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February 13th, 2016:

E-cigs shut down hundreds of immune system genes—regular cigs don’t

People who vape may have weakened defenses against infections.

WASHINGTON—It’s widely assumed that swapping cigarette puffing for vapor huffing is better for health—after all, electronic cigarettes that heat up and atomize a liquid concoction can skip all the hazards of combustion and smoke. But researchers are still scrambling to understand the health effects of e-cig use (aka vaping) and to track down the variable and undisclosed components of those vaporized mixtures. The most recent data hints at unexpected health effects unique to e-cig use.

After comparing genetic information swabbed from the noses of smokers, vapers, and non-users of both, researchers found that smoking suppresses the activity of 53 genes involved in the immune system. Vaping also suppressed those 53 immune genes—along with 305 others. The results were presented Friday at the annual conference of the American Association for the Advancement of Science in Washington.

Though research on the significance of that gene suppression is still ongoing, the initial results suggest that e-cig users may have compromised immune responses, making them potentially more vulnerable to infections and diseases.

“The gene expression changes we’re seeing are consistent with a modified immune response,” lead researcher Ilona Jaspers of the University of North Carolina at Chapel Hill told Ars. “Any time you change [the immune system], it’s probably out of balance,” she said, explaining that a hyper-immune response or a weak response is problematic. Whether the imbalance caused by e-cigs leads to boosted infection risks or other immune diseases, “we don’t know,” Jaspers added.

For the study, Jaspers and colleagues mined the noses of different groups of healthy people—around a dozen each of cigarette smokers, e-cigarette vapers, and people who didn’t use either. The researchers fit the volunteers into the three categories based on smoking “diaries” that they filled out for three weeks prior to nose-sampling. The researchers homed in on the schnoz because cellular and immune responses there can offer clues to those responses in the lungs, which are harder to sample, Jaspers noted.

Harvesting the genetic data from the participants, researchers looked at the activity of nearly 600 genes, all of which are related to controlling and mounting immune responses. Comparing smokers’ genetic information to that of non-users, the team found that the activity of 53 genes was dialed down in smokers collectively. Comparing e-cig users to smokers and non-users revealed the same dampened activity for those 53 genes but also 305 others—a total of 358 immune genes were muted in e-cig users’ noses.

In follow-up lab studies, Jaspers and colleagues tested e-cig liquid on immune cells from healthy volunteers. Specifically, the researchers collected immune cells, such as neutrophils and macrophages, that are responsible in part for swallowing up invading bacteria. When the cells were put into diluted solutions of different e-cigarette liquids, the cells weren’t as good at sucking in the microbes. The data, while preliminary, suggests that immune cells in e-cig users may be unable to prevent bacterial breaches, thus opening the gates to infection.

The researchers also looked at the gene-altering effects of different flavors of e-cigarettes on the cells in the delicate lining of the respiratory tract. The flavorings that seemed to have the most potent gene-altering effects were additives that taste like cinnamon—cinnamaldehyde—as well as butter flavors.

These flavorings are considered safe, Jaspers pointed out—but only for eating. The additives are categorized as generally recognized as safe (GRAS) for food and beverages, but they have never been tested for safety when inhaled, she adds. The point is driven home with one of the flavors, the butter-mimicking diacetyl. This flavor has been found in some e-cig flavorings, but it’s known to cause bronchiolitis obliterans, a severe disease caused by scar tissue and inflammation built up deep in the lungs. The link was discovered years ago in food manufacturing, particularly microwave popcorn factory employees who developed “popcorn worker’s lung.”

A concerning factor in e-cig use is that it’s not well known what or how much flavor additives and components are in e-cigarette liquid, Jaspers said.

The concern was echoed by clinical pharmacologist Neal Benowitz of the University of California, San Francisco. “E-cigarettes are not one thing,” he said, noting that the devices, liquids, and flavorings vary widely. “We’re really in the beginning of understanding the toxicity.”

The War on Tobacco Makes It Into the TPP Free Trade Deal

This month, the United States and 11 other countries signed the Trans-Pacific Partnership (TPP), a regional trade deal that is the centerpiece of U.S. international economic policy and President Obama’s pivot toward Asia.

Now the deal goes to Congress for approval, where opposition is rising. One hot topic in the congressional debate isn’t about what the TPP includes, but what it excludes.

The TPP is the first U.S. trade deal to exempt anti-smoking measures from the lawsuits that investors may bring under the agreement.

Tobacco companies, business groups and Republican lawmakers oppose this carve-out, arguing it undermines the investor-state dispute settlement (ISDS) system and will lead to health exceptions in future trade deals for other consumer goods such as alcohol and sugar.

Trade critics and Democrats welcome the carve-out for tobacco control measures but argue the need for that exception underscores the threat that investor-state disputes pose to other public health and environmental regulations, which aren’t carved out.

If protection for anti-smoking rules seems like small beer in the decision to approve a 12-country trade deal that took eight years to negotiate, that’s because it is. The U.S. cigarette industry long ago shifted most of its manufacturing (and the associated jobs) overseas, and agricultural tobacco production is not included in the TPP carve-out.

But if construed as an issue about ISDS generally, the stakes become higher. The margins for approving trade deals in Congress are razor thin.

To move the TPP closer to congressional passage, President Barack Obama’s administration need not reopen the trade talks to eliminate the carve-out for tobacco or extend it to other areas. But the White House must do a better job addressing the misperceptions that have arisen about the extraordinary nature of the tobacco carve-out and its implications for the potential threat that investment disputes may still pose for other health and environmental regulations.

Exceptions Are the Rule in Trade Agreements

Readers might understandably conclude from the controversy over the tobacco carve-out that exceptions are, well, exceptional in the TPP. The opposite is true.

At nearly 2,700 pages, the TPP may be the longest, most complex, and exception-filled trade agreement ever negotiated. There are exceptions to general principle (Art. 2.4.1), exceptions to exceptions (Art 2.4.7), explicit exclusions (Art. 9.11), implicit exclusions (Annex 15-A), grandfathering (Annex 18-B), optional undertakings (Art. 25.4.1), clarifications (Art. 13.2.3), caveats Art. 11.1), limiting rules of application (Art. 11.2.2-5), and, of course, carve-outs (Annex 17-D; Art. 16.9; Art. 9.7.6). Exceptions appear in nearly every chapter of the TPP, including its preamble.

The number of exceptions in U.S. trade agreements has increased over the last two decades and is a reason for the expanding length of these deals. For all the attention given to the 1994 North American Free Trade Agreement (NAFTA), it is fewer than 400 pages. This proliferation of exceptions is seen in European Union and Canadian trade deals, as well.

These changes reflect the expanding aims of trade liberalization. The traditional barriers to international commerce—tariffs and quotas—have declined dramatically over the last several decades.

As a result, governments seeking freer trade have shifted their focus to other areas like investment, services, procurement rules, regulatory cooperation and intellectual property.

But as governments have sought deeper cooperation, they have also tried to preserve space for existing legal commitments, retain regulatory independence and reassure trade-wary constituents.

Exceptions are the direct result of this careful balancing act.

In many cases, the exceptions reflect the particular subject matter excluded rather than any trade-specific concerns. Most trade deals exclude national security and tax rules. Some exclude firearms and munitions.

The TPP exempts from dispute settlement any matters related to the Treaty of Waitangi, a treaty between the U.K. and New Zealand’s Maori chiefs. Compulsory licenses, which often involve pharmaceutical patents, are the subject of a World Trade Organization declaration and exempted from the expropriation claims that investors may bring under the TPP.

Why Tobacco Is Different

The tobacco carve-out is similar to the other exceptions in the TPP. It reflects the particular status of tobacco in international law and established U.S. trade policy, and was negotiated and included at the insistence of TPP member countries.

Why should tobacco be different from any other product in U.S. trade?

To start, tobacco is the only legal consumer good that has a binding international treaty dedicated to its control and prevention. One hundred and eighty countries have ratified the Framework Convention on Tobacco Control (FCTC), making it one of the most widely subscribed treaties in the world.

This convention entered into force in 2005 and, like nearly all treaties concluded since that time, the U.S. Congress has yet to ratify it. The United States has signed the convention, however, and is fully compliant with its terms and participates in its meetings.

All 11 of the other TPP countries have ratified and are legally bound to adopt the measures prescribed by the convention. The tobacco control measures carved out in the TPP match the measures mandated in the FCTC and its implementation guidelines.

Tobacco is also the only legal consumer product with a binding U.S. executive order, signed in 2001 and still in force, prohibiting U.S. executive branch agencies from promoting its sale or export.

That order states that U.S. trade initiatives cannot be used to restrict governments’ tobacco marketing and advertising regulations, unless those regulations unfairly favor domestic tobacco products.

This executive order, issued pursuant to the president’s constitutional authority to conduct foreign affairs, operates with the full force of U.S. law.

The need to ensure that trade and investment disputes do not interfere with the tobacco control measures mandated in international law and protected in established U.S. trade policy arose with a recent shift in tobacco industry tactics.

In 2010, Philip Morris International, a Swiss corporation, began filing investment cases to block cigarette labeling and advertising laws. Cases were filed against Australia, Norway and Uruguay and threatened against poorer nations including Togo, Namibia and the Solomon Islands.

The cases generated millions of dollars in legal costs for defending governments and delayed implementation of public health laws. Uruguay would have had to drop its law had Michael Bloomberg, the former mayor of New York, not read about the case and funded its defense.

The Philip Morris lawsuits sparked widespread outcry. Tobacco use is one of the world’s leading causes of death, killing nearly twice as many people annually than HIV/AIDS, malaria and tuberculosis combined. Most of those deaths occur in poorer countries, where tobacco consumption is still growing.

Malaysia, a country in the TPP talks, demanded that tobacco be excluded from the deal entirely. The parties to the TPP settled instead on the tobacco carve-out. It enables TPP members that wish to adopt tobacco controls pursuant to the FCTC to do so without the looming threat of investment disputes. But the carve-out does not exclude tobacco farmers, who are not the target of the FCTC, from the benefits of the TPP.

Broader Implications

The Obama administration has done itself a disservice by not making the basis for the tobacco carve-out clearer. It has allowed cigarette companies to mobilize opposition by characterizing the carve-out as a campaign against ISDS that will eventually implicate products from other industries. It has also undermined the White House’s efforts to ease the public’s concerns with ISDS, which do not end with tobacco.

The TPP specifically respects the legitimacy of environmental, health and safety regulations and includes stricter limits on ISDS claims, but the value of these provisions are discounted by those citing the tobacco carve-out as proof the changes are not protective enough.

In the end, the TPP tobacco carve-out says a lot about the special role of tobacco in U.S. and international law, but less about investment disputes generally. It is an exception motivated by a unique combination: a widely subscribed treaty binding all other TPP countries, an executive order mandating U.S. trade policy, and a pattern of tobacco industry abuse in the face of a proven public health threat. It is a constellation of factors unlikely to reoccur in other health and environmental areas.

If the White House hopes to move the TPP toward congressional passage, it will need to make this argument much more forcefully. Otherwise, the TPP may have to wait to be part of the next president’s legacy, if it happens at all.

Thomas J. Bollyky is Senior Fellow for Global Health, Economics, and Development at the Council on Foreign Relations

Public Health warns against e-cig, vape pen use

Globally, the market for e-cigarettes and vaping devices is expected to grow into a $50 billion market annually, according to BIS Research.

One group locally is doing what they can to halt the expansion of nicotine electronic smoking devices. Brandy Powers is the Tobacco Education Coordinator for Page County Public Health. Powers says many of the ingredients in ESDs are not regulated, making them dangerous.

“A lot of the ingredients are unknown,” said Powers. “They list three ingredients in there, and then the rest — since they aren’t regulated by the Food and Drug Administration — they don’t have to put them on the label.”

Powers says one of the problems with the ESD market is the fact that they are marketed toward younger clientele.

“They are very tempting to youth, even youth that have never touched tobacco in their life,” said Powers. “E-cigarettes are one of the first things they pick up because they think they are safe.”

Similar to the early cigarette market, Powers says the flavors of certain ESDs are also marketed toward people under 18.

“They have over 7,500 different flavors,” said Powers. “Many of them are marketed towards youth because they are candy-flavored; cherry, watermelon, bubble gum, a lot of those things that the tobacco figured out that kids liked, a lot of these electronic companies are figuring out the same thing.”

Powers adds that many of these devices are not safe alternatives to traditional tobacco. Anyone who is considering quitting any form of tobacco can contact Quitline Iowa at (800) 784-8669, where they can receive a personalized plan to quit.

Fresh Evidence Shows Potentially Harmful Effects of E-cigarettes

E-cigarette is back in news! This time again for its harmful effects on human health. Usually considered as a safer and healthier alternative to conventional tobacco cigarettes, electronic cigarettes are not truly safe, warns a new study by University of Louisville scientists.

Using battery-powered vaporizers, or vaping as it is commonly called, is often used by people as the best and healthier way to try to quit smoking.

But e-cig is not as healthy as it is perceived, instead, the study cautions, it can speed up atherosclerosis, a disease of the arteries in which plaque builds up on the inner walls of arteries, leading to several cardiovascular ailments like heart attack, stroke and peripheral arterial disease, a condition which affects the arteries that carry blood to your head, organs, and limbs.

“Currently, we do not know whether e-cigarettes are harmful,” said Dr. Daniel J. Conklin of University of Louisville’s Division of Cardiovascular Medicine. “They do not generate smoke as do conventional cigarettes but they do generate an aerosol – the vapor – that alters indoor air quality and contains toxic aldehydes. We investigated the direct effects of these toxins on cardiovascular disease in the laboratory.”

In an experiment on mice, Conklin and colleagues tested the effects of various levels of exposure to e-cigarettes, tobacco smoke, nicotine, and smokeless tobacco or acrolein on the animals. They also exposed a group of mice to nicotine alone in order to figure out whether nicotine by itself had any ill-effect.

The research team found that exposure to tobacco smoke amplified the amount of atherosclerosis in mice while e-cigarette aerosol also increased the condition. What came as a shock for the team was that e-cigarette aerosol or smokeless tobacco exposure on their own increased atherosclerosis in the animal models.

The take away message from the findings is that most tobacco products may have cardiovascular-disease-causing potential.

Dr. Conklin said: “Somewhat surprising was the finding that either nicotine alone or acrolein alone at levels equivalent to those present in smokeless tobacco or mainstream smoke also increased atherosclerosis in mice.

“These findings indicate that multiple tobacco-derived constituents have cardiovascular disease-causing potential.”

Dr. Conklin and co-researchers presented their findings at the American Association for the Advancement of Science Annual Meeting in Washington, D.C. on Friday, Feb. 12. Dr. Conklin was among a three-member panel discussing “New and Emerging Tobacco Products: Biomarkers of Exposure and Injury.”

Earlier this month, a study by researchers at the University of California, San Diego School of Medicine and Veterans Affairs San Diego Healthcare System had warned that vaping is toxic and can directly kill lung cells, causing weakening of the immune system.

Variable and potentially fatal amounts of nicotine in e-cigarette nicotine solutions

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