Blog | Tuesday, May 27, 2014

E-cigarettes and the FDA: Where should we stand?


People have smoked tobacco for centuries, possibly thousands of years, and cigarettes were first machine made in France in the 1880s. In the U.S., smoking peaked in the year 1965 when 50% of men and 33% of women smoked, with a per capita consumption of more than 4,000 cigarettes per year. When health effects of smoking began to be widely publicized, particularly its association with lung cancer, cigarette smoking began to decline.

Nicotine, the psychoactive ingredient in cigarettes, is addictive, producing a withdrawal syndrome that is at least partially relieved by nicotine replacement. Cigarette smoking, though, also has cultural meaning, which has contributed to its popularity. For decades therapeutic nicotine replacement has been available to people who want to quit smoking, first only by prescription, but now over the counter since the 1990s. The first product, a nicotine chewing gum, was released in the late 1970’s, followed by a patch, a nasal spray and finally an inhaler. The inhaler delivered an aerosol of a nicotine solution from a cartridge attached to a small plastic mouthpiece which is absorbed primarily through the mucus membranes of the mouth. My patients told me that it tasted nasty and it made them look like they were sucking on a tampon. It was a great idea, but not very well executed.

It always seemed to me that what was really needed was a device that looked like a cigarette and delivered nicotine to smokers without the toxic chemicals that were associated with burning tobacco. Nicotine itself, other than being addictive, is not particularly toxic and certainly doesn’t cause lung disease, atherosclerosis, or cancer. In 2003 a Chinese pharmacist Hon Lik (per Wikipedia) invented the first electronic cigarette, which vaporized a solution of propylene glycol and nicotine for inhalation. Within a year a similar device was marketed in China for helping people quit smoking.

Other technology has subsequently been introduced, mainly based on the aerosolization of a nicotine solution by a battery powered heated coil inside a vaguely cigarette shaped device. Flavors are often added, and some e-cigarettes have only flavor and no nicotine. European tobacco companies have been enthusiastic about inventing and developing their versions of e-cigarettes, and Phillip Morris, a U.S. tobacco company, has bought the rights to a nicotine delivery device based on the aerosolization of nicotine by pyruvate, which would not require a battery or produce smoke.

Looking online, I see that I can buy an e-cigarette starter kit for about $25, and the e-juice (nicotine solution) to fill it for about $1/mL, and it looks like 1 mL yields about 120 puffs. I can also buy a pack of FDA-approved Nicorette inhalers, 20 in a pack, for about $30, and according to the package, a smoker would use 3-6 cartridges a day. Sounds like about $7.50 a day. The forums on e-cigarette use are all over the place, but it sounds like a heavy user might inhale 4 mL a day or so, a more moderate one 1 mL, so $1 to $4. Disposable ones can cost more. Cigarettes, depending on where you live, cost upwards of $5 a pack, as much as $14.50 in New York.

E-cigarettes have developed quite the following, and have their enthusiastic and stylish supporters. Using an e-cigarette, or cartomizer, is called “vaping” and some people are excited not just about the nicotine, but also about the devices and flavors and overall coolness of the technology. Poisoning has been reported, primarily due to young children drinking the replacement solution. There is no significant evidence of toxicity related to using the devices as recommended. The Food and Drug Administration (FDA) does not presently regulate e-cigarettes, but recently announced a plan to categorize them as a tobacco product, requiring producers to register and to share with the FDA details about how they are made and what they contain. They also would not allow free samples or purchase by anyone under the age of 18. Manufacturers would not be able to say, without proof, that e-cigarettes are safer than cigarettes and would have to say that nicotine is addictive. These proposals are still being discussed it is not clear when or if they will be adopted.

Which brings up a very important point. We don’t actually know if e-cigarettes are safe or if they help people quit smoking. It seems likely that if there is a cheaper alternative to cigarettes that gives a person the same nicotine high, tastes like pomegranate (or strawberry or whatever) rather than burning leaves, can be used in public places and costs a fraction of what cigarettes do, people will tend to prefer it. But we don’t know this. It seems likely that a product that contains nicotine rather than burning leaves with associated carbon monoxide and carcinogens will cause less health problems, but we also don’t know this.

There are so many competing e-cigarette producers that none is likely to come up with the money to support research that would be convincing of the safety and effectiveness of the whole class of products, including those made by their competitors. Some small studies are mostly encouraging. Compared to cigarette smoke extracts, the extracts of e-cigarettes are much less toxic to mouse fibroblast cells. Air quality was not significantly affected by e-cigarette use for the compounds tested, including glycols (which would be expected to be found in e-cigarette smoke) along with other standard pollutants found in high levels when cigarette smoking is present. About 400 e-cigarette users were followed for a year, to look at use of both e-cigarettes and tobacco cigarettes. E-cigarette use was about stable over the year, and for former smokers there was a 6% relapse rate to tobacco, whereas about 46% of subjects who smoked tobacco as well as e-cigarettes completely ceased using tobacco at the end of a year. One study of smokers and nonsmokers showed no significant reduction in lung function acutely after using e-cigarettes briefly, but another slightly larger study of smokers only showed a restriction of airflow in smokers after using e-cigarettes for 5 minutes. No studies have addressed long term lung effects of regular use of e-cigarettes, and this information is much more relevant.

So where should we, as physicians, stand on the subject of e-cigarettes? First and foremost, not on the side of ignorance. I hear many physicians speak out for or against e-cigarettes without knowing anything about them. My own hospital banned them, as have many other hospitals, based on not very much real information. Countries around the world ban them or regulate them or ignore them completely, based primarily on opinion. They are legal in Germany. They are regulated as a medicinal product in Denmark. They are illegal with a heavy fine in Hong Kong, but legal in China. In Hungary it is legal to buy them and use them but it is illegal to sell the nicotine solution.

I tend to think that e-cigarettes are a good invention. I suspect that if they came out several decades ago our smoking related morbidity would be much lower. They have the potential to come pretty close to eliminating tobacco smoking, much more effectively than regulation and physician nagging has done. They will not reduce nicotine addiction and have the potential to increase it, but it is not clear that nicotine addiction is a public health problem. Clearly good research is important, and it is likely that convincing evidence of safety will not be available for years, and will have difficulty finding funding. Phillip Morris probably will be first to show their product to be safe, if it is, but it will be in their best interest to make sure that data is not generalizable to other e-cigarettes.

The FDA is right to regulate the e-cigarette industry and to require that the manufacturers be honest about what is in them, since there are quite a number of chemicals that make people sick when they are aerosolized and inhaled. Even if e-cigarettes aren’t exactly food or drug or tobacco product, they are somewhere in between all of these things and their popularity gives them tremendous potential to do harm if nobody is watching. Even so, creating excessive burdens that interfere with their ability to successfully undermine the tobacco industry (about which there is truly nothing good to say) would be an error.

Janice Boughton, MD, ACP Member, practiced in the Seattle area for four years and in rural Idaho for 17 years before deciding to take a few years off to see more places, learn more about medicine and increase her knowledge base and perspective by practicing hospital and primary care medicine as a locum tenens physician. She lives in Idaho when not traveling. Disturbed by various aspects of the practice of medicine that make no sense and concerned about the cost of providing health care to every American, she blogs at Why is American Health Care So Expensive?, where this post originally appeared.