Nicotine Genes: Evidence From a 40-Year Study

 How adolescent risk becomes grownup addiction.

 Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a new report published in JAMA Psychiatry in 2013. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.


Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Cigarettes and Genetic Risk

Evidence From a 4-Decade Study.

Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a report  published last year in JAMA Psychiatry. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.

(First published March 28, 2013)

Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Graphics credit: http://www.sciencemediacentre.co.nz/

Why Do Patients With Schizophrenia Smoke So Many Cigarettes?

For sound neurological reasons, that's why.

(Originally published May 2, 2012, by The Dana Foundation)

For mental health workers, it is well known that an overwhelming majority of psychiatric patients diagnosed with schizophrenia are heavy cigarette smokers. Surveys have shown that at least 60 percent of patients exhibiting symptoms of schizophrenia are smokers, compared with a national average that hovers just above 20 percent. Writing in the New England Journal of Medicine, researcher Judith J. Prochaska, associate professor of psychiatry at the University of California in San Francisco, found that “smokers with serious mental illnesses are dying 25 years sooner, on average, than Americans overall.” And tobacco is one of the reasons why.

Cigarettes, long familiar in institutional settings as a tool for reinforcing desired behavior, are slowly disappearing from state hospitals. “For state inpatient psychiatric facilities responding to surveys,” says Prochaska, “the best estimate is that about half have adopted smoke-free policies.” Increasingly, acute nicotine withdrawal is a strong part of the mix for the recently admitted smoker with schizophrenia.

An earlier study by Prochaska and colleagues, published in Psychiatric Services, found that while 42 percent of psychiatric patients at a smoke-free San Francisco hospital were smokers, averaging slightly more than a pack per day, none of the smokers received a diagnosis of dependence or withdrawal, and none were offered treatment planning for smoking cessation.

“Smokers who were not given a prescription for nicotine replacement therapy were more than twice as likely to be discharged from the hospital against medical advice as nonsmokers and smokers who were given a prescription for nicotine replacement therapy,” the study concludes. The authors believe that “nicotine withdrawal left unaddressed may compromise psychiatric care…. Given the complicated relationship between mental illness and smoking, integration of cessation efforts into psychiatric care is recommended.”

During the first few hours after patients with schizophrenia enter smoke-free psychiatric emergency settings, more than half become agitated, and 6 percent are physically restrained, according to a recent study by Dr. Michael H. Allen and coworkers at the University of Colorado School of Medicine. Published in the American Journal of Psychiatry, the double-blind study looked at 40 patients admitted to the psychiatric emergency service of the Hospital of the University of Geneva, and found that a relatively safe and simple addition to the emergency stabilization of patients with schizophrenia—a 21 mg nicotine patch—markedly reduced agitation in patients who smoked. The practice of “forced abstinence,” which is the consequence of recent trends toward smoke-free institutions, may not be in the patient’s best interest—especially since formal smoking cessation programs are not always a part of hospital routine.

Allen and colleagues gave out either the nicotine patch or a placebo patch to 40 smokers recently admitted to the hospital with symptoms of schizophrenia. While agitation diminished over time in both the intervention group and the placebo group, “the intervention group had a 33 percent greater reduction in agitation at 4 hours and a 23 percent greater reduction at 24 hours.” The authors say that the differences are similar to those observed in industry trials of common antipsychotics. According to Allen, “forced tobacco abstinence may have the effect of increasing aggressive behavior.” For patients with schizophrenia, smoking works.

The importance of nicotine to patients with schizophrenia should not be underestimated. There are rational biological reasons why schizophrenics smoke. A review of earlier studies published in Psychiatric Services suggests that smokers with schizophrenic symptoms may be self-medicating to improve the processing of auditory stimuli, and to reduce the side-effects caused by common antipsychotic medications. 

“Neurobiological factors provide the strongest explanation for the link between smoking and schizophrenia,” writes Edward R. Lyon, the study’s author, “because a direct neurochemical interaction can be demonstrated.” Flaws in sensory gating, the process by which the brain lowers its response to a repeated sound, are believed to be involved in the auditory hallucinations common to people with schizophrenia. And sensory gating improves for schizophrenics after they load up on nicotine.  Other research has shown a reduction in expression of nicotinic receptors in schizophrenia, suggesting that a susceptibility to smoking and schizophrenia may be related.

Prochaska sees smoking among patients in psychiatric settings as the consequence of several factors, including clinicians' failure to treat nicotine addiction, as well as the role nicotine plays as an antidote to drug side effects. Patients are familiar with the side effects of the drugs they take, “so they smoke and it reduces the blood levels of their medications,” she says. “They’re less sedated, and they can focus more.”

This complicates the picture for psychiatric staff: Antipsychotic drugs are metabolized faster in smokers, leading to the need for higher doses of medication. Prochaska notes that tobacco smoke may inhibit the effect of commonly used drugs like haloperidol, and the inhibition “can be as high as an increase clearance of 40–98 percent for olanzapine, a costly medication.”

In an interview, Prochaska said that the heaviest smokers “may need to stay on cessation medications for an extended period, and that’s certainly better for them than smoking. Combination therapy also is recommended. In our studies, we combine the nicotine patch with gum or lozenge so they’re able to add to the patch to get sufficient coverage of withdrawal symptoms.”

Mental health professionals have traditionally argued that patients with schizophrenia do not want to quit smoking, but Prochaska’s work suggests otherwise. Patients in psychiatric settings are about as likely as the general population to want to quit smoking, her research shows. “There is growing evidence that smokers with mental illness are as ready to quit as other smokers and can do so without any threat to their mental health recovery,” she said.

By some estimates, people with psychiatric disorders make up almost half of the current U.S. market for tobacco products. As Prochaska has written, “nicotine dependence is the most prevalent substance use disorder among adult psychiatric patients, and it needs to be placed on the radar of psychiatric practice.”

It’s up to healthcare providers to get the ball rolling. “Many facilities are still struggling with it,” she says. “It’s not been in their purview traditionally, so changing the culture is a big piece of the solution. It’s very much a matter of trying to get tobacco treatment medicalized, having it be automatic, so that nicotine replacement is right there in the admitting orders. And ideally, working with patients while they are hospitalized to motivate smoking cessation, and supporting them when they leave.”

Photo Credit: http://www.ctri.wisc.edu/

The Genetics of Smoking

Evidence from a 40-year study. 
 
(First published March 28, 2013)

Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a report  published in JAMA Psychiatry. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.

Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Graphics Credit: http://neurologicalcorrelates.com/

Smoking and Surgery Don’t Mix

Even routine operations are riskier for smokers.

Smokers who are scheduling a medical operation might want to think seriously about quitting, once they hear the results of a new review of the impact of smoking on surgical outcomes.

A scheduled operation is the perfect incentive for smokers to quit smoking. The fact that smokers have poorer post-surgical outcomes, with longer healing times and more complications, is not a new finding. But the study by researchers from the University of California in San Francisco, and Yale University School of Medicine, published in the Journal of Neurosurgery, spells out the surgicial risks for smokers in graphic detail.

Cellular Injury

The systematic effects of nicotine and carbon monoxide in the blood of cigarette smokers result in tissue hypoxia, which is a lack of adequate blood supply caused by a shortage of oxygen.  When carbon monoxide floods the bloodstream in high concentrations, as it does in smokers, it is capable of binding with hemoglobin and thus lowering the oxygen-carrying capacity of the blood. A cascade of physiological reactions then lead to the possibility of low coagulation levels, vasoconstriction, spasms, and blood clots. 

Wound Healing and Infection

If the circulatory system is dysfunctional, healing will be impaired. “In addition,” the researchers say, “tobacco may stimulate a stress response mediated by enhanced fibroblast activity, resulting in decreased cell migration and increased cell adhesion. The net consequence is inappropriate connective tissue deposition at the surgical site, delayed wound healing, and increased risks of wound infection.”

Blood Loss

 In their review of the neurosurgical literature, the researchers found higher blood loss for smokers particularly following surgery for certain kinds of tumors and for lumbar spine injuries. Smoking causes “permanent structural changes of vessels such as vessel wall thickening,” and there is evidence that smoking is linked to “larger and more vascularized tumors, which may further contribute to intraoperative blood loss during resection.”

Cardiopulmonary Effects

Even smokers who don’t have any chronic conditions associated with smoking are at increased risk during and after surgery. Oxidative damage from smoke can cause “mucosal damage, goblet cell hyperplasia, ciliary dysfunction, and impaired bronchial function,” all of which impedes the ability to expel mucus, which increases the bacterial load, which alters the respiratory immune response, and which ultimately leads to higher rates of postoperative pneumonia in smokers.

The authors of the review note that the evidence is particularly strong in certain specialties: Cranial surgery, spine surgery, plastic surgery, and orthopedic surgery. One randomized clinical trial showed that a 4-week smoking cessation program lead to a 50 relative risk reduction for postoperative complications. Another study showed significant improvement in wound healing when patients abstained from smoking for 6 to 8 weeks prior to surgery. And a third trial of smokers cited in the study showed a major decrease in complications following surgery for the repair of acute bone fractures in patients who quit before surgery.

The authors close by suggesting that the seriousness of surgery can be used to create a “teachable moment” for patients who smoke. Other studies show consistently that “patients tend to be more likely to quit smoking after hospitalization for serious illness.” All of this makes the act of scheduling surgery a perfect point of contact with smokers in medical settings. Clinicians can neutrally lay out the facts of the matter, in a way that truly brings home the health consequences of tobacco.

Lau D., Berger M.S., Khullar D. & Maa J. (2013). The impact of smoking on neurosurgical outcomes, Journal of Neurosurgery,   1-8. DOI: 10.3171/2013.5.JNS122287

Graphics Credit:  http://www.ontarioanesthesiologists.ca/

A Weak Smoker’s Vaccine Might Be Worse Than None

New PET scans show wide responses to antibodies.

One of the brightest hopes of addiction science has been the idea of a vaccine—an antibody that would scavenge for drug molecules, bind to them, and make it impossible for them to cross the blood-brain barrier and go to work. But there are dozens of good reasons why this seemingly straightforward approach to medical treatment of addiction is devilishly difficult to perform in practice.

Last January, health care company Novartis threw in the towel on NicVax, a nicotine vaccine that failed to beat placebos in Phase III clinical trials for the FDA. And back in 2010, a report in the Archives of General Psychiatry demonstrated that a vaccine intended for cocaine addicts only generated sufficient antibodies to dull the effects of the cocaine in 38 percent of the test subjects. Moreover, it proved possible to overcome immunization by upping the cocaine dose, which sounded like an invitation to overdose.

And now, neuroscientists at the Society of Nuclear Medicine and Molecular Imaging annual meeting have presented a new study, the conclusions of which might help researchers understand why the vaccine results have been so mixed. The research “represents one of the first human studies of its kind using molecular imaging to test an investigational anti-nicotine immunization,” lead author Alexey Mukhin, professor of psychiatry and behavioral science at Duke University Medical Center, said in a prepared statement.


Subjects underwent two PET brain scan as they smoked nicotine labeled with radioactive C-11, one before the vaccine was administered, and one after. Ten subjects who developed “high-affinity antibodies” after vaccination showed a slight decrease in nicotine accumulation in the brain, as judged by the scans. However, another group of ten subjects, who showed “intermediate serum nicotine binding capacity and low affinity of antibodies” actually showed an increase in brain nicotine levels. What the PET scans showed was that “strong nicotine-antibody binding, which means high affinity, was associated with a decrease in brain nicotine accumulation. When binding was not strong, an increase in brain accumulation was observed.”

If the bond that holds the antibodies to the nicotine molecules is weak, the bond can break during passage through the blood-brain barrier, potentially allowing excess nicotine to flood in. This result, said Mukhin, tell us “we should care about not only the amount of antibody, but the quality of the antibody. We don’t want to have low-affinity antibodies because that can negate the anti-nicotine effects of the vaccination.”

Back to the drawing board? Not entirely. Another of the study authors, Yantao Zuo of Duke University Medical Center, said that “with reports of new generations of the vaccines showing potentially much higher potencies in animal studies, we are hopeful that our current findings and methodology in human research will facilitate understanding of how these work in smokers.”

Photo Credit:http://www.medgadget.com

Smokers’ Genes: Evidence From a 4-Decade Study

How adolescent risk becomes adult addiction.

 Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a new report published in JAMA Psychiatry. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.


Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Graphics Credit: http://cigarettezoom.com/

Big Tobacco Easily Evades “Light” Cigarette Ban

Color coding allows smokers to easily identify their former brands.

The tobacco industry has once again made a mockery of the Food and Drug Administration’s attempts to ban ‘light” cigarettes from the marketplace, by simply eliminated the objectionable wording and substituting an easily-decoded color scheme. In a brochure prepared for cigarette retailers marked “For trade use only: not to be shown or distributed to customers,” tobacco giant Philip Morris wrote that “some cigarettes and smokeless packaging is changing, but the product remains the same.”

Research done at Harvard demonstrates "the continued attempts of the industry to avoid reasonable regulation of tobacco products,” said Hillel Alpert, co-author of a new study on light cigarettes, in a prepared statement. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 highlights the banning of light cigarettes as a critical mission, since cigarettes marketed in this way are in fact no safer than regular cigarettes. What makes a cigarette Light or Ultra-light is a series of tiny holes drilled through the filter (See earlier post). This “filter ventilation” was calibrated to the descriptors: Ultra-lights had more holes drilled in the filter than Lights. Studies have demonstrated conclusively that such filter schemes do not make smoking safer or cut down on related diseases. A 2001 report from the National Cancer Institute documented how smokers were compensating for the ventilation holes by smoking more cigarettes, smoking them more intensely, or by blocking the filter holes with fingers or lips.

In a study for Tobacco Control, Gregory Connolly and Hillel Alpert of the Harvard School of Public Health documented the process. In 2010, Philip Morris sent manuals to retailers detailing how they were to deal with the new sales situation. Philip Morris made clear that “current pack descriptors such as light, ultra-light and mild will be removed from all packages.” All well and good. However, the Philip Morris material also specified how a series of new package names were to be doled out. Marlboro Light became Marlboro Gold. Marlboro Mild morphed into Marlboro Blue. And Marlboro Ultra-light reemerged as Marlboro Silver.

When the researchers commissioned a large public survey to document the state of affairs one year after the official “light” ban, they found that “88%-91% of smokers found it either ‘somewhat easy’ or ‘very easy’ to identify their usual brand of cigarettes by the banned descriptor names, Lights, Mediums or Ultra-Lights.” Sales figures for these brands in the first two quarters of 2010 were essentially unchanged, the authors report. They conclude that “the majority of smokers of brands in all categories correctly identified their brands’ pack color.”

The lesson here may well be that countries like Australia and the UK are on the right track: Plain packaging may be best. If lawmakers allow “misleading numbers, the use of colors, imagery, brand extensions, and other devices that contribute to deception” in place of words, nothing has really changed. “The findings of the present research strongly suggest that tobacco manufacturers have evaded one of the most important provisions of the FSPTCA for protecting the public health from the leading cause of preventable death and disease,” the authors conclude.

In a press release, co-author Gregory Connolly, director of the Center for Global Tobacco Control at Harvard, explained that the industry “was found guilty by a federal court in 2006 for deceptively promoting ‘light’ cigarettes as safer after countless smokers who switched to lights died prematurely, thinking they had reduced their health risks.”

Connolly G.N. & Alpert H.R. (2013). Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?, Tobacco Control, PMID: 23485704

Photo Credit:http://www.mydiscountcigarette.net

Big Tobacco Makes a Move Into E-Cigarettes

“A battery-operated, addiction-based market.”

While the FDA dithered, and health advocates argued, Big Tobacco began placing its bets on the e-cigarette market last year. Tobacco firm Lorillard Inc., the third largest tobacco company in America, bought privately held Blue Ecigs of Charlotte, N.C., for $135 million, driven by what the company says is a market that’s been doubling ever year since e-cigs first arrived from China in 2008.

According to the Wall Street Journal, Blue Ecigs had $30 million in revenues last year, selling through retail outlets like Walgreens, where it competes with e-brands such as NJOY and 21s Century. The FDA has announced vague plans to regulate, and state lawmakers have threatened to ban them outright, or at least place them under the same public smoking bans as cigarettes—bans that some e-smokers love to flout. (E-cigarette manufacturers, based primarily in Asia, quickly changed the electric orange glow at the end of the e-cigarette to a cool shade of blue, to help make clear to bartenders and bouncers that the thing wasn’t a lit cigarette.)

Meanwhile, Reynolds, an industry leader in smokeless products, is developing its own line of e-cigs, and is test-marketing its Vuse and Zonnic brands. “We will be in this category in 2013,” an RJ Reynolds representative said in a CNBC article by Jane Wells. “We have very big plans.”

Altria, the industry giant, is now generating $1.6 billion from smokeless tobacco products, and is expected to make a move into what is viewed as a billion-dollar industry with unlimited growth potential. Last year, the company began testing a new “nicotine-extract product” called Verve, a lozenge that can be sucked or chewed and contains about 1.5 milligrams of nicotine. Late last year, the company reportedly engaged in acquisition talks with e-cig maker Eonsmoke.

Meanwhile, the company that invented the electronic cigarette, Dragonite/Ruyan, is suing practically everybody. And the Argentinean and Venezuelan governments have attempted to ban the use and marketing of electronic cigarettes altogether.

In December, astute American TV viewers may have noticed what looked for all the world like a television commercial for cigarettes—the first since 1971, when Congress banned cigarette ads on TV. It was a commercial for NJOY Kings electronic cigarettes, a brand that currently owns about one-third of the U.S. e-cig market. Patent lawyer Mark Weiss, who founded NJOY, told Time that the company was only competing for the 45 million Americans who are current smokers, not attempting to make new recruits. In the article, Weiss noted three advantages for e-cigarettes: They’re odor free, they don’t burn tobacco, and, at about $8 per e-cigarette, Weiss claims, they’ll last you as long as two regular packs of cigarettes.

When major tobacco companies make moves like this, people notice. “I think they see this as an opportunity to get a seat at the table with opportunities to talk to the FDA about regulation over this growing category,” according to Bonnie Herzog, senior analyst and managing director of tobacco, beverage and consumer research for Wells Fargo Securities. “Lorillard wants to help steer that conversation in the right direction.”

While still a relatively modest market—no more than $500 million, compared to the $100 billion tobacco market in the U.S.—electronic cigarettes have the potential of becoming the most contentious entry in the market for nicotine delivery systems since the advent of the machine-rolled cigarette. “We think e-cigs are to tobacco what energy drinks are to beverages,” Herzog told the media.

Lorillard chairman and CEO Murray Kessler said in an earnings conference call late last year that with e-cigarettes, “you get all of the benefits of not having combustion, but on the other hand you are maintaining the behavior that cigarette smokers enjoyed.” That’s one way of putting it. And according to critics, that’s part of the problem. Anti-smoking activists often view e-cigarettes as gateway products for young adults.

They are cheaper, primarily because of heavy taxes on traditional cigarettes, and produce no second-hand smoke, only steam-like vapor that quickly dissipates. But they have had a rocky start in the U.S. An article in the Winston-Salem Journal in prime tobacco country stated that consumers have “shied away out of safety concerns since most e-cigs are made in China.” Even North Carolina health officials have expressed concerns about “limited regulatory oversight of their contents.” But according to Wells Fargo’s Herzog, Lorillard’s purchase of Blu Ecigs had the effect of “lending credibility and legitimacy to the entire category.”

Brad Rodu, professor of medicine at the University of Louisville, insisted that “tobacco manufacturers have an obligation to smokers to develop, manufacture and sell these vastly safer cigarette substitutes.” In this view, smokers smoke for the nicotine, but it’s the tar that kills them. 

In the same Winston-Salem Journal article, a professor of family and community medicine at Wake Forest School of Medicine said that “many of the carcinogens in tobacco are volatile and would vaporize, and thus be inhaled when heated. I would not recommend that product.”

It seems safe to predict that this “battery-operated, addiction-based market,” as Forbes dubbed it, will be one to watch.

High-Risk Haplotypes in Smokers

It’s getting harder to interpret genetics studies, and that’s a good thing.

Reporting the results of published studies concerned with genetic risk factors has always been a tricky proposition. Beyond the inevitable, and too often ideological nature/nurture split, there has been an unfortunate history of false positives in the rush to make news with a “gene for” alcoholism or schizophrenia or belief in God.

But single gene theories are mostly a thing of the past, and results tend to be broader and more tentative, as befits the state of our knowledge about genes and risk in a post-epigenetic landscape. Nonetheless, there’s no denying that genes play a strong role in all kinds of behaviors and processes. A large group of U.S. tobacco researchers went looking for associations between genetic risk factors and the ability to stop smoking successfully, and published their results in the American Journal of Psychiatry. The group came down strongly in favor of the proposition that genetic variations in the chromosome 15q25 region help dictate who manages to quit smoking and who does not.

The genetic variants in question are for nicotine receptors, and are called CHRNA5-CHRNA3-CHRNB4. They compose a “high-risk haplotype” that Li-Shiun Chen and coworkers believe to be involved in the ability to quit. (A haplotype is a combination of DNA sequences on a chromosome that are transmitted as a unit). People with these genetic variants “quit later than those at low genetic risk; this difference was manifested as a 2-year delay in median quit age.” However, this association tended to wash out at very high levels of smoking. Nonetheless, “pharmacological cessation treatment significantly increased the likelihood of abstinence in individuals with the high-risk haplotype,” compared to the low-risk group.

The suspicious haplotypes did not reliably predict tobacco abstinence across all groups that were studied. And any pharmacological treatment at all vastly increases abstinence rates, compared to placebo, while those who smoke the fewest cigarettes per day have the best shot at abstinence no matter what. In one sense, all the study is saying is that anti-craving drugs are more likely to be effective in smokers “who are biologically predisposed to have difficulty quitting.” Other smokers may not need them at all as a quitting aid—which is very much as common sense would have it. But further research in this area may allow medical workers to genetically identify smokers who will definitely require a pharmacological booster shot to overcome their crippling addiction.

In brief, the study says that success in quitting may be directly modulated by certain types of genetic variation among smokers. And genetic variations influencing quitting success may be different from gene variants controlling for “severity of nicotine dependence” (how many cigarettes you smoke), and whether you get addicted in the first place. It is all very complicated. But it’s the sort of thing that gives researchers hope when they contemplate deploying forms of personalized medicine in addiction treatment.

Study limitations abound. The work looked at only one genetic locus, while the success of smoking cessation might depend on multiple gene sites. The placebo arm was relatively small, and the smoking reports were obtained through a combination of biochemical confirmation and self-reporting.

Baker, T. (2012). Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success American Journal of Psychiatry DOI: 10.1176/appi.ajp.2012.11101545

Graphics Credit: (Li-Shiun Chen)

Researchers Eye a Cheap, Organic Alternative to Chantix for Smokers

Meet cytisine, available in Bulgaria for 25 cents a pill.

A clear majority of American smokers say they want to quit. But each year, only a small percentage of them manage to do it. For individual smokers, the will is there, but what’s sometimes missing is the money.

For many smokers, cessation aids like nicotine patches and anti-craving medication are effective. But they are relatively costly, and insurance coverage for such products varies widely. Chantix, the top-of-the-line smoking cessation aid introduced by Pfizer five years ago as a very expensive prescription drug, was discovered by modifying the chemical attributes of an existing plant substance called cytisine.

But what if cytisine itself, found in various plants, including the golden rain tree, a small shrub native to the Alps—worked almost as well as Chantix, but for only pennies a day? Cytisine, packaged as Tabex and marketed by a Bulgarian firm, has already been on the market in Central Europe and Russia for more than 40 years. In Russia, a four-week course of Tabex costs $6.  Chantix will cost smokers about $250 for a 12-week run, or about $3-$4 per pill. In Poland, Tabex sells for about 25 cents per pill.

Moreover, as David Biello pointed out in Scientific American, when Chantix (known as Champix in the U.K.) was first approved for use against cigarettes, “the leaves of Cytisus laburnum, or the golden rain acacia tree, were used as a tobacco substitute by soldiers in World War II.” Later, clinicians in the U.S. paid scant attention to reports of a cheap Bulgarian plant-based supplement that smokers in Russia and Central Europe were using to help break their nicotine addiction. Instead, researchers structurally modified cytisine to produce varenicline, or Chantix. It makes for a more effective drug, but there are always tradeoffs: It is expensive and time-consuming to produce drugs through a process of total syntheses, and they will always come at a considerable cost premium relative to their organic originals. That is partly how pharmacology works, and it’s a good thing, providing you have the money or the health insurance to be able to afford the finished product.

Recently, a group of researchers at a smoking cessation clinic in Poland studied the effect of cytisine, a “partial nicotine agonist,” in a clinical trial published
 in the New England Journal of Medicine. The double-blind trial showed that cytisine was not as effective as Chantix, but significantly more effective than a placebo. Dr. Robert West of University College, London, and lead author of the study, said the “net improvement in the abstinence rate with cytisine was 6 percentage points. The relative rate of abstinence in the cytisine group as compared with that in the placebo group was 3.4.”

“It wasn't compared head-to-head against the Rx drugs, but its reasonable efficacy makes it sound like a cheaper alternative,” said Dr. David Kroll, Professor and Chair of Pharmaceutical Science at North Carolina Central University. “Like nicotine, it can cause side effects like headaches and nausea,” he added.

So is cytisine an eventual possibility in the U.S., where it is not currently licensed and available? Is it something that the National Institute on Drug Abuse is interested in? When I asked NIDA director Nora Volkow that question in an interview last week, the answer was yes. “The data look very interesting,” Volkow said, referring to the New England Journal of Medicine Study.  “The beauty of cytisine is that it’s not just inexpensive, you can also get a response in three weeks.” She added that “we don’t know yet whether we can improve it,” by, for example, combining it with other cessation aids. “The main side effect of cytisine is nausea, but not suicidal ideation,” she said.

An earlier survey in the Archives of Internal Medicine of the admittedly sparse research showed similar results in several placebo-controlled double-blind studies. Cytisine, the Marxist-Socialist answer to cigarette addiction, works about as well as standard nicotine replacement therapy, like patches and gums.

“I hope this drug will be available throughout the world at a cost that every smoker can afford,” said West. And that might be a problem. Cytisine is not currently legal in the U.S. or Canada. Tabex itself was withdrawn from some of the European countries in which it was formerly available, after several Central and Eastern European countries joined the European Union and began adhering to stricter licensing rules.

Meanwhile, a third of the world is still out there smoking tobacco. It seems sensible to have some modest help available for smokers in poverty who want to quit and financially need to quit. “I have long been concerned that effective treatments to help smokers to stop are not affordable by the majority of smokers in the world,” West said. “There are still regulatory hoops to go through, but I hope that before long this drug will be available throughout the world at a cost that every smoker can afford. It should be cheaper to take this drug than to smoke, wherever you are in the world. It is not a magic cure by any means; stopping is still extremely difficult for many people. But it could save many hundreds of thousands of lives, if not millions, which is quite a thought.”

As Dr. Volkow put it: “We urgently need medications for smoking. Five million people die per year” from smoking-related causes in the U.S.

West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, & Stapleton J (2011). Placebo-controlled trial of cytisine for smoking cessation. The New England journal of medicine, 365 (13), 1193-200 PMID: 21991893

Judge Rules Against Graphic Cigarette Packs

District Court says FDA mandate would violate First Amendment.

Consumers may yet be spared graphic images of diseased lungs and smokers with holes in their throats, after R.J. Reynolds, Lorillard, and other tobacco companies prevailed over the Food and Drug Administration in the U.S. District Court for the District of Columbia today. Judge Richard Leon ruled that forcing cigarette manufacturers to offer their products only in gruesome packages was a violation of free speech, and therefore unconstitutional. The companies were granted a preliminary injunction, while the FDA regroups and lawyers rehuddle.

The judge wrote that “plaintiffs raise for the first time in our Circuit the question of whether the FDA's new and mandatory graphic images, when combined with certain textual warnings on cigarette packaging, are unconstitutional under the First Amendment. Upon review of the pleadings, the parties' supplemental pleadings, oral argument, the entire record, and the applicable law, the Court concludes that plaintiffs have demonstrated a substantial likelihood that they will prevail on the merits of their position that these mandatory graphic images unconstitutionally compel speech, and that they will suffer irreparable harm absent injunctive relief pending a judicial review of the constitutionality of the FDA's Rule.” (Complete ruling available here).

As Josh Gerstein reported at POLITICO, Leon “found that the new warnings, which occupy 50% of the front and back of cigarette packs, convert them into "mini-billboards...for [the FDA's] obvious anti-smoking agenda." Both Health and Human Services Secretary Kathleen Sebelius and FDA Commissioner Margaret Hamburg were also named in the lawsuit.

Judge Leon foresees a slippery constitutional slope if such mandates are allowed to bloom:

When one considers the logical extension of the Government's defense of its compelled graphic images to possible graphic labels that the Congress and the FDA might wish to someday impose on various food packages (i.e., fast food and snack food items) and alcoholic beverage containers (from beer cans to champagne bottles), it becomes clearer still that the public's interest in preserving its constitutional protections - and, indeed, the Government's concomitant interest in not violating the constitutional rights of its citizens - are best served by granting injunctive relief at this preliminary stage.

Graphics Credit: http://pubcit.typepad.com

Teachable Moments in the Life of a Cigarette Smoker

Child surgery makes smoking parents more likely to try quitting.

Here’s a strange one: Doctors at Mayo Clinic wanted to find out whether children undergoing surgery had any effect on the smoking behavior of their parents. And it did—but the effect appears to be short-lived.

The Mayo researchers began from the already well-tested proposition that smokers who have surgery are more likely to quit smoking. In fact, they quit at twice the rate of smokers who haven’t had surgery. Not hard to understand, intimations of mortality and all that. They pass through a teachable moment, the scientists write in Anesthesiology, defined as “an event that prompts behavioral change.” As for smokers with kids, doctors have always had recourse to two tactics for creating teachable moments for cigarette cessation. First, they could point to increased illness and asthma in the innocent children of smokers. And when that didn’t work, they could throw in the cold fact that children exposed to secondhand smoke have a higher risk of respiratory complications during and after surgical anesthesia. And in a further queasy irony, “the increased frequency of conditions such as middle ear diseases caused by secondhand smoke may also make it more likely that children will require surgery.”

For documentation, the investigators turned to the massive National Health Interview Survey (NHIS), a questionnaire served up annually to 35,000 households by personal interview. About 12% of children in the NHIS survey in 2005 were exposed to secondhand smoke. Of the thousands of children undergoing surgery, there was an increased likelihood that a parent of one of them would inaugurate a no-smoking attempt. But these quitters were no more likely to succeed in their attempt than any other quitters.

However, “parents having surgery within the previous 12 months was associated with more quit attempts, more successful attempts, and a greater intent to quit among those still smoking.” What happened to the indestructable bond between parent and child? It appears that concerns about one’s own health trump concerns about the health of offspring when it comes to quitting cigarettes. “We can only speculate about why surgery was a significant factor associated with sustained abstinence when experienced by the smoker but not the smoker’s child.”

There are plenty of limitations to these kinds of self-reported surveys, but it is hard not to speculate, along with the researchers. One obvious implication: the chances of a smoker quitting are at their maximum when parent and child both have surgeries.

“Our current findings suggest that having a child undergo surgery can serve as a teachable moment for quit attempts,” said Dr. Warner. “The scheduling of children for surgery may present us with an opportunity to provide tobacco interventions to parents, who are apparently more motivated to at least try to quit – but who need assistance to succeed.”

Shi, Y., & Warner, D. (2011). Pediatric Surgery and Parental Smoking Behavior Anesthesiology, 115 (1), 12-17 DOI: 10.1097/ALN.0b013e3182207bde

Photo Credit: http://special-needs.families.com/

For Smokers, Nowhere to Run and Nowhere to Hide

(With love and apologies to Martha and the Vandellas.)

That wonderful song goes on to declare:

'Cause I know
You're no good for me
But you’ve become
A part of me.

The song is not about cigarette addiction, but it could be. Full Disclosure: I smoked cigarettes myself for almost 25 years. And then, after several failed attempts, I quit. I out myself on this subject because a paper from the May 25 issue of the New England Journal of Medicine (NEJM) decries what the authors call the “denormalization” of smoking—and I find myself agreeing with them, smokeless though I may be. I recently visited New York, coincidentally on the day that smoking outdoors in New York City became illegal. Okay, that’s not quite fair to say—it became illegal to smoke in Central Park, or at Brighton Beach, or along the newly pedestrian mallways of Times Square. There is no smoking along the High Line. There is no smoking at any park, beach, or pedestrian mall. As both the tobacco industry and anti-smoking activists well know, this was an iconic victory that has the potential to change smoking laws in virtually every other American city.

It’s a fascinating progression, starting in the 70s when the Civil Aeronautics Board decreed non-smoking sections on domestic airline flights, to the recent New York City Council Decision to ban smoking en plein air, so to speak. Thomas Farley, New York City Health Commissioner, summed it up as follows in a public hearing: “I think in the future, we will look back on this time and say ‘How could we have ever tolerated smoking in a park?’”

I’m not so sure on that, myself. James Colgrove, Ronald Bayer, and Kathleen Bachynski of the Mailman School of Public Health at Columbia University wrote the paper, entitled “Nowhere Left to Hide? The Banishment of Smoking from Public Spaces,” in the NEJM. The authors note that more than 500 towns and cities in 43 different states have already enacted laws banning smoking “in outdoor recreation areas.” At first, as the authors summarize the history, it all seems like a sensible compromise, built on common courtesy. First airplanes and buses, then restaurants and bars, began setting aside seats for non-smokers. By the early 90s, the first data on secondhand smoke was rolling in. Schools, convention centers, and finally even private workplaces either banned smoking or created smoke-free areas. But even then, the primary motivator, according to the researchers, was that secondhand smoke was “unpleasant and annoying,” not deadly. Smokers weren’t being asked to refrain from public smoking for the good of their own health, but as a courtesy to others.

The solid scientific evidence kept accumulating, however—even though tobacco cigarettes were, and still are, completely legal products for adult Americans to purchase and consume if they so choose. Now the arguments shifted to the innocent bystanders, those within the six-foot ring, the immediate smoke zone surrounding a smoker, and the elevated risk of lung cancer, heart disease, and asthma that smokers were subjecting them to. In 1993, the Environmental Protection Agency (EPA) classified secondhand smoke as a Class A carcinogen, and more school, stadiums and offices proscribed smoking.

So far so good, really, from a public health standpoint. But now comes the bend in the road. Suddenly, parks and beaches were being added to the no-smoking roster. “As the zones of prohibition are extended from indoor to outdoor spaces, however, the evidence of physical harm to bystanders grows more tenuous.” In 2008, the authors report, “The editor of the journal Tobacco Control dismissed as ‘flimsy’ the evidence that secondhand smoke poses a threat to the health of nonsmokers in most outdoor settings.”

This confusion was much in evidence at public hearings last fall on the proposed outdoor smoking bans. While Health commissioner Farley argued that 57% of New Yorkers showed nicotine by-products in their blood, he also argued that exposing young children to adults in the carnal act of smoking was detrimental to the public health and welfare. “Families,” he said, “should be able to bring their children to parks and beaches knowing that they won’t see others smoking.” This is really quite an astonishing assertion, given the range of bad habits youngsters are exposed to as they go about a normal day in the adult world. The authors are particularly concerned about this push to stigmatize smokers. “Given the addictive nature of nicotine and the difficultly of quitting smoking, strategies of denormalization raise both pragmatic and ethical concerns.” Furthermore:

The decline in U.S. smoking rates since the 1960s has coincided with the development of a sharp gradient along the lines of socioeconomic status. Whereas about one fifth of all Americans are smokers, about one third of those with incomes below the federal poverty level smoke. These data are especially pertinent to the question of bans in parks. Since smokers are more likely to be poor and therefore dependent on free public spaces for enjoyment and recreation, refusing to allow them to smoke in those places poses potential problems of fairness.

The anti-tobacco movement, frustrated by the slow pace of gains over several years of active efforts, with rates of smoking remaining essentially unchanged, has to face the fact that an outright ban on cigarettes is a ticket to black market, crime syndicate hell. But a de facto ban is something altogether different, and “steadily winnowing the spaces in which smoking is legally allowed may be leading to a kind of de facto prohibition.” More and more employers prohibit smoking in doorways, within ten feet of doorways, anywhere on university campuses, and so on. No one has voted to make cigarette smoking illegal. But the public space in which this legal activity can be pursued is disappearing. And here is where the tough questions start: “In the absence of direct health risks to others, bans on smoking in parks and beaches raise questions about the acceptable limits for government to impose on conduct,” the authors conclude. Not to mention issues of personal autonomy, individual choice, and the stigma attached to addictive behavior. Perhaps the ACLU will soon take an interest in the civil rights of outdoor smokers, where the only health being hazarded is the smokers’ own.

Colgrove J, Bayer R, & Bachynski KE (2011). Nowhere Left to Hide? The Banishment of Smoking from Public Spaces. The New England journal of medicine PMID: 21612464

Photo Credit: www.thinkstock.com

Does Menthol Really Matter?

Nicotine experts say menthol makes addiction more likely--but differ over what to do about it.

Back in the 1920s, Lloyd “Spud” Hughes of Mingo Junction, Ohio, was working as a restaurant cashier when, legend has it, he smoked some cigarettes that had been casually stored in a tin that contained menthol crystals. Menthol, a compound found in mint plants and also manufactured synthetically, is used medicinally, and as a food flavoring. Back in Spud’s day, menthol was mostly derived by extracting crystals from the Japanese Mint plant. What we know for certain is that the mentholated cigarettes tasted so good to Spud that he patented the mixture. In 1925, the Spud Cigarette Corporation of Wheeling, West Virginia, was born, and Spud Cigarettes quickly became the 5th best selling cigarette brand in America. 

Dr. Neal L. Benowitz, Professor of Medicine and Bioengineering & Therapeutic Sciences, and Chief of the Division of Clinical Pharmacology at the University of California in San Francisco, says that Spud Hughes had “accidentally identified an additive whose pharmacologic actions reduce the irritating properties of smoke generally and nicotine specifically.” Menthol accomplishes this because it acts on receptors involved in the detection of physical stimuli like temperature and chemical irritation. “Menthol contributes to perceptions of cigarettes’ strength, harshness, or mildness, smoothness, coolness, taste, and aftertaste.” That would seem to just about cover it. But no: In their article for the New England Journal Of Medicine—“The Threat of Menthol Cigarettes to U.S. Public Health"—Benowitz and Jonathan M. Samet also claim that “menthol has druglike characteristics that interact at the receptor level with the actions of nicotine.”

And nicotine hardly needs much help establishing its grip over addiction-prone individuals. “It’s not that it’s so intensive,” Dr. Benowitz told me some years ago, when I was researching my book, The Chemical Carousel, “it’s just that it’s so reliable. Nicotine arouses you in the morning; it relaxes you in the afternoon. It’s a drug that you can dose many times per day for the purpose of modulating your mood, and it becomes highly conditioned, more than any other drug, because it’s used every single day, multiple times per day.” Benowitz, along with Dr. Michael Siegel of the Boston University School of Public Health, recently sparked intense debate when they both championed electronic cigarettes as a safe alternative to smoking tobacco cigarettes, despite the FDA’s earlier wish to keep e-cigarettes out of the country. And last month, an advisory report for the FDA by a group that included Benowitz and Samet concluded that mentholated cigarettes were no more harmful, and no more likely to cause disease, than regular cigarettes. A study in the Journal of the National Cancer Institute of 440 lung cancer patients and more than 2,000 matched patients without lung cancer showed no correlation at all between menthol and cancer. In fact, the researchers were surprised to discover that menthol smokers appear to have a lower risk of lung cancer than other smokers. Asked whether menthol cigarettes are more toxic than non-menthol cigarettes, the study's author William Blot of Vanderbilt University definitively responded: “The answer is, no, they are not.”

However, the advisory report suggested that, while menthol cigarettes may not be more dangerous, they might be more addictive than regular cigarettes.  In the May 4 New England Journal of Medicine article, Benowitz and Samet argue that because menthol cigarettes attract younger smokers by making tobacco easier to smoke, and because more of these smokers go on to become lifelong nicotine addicts due to this same cooling effect, "menthol cigarettes increase the likelihood of addiction and the degree of addiction in new smokers." Further adding to menthol’s tendency to create lifelong smokers is the fact that “some consumers, particularly blacks, hold beliefs about implicit health benefits of menthol cigarettes that may interfere with their quitting."

This is a substantial indictment of menthol as a component of cigarettes, despite the belief among some experts that it is much ado about nothing. But if that’s the case, Benowitz and Samet suggest, why has the tobacco industry fought so ferociously to exempt menthol from the list of banned flavorings over the years? And why has the industry so consistently linked its marketing of menthol cigarettes to images of “freshness” and health? The authors estimated that “by 2020 about 17,000 more premature deaths will have occurred and two million more people will have started smoking than would have been the case if menthol cigarettes were not available.” Two million additional cigarette smokers by the end of the decade does not sound especially trivial. Nonetheless, the FDA advisory report that Benowitz helped to shape stopped short of recommending an outright ban on nicotine, saying only that removal of menthol would “benefit public health.”

While not disputing the findings of the FDA Advisory Committee, Dr. Michael Siegel of Boston University expressed dismay that “despite these conclusions, the [committee] did not recommend a ban on menthol cigarettes.” There are almost 20 million menthol smokers in the U.S., Siegel argues. If even a fraction of them quite smoking due to a ban on menthol in cigarettes, “it would have a profound effect on public health.” This is, Siegel insists, precisely why politicians managed to exempt menthol from bans on various flavor additives in the first place. The Black Congressional Caucus had “vigorously denounced the exclusion of menthol” at the time, while Lorillard, maker of Newports--the leading brand of menthol cigarettes--argued that banning menthol would result in the creation of a huge black market.  Because of all this, Seigel charges, Benowitz and the committee simply “punted the issue back to the FDA.” And if anyone harbored doubts about who benefited from this non-action, in Siegel’s view, one need only look at the fact that Lorillard’s stock enjoyed a nice run-up of about 8% after the public announcement of the FDA panel’s recommendations.

Because of all this, Siegel does not believe the FDA will ever ban menthol cigarettes. In his view, the Obama administration doesn’t need the grief of added health care complexities just now, and there is no movement in Congress to make additives an issue. And since the FDA has chosen not to demand the banning of menthol, Siegel thinks the committee’s findings will serve as a convenient smokescreen for Congress. And for the makers of menthol cigarettes, it will be business as usual. A window of opportunity on the menthol issue is now closing, says Siegel, who confesses to difficulty understanding a policy that bans “every other type of cigarette flavoring—including chocolate, strawberry, banana, pineapple, cherry, and kiwi—yet exempts the one flavoring that is actually used extensively by tobacco companies to recruit and maintain smokers… Menthol is a major contributor to smoking initiation and continued addiction, and for this reason, it will continue to enjoy the protection of a federal government that seems afraid to alienate any corporation, whether it’s part of Big Pharma, Big Insurance, or Big Tobacco.”

Photo credit: http://www.nysmokefree.com/