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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
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
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
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
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
Mechanism:
–Local vasodilation
(NO-mediated)
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
0.08
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
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
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.