Smoking and the Benefits of

Cessation
Prof. Dr. Miron BOGDAN
UMF Carol Davila
 Overview: Respiratory diseases
associated with smoking
• Tobacco smoking – general features
• Tobacco smoking : Risk factor
• Chronic obstructive pulmonary disease
(COPD)
– Emphysema
– Chronic bronchitis
• Asthma
• Tuberculosis
• Lung cancer
Celli et al. Eur Respir J. 2004;23:932-946.
 General data: Tabacco
• Imported from America 400 years ago
• Initially utilized as a medicinal plant
• Very quickly: smoking
• Pipe, cigars and, after the First World War:
cigarettes
• Chewing, and snuffing

• Today, 95 % of tobacco use: cigarettes

 Why do we smoke?
• Conditioning: social, psychological,
pharmacological
• Start: psychosocial conditioning
• Adolescence : influenced by family or friends; for
women, it has become a marker of being equal to
men
• Continuing smoking : pharmacological
dependence to nicotine but also other
behavioural factors
• Genetic factors ?
 Pharmacologic dependence
• Nicotine: Pharmacologic activity.
– Tachycardia
– Enhancing the tension of the arterial wall
– Thin tremor of the extremities
– Skeletal muscles tonus, etc
• These are striking effects at the first contact! TOLERANCE!
• Psychological effects: calm, pleasure, increase in
concentration capacity, sometimes anxiety and depression
• The effects progressively diminish: they reappear in
abstinence
• ADDICTION!
 Cerebral nicotinergic receptors
• In the basal subcortical nuclei : in the “pleasure
and reward” centers -> nicotinergic receptors!
• They upgrade with repetitive stimulation!!!
• In abstinence, the lack of stimulation is full of
consequences
• There is a tendency to relapse years after
cessation, and even a life-long risk
• Conclusion: MUCH EASIER NOT TO START THAN
TO QUIT. IT’S EASIER TO QUIT EARLIER THAN
LATER.
Smoking and COPD
 Cumulative Incidence of COPD
• For continuous smokers it is 35.5% and for never smokers it is 7.8%a
40 Severe
COPDb
35 Moderate COPD
Cumulative Incidence

30 Mild COPD
25
20
15
10
5
0
Never Ex-smokers Early Interm Late Continuous
Smokers Smokers
Abstainersc
aCalculated incidence rates for COPD, men and women combined. bStaging was done according to the criteria of the American
Thoracic Society and the European Respiratory Society. cStudy participants were evaluated 4 times over a 30-year period. “Early
intermediate and late quitters” refer to those who stopped smoking between the first and second, second and third, third and fourth
evaluations, respectively. Mild=Stage 1, Moderate=Stage 2, and Severe= Stages 3 and 4.
Løkke et al. Thorax. 2006;61(11):935-939; GOLD Initiative 2006. http://www.goldcopd.com. Accessed July 19, 2007.
 COPD Mortality
• Worldwide, 80 million people have moderate-
to-severe COPD
• Half of all COPD patients die within a decade of
diagnosis
• COPD predicted to become the fourth leading
cause of death worldwide by 2030
• In 2005, 3 million people died of COPD

Anto. Eur Respir J. 2001;17:982-994; http://www.who.int/respiratory/copd/en/. Accessed April 27, 2007; World Health
Organization. http://www.who.int/en. Accessed July 19, 2007;
http://www.istockphoto.com/file_closeup/who/people_specific_attributes/body_parts/848586_puff_2_smoke_version.p
hp?id=848586. Accessed October 22, 2007.
 Radiographic Features of
Hyperinflation

http://www.mevis.de/~hhj/Lunge/imaCOPD/EmTh1136.JPG. Accessed April 27, 2007; GOLD

Initiative 2006. http://www.jend.de. Accessed October 31, 2007.
 Increased Rate of Decline in FEV1a in
•
Smokers
Susceptible smokers develop significant lung function decline
Never smoked
FEV1 (Percentage of Value at Age 25)

100 or not susceptible

to smoke
GOLD 0+1b
75
GOLD 2
Stopped at 50 years
50 Smoked regularly and
GOLD 3 susceptible to effects
of smoking
25
GOLD 4 Disability Stopped at 65 years

Death
0
25 50 75 100
Age (years)
aFEV =volume of air that can be expired in 1 second. bGOLD (Global Initiative for Chronic
1
Obstructive Lung Disease) classification of severity of COPD.
Adapted from Fletcher et al. BMJ. 1977;1:1645-1648; The GOLD Workshop Panel. Bethesda, MD:
National Heart, Lung, and Blood Institute; 2001. NIH publication 2701.
 Oxidative Stress in COPD
Cigarette Smoke
Inflammatory Cells
(Neutrophils,
Macrophages) Activation of
Nuclear Factor-κB

Decrease in Antiproteases
α1-Antitrypsin and Secretory
Tumor
Leukoprotease Inhibitor
Necrosis Interleukin-8
Factor-α

O2 , H 2 O2 Neutrophil
Increased Mucus OH•, Recruitment
Secretion ONOO−
Bronchoconstriction

Plasma Leak lsoprostanes

Barnes. Curr Opin Pharmacol. 2004;4:265; GOLD Initiative 2006. http://www.goldcopd.com.

Accessed
July 23, 2007.
 Summary: Smoking and COPD
• COPD
– Increased incidence in smokers
– Pathophysiology
• Inflammation and oxidative stress result in
– Obstructive lesions of the small conducting airways
– Dilatation and destruction of respiratory bronchioles
• Smoking induces significant lung function decline
– Smoking cessation
• Associated with improved lung function
• Reduces airway hyperresponsiveness
– Chronic bronchitis
• Increased incidence in smokers
• Smoking cessation
– Slows progression of lung disease
– Reduces mortality
Smoking and Asthma
 Asthma and Environmental Tobacco
Smoke (ETS)
• ETS aggravates asthma in childhood
• Asthmatic children whose mothers
smoke have more severe cases of
asthma compared with those whose
mothers don’t smoke
• Prenatal smoking is causally associated
with increased prevalence of asthma in
children

Chan-Yeung et al. Respirology. 2003;8:131-139; Courtesy of Getty Images.

http://delivery.gettyimages.com/xc/BB6074-
001.jpg?v=1&c=CFW&k=2&d=2EA4B0C59585DB42C1FF2DD0E5B2E618EC7C5022FB410D56.
Accessed October 11, 2007.
 Prenatal Smoking and Asthma in
Children
• Analysis of 60 studies revealed that
the risk of asthma in school- aged
children is increased if either parent
smokes
• Maternal smoking did have a
greater effect than paternal
smoking, yet the effect of the father
only was clearly significant
• Results suggest postnatal effect is
also important

aThe ratio of the odds of development of disease in exposed persons to the odds of development of
disease in nonexposed persons.
Cook et al. Thorax. 1997;52(12):1081-1094; http://www.worldofstock.com/closeups/PHE1195.php.
Accessed October 11, 2007.
 Smoking: Asthma Severity

Breathlessness (%)a
P=.004b
• Compared with Never

Attacks of
Smokers and Ex-smokers,
Current Smokers reported
– Significantly more attacks
of breathlessness
– Significantly higher severity
scores P=.01d

Scorec
Severity

Never Ex- Current

Smokers smokers Smokers
aAt rest in the last 12 months. bRelationship between attacks of breathlessness and smoking.
cSeverity score for asthma was established using an a priori decisional tree.dStrength of the relationship

between severity score and smoking.The 3 classes were coded 1, 2, and 3 for quantitative analysis.
Severity score was adjusted for age, sex, and educational level.
Siroux et al. Eur Respir J. 2000;15(3):470-477.
 Smoking and Asthma: Diminished
Response to Inhaled Corticosteroids
Change in FEV1(L)

0.20 15
P=.0003a

AM PEFb (L/M)
P=.0006a

Change in
0.15
10 P=.03a
0.10 0.17 11.74
P=NSa
5 8.30
0.05
0.06
0.00 0
Beclomethasone Beclomethasone
0.8 P=.03a
Change in PC20

NSa
Mchc

0.4 0.69
0.53

0.0
Beclomethasone
Nonsmokers Current smokers
a All
P values reflect difference in pulmonary function within groups before and after beclomethasone
therapy.
b AM PEF= AM peak expiratory flow; cPC
20 Mch=PC20 methacholine
Lazarus et al. Am J Respir Crit Care Med. 2007;175(8):783-790.
 Smoking Cessation: Improved Lung
Function in Asthmatics
Change in FEV1 (% Predicted)

P≤.01

P≤.05
P≤.05 P≤.05

1-wk 3-wk 6-wk 8-wk

Cessation Cessation Cessation Cessation
After
Steroids
Chaudhuri et al. Am J Respir Crit Care Med. 2006;174(2):127-133.
 Summary: Smoking and Asthma
• Environmental tobacco smoke aggravates asthma
in childhood
• Asthmatic children whose parents smoke have
more severe asthma than those whose parents
don’t smoke
• Exposure to pre- and postnatal smoking carries a
substantial risk of developing adult asthma
• Smoking asthmatics have a diminished response
to inhaled corticosteroids
 COPD AND CARDIOVASCULAR DISEASE

• Smoking related diseases:

– Coronary Heart Disease – Angina and Heart attack
– Endothelial dysfunction and dysmetabolism
– Peripheral vascular disease
– Abdominal Aortic Aneurysm
– Stroke
• First year after smoking cessation –
cardiovascular risk falls by 50% !!!
 Cardiac event rates among men with FVC in highest (Q1) and lowest (Q4) quartile and with 0 to 1 (ISP-)
or 2 to 5 (ISP+) ISPs in top quartile

Engstrom, G. et al. Circulation 2002;106:2555-2560

Copyright ©2002 American Heart Association

 COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser
Permanente Medical Care Program – a retrospective matched cohort study

Prevalence of Baseline Comorbidities, Case Patients, and Control Subjects

Sidney S et al Chest 2005;128;2068-2075

©2005 by American College of Chest Physicians

 Smoking: penile dysfunction!!!
More than twice the risk as compared with non-
smokers

Mechanism:
–Local vasodilation
(NO-mediated)

• Smoking cessation improves erectile

function – certain in mild forms of
disease
© BMA Tobacco Control Resource Centre 2006
Smoking and Lung Cancer
 Risk of Lung Cancer
• Current smokers have a higher risk of developing lung cancer than ex-
smokers or nonsmokers
Hazard Ratio (95% CI)a

aThe relative likelihood of experiencing a particular event or the effect of an explanatory variable on
the hazard or risk of an event.
Mannino et al. Arch Intern Med. 2003;163:1475-1480.
 Risk of Lung Cancer
• The risk of developing lung cancer is directly related to the amount
smoked
Hazard Ratio (95% CI)a

Never Smokers •30 30 to •60 ≥60

Pack/Years
Current Smokers
Pack/year was calculated by multiplying the average number of cigarettes smoked daily by the
number of years smoked and dividing the product by 20.
aThe relative likelihood of experiencing a particular event or the effect of an explanatory variable on

the hazard or risk of an event.

Mannino et al. Arch Intern Med. 2003;163:1475-1480.
 COPD: Risk Factor for Lung Cancer
• When evaluated long-term, diagnosis of COPD is a predictor of lung
cancer development
0.14
Proportion With Lung Cancer

0.12 Moderate/Severe COPD

0.10 Mild COPD

0.08

0.06 Restrictive Lung Disease

0.04
Normal Lung Function
0.02

0.0
0 5 10 15 20 25
Time Until Lung Cancer Diagnosis (Years)
Kaplan-Meier curves for incident lung cancer.
Adjusted for age, race, sex, education, smoking status, pack-years, and years since regular smoking.
Mannino et al. Arch Intern Med. 2003;163(12):1475-1480.
 Environmental Tobacco Smoke and Lung Cancer:
Dose Response
• There is a dose–response relationship between a nonsmoker’s risk of lung cancer
and the number of cigarettes and years of exposure to the smoker
5 5
4 4

Relative Riska (Log

Relative Riska (Log

3 3

Scale)
Scale)

2 2

1 1
0 1-19 10-19 ≥20 0 1-19 20-39 ≥40
Cigarettes Smoked Years Living With
Daily by Spouse Spouse Who Smokes
aThe probability of an event (developing a disease) occurring in exposed people compared with the
probability of the event in nonexposed people.
Hackshaw et al. BMJ. 1997;315(7114):980-988; Geng et al. In: Smoking and Health. Amsterdam,
The Netherlands: Elsevier Science; 1988:483-486.
 Summary: Smoking and Lung Cancer
• Risk of lung cancer increases with
– Quantity and duration of smoking
– Diagnosis and severity of COPD
– Severity of lung function
– Quantity and duration of environmental tobacco
smoke exposure
• Risk of lung cancer decreases with
– Duration of abstinence
– Age at cessation
• Risk of death from lung cancer progressively
decreases with increased duration of abstinence
 Symptoms of smoking cessation
• Anger/Frustration
• Anxiety
• Depression
• Difficulty in concetration
• Somnolence
• Fatigue
• Inpatience
• Insomnia
• Some physical troubles and tremour
 Other consequences
• Hyper appetite (sometimes, bulimia)
• Weight gain (sometimes more than 20 kg)
• Temptation of using other drugs (alcohol, etc)
• Change in drug posology
• Behavioral anomalies
• Psychological breakdowns (especially in
psychologically ill patients)
 Chronology of smoking cessation
symptoms
• Critical days: first 1-3 days
• Progressive improvement 2-3 weeks
• Progressive disappearance in the next months
BUT
• The temptation of relapsing lasts for months,
years, sometimes life-long
Fagerstrom’s score
 The 5As of Smoking Cessations
• Ask
• Advise
• Assess
• Assist
• Arrange
Pharmacologic therapy of smoking
• Nicotine substitution Therapy
– Long acting
• Patches
– Short acting
• Chewing gum
• Inhalers
• Nasal spray
• Chewable tablets
• Antidepressives
– Bupropion
• Nicotine receptor antagonist agonist
– Varenicline

1. Silagy C, et al. Cochrane Database Syst Rev. 2004;(3):CD000146. 2. Stead L, et al. Int J Epidemiol.
2005;34:1001–1003. 3. Henningfield JE, et al. CA Cancer J Clin. 2005;55:281-299.
4. Hughes JR et al. Cochrane Database Syst Rev. 2004;(4):CD000031.
 Smoking Cessation: Lung Cancer Risk
Reduction
• Lung cancer risk declines with increased duration of abstinence and
approaches that of nonsmokers
Relative Risk (95% CI)a

3.4

Nonsmokers Current Nonsmokers Recent Nonsmokers Distant

Smokers Ex- smokersb Ex- smokersc
Adjusted for age, physical activity, education, body mass index, waist circumference, alcohol use, and fruit
consumption.
aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the

event in nonexposed people. bRecent ex-smoker (quit ≤5 years at baseline). cDistant ex-smoker (quit >5 years at
baseline).
Ebbert et al. J Clin Oncol. 2003;21(5);921-926.
 Impact of Smoking Cessation on
Mortality: Men
• Risk of death from lung cancer progressively decreases with increased
duration of abstinence
16
Continuing Cigarette Smokers
Cumulative Risk % (Men)a

14
Stopped at age 60
12 Stopped at age 50
10 Stopped at age 40
8 Stopped at age 30
Lifelong Nonsmokers
6
4
2
0
45 55 65 75
Age (years)
aThe combined risks from aggregate exposures to multiple agents or stressors.
US Environmental Protection Agency National Center for Environmental Assessment. http://cfpub.epa.gov
/ncea/cfm/recordisplay.cfm?deid=54944. Accessed May 7, 2007; Peto et al. BMJ. 2000;321(7257);323-329.