Associate Professor Richard van Zyl-Smit

Smoking cessation World No Tobacco Day

Workshop 26th May

Head Lung Clinical Research Unit UCT lung Institute Head smoking cessation clinic Groote Schuur Hospital Division of Pulmonology and Department of Medicine University of Cape Town

Declarations

• I actively conduct clinical research for Novartis, Astra Zeneca, GSK, Takeda, Merck, Almirall, Boehringer Ingelheim, Sanofi, Beyer, Teva, Genetech, Roche, Mundipharma

• I have received honoraria for speaking from Aspen/GSK, Pharmadynamics, Pfizer, Astra Zeneca.

• No relationships with the tobacco or E-cigarette industry

Key points

• No more shouting / Niks meer uitskel nie!

• Must understand and deal with “whole person” and their situation.

• Must encourage individuals to change their own behaviour

• Everybody needs support to quit some will require medication to help

Case 1

• Mrs B Ored

• Married machinist at clothing factory

• Smokes 4-5 per day

• TB in 2013 stopped smoking for first month then

restarted

• Children asked her to come to the clinic

Case 2

• Mr TI Mebomb

• 64 years old finance officer for Eskom

• Hypertensive, Diabetic, overweight

• Has tried to quit several times using hypnotherapy,

yoga, cold turkey, gums, sprays and accupuncture

• Dr has told him he will die if he does not quit this

year…

Case 3

• Mr SE Curity

• 55 years old “provider of security” to Spaza Shops

• Previous CABG, recent MI,

• Smoking 30 per day - Fagerström = 9/10

• Desperate to quit but

– Highly stressful job

– Uses occasional mandrax, dagga, ( heavy in past)

– Can’t afford NRT/Varenicline.

Legislation Political will

Media/advertising Advocacy groups

Cessation programs Pharmacotherapy/

Counselling

What can we do…

Restaurants Shops Advertising

In the last ten years

The harms of smoking are well known

Tuberculosis HIV

Risk of latent infection

Progression to active disease

Mortality from TB

Post TB structural airway disease

Bronchitis

Accelerated development of COPD

Susceptibility to HIV infection

Bacterial pneumonia in

smokers

Rate of lung cancer

Possible risk of PCP

Accelerates HIV

disease progression

Susceptibility

Mortality

Complicates diagnosis

Respiratory infections

Early emphysema

Lung cancer

Smoke inhalation from tobacco and or biomass fuels

COPD and pulmonary disability

Smoking and Respiratory Health

Previous work from our lab

Thorax 2014

Human monocyte, Monocyte derived macrophage in vitro exposure model. There was impaired

cytokine production in response to BCG infection.

Second hand smoke

• Adults

– 25-30% increased risk of Cardiovascular disease

– 20-30% increased risk of Lung Cancer

• Children

– Increased risk for Intrauterine growth retardation (IUGR) and Sudden Infant Death Syndrome (SIDS)

– Increased risk for asthma, middle ear infections, respiratory infections

– Higher likelihood of starting smoking if parents smoke!

What do we know about South African smokers?

Sitas F ’04, Peer N ‘09, WHO Tobacco Atlas ’12,’15

0%

10%

20%

30%

40%

50%

60%

High income

countries

Low income

countries

RSA 1992 RSA 2003 RSA 2009 RSA 2015

Smoking rates

Men

Women

Is there anything good about smoking?

‘Skinny jeans’ Smokers weigh less! (Albanes 1987)

Nicotine affects energy homeostasis (Zoli 2012)

Improved cognitive functioning Jarvik 1991

Stress relief

Alcohol

0 1 2 3 4 580

90

100

110

120

130

140

150

160

170

180

190

200

time (hrs)

Perc

enta

ge o

f B

aselin

e

from Di Chiara Proc Natl. Acad. Sci. 1988

So why are cigarettes so addictive…?

Food

0.0 0.5 1.0 1.5 2.0

100

110

120

130

140

150

160

time(hours)

Perc

enta

ge o

f B

aselin

e

Onset of feeding from Bassareo et al. Neuroscience 1999

Dopamine response to ‘stimuli’

SEX

0.0 0.5 1.0 1.5 2.0 2.5

100

110

120

130

140

150

160

170

180

190

200

Perc

enta

ge o

f B

aselin

e

Female present and copulation onset

from Fiorino et al. J Neuroscience 1997

hrs

Nicotine

0.0 0.5 1.0 1.5 2.0 2.5 3.0

100

125

150

175

200

225

250

time(hours)

Perc

enta

ge o

f B

aselin

e

Amphetamines

0 1 2 3 4 50

100

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500

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1000

1100

time (hours)

Perc

enta

ge o

f B

aselin

e

Morphine

0 1 2 3 4 5

100

125

150

175

200

225

250

time (hours)

Perc

enta

ge o

f B

aselin

e

Cocaine

0 1 2 3 4 5

100

125

150

175

200

225

250

275

300

325

350

time(hours)

Perc

en

tage o

f B

aselin

e

from Di Chiara Proc Natl. Acad. Sci. 1988

Nicotine compared to other addictive drugs…

Nicotine

0.0 0.5 1.0 1.5 2.0 2.5 3.0

100

125

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250

time(hours)

Perc

enta

ge o

f B

aselin

e

Amphetamines

0 1 2 3 4 50

100

200

300

400

500

600

700

800

900

1000

1100

time (hours)

Perc

enta

ge o

f B

aselin

e

Morphine

0 1 2 3 4 5

100

125

150

175

200

225

250

time (hours)

Perc

enta

ge o

f B

aselin

e

Cocaine

0 1 2 3 4 5

100

125

150

175

200

225

250

275

300

325

350

time(hours)

Perc

enta

ge o

f B

aselin

e

from Di Chiara Proc Natl. Acad. Sci. 1988

Nicotine

0.0 0.5 1.0 1.5 2.0 2.5 3.0

100

125

150

175

200

225

250

time(hours)

Perc

enta

ge o

f B

aselin

e

Amphetamines

0 1 2 3 4 50

100

200

300

400

500

600

700

800

900

1000

1100

time (hours)

Perc

enta

ge o

f B

aselin

e

Morphine

0 1 2 3 4 5

100

125

150

175

200

225

250

time (hours)

Perc

enta

ge o

f B

aselin

e

Cocaine

0 1 2 3 4 5

100

125

150

175

200

225

250

275

300

325

350

time(hours)

Perc

enta

ge o

f B

aselin

e

from Di Chiara Proc Natl. Acad. Sci. 1988

Nicotine

0.0 0.5 1.0 1.5 2.0 2.5 3.0

100

125

150

175

200

225

250

time(hours)

Perc

enta

ge o

f B

aselin

e

Amphetamines

0 1 2 3 4 50

100

200

300

400

500

600

700

800

900

1000

1100

time (hours)

Perc

enta

ge o

f B

aselin

e

Morphine

0 1 2 3 4 5

100

125

150

175

200

225

250

time (hours)

Perc

enta

ge o

f B

aselin

e

Cocaine

0 1 2 3 4 5

100

125

150

175

200

225

250

275

300

325

350

time(hours)

Perc

enta

ge o

f B

aselin

e

from Di Chiara Proc Natl. Acad. Sci. 1988

Nicotine

0.0 0.5 1.0 1.5 2.0 2.5 3.0

100

125

150

175

200

225

250

time(hours)

Perc

enta

ge o

f B

aselin

e

Amphetamines

0 1 2 3 4 50

100

200

300

400

500

600

700

800

900

1000

1100

time (hours)

Perc

enta

ge o

f B

aselin

e

Morphine

0 1 2 3 4 5

100

125

150

175

200

225

250

time (hours)

Perc

enta

ge o

f B

aselin

e

Cocaine

0 1 2 3 4 5

100

125

150

175

200

225

250

275

300

325

350

time(hours)

Perc

enta

ge o

f B

aselin

e

from Di Chiara Proc Natl. Acad. Sci. 1988

Is withdrawal really that bad?

• Irritability: 2- 4 weeks

• Tiredness and lethargy: 2-4 weeks

• Poor sleep – 1 week

• Increased cough and phlegm – days to weeks

• Poor concentration – 2-4 weeks

• Hungry – 2-4 weeks

• Craving – days to weeks…

20 minutes

BP and heart rate drop

12 hours

C0 ⬇ to normal 02 ⬆to normal

48 hours

Smell and taste better

2-12 weeks

Circulation improves Lung function improves

5 years

Mouth, throat, oesophagus & bladder cancer risk ½

Cervical cancer and stroke risk ⬇ to non-smoker level

1-9 months

⬇Coughing and shortness of breath Cilia regain normal function

1 year

Coronary heart disease risk ½ that of a persistent

smoker

15 years

Coronary heart disease risk ⬇ to non smoker

level

10 years

Risk of dying from lung cancer 50% less than

active smoker

So why quit ?

Two phase approach to successful smoking cessation

S Afr Med J 2013;103(11) 89:869-876

Not interested

Let me try Freedom

from tobacco

Readiness to change

permanent exit?

contemplation

Pre-contemplation

preparation /

determination

action

maintenance

relapse

1

2 3

4

5 6

Prochaska and DiClemente, 1982

Slide courtesy Prof B Mash U Stell

• Ask

– About why they smoke, do they know the risks and benefits from quitting and do they want to quit?

• Alert

– About the benefits and options

• Assess

– Are they ready to quit

• Assist /arrange

– Get them someone/somewhere/something to help

How to get your patient/client to a point of wanting to quit?

Slide courtesy Prof B Mash U Stell

• Your goal/responsibility is not to get each patient to quit at that specific visit…

• Your aim is to inch them along the path to a point where they ask for help to quit…

Ask about smoking at each visit

Encourage them about the benefits of quitting

Give them something to read at home

Invite them to think about it and offer help if needed

The goal of each Health Care Interaction …

The balance of counselling and medication

All the counselling and support in the world will not prevent withdrawal symptoms.

All the drugs in the world will not change your social stressors, work place or relationship issues nor

concerns about your weight!

Counselling plus medication to treat nicotine withdrawal is more effective than either intervention alone.

• > 70 Cochrane reviews on smoking related subjects…

– NRT, acupuncture, hypnosis

– Electronic aids, SMS support

– Hospitalised patients

– Abrupt vs. slow reduction

– Vaccines, antidepressants

The value of steroids for lung maturity in premature

neonates

Do we have evidence for what works

Smoking cessation “medication”

• Nicotine replacement therapy

• gums, sprays, patches

• “Antidepressants”

• Nicotine receptor agonists

• ?? “Electronic cigarettes”

Efficacy of available medications

Medication Number of arms OR (95%CI Estimated abstinence rate (95%CI)

Placebo 80 1.0 13.8

Nicotine gum 15 1.5 (1.2-1.7) 19.0 (16.5-21.9)

Nicotine patch 32 1.9 (1.7-2.2) 23.4 (21.3 -25.8)

Nicotine spray 4 2.3(1.7-3.0) 26.7 (21.5-32.7)

Bupropion SR 26 2.0 (1.8-2.2) 24.2 (22.2-26.4)

Nortriptylline 5 1.8 (1.3-2.6) 22.5 (16.8-29.4)

Clonidine 3 2.1(1.2-3.7) 25.0 (15.7 -37.3)

Varenicline (2mg/day) 5 3.1 (2.5-3.8) 33.2 (28.9-37.8)

Nicotine Replacement Therapy

• Generally considered “first choice”

– Directly treats nicotine dependence and withdrawal

– Nicotine patches will be available in June 2015!

• “controller and reliever approach” highly effective:

– Patch plus gum ( more effective but more expensive!)

– OR 3.6 (2.5-5.2) / abstinence rates 36.5% (28.6-45.3)

• Can be combined with ‘antidepressants’

Antidepressants

• Bupropion SR (ZYBAN) – Effective but significant tolerability issues – NB risk of seizures – January 8th 2013 drug safety warning regarding congenital

cardiovascular malformations

• Nortriptyline – Effective but generally considered second line

• (not amitriptyline – no data)

• SSRIs ( Fluoxetine, Citalopram, Sertraline) – Not effective

Nicotine receptor agonists

• α4β2 receptor partial agonists

– ‘partially open the receptor’ – controlled dopamine release but block the effect of nicotine

– Reduces the ‘pleasure of smoking’

– Varenicline (CHAMPIX)

Varenicline

• Effective smoking cessation medication (in combination with behavioural change)

• Major side effects – nausea, bizarre dreaming, altered mood

• Black box warning regarding suicide and CVS risk

– Note: Schedule 5 medication

3 month Pooled RR (95%CI)

6 month Pooled RR (95%CI)

12 month Pooled RR (95%CI)

Varenicline vs. buproprion 1.43 (1.24-1.63) 1.34 (1.13-1.57) 1.61 (1.32 -1.93)

Varenicline vs. NRT 1.48 (1.23-1.75) 1.38 (1.15-1.64) * 1.65 (1.29-2.07)

Mills meta-analysis and MTC 2012

Suicide and self harm

• Kyla Thomas BMJ 2013

– Clinical practice database

– - 119 546 adults

• 81545 NRT,

• 6741 Bupropion

• 31 260 Varenicline

NRT Varenicline Bupropion

Incidence of Self-harm /100,000 person years (95% CI)

359.5 (279.7 - 454.9) 258.0 (155.4 - 403.0)

246.6 (67.2 -631.4)

Hazard ratio Self Harm 1 0.88 (0.52 to 1.49) 0.83 (0.3. to 2.31)

Hazard ratio Treated depression 1 0.75 (0.65 to 0.87) 0.63 (0.46 to 0.87)

• Nicotine replacement – Nicotine Spray (S2)

• 4 x 20ml = R306 up to 90 sprays/day – 3-4 weeks per dose(4) ～40 spray/day = 7 days/bottle R306/month

– Nicotine gum (S0) • 2mg/4mg (30) = R69.31 10-12 pieces per day

– 10-5/day = R70/3days ～R600-R300 per month

– Nicotine patches (Not available yet) • 52.5mg/35mg/17.5mg (7) ～R100-120?

– 4weeks x R100 =? R400 per month

• Bupropion SR (S5) • 150mg (60) R351

– 150mg BD = R351 per month

• Varenicline (S5) • 1mg (56) Starter pack and continuation phase pack

– Monthly pack = R439.50/R423.77 per month

Relative cost of specific medications (usually 3 month programme)

Estimated SEP costs Manufacturer pricing report

Pack/day = R20 = R600 /month

General approach to cessation with medication

Counselling and motivation Titrate up medication 0-7 days

Bupropion 150mg daily, then twice daily Varenicline 0.5mg build up to 1mg bd

Quit date

“12 week programme”

“Prevent” relapse

Success

“cut down on smoking”

Case 1

• Mrs B Ored

• Married machinist at clothing factory

• Smokes 4-5 per day

• TB in 2013 stopped smoking for first month then

restarted

• Children asked her to come to the clinic

Case 2

• Mr TI Mebomb

• 64 years old CEO of investment firm

• Hypertensive, Diabetic

• Has tried to quit several times using hypnotherapy,

yoga, cold turkey, gums, sprays and accupuncture

• Dr has told him he will die if he does not quit this

year…

Case 3

• Mr SE Curity

• 55 years old “provider of security” to Spaza Shops

• Previous CABG, recent MI,

• Smoking 30 per day - Fagersrtröm = 9/10

• Desperate to quit but

– Highly stressful job

– Uses occasional mandrax, dagga, ( heavy in past)

– Can’t afford NRT/Varenicline.

Bringing it back to you…

• With an unmotivated patient:

– Advise them on the benefits of quitting (don’t shout!)

– Give them something to read and chat about it next time…

• With a motivated patient…

– Assess dependence (Fagerström, CO levels)

– Assess psychological stressors/support

– Assess finances…

Practical approach in reality…

• Set quit date and decide on strategy

– Slowly cut down with or without medication to specified date

– Encourages patient to develop coping strategy/plans

• Best to have them ready before quit date

– Review as often as possible (in-person, text, cell phone apps)

– Watch out for withdrawal or side effects

– You don’t need to be a specialist – just passionate (the more the better)

– Follow up to at least 3 months – watch out for relapse

Electronic Cigarettes My personal opinion, based on the current evidence

• If you are a smoker:

– Do everything you can to quit

– E-cigarettes may help & should be safer

– Consider e-cigarettes as a stepping stone

• If you are a non-smoker

– Avoid smoking, and e-cigarettes “> 50 year lag in smoking-cancer epidemiology”

– Evidence to support public space use ban

• If you have influence with adolescents

– Counsel strongly against e-cigarette use • High potential for nicotine addiction

• ???? Better than children smoking tobacco????