels (wood, dung, charcoal) that they use for heating and cooking. This occurs mainly in other countries and is a rising problem. Nationally, things have improved. For instance, 30 years ago, Denver was famous for its dense brown cloud. Thankfully, it’s not what it used to be. But in the rest of the world  ̶  India, China, parts of Asia, parts of Africa  ̶  air pollution levels are back up to what killed people in the past. It remains a serious global health problem.

Outlook on change

Today: What were the driving factors behind your decision to take this position?

Samet: The real professional attraction was to take the leadership of a school that I think has tremendous opportunity to have impact on public health here in Colorado and the region. I’ve always been interested in taking research and doing something with it: If there is one thing that has defined my career, it’s probably that. I want to make sure we’re taking what we learn and moving it into action. On the personal side, my son and grandchildren are here. My son came to the University of Colorado in Boulder years ago for the reason any young man would go there: to rock climb. And he stayed.

Today: What are your chief goals for the school and community?

Samet: The school is special in that it crosses three universities: the University of Colorado Anschutz Medical Campus, Colorado State University and the University of Northern Colorado. We have good programs at each and complementary strengths across the three campuses. That’s something to build on. Just as an example, by drawing on CSU’s long-standing strengths at the veterinary school, we can look at the issue of antibiotic resistance. A lot of the drive behind increasing resistance is the use of antibiotics in animals.

And Colorado has a number of issues that need to be studied or addressed. Right now, there is a unique experiment going on with the legalization of marijuana. We’re in the forefront there, and we need to understand any potential consequences. There’s also rapid growth in the state and what comes with that, such as housing issues, environmental changes. These are all things in which I think the school should be involved.

Taking on challenges

Today: You’ve written a bit about the public’s losing trust in science and medical experts. Can you tell us how that works against you and your colleagues?

Samet: For those of us in public health, our research may have important consequences. As an example, showing that smoking causes lung cancer demands action. These kinds of findings may bump up against powerful interests. We know as the science unfolded on smoking and disease, the tobacco industry was always there trying to undermine the findings and their public health impact, creating doubt about the evidence. This has spread, for instance, with climate change and with vaccinations. People are, in a sense, making belief equivalent to evidence as a foundation for decision-making. For instance, a parent says: I believe childhood vaccinations cause autism, which is well discredited. Therefore, I will not vaccinate my child. At some point, this becomes a problem.

Jonathan Samet at his desk
Jonathan Samet brings an expert background in air pollution and tobacco control to the University of Colorado Anschutz Medical Campus.

Today: How would you describe progress in your other main focus area: tobacco control?

Samet: If you look nationally at the rates of cigarette smoking at the peak in 1960 or so, the majority of men were smokers. If you look now, we are down to about 17 percent of adults smoking daily. There’s tremendous progress but with new challenges. The world of tobacco control has changed really quickly with the arrival of various products that are not combustible cigarettes. We are at another turning point.

Today: You recently accepted a top award in your field from the American Public Health Association’s Epidemiology Section. You are no stranger to awards. Was there anything particularly special about this one?

Samet: This was the Wade Hampton Frost (1880–1938) award. He was essentially the first academic epidemiologist. He founded the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. I was in the line of chairs who came after him, so that was an honor for me, and I enjoyed the opportunity to talk with colleagues.

Today: What is one misperception people have about you?

Samet: Probably a workaholic perception. I do work hard,  but I have many interests outside of work. For instance, I’m passionate about jazz (and his 3- and 6-year-old grandsons). The one who just turned 6 has been riding his bike to the bike park without training wheels since he was 3. So I definitely will be cycling with them. And they are, of course, rock-climbers already. So I’m really looking forward to the outdoor activities and spending time with family.

Photo at top: Jonathan Samet recently received a top award in his field from the American Public Health Association at a ceremony in Atlanta.

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Most remaining smokers in US have low socioeconomic status

After decades of declining US smoking rates overall, most remaining smokers have low income, no college education, no health insurance or a disability, according to research from the Colorado School of Public Health at CU Anschutz.

About 15 percent of US adults – more than 36 million – continue to smoke cigarettes. Half to three-fourths of them have one or more low-socioeconomic disadvantages, and the lowest socioeconomic categories have the highest smoking rates. The study concludes that continuing tobacco use is now concentrated among the least advantaged portion of society.

“It’s unusual to find part of the population experiencing high rates of a health problem and also representing the majority of affected people,” said study author Arnold Levinson, associate professor of community and behavioral health at the Colorado School of Public Health at CU Anschutz. “But with smoking, we have this unusual situation: Americans with lower socioeconomic status today are suffering from epidemic smoking rates, and they make up nearly three-fourths of all our remaining smokers.”

The research, published February in the Journal of Health Care for the Poor and Underserved, used data from a national survey which the University of Colorado directed in 2012.

The continued epidemic can’t be blamed on lack of desire to quit or efforts to quit. According to the report, numerous studies have found no socioeconomic differences in smokers’ desires to quit or attempts to quit. Instead, the disparities persist and have widened because lower socioeconomic smokers who try to quit are less likely to succeed.

“In the last half-century, public health efforts helped cut the smoking rate by more than half, but we probably need to change our strategies for helping smokers quit,” Levinson said. “The methods that worked for the upper half of society don’t seem to be working well for the other half.”

According to the Centers for Disease Control, cigarette smoking remains the leading cause of preventable disease and death in the US, causing more than 480,000 premature deaths every year, or one of every five deaths.

Levinson said, “Now the nation’s public health system has a dual moral obligation toward smokers of low socioeconomic class. We must eliminate the disparity in smoking rates, and we must provide cessation-supporting services to the new majority of smokers.”

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