Nicotine Dependencein Young Smokers

J O’LoughlinTobacco and Health: From Cells to SocietyOctober 2014

Plan

 Background

What is Nicotine Dependence?

ND measurement

Why this interest in ND in youth?

What’s next?

NDIT Study

Background Prevalence has declined but 14%

of grade 9-12 students smoked in the last 30 days (YSS 2013)

Age at first whole cigarette is 11.8 yrs

Daily smoking begins at age 16

75-80% of adolescents try, 1/5 will escalate

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:

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)ToleranceWithdrawal Substance taken in larger amounts or over a longer period than intendedPersistent desire or unsuccessful efforts to cut down or control useGreat deal of time is spent in activities to obtain substance, use substance, or recover from its effectsImportant social, occupational, or recreational activities given up or reduced because of substance useSubstance 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 substanceCraving/strong desire/urge to use substance.

But…… 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

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

Preparatory Trying ExperimentsUses

regularly Dependent

Developattitudesand beliefs

Firstcigarettes

Smokesrepeatedly butirregularily

Smokes atleast weeklyacross a variety of situations

Physiologicneed

No longer smokes

Source: Preventing Tobacco Use Among Young People. A Report of the Surgeon General, 1994.

QuitNo longer smoke

However... 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

Cumulative Incidence of First ND Symptoms in 12-13 Year-Olds (n=95)

% w

ith

sym

pto

ms

Month

Source: DiFranza et al. Tobacco Control 2000.

Is It Plausible? 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

Preparatory TryingExperimen-

talRegular

UseAddictionDependent

NicotineDependenceSymptoms

Non-smoker

Etude NICO/NDIT 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 Younger age Single-parent family status Smoking by parents, siblings,

friends, school staff Stress Impulsivity Lower self-esteem Feeling a need to smoke Not doing well at school Susceptibility to tobacco

advertising Alcohol use Use of other tobacco products Attending a smoking-tolerant

school

Daily smoking Smoking by siblings and

friends Feeling a need to smoke Susceptibility to tobacco

advertising Use of other tobacco

products Self-perceived mental

and physical addiction

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

Do subjects follow the same trajectory or are there distinct sub-groups of trajectories?

Is development of ND related to trajectory sub-group?

Background Increased interest in trajectories – is smoking

discrete or process?

Numerous studies report trajectories (i.e., Colder et al. (2001) reported 5 classes in 11-16 year-olds: 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 Data drawn from NDIT

1293 students followed every 3 months over 5 years of follow-up

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

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

12 24 36 48 Months

Inhalation 2

Whole cigarette 3

0

Smokes monthly9

Smokes weeklyLifetime 100 cigs

19

Smokes daily23

Onset of ND Symptoms

12 24 36 48 Months

Inhalation 2

Whole cigarette 3

0

Smokes monthly9

Withdrawal 12

Smokes daily23

Cravings5

Smokes weeklyLifetime 100 cigs

19

ICD-10 Tobacco dependence

46

Tolerance 14

Early Cessation Milestones

12 24 36 48 Months

Inhalation 2

Whole cigarette 3

0

Smokes monthly9

Withdrawal 12

Smokes daily23

Cravings5

Smokes weeklyLifetime 100 cigs

19

ICD-10 Tobacco dependence

46

Stopped smoking completely and forever Really want to quit 2

Serious quit attempt 3

Not confident quitting21

Aware of difficulty quitting32

Youth Cessation

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

Youth Under-Estimate the Power Youth Under-Estimate the Power of the Puffof the Puff

Source: EQT 2006Source: EQT 2006

Many Novice Smokers Want to Quit… 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.Source: Bancej et al. Tob. Control 2007

Predictors of Youth Cessation in Longitudinal Studies

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

5 robust predictors‒ 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

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) 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, self-

esteem, 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 37 French 19 Single-parent 14 Parent(s) completed university 42Smoking in social environment   Parent(s) smoke 44 Sibling(s) smoke 30 Friends smoke 87 Teachers smoke 79Psychosocial   Cigarette package warnings make me afraid to smoke (not true)

44

Cigarette advertisements make me want to smoke (true)

23

Overweight 25Asthma 19Lifestyle   Alcohol use 74 Other tobacco products 45 Illicit drugs 35 Team sports 56

Findings 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 AdjustedOR (95%

CI)

Covariates included in multivariate model

Male1.8 (1.3, 2.5)

age, depression, VPA, worry about weight, other tobacco products

Age (y)1.3 (1.1, 1.5)

sex, cravings, withdrawal, cigarette intensity, illicit drugs, # months smoking

Parent(s) smoke 0.7 (0.5, 0.9) age, sexFamily stress 0.7 (0.5, 0.9) depression, stress, age, sexWorry about weight 0.6 (0.5, 0.8) depression, stress, age, sexCig package warnings make me afraid to smoke 1.4 (1.0, 1.9) age, sexOverweight 0.7 (0.5, 0.9) age, sexIllicit drug use 0.5 (0.4, 0.7) craving, # months smoking, age, sexTeam sports 1.5 (1.1, 1.9) VPA, age, sexTolerance 0.6 (0.4, 0.9) craving, self-medication, age, sexCraving

0.9 (0.9, 0.9)

tolerance, self-medication, withdrawal, # yrs smoking, cig intensity, cig ads, illicit drugs, age, sex

Does Anything Work? Review of 16 RCTs (2001-

6) including 6623 youth aged 12-20 - 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?

Timing - target novice smokers before cravings? (prevention vs cessation)

Content - take some/all cessation predictors into account?

(team sports? dependence)

Tailored targeting? (families, girls (overweight)/boys)

Mode of delivery? (individual, legislation, social norms)

Reflections First puff is dangerous for many

children

ND symptoms develop very rapidly in many children

Subjects with escalating trajectories developed ND much faster

Not possible to know which children will escalate

Intervention programs must move beyond social learning underpinnings if children experience physiological ND symptoms

What’s Next?

Research in Next Ten Years 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

(gene-environment, gene-gene interactions, epigenetics)