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The Pulmonologist’s Guide The Pulmonologist’s Guide to the Pulmonary Consequences to the Pulmonary Consequences
of Smoking and the Benefits of of Smoking and the Benefits of CessationCessation
OverviewOverview
Chronic obstructive pulmonary disease (COPD)Chronic obstructive pulmonary disease (COPD)– EmphysemaEmphysema– Chronic bronchitisChronic bronchitis
AsthmaAsthma
Lung cancerLung cancer
GOLD Initiative 2006. http://www.goldcopd.com. Accessed July 24, 2007;Celli et al. Eur Respir J. 2004;23:932-946.
Smoking and COPDSmoking and COPD
Cumulative Incidence of COPDCumulative Incidence of COPD For continuous smokers it is 35.5% and for never smokers it is 7.8%For continuous smokers it is 35.5% and for never smokers it is 7.8%aa
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.
Severe COPDb
Moderate COPD
Mild COPD
NeverSmokers
40
0
Cu
mu
lati
ve I
nci
den
ce 35
30
25
20
15
10
5
Ex-smokers Early Interm Late ContinuousSmokers
Abstainersc
COPD MortalityCOPD Mortality
Worldwide, 80 million people have Worldwide, 80 million people have moderate-to-severe COPDmoderate-to-severe COPD
Half of all COPD patients die within a Half of all COPD patients die within a decade of diagnosisdecade of diagnosis
COPD predicted to become the fourth COPD predicted to become the fourth leading cause of death worldwide by 2030leading cause of death worldwide by 2030
In 2005, 3 million people died of COPDIn 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.php?id=848586. Accessed October 22, 2007.
Radiographic Features of HyperinflationRadiographic 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.
COPD: PathophysiologyCOPD: PathophysiologyAirflow LimitationAirflow Limitation
Irreversible airflow limitation measured during forced Irreversible airflow limitation measured during forced expiration is caused by eitherexpiration is caused by either– An increase in the resistance of the small conducting airwaysAn increase in the resistance of the small conducting airways– An increase in lung compliance due to emphysematous lung An increase in lung compliance due to emphysematous lung
destruction destruction – Both Both
Airflow limitation is usually progressive and associated withAirflow limitation is usually progressive and associated with– Lesions that obstruct the small conducting airwaysLesions that obstruct the small conducting airways– Emphysematous destruction of the lung’s Emphysematous destruction of the lung’s
elastic recoil forceelastic recoil force– Abnormal inflammatory response to noxious particles or Abnormal inflammatory response to noxious particles or
gases, primarily caused by cigarette smokinggases, primarily caused by cigarette smoking
Hogg. Lancet. 2004;364(9435):709-721; Anderson. Neurology. 2005;64:1488-1489; Celli et al. Eur Respir J. 2004;23:932-946.
Increased Rate of Decline in FEVIncreased Rate of Decline in FEV11aa in in
SmokersSmokers Susceptible smokers develop significant lung function declineSusceptible smokers develop significant lung function decline
aFEV1 =volume of air that can be expired in 1 second. bGOLD (Global Initiative for Chronic 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.
FE
V1
(Per
cen
tag
e o
f V
alu
e at
Ag
e 25
)
Age (years)
100
0
75
50
25
10025 50 75
Never smoked or not susceptible to smoke
Stopped at 50 years
Stopped at 65 years
GOLD 0+1b
GOLD 2
GOLD 3
GOLD 4 Disability
Death
Smoked regularly and susceptible to effects of smoking
Air Trapping Links Pathophysiology and Air Trapping Links Pathophysiology and Patient-Centered Outcomes in COPDPatient-Centered Outcomes in COPD
Cooper. Am J Med. 2006;119(10A):S21-S31.
Poor Health-Related Quality of LifePoor Health-Related Quality of Life
Activity LimitationActivity
LimitationDyspneaDyspnea
Air TrappingAir Trapping
HyperinflationHyperinflation
Airflow ObstructionAirflow Obstruction
Patient-CenteredOutcomes
AnxietyAnxiety
TachypneaTachypnea Ventilatory Requirement Ventilatory Requirement
DeconditioningDeconditioning
COPDCOPD
HypoxemiaHypoxemia ExacerbationsExacerbations
Inflammatory Mechanisms in COPDInflammatory Mechanisms in COPDCigarette Smoke
and Other Irritants
Cigarette Smoke and Other Irritants
Epithelial Cells Alveolar Macrophage
ProteasesNeutrophil ElastaseCathepsinsMatrix Metalloproteinases
ProteasesNeutrophil ElastaseCathepsinsMatrix Metalloproteinases
Protease InhibitorsProtease Inhibitors
Neutrophil
CD8+ T Lymphocytes
MCP-1
Alveolar-Wall Destruction
(Emphysema)Mucus Hypersecretion
(Chronic Bronchitis)MCP-1=monocyte chemotactic protein-1.Adapted from Barnes. Curr Opin Pharmacol. 2004;4(3):265; Celli et al. Eur Respir J. 2004;23:932-946.
Neutrophil Chemotactic FactorsInterleukin-8, Leukotriene B4
Neutrophil Chemotactic FactorsInterleukin-8, Leukotriene B4
040
58
3.4
270
20
0
50
100
150
200
250
300
350
400
450
500
2.6
1400
750
7.8300
4000
0
500
1000
1500
2000
2500
3000
3500
4000
4500
COPD: Pulmonary Inflammatory ResponseCOPD: Pulmonary Inflammatory Response Cigarette smoke induces a significant inflammatory response in the Cigarette smoke induces a significant inflammatory response in the
lungs of patients with emphysemalungs of patients with emphysema
CD4=T lymphocyte; CD8=T lymphocyte; CD20=B lymphocyte; Eos=eosinophils; Macro=macrophages; PMN=polymorphonuclear. aP<.01 from control and mild. bLung tissue from respective patients was obtained following lung resection.Retamales et al. Am J Respir Crit Care Med. 2001;164(3):469-473.
PMN, ×10
12
Macro,
×1012
Eos, ×10
8
CD4, ×10
12
CD8, ×10
12
CD20, ×
1012
PMN, ×10
12
Macro,
×1012
Eos, ×10
8
CD4, ×10
12
CD8, ×10
12
CD20, ×
1012
Infla
mm
ator
y C
ells
a
a
a
a
a
Normal lung functionb Severe emphysemab
Infla
mm
ator
y C
ells
Oxidative Stress in COPDOxidative Stress in COPD
Decrease in Antiproteases1-Antitrypsin and Secretory
Leukoprotease Inhibitor
Decrease in Antiproteases1-Antitrypsin and Secretory
Leukoprotease Inhibitor
Increased MucusSecretion
Plasma Leak lsoprostanes
Bronchoconstriction
NeutrophilRecruitment
Interleukin-8
Activation ofNuclear Factor-B
TumorNecrosisFactor-
O2, H2O2
OH, ONOO
Cigarette SmokeInflammatory Cells
(Neutrophils, Macrophages)
Cigarette SmokeInflammatory Cells
(Neutrophils, Macrophages)
Barnes. Curr Opin Pharmacol. 2004;4:265; GOLD Initiative 2006. http://www.goldcopd.com. Accessed July 23, 2007.
Pathology of COPD: Obstruction of Small Pathology of COPD: Obstruction of Small Conducting AirwaysConducting Airways
Normal small airway Mucus plug
Inflamed airway, lumen partly filled with mucus and cells
Airway surrounded by connective tissue,might restrict normal enlargement of lumen
Hogg. Lancet. 2004;364(9434):709-721; GOLD Initiative 2006. htt://www.goldcopd.com. Accessed July 24, 2007.
Pathology of COPD: Pathology of COPD: Emphysematous Lung DestructionEmphysematous Lung Destruction
The centrilobular pattern of The centrilobular pattern of emphysematous destruction emphysematous destruction is most closely associated is most closely associated with cigarette smokingwith cigarette smoking
Centrilobular emphysema Centrilobular emphysema results from dilatation and results from dilatation and destruction of the respiratory destruction of the respiratory bronchiolesbronchioles Centrilobular
emphysematous lesion
Hogg. Lancet. 2004;364(9435):709-721.
COPD: Pathology of EmphysemaCOPD: Pathology of Emphysema
http://db2.photoresearchers.com/cgi-bin/big_preview.txt?image_iid=10991009. Accessed October 19, 2007; http://pathhsw5m54.ucsf.edu/case25/images25/cle.jpg. Accessed April 27, 2007; Hogg. Lancet. 2004;364(9435):709-721.
Histopathology ofemphysema
Section of lung with both panacinar panlobular and centrilobular emphysema
Pathophysiology: Inhibition of Pulmonary Pathophysiology: Inhibition of Pulmonary Artery Endothelial Cell AngiogenesisArtery Endothelial Cell Angiogenesis
aEndothelial monolayer wound repair distance is expressed as the difference between width of the wound before CSE exposure and after CSE exposure (mm). P.05 vs 0 (control).Su et al. Am J Physiol Lung Cell Mol Physiol. 2004;287(4):L794-800.
Cigarette smoke extract (CSE) inhibits angiogenesis of pulmonary Cigarette smoke extract (CSE) inhibits angiogenesis of pulmonary artery endothelial cellsartery endothelial cells
Impaired angiogenesis may impede the pulmonary repair process Impaired angiogenesis may impede the pulmonary repair process and contribute to altered structural remodelingand contribute to altered structural remodeling
Rep
air
Dis
tan
ce (
mm
)a
0 2.5 5.0 7.5 10Cigarette Smoke Extract (%)
.35
0
.20
.10
.05
.15
.25
.30
Smoking Cessation: Improvement in Smoking Cessation: Improvement in Postbronchodilator FEVPostbronchodilator FEV11 Decline Decline
Anthonisen et al. JAMA. 1994;272(19):1497-1505; Kanner et al. Am J Med. 1999;106(4):410-416.
Follow up (y)
Po
stb
ron
cho
dil
ato
r F
EV
1 L
2.4
2.5
2.6
2.7
2.8
2.9
Screen 2 1 2 3 4 5
Sustained Quitters
Continuous Smokers
Susceptible smokers develop significant lung function declineSusceptible smokers develop significant lung function decline
Smoking Cessation: Improvement in FEVSmoking Cessation: Improvement in FEV11
Scanlon et al. Am J Respir Crit Care Med. 2000;161:381-390.
Annual Visits (AV)
72
74
76
78
80
82
Baseline AV 1 AV 2 AV 3 AV 4 AV 5
Pred
icte
d FE
V 1 (%
)
Sustained Quitters
Continuous Smokers
134
3723152
54208
146
2335
2059
1818
1652
2682
840
507541
599673
124
0
50
100
150
200
Smoking Cessation: Effects on Airway Smoking Cessation: Effects on Airway HyperresponsivenessHyperresponsiveness Smoking cessation improves bronchial hyperresponsivenessSmoking cessation improves bronchial hyperresponsiveness
PC
20
AM
P m
g/m
L-1
cP
C2
0 M
ch m
g/m
L-1
b
a P.05 before quitting vs 12 months after quitting. bPC20 Mch=provocative concentration of methacholine (Mch) that inducesa 20% fall in FEV1. c PC20 AMP=provocative concentration of adenosine-5 ‘ monophosphate (AMP) that induces a 20% fall in FEV1.
Willemse et al. Eur Respir J. 2004;24(3):391-396.
0
2
4
6
8
10
176a
44
Baseline 12 Months After Quitting
Baseline 12 Months After Quitting
8.1a
2.57
Smoking Cessation: Airway Inflammation Smoking Cessation: Airway Inflammation and COPDand COPD Cross-sectional studies suggest ongoing inflammation Cross-sectional studies suggest ongoing inflammation
in ex-smokers in ex-smokers
Willemse et al evaluated the effect of smoking cessation on airway Willemse et al evaluated the effect of smoking cessation on airway inflammation ininflammation in– Smokers with COPDSmokers with COPD– Smokers with normal lung functionSmokers with normal lung function
Upon smoking cessationUpon smoking cessation– COPD candidates had persistent airway inflammation and increased COPD candidates had persistent airway inflammation and increased
sputum inflammatory cells sputum inflammatory cells – Asymptomatic smokers had either significant reduction in sputum Asymptomatic smokers had either significant reduction in sputum
inflammatory cells or demonstrated no changeinflammatory cells or demonstrated no change
Observed persistent inflammation in patients with COPD may be related Observed persistent inflammation in patients with COPD may be related to repair of tissue damage in the airwaysto repair of tissue damage in the airways
Willemse et al. Eur Resp J. 2005;26(5):835-845.
Notes Continuationof Previous Slide
Smoking Cessation: Effects on Smoking Cessation: Effects on Respiratory SymptomsRespiratory Symptoms
aAdjusted for sex, age, clinic, body mass index, baseline cigarettes/day, nonwhite race, dust/fume exposure, years of education, lung problems before 16 years of age, FEV1 % predicted, bronchodilator response %, Mch reactivity, and baseline symptoms. Mean prevalence at first through the fifth annual visits. bFor all variables evaluated.Kanner et al. Am J Med. 1999;106(4):410-416.
43.6 42.2
55.451.6
58.764.960.664.7
0
10
20
30
40
50
60
70
Baseline Symptom
Cough≥3 month/year
Phlegm≥3 month/year
Wheezing Dyspnea
Intervention Usual care
Rep
ort
ed S
ymp
tom
s at
Bas
elin
e (%
)a
P.00001b
Chronic BronchitisChronic Bronchitis
Chronic inflammatory process associated with Chronic inflammatory process associated with – Increased production of mucusIncreased production of mucus– Defective mucociliary clearanceDefective mucociliary clearance– Disruption of the epithelial barrierDisruption of the epithelial barrier
Smoking increases neutrophil recruitment to the lungSmoking increases neutrophil recruitment to the lung
Productive cough for a minimum of 3 months a yearProductive cough for a minimum of 3 months a year
Approximately 2 out of 5 continuous smokers ultimately Approximately 2 out of 5 continuous smokers ultimately develop chronic bronchitis develop chronic bronchitis
Approximately half of smokers who have chronic Approximately half of smokers who have chronic bronchitis develop COPDbronchitis develop COPD
Pelkonen et al. Chest. 2006;130(4):1129-1137; Hill et al. Eur Respir J. 2000;15(5):886-890; Hogg. Lancet. 2004;364(9435):709-721; Celli et al. Eur Respir J. 2004;23:932-946.
Incidence of Chronic BronchitisIncidence of Chronic Bronchitis The cumulative incidence of chronic bronchitis was 42% in continuous The cumulative incidence of chronic bronchitis was 42% in continuous
smokers compared with 26% and 22% in ex-smokers and never- smokers compared with 26% and 22% in ex-smokers and never- smokers, respectivelysmokers, respectivelybb
CIa
of
Ch
ron
ic B
ron
chit
is (
%) Continuous Smokers
Ex-smokers
Never Smokers
40 45 50 55 60 65 70 7505
101520253035404550
Age in Years
aCumulative incidence. b1711 middle-aged men belonging to 2 groups were followed up for up to 40 years.Pelkonen et al. Chest. 2006;130(4):1129-1137.
Chronic Bronchitis: Effects of Smoking Chronic Bronchitis: Effects of Smoking CessationCessation
Smoking cessation in chronic bronchitis results inSmoking cessation in chronic bronchitis results in
– Reduction in IL-8 concentration in airways Reduction in IL-8 concentration in airways
– Decreased neutrophil recruitment Decreased neutrophil recruitment
– Slowed progression of lung diseaseSlowed progression of lung disease
Hill et al. Eur Respir J. 2000;15(5):886-890.
Chronic Bronchitis: Effect of Smoking Chronic Bronchitis: Effect of Smoking Reduction on SurvivalReduction on Survival
Decrease in daily smokinga
No changeb
Cu
mu
lati
ve S
urv
ival
P
rob
abil
ity
(%)
5 10 15 20 25 300
102030405060708090
100
Years of Follow-up After the First Report of Chronic Bronchitis
Based on the Cox model (P<.001), adjusted for age, pulmonary function, and the study year of examination at which chronic bronchitis was diagnosed for the first time. Decrease in daily smoking was calculated as a change in the mean number of cigarettes per day.aOn average, smokers had reduced their smoking by 13 cigarettes (SD, 5); their previous consumption had been 22 cigarettes (SD, 5). bSubjects smoked on average 19 cigarettes per day (SD, 6).Pelkonen et al. Chest. 2006;130(4):1129-1137.
Summary: Smoking and COPDSummary: Smoking and COPD
COPDCOPD– Increased incidence in smokersIncreased incidence in smokers– PathophysiologyPathophysiology
• Inflammation and oxidative stress result in Inflammation and oxidative stress result in – Obstructive lesions of the small conducting airwaysObstructive lesions of the small conducting airways– Dilatation and destruction of respiratory bronchiolesDilatation and destruction of respiratory bronchioles
• Smoking induces significant lung function declineSmoking induces significant lung function decline
– Smoking cessationSmoking cessation• Associated with improved lung functionAssociated with improved lung function• Reduces airway hyperresponsivenessReduces airway hyperresponsiveness
– Chronic bronchitisChronic bronchitis• Increased incidence in smokersIncreased incidence in smokers• Smoking cessationSmoking cessation
– Slows progression of lung diseaseSlows progression of lung disease– Reduces mortalityReduces mortality
Smoking and AsthmaSmoking and Asthma
Asthma and Environmental Tobacco Asthma and Environmental Tobacco Smoke (ETS)Smoke (ETS)
ETS aggravates asthma in ETS aggravates asthma in childhoodchildhood
Asthmatic children whose mothers Asthmatic children whose mothers smoke have more severe cases of smoke have more severe cases of asthma compared with those whose asthma compared with those whose mothers don’t smokemothers don’t smoke
Prenatal smoking is causally Prenatal smoking is causally associated with increased associated with increased prevalence of asthma in childrenprevalence 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 Prenatal Smoking and Asthma in ChildrenChildren
Analysis of 60 studies revealed Analysis of 60 studies revealed that the risk of asthma in school- that the risk of asthma in school- aged children is increased if aged children is increased if either parent smokes; Odds either parent smokes; Odds Ratio (OR)Ratio (OR)aa=1.21 (95% CI, 1.10-=1.21 (95% CI, 1.10-1.34)1.34)
Maternal smoking did have a Maternal smoking did have a greater effect than paternal greater effect than paternal smoking, yet the effect of the smoking, yet the effect of the father only was clearly significant father only was clearly significant
Results suggest postnatal effect Results suggest postnatal effect is also importantis 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.
Asthma: Effects of Environmental Tobacco Asthma: Effects of Environmental Tobacco Smoke in Utero or Early ChildhoodSmoke in Utero or Early Childhood
Exposure to pre- and postnatal smoking carries a substantial risk for Exposure to pre- and postnatal smoking carries a substantial risk for developing adult asthmadeveloping adult asthma
aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for sex, age, educational level, active smoking in terms of both smoking habits and pack/years, occupational exposure, and hay fever. In addition, when estimating the ORs for the 3 maternal smoking variables, adjustment was made for exposure to smoking from other household members.Skorge et al. Am J Resp Crit Care Med. 2005;172:61-66.
1 1 1
3.5
1.9
2.9
0
1
2
3
4
5
6
7
Od
ds
Rat
io (
95%
CI)
a
Prenatal Postnatal Pre- and Postnatal
No exposure to maternal smoking
Exposure to maternal smoking
Smoking: Asthma SeveritySmoking: Asthma Severity
Compared with Never Compared with Never Smokers and Ex-Smokers and Ex-smokers, Current smokers, Current Smokers reportedSmokers reported– Significantly more Significantly more
attacks of attacks of breathlessnessbreathlessness
– Significantly higher Significantly higher severity scoresseverity scores
60.6 60.3
89.2
0
20
40
60
80
100
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 betweenseverity 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.
Never Smokers
Ex-smokers
CurrentSmokers
Att
acks
of
Bre
ath
less
nes
s (%
)aS
ever
ity
Sco
rec
2.21 2.232.66
0
1
2
3
P=.004b
P=.01d
Asthmatic Smokers: Smoking DurationAsthmatic Smokers: Smoking Duration
Siroux et al. Eur Respir J. 2000;15(3):470-477.
Duration of Smoking/ Years
0
Cu
rren
tly
Sm
oki
ng
(Wo
men
)C
urr
entl
y S
mo
kin
g(M
en)
10
20
30 40 500
0.2
0.4
0.6
0.8
1.0
0
0.2
0.4
0.6
0.8
1.0 Childhood onset
Adult onset
Nonasthmatic
10
20
30 40 500
Smoking and Asthma: Diminished Smoking and Asthma: Diminished Response to Inhaled CorticosteroidsResponse to Inhaled Corticosteroids
a All P values reflect difference in pulmonary function within groups before and after beclomethasone therapy. b AM PEF= AM peak expiratory flow; cPC20 Mch=PC20 methacholine Lazarus et al. Am J Respir Crit Care Med. 2007;175(8):783-790.
0.20
0.15
0.10
0.05
0.00Ch
ang
e in
FE
V1(
L)
Beclomethasone
15
10
5
0
Ch
ang
e in
A
M P
EF
b (
L/M
)
Beclomethasone
0.8
0.4
0.0
Ch
ang
e in
PC
20
Mch
c
Beclomethasone
P=.0003a
P=NSa
P=.0006a
P=.03a
P=.03a
NSa
Nonsmokers Current smokers
0.17
0.06
0.530.69
11.74
8.30
Smoking Cessation: Improved Lung Smoking Cessation: Improved Lung Function in AsthmaticsFunction in Asthmatics
Chaudhuri et al. Am J Respir Crit Care Med. 2006;174(2):127-133.
0
10
20
30
40
1-wkCessation
3-wkCessation
6-wkCessation
8-wkCessation
AfterSteroids
Ch
ang
e in
FE
V1 (%
Pre
dic
ted
)
P≤.05P≤.05
P≤.05
P≤.01
Summary: Smoking and AsthmaSummary: Smoking and Asthma
Environmental tobacco smoke aggravates asthma in Environmental tobacco smoke aggravates asthma in childhoodchildhood
Asthmatic children whose parents smoke have more Asthmatic children whose parents smoke have more severe asthma than those whose parents don’t smokesevere asthma than those whose parents don’t smoke
Exposure to pre- and postnatal smoking carries a Exposure to pre- and postnatal smoking carries a substantial risk of developing adult asthmasubstantial risk of developing adult asthma
Smoking asthmatics have a diminished response to Smoking asthmatics have a diminished response to inhaled corticosteroidsinhaled corticosteroids
Smoking and TuberculosisSmoking and Tuberculosis
Smoking: Risk of Smoking: Risk of Mycobacterium Mycobacterium TuberculosisTuberculosis Infection Infection Smoking may increase the risk of Smoking may increase the risk of M tuberculosisM tuberculosis infection infection
aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for pack/years, age, sex, and taking into account possible clustering at address level.den Boon et al. Thorax. 2005;60(7):555-557.
1.00
1.901.771.77
0.0
1.0
2.0
3.0
Pack/Years5 5-15 15
Od
ds
Rat
io (
95%
CI)
a
Never Smokers
Current Smokers
Smoking and Pulmonary TBSmoking and Pulmonary TB
aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Crude OR was adjusted for age. To minimize the effect of other confounders the study population was restricted to men aged 20 to 50 years only.TB=tuberculosis.Kolappan et al. Thorax. 2002;57(11):964-966; www.medscape.com/viewarticle/452428_2. Accessed May 13, 2007.
1.00
2.24
0.0
1.0
2.0
3.0
4.0
Od
ds
Rat
io (9
5% C
I)a
NonsmokersNonsmokers
Smoking is a risk factor for the development of pulmonary TBSmoking is a risk factor for the development of pulmonary TB
Current SmokersCurrent Smokers
Potential Pathogenetic Mechanisms of Potential Pathogenetic Mechanisms of Smoking-Induced TB ReactivationSmoking-Induced TB Reactivation
Nicotine binding to the Nicotine binding to the -7 subunit of the nicotinic acetylcholine -7 subunit of the nicotinic acetylcholine receptors may trigger a cascade of events that result in TB reactivationreceptors may trigger a cascade of events that result in TB reactivation
iNOS=inducible nitric oxide synthase; NO=nitric oxide; MTb=Mycobacterium tuberculosisDavies et al. Trans R Soc Trop Med Hyg. 2006;100:291-298.
TNF-TNF-
(–)(–)
(–)(–)
-7-7
()()
ArginineArginine
iNOSiNOS
NONOLatentLatent
MTbMTb
Neutralizing antibodyto TNF-
Neutralizing antibodyto TNF-
NicotineNicotine
PhagosomePhagosome
PhagosomePhagosome
Environmental Tobacco Smoke: Risk of Environmental Tobacco Smoke: Risk of Active TB Immediately Following Active TB Immediately Following InfectionInfection Environmental tobacco smoke (ETS) exposure is a risk factor for the Environmental tobacco smoke (ETS) exposure is a risk factor for the
development of active pulmonary TB immediately following infectiondevelopment of active pulmonary TB immediately following infection
aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.Altet et al. Tuber Lung Dis. 1996;77(6):537-544.
1.00
5.29
0
2
4
6
8
10
12
14
Exposed to Smoking
Od
ds
Rat
io (9
5% C
I)a P.00005
Not Exposed to Smoking
Odds Ratioa (95% CI)
Environmental Tobacco Smoke: Risk of Environmental Tobacco Smoke: Risk of Active TB Immediately Following Active TB Immediately Following Infection (cont’d)Infection (cont’d) The risk of developing active pulmonary TB following infection The risk of developing active pulmonary TB following infection
increases with the number of cigarettes smoked daily by household increases with the number of cigarettes smoked daily by household adultsadults
aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Odds ratio adjusted for sex, age, and father's social class IV-V using multiple logistic regression analysis. Altet et al. Tuber Lung Dis. 1996;77(6):537-544.
1.00
7.76
3.95
1.61
0 3 6 9 12 15 18
None
21-40
40
1-20
P.01
P.001
Cig
aret
tes/
Day
Smoking: Adherence to Latent TB Smoking: Adherence to Latent TB Infection (LTBI) TherapyInfection (LTBI) Therapy
Nonsmokers are more likely Nonsmokers are more likely to be adherent with LTBI to be adherent with LTBI therapytherapy
As a result of their reduced As a result of their reduced LTBI compliance, smokers LTBI compliance, smokers increased their risk of increased their risk of developing active TBdeveloping active TB
Lavigne et al. BMC Public Health. 2006;6:66.
Current Current SmokerSmoker
1.8
1.0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
OR
fo
r C
om
pli
ance
(95
% C
I)
NonsmokersNonsmokers
Smoking: TB-Related MortalitySmoking: TB-Related Mortality
In India, approximately 32% of TB deaths may be In India, approximately 32% of TB deaths may be attributed to bidiattributed to bidiaa smoking smoking
aBidi is a cheap smoking stick made by rolling a dried, rectangular piece of temburni leaf with about 0.2 g of sun-dried, flaked tobacco. bThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age, education, and smokeless tobacco use. Pednekar et al. Prev Med. 2007;44(6):496-498.
1.00
2.60
2.12
0.0
1.0
2.0
3.0
4.0
Never Smokers Cigarette Smokers Bidi Smokers
Rel
ativ
e R
isk (9
5% C
I)b
Smoking and Lung CancerSmoking and Lung Cancer
Risk of Lung CancerRisk of Lung Cancer
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.
Current smokers have a higher risk of developing lung cancer than ex-Current smokers have a higher risk of developing lung cancer than ex-smokers or nonsmokerssmokers or nonsmokers
8.4
3.6
1.0
0
2
4
6
8
10
12
14
16
18
Never Smokers Ex-smokers Current Smokers
Haz
ard
Rat
io (
95%
CI)
a
Risk of Lung CancerRisk of Lung Cancer
The risk of developing lung cancer is directly related to the amount The risk of developing lung cancer is directly related to the amount smokedsmoked
1.02.9
9.0
19.9
0
5
10
15
20
25
30
35
40
Never Smokers 30 30 to 60 60
Pack/YearsCurrent Smokers
Haz
ard
Rat
io (
95%
CI)
a
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 CancerCOPD: Risk Factor for Lung Cancer
When evaluated long-term, diagnosis of COPD is a predictor of lung When evaluated long-term, diagnosis of COPD is a predictor of lung cancer developmentcancer development
Moderate/Severe COPD
Mild COPD
Normal Lung Function
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.
Pro
po
rtio
n W
ith
Lu
ng
Can
cer
Time Until Lung Cancer Diagnosis (Years)
0.14
0.12
0.10
0.06
0.02
0.00 5 10 15 20 25
Restrictive Lung Disease
0.08
0.04
2.8
1.41
0
1
2
3
4
5
Impairment of Lung Function:Impairment of Lung Function:Risk Factor for Lung CancerRisk Factor for Lung Canceraa
Degree of impairment correlates with risk of lung cancerDegree of impairment correlates with risk of lung cancer
aFrom the National Health and Nutrition Examination Survey (NHANES) I, 1971-1975, and follow-up through 1992. bThe relative likelihood of experiencing a particular event or the effect of an explanatory variable on the hazard or risk of an event. cDefined as FEV1/FVC of <70% and FVC of 80%. dDefined as FEV1/FVC of <70% and FVC of <80% predicted. FVC=forced vital capacity. Mannino et al. Arch Intern Med. 2003;163(12):1475-1480.
Haz
ard
Rat
io (
95%
CI)
b
NormalLung Function
Mild COPDc
Moderate/Severe COPDd
Environmental Tobacco Smoke and Lung Environmental Tobacco Smoke and Lung Cancer: Dose ResponseCancer: Dose Response There is a dose–response relationship between a nonsmoker’s risk of lung 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 smokercancer and the number of cigarettes and years of exposure to the smoker
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.
Rel
ativ
e R
iska
(Lo
g S
cale
)
0 1-19 10-19 20Cigarettes Smoked
Daily by Spouse
Rel
ativ
e R
iska
(Lo
g S
cale
)0 1-19 20-39 40
Years Living WithSpouse Who Smokes
1
2
3
4
5
1
2
3
4
5
Lung Cancer Risk by Smoking StatusLung Cancer Risk by Smoking Status
Reducing tobacco consumption markedly decreases lung cancer Reducing tobacco consumption markedly decreases lung cancer risk risk
a The relative likelihood of experiencing a particular event, or the effect of an explanatory variable on the hazard or risk of an event.Adjusted for sex, cohort of origin, inhalation habits (yes/no), tobacco type (cigarettes, cigars/pipe/cheroots, mixed), and years as smokers (continuous). bCompared with heavy smokers, (15 cigarettes/day), reducers (reduced from ≥15 cigarettes/day by minimum of 50% without quitting), light smokers (1-14 cigarettes/day).Godtfredsen et al. JAMA. 2005;294(12);1505-1510.
HeavySmokers
Reducersb LightSmokersb
Ex-smokersb
Never SmokersbQuitters
0
0.2
0.4
0.6
0.8
1
Haz
ard
Rat
io (
95%
CI)a
0.09
0.17
0.44
0.5
0.73
0
0.2
0.4
0.6
0.8
1
Smoking Cessation: Smoking Cessation: Lung Cancer Risk ReductionLung Cancer Risk Reduction Lung cancer risk declines with increasing duration of abstinenceLung cancer risk declines with increasing duration of abstinence
aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Compared with current smokers.Data for relative risk given as median (range). Ebbert et al. J Clin Oncol. 2003;21(5);921-926.
Years of Smoking Abstinence
Rel
ativ
e R
isk
(95%
CI)
a Iowa Women’s Health Study
0-5 6-10 11-20 21-30 30
1.0 1.0 1.0
10.9
16.6
0
4
8
12
16
20
24
Smoking Cessation: Lung Cancer Risk Smoking Cessation: Lung Cancer Risk ReductionReduction
Lung cancer risk declines with increased duration of abstinence and Lung cancer risk declines with increased duration of abstinence and approaches that of nonsmokersapproaches that of nonsmokers
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.
Rel
ativ
e R
isk
(95%
CI)
a
Current Smokers
Recent Ex- smokersb
DistantEx- smokersc
3.4
Nonsmokers Nonsmokers Nonsmokers
Smoking Cessation: Effects on MortalitySmoking Cessation: Effects on Mortality
CHD=coronary heart disease; CVD=cardiovascular disease.Athonisen et al. Ann Intern Med. 2005;142(4):233-239.
4
2
1
0
Rat
e o
f D
eath
per
100
0 P
erso
n-Y
ears
OtherCHD CVD Lung Cancer
Other Cancer
Respiratory Disease
Unknown
Causes of Death
Sustained Quitters Intermittent Quitters Continuing Smokers
3
Impact of Smoking Cessation on Impact of Smoking Cessation on Mortality: MenMortality: Men Risk of death from lung cancer progressively decreases with increased Risk of death from lung cancer progressively decreases with increased
duration of abstinenceduration of abstinence
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.
16
750
45Age (years)
12
8
4
Continuing Cigarette Smokers
Stopped at age 60
Stopped at age 50
Stopped at age 40
Stopped at age 30
Lifelong Nonsmokers
14
10
6
2
6555
Cu
mu
lati
ve R
isk
% (
Men
)a
0
0.1
0.2
0.3
0.4
0.5
0.6
Impact of Smoking Cessation on Impact of Smoking Cessation on Mortality: WomenMortality: Women Risk of death from lung cancer among women who quit before age Risk of death from lung cancer among women who quit before age
50 is substantially lower than the risk among current smokers 50 is substantially lower than the risk among current smokers
aThe relative likelihood of experiencing a particular event, or the effect of an explanatory variable on the hazard or risk of an event. Adjusted for age at enrollment (years), university education (yes/no), BMI (kg/m2) moderate physical activity (hours/week in quartiles, plus missing), alcohol consumption (g/day), HRT use (ever/never), total fat (g/day), cereal fiber (g/day), beta carotene (µg/day), vitamin A (IU/day), vitamin C (µg/day), and vitamin E (µg/day); bP.01; cP.001.Zhang et al. Ann Epidemiol. 2005;15(4):302-309.
Haz
ard
Rat
io (9
5% C
I)a
0.06b0.1c
30 Years 30-39 Years 40-49 Years
0.26c
Age at Quitting
Summary: Smoking and Lung CancerSummary: Smoking and Lung Cancer
Risk of lung cancer increases with Risk of lung cancer increases with – Quantity and duration of smokingQuantity and duration of smoking– Diagnosis and severity of COPDDiagnosis and severity of COPD– Severity of lung functionSeverity of lung function– Quantity and duration of environmental tobacco smoke Quantity and duration of environmental tobacco smoke
exposureexposure
Risk of lung cancer decreases withRisk of lung cancer decreases with– Duration of abstinenceDuration of abstinence– Age at cessationAge at cessation
Risk of death from lung cancer progressively decreases Risk of death from lung cancer progressively decreases with increased duration of abstinence with increased duration of abstinence