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ScienceWeek
ScienceWeek
April 11, 2003
Vol. 7 Number 15
An Online Digest of Research in the Sciences
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There does not exist a category of science to which one can give
the name applied science. There are science and the applications
of science, bound together as the fruit of the tree which bears
it.
-- Louis Pasteur (1822-1895)
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Section 1
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Symposium: Medical Biology: Tobacco Dependence
1. Introduction
2. Tobacco as a Public Health Problem
3. Tobacco Dependence
4. Effects of Passive Smoking
5. The Problem of Cigarette Advertising
6. Tobacco Control
7. Pharmaceutical Companies and Tobacco Companies
Notices and Subscription Information
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Section 2
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1. INTRODUCTION
TOBACCO: AN INDUSTRY OR A PLAGUE?
One of the ironies of contemporary society is that toxic
chemicals that enter the body through the digestive tract are
more tightly regulated by governments than toxic chemicals that
enter the body through the lungs. If the plant called "lettuce"
were found to cause millions of cases of cancer, stroke, heart
disease, and lung disease, lettuce would quickly vanish as a
marketable commodity, no matter how many lettuce growers squealed
in protest. But the plant tobacco, which does cause millions of
cases of cancer, stroke, heart disease, and lung disease, is not
only still a marketable commodity in the US, but more young
people than ever in the US, and more people worldwide, are
smoking cigarettes. In the US, a contagious disease that caused
as many deaths as cigarette-selling would be called a plague;
instead, in the US, cigarette-selling is called an "industry".
But if cigarette-selling is an industry, it's an industry devoted
to the sale of an addictive lethal drug, a drug no less lethal
because it kills people in 20 or more years rather than killing
people immediately.
SYMPTOMS OF TOBACCO-NICOTINE POISONING:
Excitement, confusion, muscular twitching, weakness, abdominal
cramps, clonic convulsions, depression, rapid respirations,
palpitations, collapse, coma, central nervous system paralysis,
respiratory failure.
Merck Manual of Diagnosis and Therapy 17th Edition, Merck
Research Laboratories 1999, p. 2643.
ON THE PHARMACOLOGY OF NICOTINE
Nicotine (l-methyl-2-[3-pyridyl]pyrrolidine) is one of the
several alkaloids that can be extracted from tobacco leaves. When
nicotine was first isolated in 1828 by Posselt and Reimann, it
was found to constitute about 5% of the total weight of the dry
plant leaves. However, this relatively minor fraction imbues
tobacco with many physiological and psychological effects when
the leaves are smoked, chewed, or snorted (as snuff) and the
nicotine is absorbed into the human bloodstream. Without
Nicotine, it is quite likely that tobacco would be regarded as a
useless weed.
In 1988, the U.S. Surgeon General reported that evidence had been
accumulating for a long time showing that using tobacco products
has unfavorable consequences for human health. Because nicotine
consumption is a critical aspect of smoking-related
reinforcement, the Surgeon General proposed that nicotine be
included with alcohol, the opiates, amphetamines, and cocaine in
the category of addictive or dependency-producing drugs. Indeed,
the widespread use of tobacco makes it the prime source of
preventable premature death among Americans and members of many
other societies where smoking is commonplace.
The widespread use of tobacco began after Europeans learned about
it from crew members of the Columbus voyages in the latter part
of the fifteenth century who saw the indigenous Americans smoking
tobacco leaves for hedonistic, ritual, or magical purposes. These
effects were later traced to the action of nicotine, which is one
of many cholinomimetics that have been used for these purposes,
such as lobeline, arecoline, hyoscine, muscarine, physostigmine,
pilocarpine, and morphine. When tobacco plants were brought to
Europe they were given the name Nicotiana tabacum in honor of
Jean Nicot (1530-1600). Nicot had introduced tobacco chewing to
Catherine de Medici and had promoted the importation and
cultivation of the plant, believing it to have medicinal value.
As one of the several plant substances mentioned above, nicotine
became far better known than most other cholinotropic substances
because it confers an interoceptive "pleasurable effect" or
euphoria that has instigated and sustained tobacco use by large
proportions of human populations virtually the world over.
Inhaled tobacco smoke contains a complex mixture of substances
including carbon monoxide (CO) and thousands of different
particulate substances such as carcinogenic hydrocarbons that are
generated by the tobacco combustion process. These inhalants make
up tobacco "tar", which provides the principal taste and smell of
the smoke. Unfortunately, tobacco tar and CO are responsible for
most of the diseases associated with long-term tobacco use.
The major psychoactive ingredient in tobacco is nicotine. A
typical American cigarette contains approximately 9 mg of
nicotine, and the yield to the smoker is about 1 mg. When tobacco
smoke is inhaled, nicotine readily passes through the absorbent
surface of the lungs, whose total area has been estimated to be
about equal to the surface of a tennis court. Nicotine is
absorbed to a lesser degree through the membranes of the mouth
and nostrils when tobacco is chewed or snorted.
When tobacco smoke is inhaled, 25% of the nicotine reaches the
brain in about 7 seconds, about twice as fast as when the drug is
administered intravenously. Thus, for nicotine, tobacco smoke
inhalation via the modern cigarette is the fastest and the most
efficient method of drug delivery to the brain.
Adapted from R.S. Feldman et al: Principles of
Neuropsychopharmacology. Sinauer Associates 1997, p.591.
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2. TOBACCO AS A PUBLIC HEALTH PROBLEM
EFFECTS OF MATERNAL CIGARETTE SMOKING
X. Wang et al (Boston University, US) discuss the effects of
maternal cigarette smoking, the authors making the following
points:
1) In the US, 65 percent of all infant deaths occur among low-
birth-weight infants (less than 2500 grams), with such infants
accounting for 7.6 percent of all live-born infants. The etiology
of low birth weight is largely unknown, but both environmental
and genetic factors may play a role. Numerous studies have
demonstrated that maternal cigarette smoking during pregnancy is
associated with reduced birth weight or increased risk of low
birth weight.
2) In 1997, 13.2 percent of US women reported smoking cigarettes
during pregnancy. Maternal cigarette smoking is identified as the
single largest modifiable risk factor for intrauterine growth
restriction in developed countries. However, not all women who
smoke cigarettes during pregnancy have low-birth-weight infants.
The reason for this variability is largely unknown, but may be
related to maternal genetic susceptibility.
3) Tobacco smoke contains approximately 4000 compounds. The most
important carcinogens in tobacco smoke are polycyclic aromatic
hydrocarbons, arylamines, and N-nitrosamines. The ability of an
individual to convert toxic metabolites of cigarette smoke to
less harmful moieties is important for minimizing the adverse
health effects of these compounds. Using polycyclic aromatic
hydrocarbons (PAHs) as an example, the metabolic processing of
these compounds in humans involves 2 phases: a) an activation
process, in which the inhaled hydrophobic PAHs are converted
mainly via aryl hydrocarbon hydroxylase activity into hydrophilic
reactive electrophilic intermediates that can bind covalently to
macromolecules, especially to DNA. These intermediates may be
more toxic than the original form; b) a detoxification process,
in which these metabolic intermediates are detoxified by enzymes
via transformation into conjugate forms sufficiently polar to be
excreted from the body.
4) The authors investigated the correlation between polymorphisms
of 2 metabolic genes (CYP1A1 and GSTT1) and the relation between
maternal cigarette smoking and infant birth weight. 741 human
mothers were involved in the study. The authors report that
maternal CYP1A1 and GSTT1 genotypes modified the association
between maternal cigarette smoking and infant birth weight,
indicating an interaction between metabolic genes and cigarette
smoking.
J. Am. Med. Assoc. 2002 287:195
Related Background:
SMOKING PREVALENCE AMONG ADULTS IN THE US 1998
The US Centers for Disease Control and Prevention (CDC) presents
the results of a 1998 survey administered to a nationally
representative sample (n = 32,440) of the US non-
institutionalized civilian population aged >= 18 years. The
report makes the following points:
1) Participants were asked, "Have you smoked at least 100
cigarettes in your entire life? and "Do you now smoke cigarettes
every day, some days, or not at al?" "Current smokers" were
defined as persons who reported both having smoked greater than
or equal to 100 cigarettes during their lifetime and having
smoked every day or some days at the time of the interview.
"Former smokers" were defined as those who had smoked >= 100
cigarettes during their lifetime but did not currently smoke.
2) In 1998 in the US, an estimated 47.2 million adults (24.1
percent of the adult population), comprising 24.8 million men
(26.4 percent) and 22.4 million women (22.0 percent) were current
smokers. Overall, 19.7 percent of adults were every day smokers,
and 4.2 percent were some day smokers. Every day smokers
constituted 82.4 percent of all smokers.
3) Prevalence of smoking was highest among persons aged 18 to 24
years (27.9 percent) and aged 25 to 44 years (27.5 percent), and
lowest among persons aged >= 65 years (10.9 percent).
4) Among specific groups, prevalence of current smoking was as
follows:
... ... American Indians/Alaska Natives: 40 percent
... ... Non-Hispanic whites: 25 percent
... ... Non-Hispanic blacks: 24.7 percent
... ... Hispanics: 19.1 percent
... ... Asian/Pacific Islanders: 13.7 percent
5) Current smoking prevalence was lowest among persons with at
least 16 years of education (11.3 percent) and highest among
persons with 9 to 11 years of education (36.8 percent). Smoking
prevalence was higher among persons living below the poverty
level (32.3 percent) than among those living at or above the
poverty level (23.5 percent).
6) In 1998, an estimated 44.8 million adults (22.9 percent of the
adult population) were former smokers (25.7 million men and 19.1
million women). Former smokers constituted 48.7 percent of
persons who had ever smoked >= 100 cigarettes. Among current
daily smokers in 1998, an estimated 15.2 million (39.2 percent)
had stopped smoking for at least 1 day during the preceding 12
months because they were trying to stop smoking.
7) The report concludes: "A comprehensive approach to tobacco
control will require treatment for nicotine dependence and
efforts at national, state, and local levels to reduce youth
smoking, promote smoke-free environments, support
countermarketing efforts, and eliminate disparities in tobacco
use among population subgroups. Increased attention must be
focused on groups that show no decline in smoking prevalence,
including persons aged 18 to 24 years, adults with low education
levels, and American Indians/Alaska Natives. Approaches with the
widest scope (i.e., economic, regulatory, and comprehensive) are
likely to have the greatest long-term population impact."
CDC Morbidity and Mortality Weekly Report 2000 49:881
Related Background:
BIDI USE AMONG US URBAN YOUTH
"Bidis" are small brown hand-rolled cigarettes primarily made in
India and southeast Asian countries, and consisting of tobacco
wrapped in a tendu or temburni leaf (Diospyros melanoxylon). In
the US, bidis are purchased for $1.50 to $4.00 for one package of
20 and are available in different flavors (e.g., cherry,
chocolate, and mango). Bidi use was first observed in the US
during the mid-1990s and is apparently now widespread among
various minority youth groups. Adolescents report a preference
for the taste of bidis over cigarettes and a belief that bidis
are less expensive, easier to buy, and safer than cigarettes. The
US Centers for Disease Control and Prevention (CDC) recently
presented a report on bidi use, the report making the following
points:
1) Preliminary data collected from a sample of adolescents
surveyed during March and early April 1999 in Massachusetts (US)
on the prevalence of bidi use among urban youth indicate that of
642 youth surveyed, 40 percent had smoked bidis at least once
during their lifetimes and 16 percent were current bidi smokers.
2) When tested on a standard smoking machine, bidis produced
higher levels of carbon monoxide, nicotine, and tar than
cigarettes, with one study reporting that bidis produced
approximately 3 times the amount of carbon monoxide and nicotine
and approximately five times the amount of tar as cigarettes.
Because of low combustibility of the tendu leaf wrapper, bidi
smokers inhale more often and more deeply, breathing in greater
quantities of tar and other toxins than cigarette smokers. Like
all tobacco products, bidis are mutagenic and carcinogenic. Bidi
smokers risk coronary heart disease, cancers of the oral cavity,
pharynx, larynx, lung, esophagus, stomach, and liver. Mortality
of both the fetus and newborn infant is also associated with bidi
use during pregnancy.
3) The report states that this investigation is the first in the
US to estimate the prevalence of bidi smoking among students in
grades 7 through 12, and that preliminary findings from this
study support the need for additional research on bidis,
particularly on smoking prevalence among youth from differing
geographic, educational, and socioeconomic backgrounds.
CDC Morbidity and Mortality Weekly Report 1999 48:796
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3. TOBACCO DEPENDENCE
ON THE TOBACCO INDUSTRY AND NICOTINE AS AN ADDICTIVE DRUG
In 1994 the state of Minnesota filed suit against the tobacco
industry, and although this trial is now history, there are many
people who feel the legacy of the trial will carry on into the
21st century because of the revelations contained in the millions
of pages of previously secret internal tobacco industry documents
made public in the trial.
R.D. Hurt and C.R. Robertson now present an extensive review of
the material in a medical journal from the perspective of medical
science, and the authors make the following points:
1) The litigation tobacco industry documents reveal that for
decades the tobacco industry knew and internally acknowledged
that *nicotine is an addictive drug and that cigarettes are the
ultimate nicotine delivery device. The following statements by
executives, for example, are found in tobacco industry documents:
"Very few consumers are aware of the effects of nicotine, i.e.,
its addictive nature and that nicotine is a poison." (H.D.
Steele, Brown and Williamson Tobacco Company, 1978). And in
another Brown and Williamson memo: "Nicotine is the addicting
agent in cigarettes." (A.J. Mellman, Brown and Williamson Tobacco
Company, 1983). Concerning cigarettes as a drug delivery device,
the litigation documents reveal that C.E. Teague Jr., assistant
director of research at R.J. Reynolds Tobacco Company, wrote in
1972 in an internal memorandum: "In a sense, the tobacco industry
may be thought of as being a specialized, highly ritualized and
stylized segment of the pharmaceutical industry. Tobacco
products, uniquely, contain and deliver nicotine, a potent drug
with a variety of physiological effects... Thus a tobacco product
is, in essence, a vehicle for delivery of nicotine."
2) The authors report that perhaps their most surprising finding
in the document review was the evidence of tobacco industry
efforts spanning 3 decades to alter the chemical form of nicotine
to increase the percentage of freebase nicotine delivered to
smokers. Depending on pH, nicotine exists as a diprotonated salt,
a monoprotonated salt, or an uncharged neutral species. The salt
forms are called the "bound" forms, and the neutral species is
called the "freebase" form. Nicotine favors the salt form at low
values of pH (e.g., pH = 3) and the freebase form at high values
of pH (e.g., pH = 8). Freebase nicotine apparently crosses
biological membranes more easily than the charged counterparts,
and this affects the physiological response to the drug.
3) The tobacco industry was apparently well aware of these
properties of nicotine as far back as 1966, and for 3 decades the
tobacco industry had a focus on developing high pH delivery of
nicotine to increase its physiological effects. The authors
conclude: "When the breadth and depth of tobacco industry actions
are understood, it becomes evident that allowing a tobacco
settlement that honors the industry demands for legal and
financial immunity would be a public health disaster of epic
proportions and would allow the industry to continue to promote
its deadly product throughout the 21st century. Congress must use
its power to stop the carnage of more than 400,000 Americans
dying each year of cigarette-related diseases."
J. Am. Med. Assoc. 1998 280:1173
Notes:
... ... *nicotine: The alkaloid nicotine [3-(1-methyl-
pyrrolidyl)pyridine] is a tertiary amine composed of pyridine and
pyrrolidine rings. The current consensus among
neuropharmacologists is that nicotine is the psychoactive drug
primarily responsible for the addictive nature of tobacco use.
Nicotine is highly selective for so-called "nicotinic receptors"
for *acetylcholine in the peripheral and central nervous systems,
and activation of these receptors is the likely source of the
psychoactive effects of the drug. The nicotinic-acetylcholine
receptor is a molecularly well-characterized receptor, and its
activation evidently leads to conformation changes in its 5
subunits that result in a transient increase of permeability of
the neuron membrane to the sodium ion. The nicotinic-
acetylcholine receptor is therefore characterized as a
neurotransmitter-gated ion channel. Concentrations of nicotine in
blood rise quickly during cigarette smoking and peak at its
completion. Nicotine is also deposited in the lungs, spleen,
liver, and brain, where concentrations are typically twice those
of measurable blood concentrations. Nicotine readily crosses the
*blood-brain barrier, leading to the release of acetylcholine,
*norepinephrine, *dopamine, *serotonin, *vasopressin, *growth
hormone, *cortisol, *prolactin, *neurophysin 1, and
*adrenocorticotropic hormone, and release of these substances
causes various neuropharmacological effects. Apart from the
neuropharmacological effects of nicotine, nicotine and other
constituents in cigarette smoke elevate blood pressure, cause
*tachycardia, *arrhythmia, and *vasoconstriction in *cutaneous
tissue and skin; lower body temperature; inhibit *diuresis;
increase *gastrointestinal tonus; antagonize ulcer healing; and
decrease pain threshold.
... ... *acetylcholine: A prevalent *neurotransmitter substance,
both in the brain and in the peripheral nervous system, where it
controls the actions of skeletal and smooth muscle.
... ... *neurotransmitter substance: Neurotransmitters are
chemical substances released at the terminals of nerve axons in
response to the propagation of an impulse to the end of that
axon. The neurotransmitter substance diffuses into the synapse,
the junction between the presynaptic nerve ending and the
postsynaptic neuron, and at the membrane of the postsynaptic
neuron the transmitter substance interacts with a receptor.
Depending on the type of receptor, the result may be an
excitatory or an inhibitory effect on the postsynaptic nerve
cell.
... ... *blood-brain barrier: A selective mechanism opposing the
passage of most ions and large molecular-weight compounds from
the blood to brain tissue, the mechanism operating in a
continuous layer of endothelial cells connected by tight
junctions between cells. (Endothelial cells are flat cells
forming a layer lining blood vessels, lymphatic vessels, the
heart, etc.)
... ... *norepinephrine: The principal neurotransmitter substance
released from nerve endings of the sympathetic nervous system.
(The sympathetic nervous system is a part of the autonomic
nervous system involved in the mobilization of energy resources
during stress and arousal.
... ... *dopamine: A neurotransmitter substance.
... ... *serotonin: A neurotransmitter substance involved in
nearly everything occurring in the brain, including psychological
states such as anxiety and depression, and dysfunctions producing
migraine and epilepsy.
... ... *vasopressin: A peptide hormone important in the
regulation of *diuresis.
... ... *growth hormone: A vertebrate polypeptide hormone that
regulates growth. In general, hormones are signaling molecules
secreted into the blood stream by endocrine cells and acting on
target cells that possess receptors for the hormone.
... ... *cortisol: A corticosteroid hormone secreted by the
adrenal gland.
... ... *prolactin: A polypeptide hormone synthesized and
released by the pituitary gland.
... ... *neurophysin 1: Neurophysins are a family of proteins
synthesized in the hypothalamus, and function as carriers in the
transport and storage of a number of hypothalamic-pituitary
hormones.
... ... *adrenocorticotropic hormone: (ACTH) A pituitary hormone.
... ... *tachycardia: Rapid beating of the heart, conventionally
applied to rates over 100 per minute.
... ... *arrhythmia: Irregularity of the heartbeat.
... ... *vasoconstriction: Narrowing of the blood vessels.
... ... *cutaneous tissue: In general, tissue associated with
skin.
... ... *diuresis: Excretion of large volumes of urine.
... ... *gastrointestinal tonus: In general, contraction of
gastrointestinal muscle.
Related Background:
TREATMENT OF TOBACCO USE AND DEPENDENCE
Nancy A. Rigotti (Harvard University, US) discusses tobacco use
and dependence, the author making the following points:
1) Tobacco use is the leading preventable cause of death in the
US, responsible for more than 400,000 deaths annually, or 1 of
every 5 deaths.(1) Half of regular smokers die prematurely of a
tobacco-related disease. The potential health benefits of smoking
cessation are substantial. Cessation reduces the risk of tobacco-
related diseases, slows the progression of established tobacco-
related diseases, and increases life expectancy, even when
smokers stop smoking after the age of 65 years or after the
development of a tobacco-related disease.(2)
2) An estimated 70 percent of smokers see a physician each year,
providing physicians with substantial opportunity to influence
smoking behavior.(3) However, that opportunity presents
challenges. Many patients continue to smoke despite knowing about
or experiencing the health consequences of tobacco use. Some who
try to quit repeatedly fail. Most mistakenly believe that
stopping smoking requires only willpower and are unaware that
effective treatments are available. Smoking is best regarded as a
chronic disease that requires a long-term management strategy,
rather than a quick fix.(3)
3) Currently, 23.5 percent of U.S. adults (25.7 percent of men
and 21.5 percent of women) smoke cigarettes.(4) Nearly all
smokers acknowledge that tobacco use is harmful to health but
underestimate the magnitude of their own risk. Few know the full
spectrum of health risks.(2,5) For many smokers, the risk of
future disease does not outweigh the current perceived benefits
of smoking or barriers to cessation. Yet 70 percent of smokers
report that they want to quit. Approximately one third of smokers
try to stop smoking each year, but only 20 percent of them seek
help. Fewer than 10 percent of smokers who attempt to quit on
their own are successful over the long term. Smokers have a
higher rate of success when they seek help with quitting. Even
then, several attempts are often required before long-term
abstinence is achieved.
4) The chief physiological obstacle to quitting is the addictive
nature of nicotine. Nicotine causes tolerance and physical
dependence. When tobacco use is stopped, there is a withdrawal
syndrome characterized by irritability, anger, impatience,
restlessness, difficulty concentrating, insomnia, increased
appetite, anxiety, and depressed mood. Symptoms of nicotine
withdrawal are nonspecific, vary widely in intensity and
duration, and are not correctly identified by smokers. Symptoms
begin a few hours after the last cigarette, peak two to three
days later, and wane over a period of several weeks or months.
References (abridged):
1. Tobacco use -- United States, 1900-1999. MMWR Morb Mortal Wkly
Rep 1999;48:986-993. [Erratum, MMWR Morb Mortal Wkly Rep
1999;48:1027.]
2. Department of Health and Human Services. The health benefits
of smoking cessation: a report of the Surgeon General.
Washington, D.C.: Government Printing Office, 1990. (DHHS
publication no. (CDC) 90-8416.)
3. A clinical practice guideline for treating tobacco use and
dependence: a US Public Health Service report. JAMA
2000;283:3244-3254.
4. Cigarette smoking among adults -- United States, 1999. MMWR
Morb Mortal Wkly Rep 2001;50:869-873.
5. Ayanian JZ, Cleary PD. Perceived risks of heart disease and
cancer among cigarette smokers. JAMA 1999;281:1019-1021.
New Engl. J. Med. 2001 346:506
Related Background:
EFFECTIVE TOBACCO DEPENDENCE TREATMENT
M.C. Fiore et al (University of Wisconsin, US) discuss tobacco
dependence, the authors making the following points:
1) More than at any time in the past, clinicians, public health
professionals, and policy makers now possess sufficient evidence
to implement effective tobacco dependence treatment programs and
policies. Clinical, health system, and community interventions
can each independently foster tobacco cessation.(1,2) A
transdisciplinary approach that incorporates all of these
components holds the greatest promise for reducing population-
based rates of tobacco use. If these interventions are
implemented broadly, a larger proportion of the 46 million US
adult smokers will try to quit. Among those who do try, the
likelihood of successful cessation will increase substantially.
In 1999, the proportion of US adults who had successfully quit
(45.7 million [23.1%]) approached that of individuals who
continued to smoke (46.5 million [23.5%]).(3) This statistical
equivalence highlights the progress achieved over the last half-
century. It also reveals the challenges we face in the new
century if more individuals are to successfully quit.
2) The fact that 50% of persons who have ever smoked have now
quit is evidence that cessation can yield significant net
decreases in smoking prevalence. To further decrease prevalence,
increased rates of cessation are necessary. The US Public Health
Service (PHS) publication Tracking Healthy People 2010(4) set a
national goal of reducing tobacco use to 12% or less among adults
by the end of this decade. Two recent publications provide a
blueprint for achieving one aspect of that goal (increasing
cessation rates nationally): the PHS Clinical Practice Guideline
Treating Tobacco Use and Dependence,(5) and the Centers for
Disease Control and Prevention (CDC) Guide to Community
Preventive Services: Tobacco Use Prevention and Control.
Together, these documents outline specific, state-of-the-art
clinician, health care system, and community interventions that
can boost cessation success significantly.
3) Implementing the CDC and PHS guideline recommendations is
important, because data suggest that there exists a group of
smokers that may be more heavily dependent than in the past and
that these individuals may have a more difficult time quitting.
The epidemiology of tobacco use has continued its 50-year
evolution from an equal opportunity addiction to a behavior that
now affects primarily the most socioeconomically disadvantaged
members of society. For example, in 1999, among those with
masters, professional, or doctoral degrees, only 8.5% used
tobacco. Conversely, 44.4% of those with only a high school
General Educational Development degree used tobacco. Individuals
living below the poverty level had a significantly higher smoking
rate (33.1%) than did those living at or above the poverty level
(24.4%).(3) Recently, college students demonstrated an exception
to the above epidemiological observation. A 1999 survey of
nationally representative 4-year colleges found that 45.7% of
students reported use of a tobacco product in the past year and
32.9% reported that they were current users, indicating a
particular need for assessment and intervention in this
population.
References (abridged):
1. National Cancer Institute. Population Based Smoking Cessation:
Proceedings of a Conference on What Works to Influence Cessation
in the General Population. Bethesda, Md: US Dept of Health and
Human Services, National Institutes of Health; 2000. NIH
publication 00-4892
2. Houston T, Kaufman NJ. Tobacco control in the 21st century:
searching for answers in a sea of change [editorial]. JAMA.
2000;284:752-753
3. Cigarette smoking among adults -- United States, 1999. MMWR
Morb Mortal Wkly Rep. 2001;50:869-873
4. US Department of Health and Human Services. Tracking Healthy
People 2010. Washington, DC: US Government Printing Office; 2000
5. Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use and
Dependence: Clinical Practice Guideline. Rockville, Md: US Dept
of Health and Human Services; 2000
J. Am. Med. Assoc. 2002 288:1768
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4. EFFECTS OF PASSIVE SMOKING
ACUTE EFFECTS OF PASSIVE SMOKING ON THE CORONARY CIRCULATION IN
HEALTHY YOUNG ADULTS
R. Otsuka et al (Osaka City University, JP) discuss passive
smoking, the authors making the following points:
1) Passive smoking has been identified as an important risk
factor for cardiovascular disease.(1-5) In 1992, the American
Heart Association concluded that the risk of death due to heart
disease is increased by about 30% among those exposed to
environmental tobacco smoke at home, and could be much higher in
those exposed at the workplace, where higher levels of
environmental tobacco smoke may be present. There is evidence
that exposure of nonsmokers to environmental tobacco smoke breaks
down the serum antioxidant defenses and is associated with
impairment of endothelium-dependent function of arterial walls.
However, the acute effects of passive smoking on the coronary
circulation in nonsmokers have not been evaluated.
2) Coronary flow velocity reserve (CFVR), a measure of
endothelial function in the coronary circulation, can be
noninvasively measured in the left anterior descending coronary
artery (LAD) using transthoracic Doppler echocardiography (TTDE).
The authors report a study to determine the acute effects of
passive smoking on coronary circulation using measurement of CFVR
by TTDE. A cross-sectional study was conducted from September
2000 to November 2000 among 30 Japanese men (mean age, 27 years;
15 healthy nonsmokers and 15 asymptomatic active smokers) without
history of hypertension, diabetes mellitus, or hyperlipidemia.
Coronary flow velocity reserve, calculated as the ratio of
hyperemic to basal coronary flow velocity induced by intravenous
infusion of adenosine triphosphate, was measured in each
participant before and after a 30-minute exposure to
environmental tobacco smoke.
3) The authors report that heart rate and blood pressure
responses to adenosine triphosphate infusion were not affected by
passive smoking exposure in either group. Passive smoking
exposure had no effect on basal coronary flow velocity in either
group. Mean (SD) CFVR in nonsmokers was significantly higher than
that in active smokers before passive smoking exposure (4.4
[0.91] vs 3.6 [0.88], respectively, while CFVR after passive
smoking exposure did not differ between groups. Passive smoking
exposure significantly reduced mean (SD) CFVR in nonsmokers (4.4
[0.91] vs 3.4 [0.73], respectively).
The authors conclude: "Passive smoking substantially reduced CFVR
in healthy nonsmokers. This finding provides direct evidence that
passive smoking may cause endothelial dysfunction of the coronary
circulation in nonsmokers."
References (abridged):
1. Taylor AE, Johnson DC, Kazemi H. Environmental tobacco smoke
and cardiovascular disease: a position paper from the Council on
Cardiopulmonary and Critical Care, American Heart Association.
Circulation. 1992;86:699-702
2. Wells AJ. Passive smoking as a cause of heart disease. J Am
Coll Cardiol. 1994;24:546-554
3. Kritz H, Scmidt P, Sinzinger H. Passive smoking and
cardiovascular risk. Arch Intern Med. 1995;155:1942-1948
4. Glantz SA, Parmley WW. Passive smoking and heart disease:
mechanisms and risk. JAMA. 1995;273:1047-1053
5. Steenland K, Thun M, Lally C, Health C Jr. Environmental
tobacco smoke and coronary heart disease in American Cancer
Society CPS-II cohort. Circulation. 1996;94:622-628
J. Am. Med. Assoc. 2001 286:436
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5. THE PROBLEM OF CIGARETTE ADVERTISING
THE MASTER SETTLEMENT AGREEMENT WITH THE TOBACCO INDUSTRY AND
CIGARETTE ADVERTISING IN MAGAZINES
C. King et al (Boston University, US) discuss cigarette
advertising, the authors making the following points:
1) Reducing cigarette smoking among adolescents is a public
health priority.(1,2) Research suggests that the advertising and
promotion of cigarettes strongly influence the initiation of
smoking.(3-5) Thus, reducing the exposure of children to
cigarette advertising is important. There is evidence, however,
that cigarette companies may have targeted young people in their
magazine advertising and that cigarette advertising in magazines
is likely to reach a substantial number of young people. In
November 1998, the attorneys general of 46 states signed a Master
Settlement Agreement with the four largest tobacco companies in
the United States. The agreement states that cigarette companies
may not "take any action, directly or indirectly, to target
youth... in the advertising, promotion or marketing of tobacco
products." In June 2000, Philip Morris announced that beginning
in September 2000 it would restrict its cigarette advertising to
magazines whose proportion of young readers was less than 15
percent and that had fewer than 2 million readers from 12 to 17
years old. R.J. Reynolds declined to adopt a similar policy.
2) Monitoring and enforcing the tobacco settlement require a
careful examination of the trends in cigarette advertising in
magazines and the exposure of young people to this advertising.
The authors studied advertising expenditures and exposure before
and after the Master Settlement Agreement and evaluated the
effectiveness of restricting cigarette advertising to magazines
for which young readers represent less than 15 percent of the
overall readership and that have fewer than 2 million young
readers.
3) The authors report they analyzed the trends in expenditures
for advertising for 15 specific brands of cigarettes and the
exposure of young people to cigarette advertising in 38 magazines
between 1995 and 2000. In 2000 dollars, the overall advertising
expenditures for the 15 brands of cigarettes in the 38 magazines
were $238.2 million in 1995, $219.3 million in 1998, $291.1
million in 1999, and $216.9 million in 2000. Expenditures for
youth brands in youth-oriented magazines were $56.4 million in
1995, $58.5 million in 1998, $67.4 million in 1999, and $59.6
million in 2000. Expenditures for adult brands in youth-oriented
magazines were $72.2 million, $82.3 million, $108.6 million, and
$67.6 million, respectively. In 2000, magazine advertisements for
youth brands of cigarettes reached more than 80 percent of young
people in the United States an average of 17 times each.
4) The authors conclude: "The Master Settlement Agreement with
the tobacco industry appears to have had little effect on
cigarette advertising in magazines and on the exposure of young
people to these advertisements."
References (abridged):
1. Johnston LD, O'Malley PM, Bachman JG. The Monitoring the
Future national results on adolescent drug use: overview of key
findings, 1999. Bethesda, Md.: National Institute on Drug Abuse,
2000. (NIH publication no. 00-4690.)
2. Tobacco use among middle and high school students -- United
States, 1999. MMWR Morb Mortal Wkly Rep 2000;49:49-53
3. Department of Health and Human Services. Preventing tobacco
use among young people: a report of the Surgeon General. Atlanta:
National Center for Chronic Disease Prevention and Health
Promotion, Office on Smoking and Health, 1994.
4. Pierce JP, Choi WS, Gilpin EA, Farkas AJ, Berry CC. Tobacco
industry promotion of cigarettes and adolescent smoking. JAMA
1998;279:511-515. [Erratum, JAMA 1998;280:422.]
5. Biener L, Siegel M. Tobacco marketing and adolescent smoking:
more support for a causal inference. Am J Public Health
2000;90:407-411
New Engl. J. Med. 2001 345:504
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6. TOBACCO CONTROL
THE FUTURE OF THE GLOBAL TOBACCO TREATY NEGOTIATIONS
Henry A. Waxman ((House of Representatives, US) discusses the
Global Tobacco Treaty, the author making the following points:
1) Government officials around the world now recognize what
industry executives have long understood -- the tobacco business
is fundamentally a global enterprise.(1) The sale of raw leaf and
finished products, the smuggling of cigarettes to evade taxes,
and the effects of print and television advertising all cross
national borders. The consequences of this enterprise are
staggering -- by the year 2020, an estimated 8.4 million people
will die annually from tobacco-related diseases, more than two
thirds of them in developing countries.(2) If current trends
continue, more people will perish annually from tobacco-related
illness than from any single disease.
2) To respond to this global public health crisis, in 1995 the
World Health Assembly of the World Health Organization inquired
into the feasibility of an international treaty on tobacco
control.(3) Experts in international law found that a legally
binding agreement could be used to establish standards for
international tobacco control, assist governments in developing
effective domestic legislation, and create a global mechanism to
counter the political influence of the tobacco industry.(4) In
1999, the World Health Assembly authorized the start of
negotiations,(5) and representatives from more than 160 countries
have subsequently met three times to negotiate the treaty, which
is called the Framework Convention on Tobacco Control (FCTC). At
least two more sessions are planned before the FCTC is ready for
ratification by individual nations in 2003.
3) The United States has a crucial role in the FCTC process and
should lead the effort to develop a strong treaty. The United
States supports tobacco-control programs on several continents.
Indeed, some of the most compelling evidence of the effectiveness
of antitobacco policies comes from state programs in the United
States. Yet the United States also exports more cigarettes than
any other nation in the world -- more than one of every five
traded, representing billions of dollars in revenue for U.S.
tobacco companies. With negotiations at a midpoint, and in many
ways at a crossroads, it is important to evaluate the public
health implications of U.S. actions critically.
4) The author concludes: "We know more about the harm of tobacco
consumption and effective ways to reduce this harm than about
perhaps any other major cause of human suffering. That knowledge
not political influence or campaign contributions should guide
U.S. actions in these crucial public health negotiations."
References (abridged):
1. Hill DA. Implications of Pesticide Use on the Tobacco Trade,
1988: Aug 15. Available from: URL: http://www.pmdocs.com Bates No
2501269834/9846
2. Murray CJ, Lopez AD. Alternative projections of mortality and
disability by cause 1990-2020: Global Burden of Disease Study.
Lancet 1997;349:1498-1504
3. An international strategy for tobacco control. Geneva: World
Health Organization, 1995. (Document no. A48/VR/12.)
4. Taylor AL, Roemer R. International strategy for tobacco
control. Geneva: World Health Organization, 1996. (Document no.
WHO/PSA/96.6.)
5. Towards a WHO framework convention on tobacco control. Geneva:
World Health Organization, 1999. (Document no. A52/VR/9.)
New Engl. J. Med. 2002 346:936
Related Background:
STATE EXPENDITURES FOR TOBACCO-CONTROL PROGRAMS AND THE TOBACCO
SETTLEMENT
C.P. Gross et al (Yale University, US) discuss tobacco control,
the authors making the following points:
1) It has been four years since the tobacco industry reached
settlement agreements with all 50 states, and it has been
suggested that the settlement is not living up to its promise.(1)
Despite the newly imposed marketing restrictions, the 24 percent
increase in marketing expenditures by the tobacco industry in the
year after the settlement (to a total of $8.24 billion) was the
highest ever reported.(2) There has been no significant decrease
in youth-directed magazine advertisements.(3,4) Paradoxically,
the tobacco industry continues to enjoy increasing revenues:
although the price of cigarettes increased by up to 50 percent in
the two years after the settlement, cigarette sales decreased by
only about 10 percent in the same period.(2,5)
2) The primary goal of the settlement, however, has been
described as promoting public health rather than punishing the
tobacco industry. In fact, the Master Settlement Agreement
specifically states that one of the goals for the agreement was
to support "tobacco related public health measures." As a result,
it was hoped that the states would invest a considerable
proportion of their settlement revenue in comprehensive tobacco-
control programs. Several studies indicate that over the past
decade, states with such programs had a decline in cigarette
consumption that was significantly greater than the national
average. It has been estimated that the California program alone
has saved more than 33,000 lives since its inception. The Centers
for Disease Control and Prevention (CDC) performed an evidence-
based analysis of successful state tobacco-control programs and
issued a minimal funding recommendation for each state. These
recommendations, which are based on the smoking rate and the
population age distribution of each state, range from about $5 to
$15 per capita.
3) The authors report they evaluated state expenditures for
tobacco-control programs in fiscal year 2001 in the context of
the amount of tobacco-settlement funds received and allocated to
tobacco-control programs and in the context of other state-level
economic and health data. The authors report that in 2001 the
average state received $28.35 per capita from the tobacco
settlement but allocated approximately 6 percent of these funds
to tobacco-control programs. The average state dedicated $3.49
per capita (range, $0.10 to $15.47) to tobacco-control programs.
The proportion of settlement funds allocated to tobacco-control
programs varied from 0 to 100 percent and was strongly related to
levels of tobacco-control funding. States with higher smoking
rates tended to invest less per capita in tobacco-control
programs, as did tobacco-producing states (the mean per capita
expenditure was $1.20, as compared with $3.81 in non tobacco-
producing states. In a multivariate analysis, the proportion of
the settlement revenue allocated to tobacco-control programs was
the primary determinant of the level of total funding; the state
tobacco-related health burden was unrelated to program funding.
4) The authors conclude: "State health needs appear to have
little effect on the funding of state tobacco-control programs.
Because only a very small proportion of the tobacco settlement is
being used for tobacco-control programs, the settlement
represents an unrealized opportunity to reduce morbidity and
mortality from smoking."
References (abridged):
1. Kessler DA, Myers ML. Beyond the tobacco settlement. N Engl J
Med 2001;345:535-537
2. Federal Trade Commission Cigarette Report for 1999.
Washington, D.C.: Federal Trade Commission, 2001:2-3.
3. King C III, Siegel M. The Master Settlement Agreement with the
tobacco industry and cigarette advertising in magazines. N Engl J
Med 2001;345:504-511
4. Chung PJ, Garfield CF, Rathouz PJ, Lauderdale DS, Best D,
Lantos J. Youth targeting by tobacco manufacturers since the
Master Settlement Agreement: the first study to document
violations of the youth-targeting ban in magazine ads by the
three top U.S. tobacco companies. Health Aff (Millwood)
2002;21:254-263.
5. All urban consumers. Washington, D.C.: Department of Labor,
2002. (Accessed September 10, 2002, at www.bls.gov/data/home.htm
)
New Engl. J. Med. 2002 347:1080
Related Background:
USING TOBACCO-INDUSTRY MARKETING RESEARCH TO DESIGN MORE
EFFECTIVE TOBACCO-CONTROL CAMPAIGNS
P.M. Ling and S.A. Glantz (University of California San
Francisco, US) discuss tobacco control, the authors making the
following points:
1) Most analyses of tobacco-industry marketing have been designed
to demonstrate that the industry targeted youth.(1-3) The
industry also conducts extensive research on adults, particularly
young adults aged 18 to 24 years. The industry's interest in
young adults is not surprising,(4) since they compose its
youngest legal marketing target, vastly outnumber teen
smokers,(5) are making the transition from smoking initiation to
becoming fully addicted smokers, and are role models for teens.
Tobacco companies have used detailed studies of young adult
smokers' motivations, aspirations, activities, and environment to
guide cigarette marketing and advertising campaigns.
2) Tobacco marketers divide actual and potential smokers into
segments: groups of consumers who respond similarly to a given
set of marketing messages on the basis of needs, characteristics,
or behavior. Market segments can be defined by many criteria,
including demographics, geography, attitudes, preferred product
benefits, usage, and competitive products. In contrast to public
health, which designs tobacco-control programs according to
demographics or constituencies, the industry defines target-
market segments primarily by using consumer desires and needs.
3) Throughout the past 40 years, tobacco marketers have paid
increasing attention to young adults' psychological and
attitudinal profiles, physical environment, and activities.
Advertising images were integrated into environments where young
adults work, study, and socialize, and smoking was presented as a
normal adult behavior, with brand images designed to appeal to
specific psychological profiles. Since the 1980s, market segments
have increasingly reflected smokers' concerns about price and the
eroding social acceptability of smoking.
4) In summary: To improve tobacco-control efforts by applying
tobacco-industry marketing research and strategies to clinical
and public health smoking interventions, the authors analyzed
previously secret tobacco-industry marketing documents. In
contrast to public health, the tobacco industry divides markets
and defines targets according to consumer attitudes, aspirations,
activities, and lifestyles. Tobacco marketing targets smokers of
all ages; young adults are particularly important. During the
1980s, cost affected increasing numbers of young and older
smokers. During the 1990s, eroding social acceptability of
smoking emerged as a major threat, largely from increasing
awareness of the dangers of secondhand smoke among nonsmokers and
smokers. The authors suggest that physicians and public health
professionals should use tobacco-industry psychographic
approaches to design more relevant tobacco-control interventions.
Efforts to counter tobacco marketing campaigns should include
people of all ages, particularly young adults, rather than
concentrating on teens and young children. Many young smokers are
cost sensitive. Tobacco-control messages emphasizing the dangers
of secondhand smoke to smokers and nonsmokers undermine the
social acceptability of smoking.
References (abridged):
1. Perry CL. The tobacco industry and underage youth smoking.
Arch Pediatr Adolesc Med. 1999;153:935-941
2. Pollay RW. Targeting youth and concerned smokers. Tob Control.
2000;9:136-147
3. Hastings G, MacFadyen L. A day in the life of an advertising
man. BMJ. 2000;321:366-371
4. Ling PM, Glantz SA. Why and how the tobacco industry sells
cigarettes to young adults: evidence from industry documents. Am
J Public Health. 2002;92:908-916
5. Johnston ME, Daniel BC, Levy CJ. Young smokers prevalence,
trends, implications, and related demographic trends [Philip
Morris USA Research Center article]. March 31, 1981. Bates No.
1000390803/0855. Available at:
http://www.pmdocs.com/getallimg.asp?DOCID=1000390803/0855
J. Am. Med. Assoc. 2002 287:2983
Related Background:
ON EDUCATING PHYSICIANS CONCERNING TOBACCO DEPENDENCE
Tobacco use is the leading cause of preventable death and
disability in the US, accounting for nearly 500,000 premature
deaths per year. Although 70 percent of smokers visit a physician
each year, most patients are not advised or assisted in an
attempt to quit smoking. A 1991 survey indicated that only 21
percent of practicing physicians felt their formal medical
training prepared them to help patients stop smoking.
L.H. Ferry et al (3 authors at Loma Linda University, US) now
present the results of a survey designed to assess the content
and extent of tobacco curricula in US undergraduate medical
education. In this context, the phrase "tobacco curricula"
includes epidemiology of tobacco use, prevention, risk of
tobacco-related diseases, and tobacco dependence treatment. The
phrase "smoking cessation" includes behavior modification
techniques, pharmacotherapy, and counseling skills. The authors
received data from 122 US medical schools (98.6 percent of the
total medical schools in the US). The authors report that a
majority of US medical school graduates are not adequately
trained to treat nicotine dependence. The authors suggest that
the major deficit is the lack of smoking cessation instruction
and evaluation in the clinical years of medical training, and
that a model core tobacco curricula that meets national
recommendations should be developed and implemented in all US
medical schools. The authors conclude: "Until all medical schools
place sufficient emphasis on the knowledge base and intervention
skills needed to prevent and treat chronic tobacco-related
diseases, it is unlikely we will see a decline in tobacco-related
morbidity and mortality. However, if medical schools provide
universal training of medical students in nicotine dependence
intervention, tobacco users will have access to the professional
expertise they need to end the deadly cycle of nicotine
addiction."
J. Am. Med. Assoc. 1999 282:825
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7. PHARMACEUTICAL COMPANIES AND TOBACCO COMPANIES
FINANCIAL TIES AND CONFLICTS OF INTEREST BETWEEN PHARMACEUTICAL
AND TOBACCO COMPANIES
B. Shamasunder and L. Bero (University of California San
Francisco, US) discuss conflicts of interest, the authors making
the following points:
1) Financial ties between companies producing addictive tobacco
products and companies producing drugs to treat or alleviate the
addiction are a potential conflict of interest. Several types of
financial ties can exist. For example, one company could be the
sole supplier of a product that is needed by another company. Or,
a company could be financially dependent on sales from another
company. Corporate diversification also results in financial ties
between companies.
2) Corporate diversification leads to a network of holding
companies, parent companies, and subsidiaries that are
financially connected but operate seemingly independently.(1-2)
Diversification can contribute to financial stability, but it
also allows corporate negotiations to occur with little public
knowledge and can hide financial ties that are potential
conflicts of interest.
3) The diversification of the tobacco industry is well-
documented.(3-4) The tobacco industry has systematically acquired
companies that manufacture unrelated consumer products such as
cookies, macaroni and cheese, candy, and pharmaceuticals. The
tobacco industry has used its financial ties to pressure a
variety of industries to oppose tobacco control.(5) The
pharmaceutical industry also maintains diversified interests and
is involved in the sale of multiple products such as chemicals,
pesticides, plastics, and pharmaceuticals.(2) Thus, corporate
diversification has resulted in financial ties between
pharmaceutical companies that market nicotine replacement
therapies (NRTs) and the tobacco industry.
4) In summary: Corporate diversification allows for well-hidden
financial ties between pharmaceutical and tobacco companies,
which can cause a conflict of interest in the development and
marketing of pharmaceutical products. In their investigation of
tobacco company documents released and posted on the Internet as
a result of the Master Settlement Agreement, the authors report
they have found that these financial ties have fostered both
competition and collaboration between the tobacco and
pharmaceutical industries. The authors present present 3 case
studies. One shows how tobacco companies pressured pharmaceutical
companies to scale back their smoking cessation educational
materials that accompanied Nicorette. The second shows how they
restricted to whom the pharmaceutical company could market its
transdermal nicotine patch. In the third case, the authors show
how subsidiary tobacco and pharmaceutical companies of a parent
company collaborated in the production of a nicotine-release gum.
The authors suggest that because tobacco cessation product
marketing has been altered as a result of these financial
conflicts, disclosure would serve the interest of public health.
References (abridged):
1. Markides CC. To diversify or not to diversify. Harvard
Business Review. 1997;75:93-99
2. Krantz A. Diversification of the drug discovery process. Nat
Biotechnol. 1998;16:1294
3. Blum A. Diversification in the tobacco industry. NY State J
Med. 1985:328-334
4. Joossens L. Diversification is the future for many tobacco
farmers. Tob Control. 1996;5:177-178
5. Landman A. Push or be punished: tobacco industry documents
reveal aggression against businesses that discourage tobacco use.
Tob Control. 2000;9:339-346
J. Am. Med. Assoc. 2002 288:738
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