Nicotine dependence can be diagnosed when a patient experiences

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Nicotine dependence can be diagnosed when a patient experiences
Nicotine Dependence
in Young Smokers
J O’Loughlin
Tobacco and Health: From Cells to Society
October 2014
Plan
Background
What is Nicotine Dependence?
ND measurement
Why this interest in ND in youth?
NDIT Study
What’s next?
Background

Prevalence has declined but 14% of
grade 9-12 students smoked in the
last 30 days (YSS 2013)
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Age at first whole cigarette is 11.8
yrs
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Daily smoking begins at age 16
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75-80% of adolescents try, 1/5 will
escalate
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14% of those who try do so for the
first time after high school (young
adult onset)
Background

Early smokers smoke more, longer, less likely to quit

Smoking co-occurs with alcohol, illicit drugs,
gambling

Young smokers at higher risk of premature death

Prevention programs not effective (little known
about mechanisms of onset and progression)

Cessation in youth is a relatively new concept
Youth Smoking Differs From Adults

More environmental constraints (home, school,
financial, legal, availability of cigarettes)

Sporadic, irregular smoking patterns

Share cigarettes with friends or just smoke a few puffs

ND symptoms experienced/reported differently by
youth (unknown symptoms, different terminology)

No generally accepted measure to assess ND in youth
What is Nicotine Dependence?
DSM-V Tobacco Use Disorder
A maladaptive pattern of substance use leading to clinically significant impairment or distress,
as manifested by 2 (or more) of the following, occurring within a 12-month period:
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Recurrent substance use resulting in a failure to fulfill major role obligations at work,
school, or home
Recurrent use in situations in which it is physically hazardous
Continued use despite persistent or recurrent social or interpersonal problems caused or
exacerbated by the effects of the substance (e.g., arguments with spouse about
consequences of intoxication, physical fights)
Tolerance
Withdrawal
Substance taken in larger amounts or over a longer period than intended
Persistent desire or unsuccessful efforts to cut down or control use
Great deal of time is spent in activities to obtain substance, use substance, or recover
from its effects
Important social, occupational, or recreational activities given up or reduced because of
substance use
Substance use is continued despite knowledge of having a persistent or recurrent
physical or psychological problem that is likely to have been caused or exacerbated by
the substance
Craving/strong desire/urge to use substance.
But……
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Several DSM-V criteria rarely endorsed by regular
tobacco users
Less validity in predicting consequences of nicotine
dependence (e.g. relapse) than nicotine-specific
measures such as time-to-first-cigarette after
awakening and cigarettes smoked/day (cigs/day)
Nicotine dependence can be diagnosed when a patient
experiences a recurrent and periodic wanting, craving,
or needing for tobacco (Joe DiFranza).
How Do We Measure Nicotine Dependence
(Symptoms) in Youth?
ND Indicators
Multidimensional Measures
 ICD-10 criteria
(diagnostic)
 HONC (theory-based)
 Stanford Dependence
Index
 Nonnemaker
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Symptom Clusters
ND/cravings (loss of
control, failed quit attempt,
strong cravings)
Self-medication (helps to
feel better, relaxation,
gives energy)
Withdrawal symptoms
(restlessness, difficulty
concentrating, depressed
mood)
Nicotine Dependence Scale
Nonnemaker et al., 2004
Why The Interest in ND in
Young Smokers?
Five Stages of Onset
No longer smoke
No longer
smokes
Preparatory
Trying
Develop
attitudes
and beliefs
First
cigarettes
Experiments
Smokes
repeatedly but
irregularily
Quit
Uses
regularly
Smokes at
least weekly
across a
variety of
situations
Source: Preventing Tobacco Use Among Young People.
A Report of the Surgeon General, 1994.
Dependent
Physiologic
need
However...
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Children inhale and absorb as much nicotine/cig as
adults, even at first
Tolerance develops soon after first cigarette
Children report ND symptoms, cravings, even before
daily smoking
Children who quit report withdrawal symptoms related
to number of cigarettes/day
Children may have more difficulty quitting than adults
% with symptoms
Cumulative Incidence of First ND
Symptoms in 12-13 Year-Olds (n=95)
Month
Source: DiFranza et al. Tobacco Control 2000.
Is It Plausible?
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Nicotine increases the number of
nicotinic receptors in brain areas
associated with pleasure pathways
Neurological changes begin as
early as the second dose of
nicotine
Speed of changes compatible with
early appearance of ND
Role of Nicotine in Natural
History of Onset
Factors
Psychosocial
Environmental
Non-smoker
Preparatory
Trying
Experimental
Regular
Use
Nicotine
Dependence
Symptoms
Addiction
Dependent
Etude NICO/NDIT
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Ongoing 13-year longitudinal
cohort
n=1293 grade 7 students (age
12-13) in 10 high schools
Baseline reponse: 56%
Follow-up response: 94%
n=950 blood/saliva DNA; n=500
parental DNA
Anthropometric measures, BP,
parental data, env’t data
Among more importnant
contributions: predictors of onset
and daily smoking
Predictors of Adolescent Smoking
Initiation
Daily smoking
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Younger age
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Smoking by siblings and
friends
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Single-parent family status
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Feeling a need to smoke
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Smoking by parents, siblings,
friends, school staff
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Susceptibility to tobacco
advertising
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Stress
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Use of other tobacco
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Impulsivity
products
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Lower self-esteem
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Self-perceived mental and
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Feeling a need to smoke
physical addiction
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Not doing well at school
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Susceptibility to tobacco advertising
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Alcohol use
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Use of other tobacco products
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Attending a smoking-tolerant
school
O’Loughlin et al. Determinants of first puff and daily cigarette smoking in adolescents.
AJE 2009; DOI: 10.1093/aje/kwp179
Trajectories of Cigarette Use Onset
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Do subjects follow the same
trajectory or are there distinct
sub-groups of trajectories?
Is development of ND related to
trajectory sub-group?
Background
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Increased interest in trajectories – is smoking discrete
or process?
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Numerous studies report trajectories (i.e., Colder et al.
(2001) reported 5 classes in 11-16 year-olds:
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early rapid
late moderate
late slow escalators
stable light
stable puffers
But follow-up is anchored at arbitrary time 0 on a scale
of age (not smoking onset) and time intervals between
follow-ups are wide
Methods
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Data drawn from NDIT
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1293 students followed every 3
months over 5 years of follow-up
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369 baseline never smokers
followed over 31 months after
initiation
Used latent class growth modeling
to describe cigarettes
smoked/month over time after first
puff
Smoking Trajectories
Rapid escalators (6%)
Moderate escalators (11%)
Slow escalators (11%)
Non-progressing low-intensity onset (72%)
Time to ND in Four Trajectory Classes
Non-progressing low-intensity onset (72%)
Slow escalators (11%)
Moderate escalators (11%)
Rapid escalators (6%)
Natural History of Onset
Natural History of Nicotine Dependence

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How quickly do symptoms of nicotine dependence
develop in relation to first puff?
In this more “qualitative” study, we used survival
analysis to describe time from first puff to milestones in
the smoking onset process
Natural History of Smoking Onset
0
12
24
Smokes daily
23
Smokes monthly
9
Whole cigarette
3
Inhalation
2
Smokes weekly
Lifetime 100 cigs
19
36
48 Months
Onset of ND Symptoms
0
12
24
36
48 Months
Tolerance
14
Cravings
5
Smokes daily
Withdrawal
23
12
Smokes monthly Smokes weekly
9
Lifetime 100 cigs
19
Whole cigarette
3
Inhalation
2
ICD-10 Tobacco
dependence
46
Early Cessation Milestones
Stopped smoking completely and forever
Really want to quit
2
Not confident quitting
21
Serious quit attempt
3
0
Aware of difficulty quitting
32
12
24
Cravings
5
Smokes daily
Withdrawal
23
12
Smokes monthly Smokes weekly
9
Lifetime 100 cigs
19
Whole cigarette
3
Inhalation
2
36
48 Months
ICD-10 Tobacco
dependence
46
Youth Cessation
Youth Under-Estimate the Power
of the Puff
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97% of puffers, 83% of occasionnal
smokers, and 33% of daily smokers
believe that they are not dependent
97% of puffers, 87% of occasionnal
smokers, and 70% of daily smokers
believe that they can stop smoking
easily
Source: EQT 2006
Many Novice Smokers Want to Quit…
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Review of 52 national population-based
studies 1990-2005 on prevalence,
frequency, duration of cessation attempts in
smokers aged 10-20
68% try to quit each year
> half make several attempts
Most do not succeed
34% relapse within 1 week
92% relapse within 1 year
Cessation surveillance, research and
programs should extend to young
adolescents and non-daily smokers
Source: Bancej et al. Tob. Control 2007
Predictors of Youth Cessation in Longitudinal
Studies
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Reviewed 4502 titles (1984-2010), 871
abstracts; 9 retained
Difficulties
- lack theoretical underpinnings
- Differing definitions, measures,
measures of effect
findings for many factors inconclusive
many factors unexplored
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5 robust predictors
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no friends who smoke
no intentions to smoke
resists peer pressure to smoke
older at first cigarette use
negative beliefs about smoking.
Source: Cengelli et al. Tob Control 2012;21:355-62.
Socioecologic Study of Cessation
Predictors In Adolescent Smokers
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Data drawn from NDIT
All ever smokers in secondary school (20 cycles)
Outcome: stopped smoking for >12 consecutive months (144
of 308 ever-smokers attained outcome)
Data on 37 potential predictors drawn from cycle before
outcome Data on covariates (r>0.2 with exposure of interest)
lagged by 2 cycles
Multiple imputation
Single participant included multiple times in analytic database
Total of 37 models, one for each potential predictor
Used logistic regression within a GEE framework
Potential Predictors (n=37)
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Selected based on the strength of evidence, availability of data in NDIT,
utility in designing interventions
Socio-demographic (sex, age, language, single-parent family, parental
education)
Social environment (parent(s) smoke, sibling(s) smoke, friends smoke,
teachers smoke)
Psychological (stress, depression, impulsivity, novelty-seeking, selfesteem, worry about weight)
Psychosocial (susceptibility to cig package warnings, to tobacco ads)
Overweight; asthma
Lifestyle (alcohol, other tobacco products, illicit drugs, physical activity
(LPA, MPA, VPA), team sports, TV)
Nicotine dependence (tolerance, cravings, self-medication, withdrawal,
cigarette duration, cigarette intensity
Context (tolerance of smoking in school, community (depanneurs,
restaurants).
Baseline Characteristics
Sociodemographic
Male
French
Single-parent
Parent(s) completed university
Smoking in social environment
Parent(s) smoke
Sibling(s) smoke
Friends smoke
Teachers smoke
Psychosocial
Cigarette package warnings make me afraid to smoke
(not true)
Cigarette advertisements make me want to smoke
(true)
Overweight
Asthma
Lifestyle
Alcohol use
Other tobacco products
Illicit drugs
Team sports
%
37
19
14
42
44
30
87
79
44
23
25
19
74
45
35
56
Findings
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Abstinence varied from 0-52%
Intervention > control in 14/16 comparisons
4/16 statistically significant (2/4 not biochemically
validated)
3 school-based programs
1 motivational interviewing in health care setting
But…..many difficulties with this literature
(intervention concept, small samples, short follow-up,
differing definitions)
Much more research is needed
Results from Logistic Regression Models of the Association
Between Predictor Variables and Cessation in Adolescents
Predictor variable
Male
Age (y)
Parent(s) smoke
Family stress
Worry about weight
Cig package warnings make me
afraid to smoke
Overweight
Illicit drug use
Team sports
Tolerance
Craving
Adjusted
OR (95% CI)
1.8 (1.3, 2.5)
1.3 (1.1, 1.5)
0.7 (0.5, 0.9)
0.7 (0.5, 0.9)
0.6 (0.5, 0.8)
1.4 (1.0, 1.9)
0.7 (0.5, 0.9)
0.5 (0.4, 0.7)
1.5 (1.1, 1.9)
0.6 (0.4, 0.9)
0.9 (0.9, 0.9)
Covariates included in multivariate
model
age, depression, VPA, worry about weight, other
tobacco products
sex, cravings, withdrawal, cigarette intensity, illicit
drugs, # months smoking
age, sex
depression, stress, age, sex
depression, stress, age, sex
age, sex
age, sex
craving, # months smoking, age, sex
VPA, age, sex
craving, self-medication, age, sex
tolerance, self-medication, withdrawal, # yrs
smoking, cig intensity, cig ads, illicit drugs, age, sex
Does Anything Work?
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Review of 16 RCTs (2001-6)
including 6623 youth aged 1220
11 behavioral
1 acupuncture
4 pharmacologic
Outcome: 5-day point
prevalence of abstinence
12/16 validated by CO/saliva
cotinine
Drop-out: 8-64%
Source: Gervais et al. Drogues, santé, et société 2007;6:ii1-ii26.
Rethink intervention?
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Timing - target novice smokers before cravings? (prevention vs
cessation)
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Content - take some/all cessation predictors into account? (team
sports? dependence)
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Tailored targeting? (families, girls (overweight)/boys)
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Mode of delivery? (individual, legislation, social norms)
Reflections

First puff is dangerous for many
children
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ND symptoms develop very rapidly
in many children
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Subjects with escalating trajectories
developed ND much faster
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Not possible to know which children
will escalate
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Intervention programs must move
beyond social learning
underpinnings if children experience
physiological ND symptoms
What’s Next?
Research in Next Ten Years
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Well-powered longitudinal studies on
risk for onset to develop better
underpinnings for prevention
(incorporating socio-ecological and life
course perspectives)
Natural course of onset, ND, cessation
Cessation in children and adolescents
(NRT and Zyban for children?)
Studies on methods (what is smoking
in kids? Cessation?)
More qualitative research
Genes, genes, and more genes (geneenvironment, gene-gene interactions,
epigenetics)

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