The epidemiology of smoking: Health consequences and benefits of cessation

Abstract

Tobacco use is the single most important preventable health risk in the developed world, and an important cause of premature death worldwide. Smoking causes a wide range of diseases, including many types of cancer, chronic obstructive pulmonary disease, coronary heart disease, stroke, peripheral vascular disease, and peptic ulcer disease. In addition, smoking during pregnancy adversely affects fetal and neonatal growth and development. Recent decades have seen a massive expansion in tobacco use in the developing world and accelerating growth in smoking among women in the developed world. Globally, smoking-related mortality is set to rise from 3 million annually (1995 estimate) to 10 million annually by 2030, with 70% of these deaths occurring in developing countries. Many of the adverse health effects of smoking are reversible, and smoking cessation treatments represent some of the most cost effective of all healthcare interventions. Although the greatest benefit accrues from ceasing smoking when young, even quitting in middle age avoids much of the excess healthcare risk associated with smoking. In order to improve smoking cessation rates, effective behavioural and pharmacological treatments, coupled with professional counselling and advice, are required. Since smoking duration is the principal risk factor for smoking-related morbidity, the treatment goal should be early cessation and prevention of relapse.

Full text

The Epidemiology of Smoking
Health Consequences and Benefits of Cessation
Karl Fagerström
Fagerstrom Consulting, Helsingborg, Sweden
Abstract Tobacco use is the single most important preventable health risk in the devel-
oped world, and an important cause of premature death worldwide. Smoking
causes a wide range of diseases, including many types ofcancer, chronic obstruc-
tive pulmonary disease, coronary heart disease, stroke, peripheral vascular dis-
ease, and peptic ulcer disease. In addition, smoking during pregnancy adversely
affects fetal and neonatal growth and development. Recent decades have seen a
massive expansion in tobacco use in the developing world and accelerating
growth in smoking among women in the developed world. Globally, smoking-
related mortality is set to rise from 3 million annually (1995 estimate) to 10
million annually by 2030, with 70% of these deaths occurring in developing
countries.
Many of the adverse health effects of smoking are reversible, and smoking
cessation treatments represent some of the most cost effective of all healthcare
interventions. Although the greatest benefit accrues from ceasing smoking when
young, even quitting in middle age avoids much of the excess healthcare risk
associated with smoking. In order to improve smoking cessation rates, effective
behavioural and pharmacological treatments, coupled with professional counsel-
ling and advice, are required. Since smoking duration is the principal risk factor
for smoking-related morbidity, the treatment goal should be early cessation and
prevention of relapse.
REVIEW ARTICLE Drugs 2002; 62 Suppl. 2: 1-9
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According to World Health Organization
(WHO) estimates, there are currently 1.1 billion
tobacco smokers worldwide, representing about
one-third of the entire population aged 15 years
and over (table I).[1] The majority of these smokers
are found in developing countries (800 million)
and most are male (700 million). Globally, it is
estimated that some 47% of men and 12% of
women smoke (see table I).
Smoking rates vary widely between regions and
between countries within the same region. The
prevalence of smoking in men is currently highest
in countries of the Western Pacific region, such as
South Korea (68%), China (61%) and Japan
(59%).[1] In Europe, where almost one-half of adult
males are regular smokers, the prevalence ranges
from 63% of men in the Russian Federation to 17%
in Sweden.[2] Among women, the regional pattern
of smoking is quite different, with a sharp contrast
seen between prevalences in the developed world
(24%) and the developing world (7%). Thus, one-
third of women in Norway and Denmark smoke,
compared with fewer than 5% of those in the Indian
subcontinent.
In many countries the number of young people
who smoke is increasing: for example, in the

United States, 17% of high school seniors smoked
in 1992, but in 1995 this had increased to 22%.[1]
This is compounded by the fact that smoking prev-
alence among the young is frequently high. For
example, among British 15-year-olds, 28% of boys
and 33% of girls are regular smokers (defined as
usually smoking at least one cigarette a week).[3]
Assuming that current trends in tobacco use con-
tinue, by 2030 the number of smokers worldwide
will have grown to 1.64 billion, with a correspond-
ing increase in tobacco-related diseases and
deaths.[1]
As tobacco consumption rises, there is gener-
ally a lag of approximately 30 to 40 years before a
resulting increase in smoking-related mortality.[1]
Currently, tobacco use causes an estimated 3 mil-
lion annual deaths worldwide, of which 1.9 million
occur in the developed world.[1] Although the rate
of increase in smoking-related mortality in the de-
veloped world shows signs of slowing among men,
it continues to accelerate among women. More-
over, with the massive expansion over recent de-
cades in tobacco consumption in the developing
world, smoking-related mortality is set to rise sub-
stantially. Without concerted action, it is estimated
that the number of deaths worldwide will grow to
10 million annually by 2030, with 70% of these
occurring in developing countries. Tobacco is pre-
dicted to become the leading single cause of death
by the 2020s, causing more than one in every eight
deaths. Furthermore, half of all lifetime smokers
will die prematurely as a result of tobacco use.[4]
1. Tobacco Dependence
All tobacco products contain nicotine, which is
readily absorbed in the lungs, mouth and nose.
Nicotine from tobacco smoke is rapidly absorbed
via the pulmonary alveolar circulation and is deliv-
ered across the blood-brain barrier within 10 to 20
seconds of inhalation.[5] Nicotine is widely
recognised as being highly addictive:[6] a greater
proportion of casual users of tobacco graduate to
addictive patterns of use than users of cocaine,
morphine or alcohol.[7] Indeed, tobacco depend-
ence is classified as a mental and behavioural dis-
order according to the WHO International Classi-
fication of Diseases, ICD-10.[8] As an addictive
substance, nicotine displays positive reward-rein-
forcing properties,[9] as reflected by the compul-
sive drug-seeking behaviour seen in some smok-
ers, and the appearance of an abstinence syndrome
marked by withdrawal symptoms and craving after
cessation of exposure (table II).[10-12]
Nicotine binds to cholinergic nicotinic recep-
tors in the brain, autonomic ganglia and neuromus-
cular junctions, of which the central neuronal re-
ceptors are most relevant to the drug’s behavioural
effects.[9] Nicotinic receptor activation by nicotine
facilitates the release of various neurotransmitters,
including acetylcholine, noradrenaline, dopamine,
serotonin, beta-endorphin, and gamma-amino-
butyric acid (GABA). Of these, dopamine acting
Table II. Common signs and symptoms associated with nicotine
withdrawal
Symptom Incidence
self-quitters
(%) [10]
clinical assessment
(%)[11]
Irritability/aggression 38 80
Depression 31 60[12]
Anxiety 49 87
Restlessness 46 71
Poor concentration 43 73
Increased appetite 53 67
Urges to smoke 37 62
Awakenings 39 24
Decreased heart rate 61 79
Table I. Estimated smoking prevalence in those 15 years or older
in the early 1990s (Reproduced from the World Health Organiza-
tion,[1] with permission.)
Region Men (%) Women (%)
Africa 29 4
The Americas 35 22
Eastern
Mediterranean
35 4
Europe 46 26
South-east Asia 44 4
Western Pacific 60 8
Developed
countries
42 24
Developing
countries
48 7
Global 47 12
2Fagerström
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through the dopaminergic mesolimbic pathway
has been implicated in the behavioural reinforcing
effects of nicotine.[13,14] Chronic or repeated expo-
sure to nicotine results in sensitisation to its effects
on dopamine release.[15,16] This sensitisation of
mesolimbic pathways may be of relevance to the
development of nicotine-craving behaviour. Inde-
pendently, chronic exposure to nicotine also
causes nicotinic receptor desensitisation and com-
pensatory receptor up-regulation (i.e. an increase
in nicotinic receptor density), which may account
for tolerance to the psychopharmacological effects
of nicotine.[17]
Although nicotine is a psychostimulant drug,
smokers may experience relaxant effects and de-
creased tension, as well as mild euphoria and en-
hanced alertness, concentration and cognitive
function. It is unclear whether the positive rewards
of smoking (enhanced performance and mood) are
due to an intrinsic enhancement effect of nicotine
or to relief of symptoms of withdrawal.[9] Symp-
toms of nicotine withdrawal include craving, de-
pression, anxiety, difficulty in concentrating, dys-
phoria, increased appetite, insomnia, irritability,
frustration, anger, restlessnessand decreased heart
rate (see table II). Most of these symptoms peak
within 48 hours after the last cigarette and then
gradually decline in intensity, but some symptoms
such as craving for nicotine, increased appetite and
impaired concentration may continue for several
months or years.[18] However, some symptoms that
are thought of as withdrawal symptoms are not true
withdrawal symptoms, but are direct effects of
nicotine. For example, nicotine increases energy
turnover, making weight control more difficult af-
ter quitting. The same can be said about attention
and concentration, since these improve with nicot-
ine use. As such, nicotine meets the criteria set
down by the American Psychiatric Association
‘Diagnostic and Statistical Manual of Mental
Health Disorders’ (DSM-IV) for definition of a
drug of dependence (table III).[18]
2. Psychosocial Correlates of
Smoking Behaviour
2.1 Social Correlates
In the developed world, particularly in those
with well developed anti-smoking campaigns/pol-
icies, smoking is strongly related to socioeco-
nomic status, being more prevalent among the
poor, semi-skilled manual occupation groups, the
unemployed, poor educational achievers, and sin-
gle mothers.[19] Moreover, this demarcation be-
tween social groups is becoming more accentu-
ated: in the last 3 decades, smoking prevalence fell
by more than 50% in the most advantaged sections
of British society but remained unchanged in the
most deprived groups.[20] Similarly, smoking ces-
sation rates in the United Kingdom show a strong
inverse relationship with social deprivation.
2.2 Psychiatric Correlates
Depression is an important risk factor for nicot-
ine addiction. Smokers are more likely to have a
history of major depression – and such smokers are
much less likely to quit than those with no history
of depression.[9] It has been suggested that this as-
Table III. American Psychiatric Association ‘Diagnostic and Statis-
tical Manual of Mental Health Disorders’ (DSM-IV) criteria for drug
dependence[18]
A maladaptive pattern of substance use, leading to
clinically significant impairment or distress, as manifested
by three or more of the following occurring at any time in
the same 12-month period
1. Tolerance: Need for markedly increased dose to achieve
desired effect OR markedly diminished effect with continued use
2. Withdrawal: The characteristic withdrawal syndrome for the
substance OR the same or closely related substance is taken to
relieve/avoid withdrawal symptoms
3. Substance is taken in larger doses or over a longer time than
was intended
4. Persistent desire or unsuccessful efforts to cut down or control
substance use
5. Much time is devoted to activities necessary to obtain/use the
substance or recover from its effects
6. Important social, occupational or recreational activities are
abandoned/reduced because of substance use
7. Substance use is continued despite awareness of a
persistent/recurrent physical or psychological problem that is
likely to have been caused/exacerbated by the substance
Epidemiology of Smoking 3
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sociation between depression and cigarette smok-
ing may be due to a common genetic predisposition
to the two disorders.[21] Other risk factors for nicot-
ine addiction include schizophrenia (70 to 90% of
schizophrenic patients are smokers) and polydrug
abuse, in particular alcohol, cocaine and heroin.[9]
As such, it is likely that most who continue to
smoke will be among those with psychiatric or
other social problems. Furthermore, it is likely that
these smokers will be more dependent on tobacco
and less interested in quitting.
3. Health Consequences of Smoking
Cigarette smoke contains some 4000 com-
pounds, including carbon monoxide, ammonia and
known carcinogens such as nitrosamines and poly-
cyclic aromatic hydrocarbons.[22]
Tobacco-related disease is the leading cause of
preventable death in much of the developed world,
accounting for an estimated one in every five
deaths.[23] Half of all long-term regular smokers
who begin smoking during adolescence can expect
to die from tobacco use, and 50% of these die pre-
maturely during middle age, losing some 20 to 25
years of life expectancy compared with non-smok-
ers.[4] The risk is greatest for those who start smok-
ing regularly when teenagers.
Smoking predisposes the smoker to a large
number of diseases, including many types of can-
cer (lung, oesophagus, bladder, kidney, stomach,
pancreas), chronic obstructive pulmonary disease
(COPD), coronary heart disease, stroke, peripheral
vascular disease, and peptic ulcer disease. Smok-
ing during pregnancy can cause spontaneous abor-
tion, stillbirth, prematurity, low birthweight, and
sudden infant death syndrome (SIDS).[19,24] In ad-
dition, smoking during pregnancy can also have an
adverse effect on the toddler’s behaviour,[25] inter-
fere with cognitive and academic performance,[26]
and increase the likelihood of the child becoming
a smoker later in life.[27] In the United States, cig-
arette smoking is responsible for 80% of all
chronic lung disease and one-third of all deaths
from heart disease and cancer.[24,28]
For non-smokers, passive exposure to environ-
mental tobacco smoke (ETS) increases the risk of
lung cancer, heart disease, and respiratory illness.
Among infants and children, ETS increases therisk
of SIDS and causes asthma and respiratory infec-
tions. In the United Kingdom 17 000 children un-
der the age of 5 years are hospitalised every year
with illnesses caused by ETS.
3.1 Respiratory System
Smoking directly irritates and damages the re-
spiratory tract and confers a higher risk of devel-
oping major lung diseases, including COPD (i.e.
chronic bronchitis and emphysema), pneumonia,
and influenza.[29] The deterioration in pulmonary
function associated with COPD is directly related
to the duration of smoking and the number of pack-
years (the number of packs smoked per day multi-
plied by the duration of smoking in years).[30]
Cigarette smoking during adolescence retards
lung development and reduces the level of maxi-
mum lung function, with the result that the normal
age-related decline in pulmonary function starts
from a lower baseline and at an earlier age.[31] Fur-
thermore, smoking during adolescence results in
mild airway obstruction and increases the risk of
developing COPD in adulthood.[32]
Cigarette smoking is the major cause of all his-
tological types of lung cancer.[29] During the past
half century, lung cancer rates among women in
the developed world have risen in parallel with the
increase in cigarette smoking, to the extent that this
is now the leading cause of female cancer deaths
in the United States. Among men, the risk of lung
cancer is elevated 20-fold in smokers compared
with non-smokers.[33]
3.2 Cardiovascular System
Smoking acts both independently of, and syner-
gistically with, other major risk factors for coro-
nary heart disease. Fatal myocardial infarction is
4-times more common in young male smokers than
in non-smokers of the same age.[34] Similarly, the
progression of atherosclerosis in the carotid arter-
ies is directly related to total pack-years of tobacco
4Fagerström
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exposure, and may be cumulative and irre-
versible.[35] Furthermore, the relative risk of stroke
increases about 3-fold with smoking and is de-
pendent on the number of cigarettes smoked.[36]
Smoking is also a risk factor for transient isch-
aemic attacks[37] and peripheral vascular disease,
in particular Buerger’s disease, a progressive in-
flammatory occlusive condition, which frequently
necessitates limb amputation.[34]
3.3 Gastrointestinal System
Smoking is a risk factor for oral, oesophageal,
pancreatic and colorectal cancers.[38,39] For exam-
ple, pancreatic cancer is twice as common among
smokersasinnon-smokers.
[33] The risk of devel-
oping gastric and duodenal ulcers[40,41] or Crohn’s
disease[42] increases with smoking: furthermore,
the prognosis for these diseases improves in pa-
tients who stop smoking compared with those who
do not.[43,44] In contrast, smoking has a protective
effect in ulcerative colitis.[45]
3.4 Reproduction and Growth
Smoking during pregnancy adversely affects
the fetus and, in later years, ETS can affect the
neonatal infant and the growing child.[46] Adverse
sequelae include an increased risk of miscarriage
(2- to 3-fold), stillbirth, low birthweight (4-fold
increase in risk), SIDS, and impaired physical and
intellectual development.[46-49]
3.5 Other Systems
Smoking has been associated with a 40% in-
crease in the risk of cataracts[47] and a 2- to 3-fold
increase in risk of macular degeneration.[50,51]
Some studies have also linked smoking with pre-
mature wrinkling, atopic dermatitis[52] and psoria-
sis.[53] Smoking is also associated with loss of bone
mineral density and osteoporosis in the el-
derly,[54,55] and has been implicated as a contribu-
tory factor in one in eight hip fractures.[55] In the
genito-urinary system, smoking is a risk factor for
renal and bladder cancers.[56]
4. Costs Associated with Smoking
Tobacco use is associated with huge societal
and economic costs arising from the healthcare
burden of smoking-related morbidity and mortal-
ity. These include the costs imposed by smokers
(use of healthcare resources, absence from work,
loss of productivity, statutory sick pay, etc.) and
the costs of the harmful effects of ETS on non-
smokers.
The treatment of smoking-related morbidity
represents a significant cost burden to healthcare
providers. According to World Bank estimates,
smoking-related expenditure accounts for 6 to
15% of total annual healthcare costs in high-in-
come countries.[57] In the United Kingdom, smok-
ing-related illness costs the National Health Ser-
vice an estimated £1.5 billion each year.[58] By
2030, four-fifths of smokers will be in developing
countries, and the economic costs associated with
tobacco-related diseases are likely to impose a se-
rious strain on their limited healthcare resources.
Against this background, smoking cessation treat-
ments represent some of the most cost effective of
all healthcare interventions.[58,59]
5. Health Benefits of Smoking Cessation
People who smoke for 10 years or more show a
substantially higher rate of death, disease and dis-
ability than non-smokers. Nevertheless, many
smoking-related adverse effects are reversible
upon smoking cessation. Although risks to the re-
spiratory system in particular continue to plague
the ex-smoker for years after quitting, risks to cer-
tain other organ systems decline in accordance
with the duration of abstinence.[56] While the
greatest benefit is obtained from stopping smoking
when young, even quitting in middle age avoids
much of the excess risk,[60] so that 15 years after
quitting smoking the risk of death among ex-smok-
ers is no greater than the risk in those who have
never smoked.[56]
Epidemiology of Smoking 5
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5.1 Respiratory System
Pulmonary function improves by approxi-
mately 5% within several months of quitting smok-
ing;[30] with sustained abstinence, the rate of de-
cline in pulmonary function continues to slow and
the risk of COPD diminishes (figure 1).[61] Like-
wise, smoking cessation reduces the risk of lung
cancer, the severity and progression of premalig-
nant histological changes, and the risk of further
neoplasms. Smoking cessation also improves sur-
vival rates in patients who have cancer.[56,62] The
magnitude of the reduction in cancer risk increases
with the duration of abstinence: after 10 years the
risk is reduced by 30 to 50%.[63]
5.2 Cardiovascular System
The excess risk of coronary heart disease halves
within one year of stopping smoking, and after 15
years is equivalent to that in non-smokers.[56] Like-
wise, the excess risk of stroke is reported to return
to that of non-smokers within 5 to 15 years of
smoking cessation,[57] although this claim is dis-
puted by a more recent study suggesting that an
elevated risk persists for at least 20 years after ces-
sation.[64] For patients with peripheral vascular dis-
ease, the prognosis is considerably improved by
stopping smoking.[56]
5.3 Gastrointestinal System
In general, patients with Crohn’s disease who
stop smoking for at least a year have a more benign
disease course – similar to that in non-smokers.
During a prospective 12- to 18-month cohort study,
therateofCrohn’sdiseaseflare-upinthosewho
continued to smoke (46%) was twice that in those
who stopped smoking (23%).[65] Similarly, fewer
duodenal ulcer relapses were reported in former
smokers (14%) compared with those who contin-
ued to smoke (25%) during maintenance therapy
with ranitidine.[66]
Clear reductions in colorectal cancer mortality
rates have been observed in former smokers com-
pared with those who continued to smoke, al-
though the rates were lowest among lifelong non-
smokers.[67]
5.4 Reproduction and Growth
It is suggested that smoking reduces fecundity,
and women who have difficulty conceiving are rec-
ommended to stop smoking.[68] Furthermore,
smoking cessation in pregnancy is considered the
most effective method of reducing negative preg-
nancy outcomes such as fetal growth retardation,
preterm delivery and perinatal mortality.[69]
5.5 Other Systems
The risk of oral and oesophageal cancer halves
within 5 years of smoking cessation, although it
remains elevated compared with that in non-smok-
ers. Similarly, the risk of pancreatic cancer de-
clines after quitting smoking, albeit only partially.
The risk of bladder cancer is halved within a few
years of quitting smoking, but nevertheless re-
mains elevated for decades.[56]
6. Long-Term Management of
Smoking Cessation
Cigarette smoking is a highly addictive behavi-
our: even after an acute myocardial infarction,half
of smokers continue with the habit. As most smok-
ers who do attempt to quit require multiple at-
tempts before finally succeeding, tobacco depend-
FEV
1
(% of value at age 25)
100
75
50
25
0
25 50 75
Disability
Death
Age (years)
Never smoked or not susceptible to smoke
Smoked regularly and susceptible to its effects
Stopped at 45 years
Stopped at 65 years
Fig. 1. Theeffectofsmokingonlungfunctionwithage.FEV1=
forced expiratory volume in 1 second. (Reproduced with per-
mission from Fletcher C, Peto R. The natural history of chronic
airflow obstruction. BMJ 1977; 1: 1645-8.[ 61] Copyright©BMJ
Publishing Group.)
6Fagerström
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ence can be considered a chronic, relapsing disor-
der.[70] While in countries with the good anti-
smoking campaigns/policies up to 80% (54% in
the European Union) of smokers state that they
want to quit, fewer than half succeed in stopping
permanently before the age of 60 years.[1]
In order to improve smoking cessation rates, ef-
fective treatment is needed. Current smoking ces-
sation interventions include behavioural and phar-
macological treatments, with pharmacotherapy
(such as sustained-release bupropion and nicotine
replacement therapy) being the recommended
first-line approach.[70-72] However, the success of
these interventions depends not only on the moti-
vation of the individual to quit smoking, but also
on the availability of health professionals to help
the patient choose the level of required support that
is appropriate to their needs. Since smoking dura-
tion is the risk factor for smoking-related morbid-
ity, the treatment goal should be cessation as early
as possible in the course of the addiction, coupled
with prevention of relapse.
In conclusion, smoking cessation is associated
with numerous short- and long-term health and
economic benefits. The greatest benefit accrues
from smoking cessation when young, but even
quitting in middle age avoids much of the
healthcare risk and the associated cost of treat-
ment. As such, great efforts should be made to re-
duce the prevalence of smoking worldwide,partic-
ularly in developing countries where smoking is on
the increase.
Acknowledgements
This report was commissioned by the publisher. The
author has done consulting for all pharmaceutical companies
that market smoking cessation products.
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Correspondence and offprints: Karl Fagerström, Fagerstrom
Consulting, Kavelleristen 9, Berga Allê 1, 254-52
Helsingborg, Sweden.
E-mail: karl.fagerstrom@swipnet.se
Epidemiology of Smoking 9
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