The Primary Care Physician’s Guide The Primary Care Physician’s Guide to the Systemic Effects of Smoking to the Systemic Effects of Smoking

and the Benefits of Cessationand the Benefits of Cessation

OverviewOverview

Smoking and Smoking and

– MalignancyMalignancy

– Renal diseaseRenal disease

– Dermatologic effectsDermatologic effects

– Effects on the oral cavityEffects on the oral cavity

– Endocrinologic effectsEndocrinologic effects

Smoking and MalignancySmoking and Malignancy

MalignancyMalignancy

– Lung Lung

– Pancreas Pancreas

– Esophagus Esophagus

– KidneyKidney

– BladderBladder

– GastricGastric

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/Years

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.

0.0

2.0

4.0

6.0

8.0

10.0

Risk of Pancreatic Cancer Risk of Pancreatic Cancer

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people.Lin et al. Cancer Causes Control. 2002;13:249-254.

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

MaleMaleSmokersSmokers

FemaleFemaleSmokersSmokers

Males Smoking Males Smoking 40 Cigarettes40 Cigarettes

per Dayper Day

NonsmokersNonsmokers

1.61.71.0

3.3

Risk of Pancreatic CancerRisk of Pancreatic Cancer

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people.Relative risk measured with reference to current smokers. Reference RR of 1 refers to current smokers.Fuchs et al. Arch Intern Med. 1996;156:2255-2260.

Former smokers reduced their risk of developing pancreatic cancer by Former smokers reduced their risk of developing pancreatic cancer by almost 50% within 3-10 years of quitting, compared with the risk in current almost 50% within 3-10 years of quitting, compared with the risk in current smokerssmokers

Re

lati

ve

Ris

k (

95

% C

I)R

ela

tiv

e R

isk

(9

5%

CI)

aa

1.21.2

1.01.0

0.80.8

0.60.6

0.40.4

0.20.2

0.00.0CurrentCurrent 22 3-103-10 11-1511-15 1616 NeverNever

Time Since Quitting Smoking (years)Time Since Quitting Smoking (years)

Risk of Esophageal CancerRisk of Esophageal Cancer

Smokers have an approximately Smokers have an approximately 3-fold increased risk of 3-fold increased risk of esophageal squamous cell cancer esophageal squamous cell cancer

Ex-smokers have a lower risk of Ex-smokers have a lower risk of squamous cell esophageal cancer squamous cell esophageal cancer than current smokersthan current smokers

Ten years after cessation of Ten years after cessation of smoking, ex-smokers still have a smoking, ex-smokers still have a 2-fold increased risk 2-fold increased risk

Nature Clinical Practice. http://www.nature.com/ncpgasthep/journal/v2/n1/fig_tab/ncpgasthep0072_ft.html. Accessed September 19, 2007. Bosetti et al. Oral Oncol. 2006;42:957-964; Wu et al. Cancer Causes Control. 2001;12:721-732.

1.001.001.00

1.50

2.12

2.80

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Risk of Esophageal and Gastric CancerRisk of Esophageal and Gastric Cancer

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age, sex, race, birthplace, and education.Wu et al. Cancer Causes Control. 2001;12:721-732.

Od

ds

Rat

io (

95%

CI)

Od

ds

Rat

io (

95%

CI)

aa

Never Smokers Current Smokers

Smokers have an increased risk of developing esophageal, gastric, and Smokers have an increased risk of developing esophageal, gastric, and distal gastric cancerdistal gastric cancer

Esophageal Adenocarcinoma

(n=222)

Gastric Cardia Adenocarcinoma

(n=277)

Distal Gastric Adenocarcinoma

(n=443)

2.092.16

1.40

2.26

1.361.10

1.50 1.61

0.84

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

Risk of Esophageal and Gastric CancerRisk of Esophageal and Gastric CancerO

dd

s R

atio

(95

% C

I)O

dd

s R

atio

(95

% C

I)aa

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age, sex, race, birthplace, and education.Wu et al. Cancer Causes Control. 2001;12:721-732.

20

Years of Smoking

21-40 ≥41

Increased risk of developing GI cancers is dependent upon the number Increased risk of developing GI cancers is dependent upon the number of years smokedof years smoked

Esophageal adenocarcinoma(n=222)

Gastric cardia adenocarcinoma(n=277)

Distal gastric adenocarcinoma(n=443)

Risk of Bladder CancerRisk of Bladder Cancer

Smoking is one of the most Smoking is one of the most important risk factors associated important risk factors associated with bladder cancerwith bladder cancer

Prevention of cigarette smoking Prevention of cigarette smoking would result in 50% fewer men would result in 50% fewer men and 23% fewer women with and 23% fewer women with bladder cancerbladder cancer

Current cigarette smokers have Current cigarette smokers have an approximately 3-fold an approximately 3-fold greater risk of bladder cancer greater risk of bladder cancer than nonsmokersthan nonsmokers

Zeegers et al. World J Urol. 2004;21:392-401; Urology channel. http://www.urologychannel.com/bladdercancer/index.shtml. Accessed September 20, 2007

Risk of Renal CancerRisk of Renal Cancer

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Hunt et al. Int J Cancer. 2005;114:101-108.

0.98

1.60 1.58

2.03

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

1-9 20WomenMen

1-9 20 Cigarettes/Day

Relative risk for developing renal cancer is increased with greater Relative risk for developing renal cancer is increased with greater cigarette consumptioncigarette consumption

1.21

1.75

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Risk of Renal Cell Cancer Decreases With Risk of Renal Cell Cancer Decreases With Longer Duration of AbstinenceLonger 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. bShort-term ex-smokers were those who had quit smoking <10 years before diagnosis. cLong-term ex-smokers were those who had quit smoking >10 years ago (reported categories). Hunt et al. Int J Cancer. 2005;114:101-108.

Short-term Long-termMale Ex-smokers

bb

cc

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

Relative risk for developing renal cell cancer decreases with length Relative risk for developing renal cell cancer decreases with length of time from smoking cessationof time from smoking cessation

Summary: Smoking and CancerSummary: Smoking and Cancer

Smoking is associated with an increased risk of Smoking is associated with an increased risk of developing the following cancers: developing the following cancers: – LungLung – Gastric– Gastric– Pancreatic Pancreatic – Bladder – Bladder – EsophagealEsophageal – Renal– Renal

The risk of developing some cancers may be related to The risk of developing some cancers may be related to the duration and amount smokedthe duration and amount smoked

Ex-smokers may have a reduced cancer risk compared Ex-smokers may have a reduced cancer risk compared with current smokerswith current smokers

Risk of developing cancer may decrease with longer Risk of developing cancer may decrease with longer duration of abstinenceduration of abstinence

Endocrine Effects of SmokingEndocrine Effects of Smoking

Osteoporosis Osteoporosis

Thyroid diseaseThyroid disease

Insulin resistance/diabetesInsulin resistance/diabetes

Osteoporosis Risk and SmokingOsteoporosis Risk and Smoking

Epidemiology of Hip Fracture in SmokersEpidemiology of Hip Fracture in Smokers

Smoking is a risk factor for hip fracture in postmenopausal Smoking is a risk factor for hip fracture in postmenopausal womenwomen

In current postmenopausal smokers relative to In current postmenopausal smokers relative to nonsmokers, the risk of hip fracture is 17% greater at age nonsmokers, the risk of hip fracture is 17% greater at age 60, 41% greater at age 70, and 71% greater at age 8060, 41% greater at age 70, and 71% greater at age 80

Of all hip fractures in women, 1 in 8 may be attributable Of all hip fractures in women, 1 in 8 may be attributable to smokingto smoking

Smoking increases the lifetime risk of postmenopausal hip Smoking increases the lifetime risk of postmenopausal hip fracture by about half, from an estimated 12% to 19% in fracture by about half, from an estimated 12% to 19% in women up to the age of 85, and from 22% to 37% up to women up to the age of 85, and from 22% to 37% up to the age of 90 the age of 90

Law et al. BMJ. 1997;315:841-846.

Bone Mineral Density (BMD):Similar in Bone Mineral Density (BMD):Similar in Premenopausal Smokers and NonsmokersPremenopausal Smokers and Nonsmokers

aBMD differences were recorded as a proportion of 1 standard deviation (SD), because absolute bone density units varied among studies. White circles refer to 2 studies and yellow circles to 10 studies.Differences are recorded as a proportion of 1 SD in BMD. The regression line is drawn through the data points to estimate the average values for the variable on the vertical scale (y) according to values of the variable on the horizontal scale (x).Law et al. BMJ. 1997;315:841-846.

In premenopausal women, there is little difference in BMD between In premenopausal women, there is little difference in BMD between smokers and nonsmokerssmokers and nonsmokersaa

Dif

fere

nce

s in

Bo

ne

Den

sity

(S

D)a

1.0

0.5

0

(0.5)

20(1.0)

30 40 50 55Age

Bone Mineral Density: Differences Between Bone Mineral Density: Differences Between Postmenopausal Smokers and NonsmokersPostmenopausal Smokers and Nonsmokers

aBone mineral density (BMD) differences were recorded as a proportion of 1 standard deviation, because absolute bone density units varied among studies. White circles refer to 2 studies and yellow circles refer to 22 studies.The regression line is drawn through the data points to estimate the average values for the variable on the vertical scale (y) according to values of the variable on the horizontal scale (x). Law et al. BMJ. 1997;315:841-846.

Postmenopausal bone loss is greater in current smokers than nonsmokersPostmenopausal bone loss is greater in current smokers than nonsmokers Bone density diminishes by about an additional 2% for every 10-year Bone density diminishes by about an additional 2% for every 10-year

increase in age, with a difference of 6% at age 80 increase in age, with a difference of 6% at age 80

Dif

fere

nce

s in

Bo

ne

Den

sity

(S

D)a

1.0

0.5

0

(0.5)

45(1.0)

50 70 8060Age

Bone Mineral Density in Elderly WomenBone Mineral Density in Elderly Women

aP<.05 compared with nonsmokers. Values are adjusted means and standard error of adjusted means. Means are compared by adjusted covariance for alcohol intake, total body BMD, height, weight, dietary calcium, and caffeine intake.Rapuri et al. Bone. 2000;27(3):429-436.

Heavy smokers have an increased reduction in bone mineral density Heavy smokers have an increased reduction in bone mineral density (BMD) compared with light and nonsmokers(BMD) compared with light and nonsmokers

Nonsmokers0.000.74

0.76

0.78

0.80

0.82

0.84

BM

D (

g/c

m2 )

1 ≥1 Pack/Day

Total Femur

a

Nonsmokers0.00

0.94

0.96

0.98

1.00

1.02

BM

D (

g/c

m2 )

1 ≥1 Pack/Day

Total Body

a

Cigarettes/Day Current Smokers

Cigarettes/DayCurrent Smokers

Relation of Smoking to Relation of Smoking to Thyroid DiseaseThyroid Disease

Smoking as a Risk Factor for Thyroid Smoking as a Risk Factor for Thyroid Dysfunction in WomenDysfunction in Women

aAttributable risk is used to quantify risk in the exposed group that is attributable to the exposure. Vestergaard et al. Thyroid. 2002;12(1):69-75.

Disease StateDisease State Attributable RiskAttributable Riskaa

Graves’ diseaseGraves’ disease 45%45%

Nodular goiterNodular goiter 28%28%

Autoimmune hypothyroidismAutoimmune hypothyroidism 23%23%

Female smokers have an increased risk of Graves’ disease, Female smokers have an increased risk of Graves’ disease, toxic nodular goiter, and autoimmune hypothyroidismtoxic nodular goiter, and autoimmune hypothyroidism

Smoking and Graves’ DiseaseSmoking and Graves’ Disease

Increased susceptibility to Graves’ Increased susceptibility to Graves’ diseasedisease

Increased incidence and clinical Increased incidence and clinical severity of ophthalmopathyseverity of ophthalmopathy

Smoking abstinence may result in Smoking abstinence may result in a decrease in morbidity in womena decrease in morbidity in women

http://db2.photoresearchers.com/cgi-bin/big_preview.txt?image_iid=10791029. Accessed October 23, 2007; Vestergaard. Eur J Endocrinol. 2002;146:153-161.

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Smoking as a Predictor of Graves’ DiseaseSmoking as a Predictor of Graves’ Disease

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, duration of oral contraceptive use, age at menarche, parity, recent pregnancy, menopausal status, body mass index (BMI), alcohol intake, and physical activity level.Holm et al. Arch Intern Med. 2005;165:1606-1611.

Nonsmokers Ex-smokers Current Smokers 1-14 15-24 25

Women who smoke Women who smoke 25 cigarettes daily have the greatest risk of 25 cigarettes daily have the greatest risk of Graves’ diseaseGraves’ disease

Among women who previously smoked, risk of Graves’ disease Among women who previously smoked, risk of Graves’ disease decreases with prolonged smoking cessationdecreases with prolonged smoking cessation

Haz

ard

Rat

io (9

5% C

I)a

Cigarettes/DayCurrent Smokers

Smoking: A Risk Factor for Smoking: A Risk Factor for HypothyroidismHypothyroidism Nystrom et alNystrom et al

– 12-year follow-up of 1462 12-year follow-up of 1462 randomly selected women randomly selected women in 5 age strata, evaluated in 5 age strata, evaluated longitudinallylongitudinally

– Strong association found Strong association found between smoking at time of between smoking at time of initial screening and later initial screening and later development of development of hypothyroidismhypothyroidism

– Relative riskRelative riskaa for woman for woman smoker to develop smoker to develop hypothyroidism is 3.9 hypothyroidism is 3.9 (95% CI, 1.6-9.1)(95% CI, 1.6-9.1)

aThe relative likelihood of experiencing a particular event or the effect of an explanatory variable on the hazard or risk of an event.Nyström et al. J Endocrinol Invest. 1993;16:129-131.

Insulin Resistance and SmokingInsulin Resistance and Smoking

Insulin Resistance Syndrome in Male Insulin Resistance Syndrome in Male SmokersSmokers A syndrome in which endogenous insulin fails to produce A syndrome in which endogenous insulin fails to produce

an adequate physiologic response from fat, muscle, and an adequate physiologic response from fat, muscle, and liver cells liver cells

Compared with nonsmoking men of similar age and BMI, Compared with nonsmoking men of similar age and BMI, smokers hadsmokers had– Insulin resistanceInsulin resistance

• Higher fasting levels of triglyceridesHigher fasting levels of triglycerides• Lower HDL-CLower HDL-C• Elevated C-peptide levels, consistent with compensatory Elevated C-peptide levels, consistent with compensatory

increase in insulin release as a result of insulin resistanceincrease in insulin release as a result of insulin resistance• Larger adipose mass at the expense of lean body tissue Larger adipose mass at the expense of lean body tissue

without increased weight without increased weight • Lipid intoleranceLipid intolerance

Eliasson et al. Atherosclerosis. 1997;129:79-88.

Type 2 Diabetes MellitusType 2 Diabetes Mellitus

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people; bP=.0383; cP=.0043.Adjusted for ex-and current smokers, age, BMI, waist/hip ratio, alcohol consumption (yes/no).Beziaud et al. Diabetes Metab. 2004;30:161-166.

Risk of Type 2 Diabetes Mellitus: MenRisk of Type 2 Diabetes Mellitus: Men History of current or past smoking is associated with an elevated History of current or past smoking is associated with an elevated

risk of diabetes mellitusrisk of diabetes mellitus

1.49

1.00

1.31

0.0

0.5

1.0

1.5

2.0

Nonsmokers Ex-smokers Current Smokers

b

c

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

Aged 20-69 Years

1.711.79

1.00

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Risk of Developing Type 2 Diabetes: MenRisk of Developing Type 2 Diabetes: Men

Nonsmokers Light Smokers(1-19/Day)

Moderate/Heavy Smokers(20/Day)

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age and BMI. Wannamethee et al. Diabetes Care. 2001;24(9):1590-1595.

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

Smoking is associated with an increased risk of diabetesSmoking is associated with an increased risk of diabetes

Cigarettes/DayCurrent Smokers

1.201.42

0.95

1.89

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Smoking Cessation and Risk of Type 2 Smoking Cessation and Risk of Type 2 DiabetesDiabetes

Time Since Quitting (Years at Screening)

5 5-10 11-19 20

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

Risk of developing diabetes decreases with increased duration of Risk of developing diabetes decreases with increased duration of cessationcessation

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age and BMI. Wannamethee et al. Diabetes Care. 2001;24(9):1590-1595.

Smoking-Associated Hyperglycemia: Smoking-Associated Hyperglycemia: PathophysiologyPathophysiology

Increase in free fatty acids might be cause of insulin Increase in free fatty acids might be cause of insulin resistanceresistance

Cigarette smoking may release free radicals that could Cigarette smoking may release free radicals that could reduce insulin sensitivityreduce insulin sensitivity

Tobacco use can stimulate epinephrine and Tobacco use can stimulate epinephrine and norepinephrinenorepinephrine

Direct toxic effect on pancreatic cells has been Direct toxic effect on pancreatic cells has been suggestedsuggested

Beziaud et al. Diabetes Metab. 2004;30:161-166.

Summary: Smoking and the Endocrine Summary: Smoking and the Endocrine SystemSystem Postmenopausal bone loss is greater in smokers than in Postmenopausal bone loss is greater in smokers than in

nonsmokersnonsmokers

Women who smoke have an increased risk of developing Women who smoke have an increased risk of developing Graves’ diseaseGraves’ disease

Smoking is associated with an increased incidence and Smoking is associated with an increased incidence and clinical severity of Graves’ ophthalmopathyclinical severity of Graves’ ophthalmopathy

Male smokers have a higher incidence of insulin resistance Male smokers have a higher incidence of insulin resistance than male nonsmokersthan male nonsmokers

Smokers are at increased risk of developing diabetes Smokers are at increased risk of developing diabetes

Risk of type 2 diabetes decreases with increased duration Risk of type 2 diabetes decreases with increased duration of smoking abstinenceof smoking abstinence

Smoking and Renal DiseaseSmoking and Renal Disease

Chronic kidney disease (CKD)Chronic kidney disease (CKD)

Decreased renal functionDecreased renal function

Decreased glomerular filtration rate (GFR)Decreased glomerular filtration rate (GFR)

Increased relative risk of proteinuriaIncreased relative risk of proteinuria

1.0

2.18

1.09

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Nonsmokers Ex-smokers Current Smokers

Smoking and Risk of Chronic Kidney DiseaseSmoking and Risk of Chronic Kidney DiseaseO

dd

s R

atio

(95

% C

I)a

CKD=kidney damage for 3 or more months, defined in this study as an estimated GFR of less than 60 mL/minute per 1.73 m 2. Ex-smoker is anyone who smoked >100 cigarettes in his/her lifetime, but had stopped smoking at least 1 year prior to examination. aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age, sex, education, BMI, current nonsteroidal anti-inflammatory drug (NSAID) usage, hypertension, diabetes, CV disease history, and heavy drinking.Shankar et al. Am J Epidemiol. 2006;164(3):263-271.

Smoking is associated with an increased risk of chronic kidney disease (CKD)Smoking is associated with an increased risk of chronic kidney disease (CKD)

Compared with current smokers, ex-smokers have a reduced risk of CKDCompared with current smokers, ex-smokers have a reduced risk of CKD

Risk of Chronic Kidney Disease In SmokersRisk of Chronic Kidney Disease In Smokers

aThe ratio of the odds of the development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age, sex, education, alcohol, and use of paracetamol and salicylates. Analyses of cigarette smoking also adjusted for pipe smoking, cigar smoking, and snuff use.Ejerblad et al. J Am Soc Nephrol. 2004;15:2178-2185.

OR

(95

% C

I)a

OR

(95

% C

I)a

There is a dose-response relationship between the quantity and There is a dose-response relationship between the quantity and duration of smoking and risk of chronic kidney disease (CKD)duration of smoking and risk of chronic kidney disease (CKD)

1.231.00

1.40

0.0

0.5

1.0

1.5

2.0

2.5

NeverSmokers

21-40 >40

Duration of Cigarette Smoking (y)

1.52

1.00

1.32

0.0

0.5

1.0

1.5

2.0

2.5

NeverSmokers

16-30 >30

Packs/YearCurrent Smokers

1.00 1.00

1.71

2.693.3

2.4

0

1

2

3

4

5

6

7

1+ Proteinuria 2+ Proteinuria

Nonsmokers Ex-smokers Current Smokers

Risk of Proteinuria in SmokersRisk of Proteinuria in Smokers

aThe probability of an event (developing a disease) occurring in exposed people compared with the probabilityof the event in nonexposed people. Halimi et al. Kidney Int. 2000;58:1285-1292.

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

P=.0001P=.01

P=.0009P=.01

Current and ex-smokers have an increased risk of proteinuriaCurrent and ex-smokers have an increased risk of proteinuria

1.00

2.20

0

1

2

3

4

5

Never Smokers CurrentSmokers

Male Smokers with Type 2 Diabetes: Decline Male Smokers with Type 2 Diabetes: Decline in Renal Functionin Renal Function

Pat

ien

ts W

ith

a

Lo

w e

-GF

R (

%)a

aGFR is the volume of fluid filtered from the renal glomerular capillaries into the Bowman's capsule per unit time.Estimated GFR (e-GFR) was calculated with the abbreviated Modification of Diet in Renal Disease (MDRD) formula. Low GFR was defined as e-GFR <60 mL/min per 1.73 m2, a value that has been suggested to be the cutoff point for the definition of CKD. bAdjusted for duration of disease, GHb, albuminuria, and dyslipidemia.De Cosmo et al. Diabetes Care. 2006;29(11):2467-2470.

P=.03 P=.02

Smokers are at increased risk for renal insufficiency. Consequently, significantly Smokers are at increased risk for renal insufficiency. Consequently, significantly more smokers experience reductions in GFR than nonsmokers.more smokers experience reductions in GFR than nonsmokers.aa

Ad

just

ed O

dd

s R

atio

(9

5% C

I)b

12.00

20.90

02468

10121416182022

Never Smokers CurrentSmokers

Summary: Smoking and Renal Disease Summary: Smoking and Renal Disease

Smokers have a higher risk ofSmokers have a higher risk of

– Decreased renal functionDecreased renal function

– Decreased glomerular filtration rate (GFR) Decreased glomerular filtration rate (GFR)

– ProteinuriaProteinuria

– Chronic Kidney Disease (CKD)Chronic Kidney Disease (CKD)

• Risk of CKD is dose relatedRisk of CKD is dose related

Smoking and the SkinSmoking and the Skin

Characteristic signsCharacteristic signs

Cutaneous manifestationsCutaneous manifestations

Squamous cell carcinomaSquamous cell carcinoma

Adverse effects on wound healingAdverse effects on wound healing

Characteristic Signs of SmokingCharacteristic Signs of Smoking

Clinical SignsClinical Signs SynonymsSynonyms DescriptionDescription

Harlequin nailHarlequin nail Quitter’s nailQuitter’s nail Demarcation line in the nailDemarcation line in the nail

Smoker’s comedonesSmoker’s comedones Large comedones with furrows and Large comedones with furrows and nodulesnodules

Smoker’s faceSmoker’s face a) Lines or wrinklesa) Lines or wrinklesb) Gauntnessb) Gauntnessc) Graying of the skinc) Graying of the skind) Plethoric complexiond) Plethoric complexion

Smoker’s melanosisSmoker’s melanosis Pigmentation of the gingivaPigmentation of the gingiva

Smoker’s moustacheSmoker’s moustache Moustache discolorationMoustache discoloration

Smoker’s nailSmoker’s nail Nicotine signNicotine sign Nail discolorationNail discoloration

Smoker’s palateSmoker’s palate Nicotine stomatitis, leukokeratosis Nicotine stomatitis, leukokeratosis nicotina palatinicotina palati

Coloration of the palatal mucosaColoration of the palatal mucosa

Smoker’s tongueSmoker’s tongue Leukokeratosis nicotina glossiLeukokeratosis nicotina glossi Pink-colored depressionsPink-colored depressions

Snuff dipper’s lesionSnuff dipper’s lesion Smokeless tobacco keratosis, Smokeless tobacco keratosis, tobacco pouch keratosistobacco pouch keratosis

White lesion in the oral cavity where White lesion in the oral cavity where smokeless tobacco is heldsmokeless tobacco is held

Freiman et al. J Cutan Med Surg. 2004;8(6):415-423.

Cutaneous Manifestations of SmokingCutaneous Manifestations of Smoking

Prominent periorbital lines Prominent periorbital lines

GauntnessGauntness

Graying of the skinGraying of the skin

PlethoricPlethoricaa complexion complexion

aPlethoric denotes a red florid complexion.Freiman et al. J Cutan Med Surg. 2004;8(6):415-423.

Cutaneous Manifestations of SmokingCutaneous Manifestations of Smoking

Discoloration of the nail Discoloration of the nail in smokersin smokers

Demarcation line in the nailDemarcation line in the nail

Freiman et al. J Cutan Med Surg. 2004;8(6):415-423.

Smoking and Cutaneous Squamous Cell Smoking and Cutaneous Squamous Cell Carcinoma (SCC)Carcinoma (SCC)

Smokers have a 50% Smokers have a 50% greater chance of greater chance of developing cutaneous developing cutaneous SCC than nonsmokersSCC than nonsmokers

Current smokers are at Current smokers are at higher risk for cutaneous higher risk for cutaneous SCC than ex-smokersSCC than ex-smokers

Grodstein et al. J Nat Cancer Inst. 1995; 8714:1061–1066; Hertog et al. J Clin Oncol. 2001; 191:231–238.http://images.google.com/imgres?imgurl=http://www.medscape.com/content/2001/00/41/08/410808/art-smj9406.14.fig4.jpg&imgrefurl=http://www.medscape.com/viewarticle/410808_3&h=291&w=400&sz=24&hl=en&start=0&tbnid=YJSjToEbzbOMcM:&tbnh=90&tbnw=124&prev=/images%3Fq%3Dsquamous%2Bcell%2Bcancer,%2Blip%26gbv%3D2%26svnum%3D10%26hl%3Den%26safe%3Dactive%26sa%3DG. Accessed October 19, 2007.

Adverse Effects of Smoking on Wound Adverse Effects of Smoking on Wound HealingHealing

Decreases cutaneous Decreases cutaneous blood flowblood flow

Significantly decreases Significantly decreases immune response, leading immune response, leading to poor wound healingto poor wound healing

Largest risk factor for Largest risk factor for complications related to wound complications related to wound healing in postoperative healing in postoperative arthroplasty study arthroplasty study

Delays wound repairsDelays wound repairs

Freiman et al. J Cutan Med Surg. 2004;8(6):415-423; KCI. http://db2.photoresearchers.com/search/SE6944. Accessed October 23, 2007.

Smoking: Postoperative Wound Smoking: Postoperative Wound ComplicationsComplications

Manassa et alManassa et al– 132 postabdominoplasty 132 postabdominoplasty

patients evaluatedpatients evaluated– Wound-healing Wound-healing

complications assessedcomplications assessedaa – Significantly increased Significantly increased

postoperative wound postoperative wound complicationscomplications

• Smokers 47.9% Smokers 47.9% • Nonsmokers 14.8% Nonsmokers 14.8%

((PP<.01)<.01)

aComplications, evaluated prior to discharge, were noted when medical intervention such as debridement, treatment for infection, lavage after fat necrosis, or a secondary skin closure after skin slough was necessary.Manassa et al. Plast Reconstr Surg. 2003;111(6):2082-2087.

Smoking: Postoperative Wound InfectionSmoking: Postoperative Wound Infection

SmokingSmoking– Decreases blood flow to damaged skin resulting in the Decreases blood flow to damaged skin resulting in the

disruption of repair and response to foreign contaminantsdisruption of repair and response to foreign contaminants– Independent predictor of wound infection in ventral hernia Independent predictor of wound infection in ventral hernia

repairrepair

Abstinence from smoking reduces incisional wound Abstinence from smoking reduces incisional wound infectioninfection

– Infection rate 12% (continuous smokers) vs 1% Infection rate 12% (continuous smokers) vs 1% (abstainers), (abstainers), PP<.05<.05

Morecraft. J Hand Surg. 1994;19: 1-7. Finan et al. Am J Surg. 2005;190:676-681; Sorensen et al. Ann Surg. 2003;238(1):1-5.

Summary: Smoking and Dermatologic Summary: Smoking and Dermatologic DiseaseDisease

SmokingSmoking– Causes characteristic skin changes Causes characteristic skin changes – Increases the incidence of squamous cell skin cancerIncreases the incidence of squamous cell skin cancer– Delays wound healing and increases risk of wound Delays wound healing and increases risk of wound

infectionsinfections

Effects of Smoking on the Oral CavityEffects of Smoking on the Oral Cavity

PeriodontitisPeriodontitis

StomatitisStomatitis

Oral cancerOral cancer

Smoking-Attributable PeriodontitisSmoking-Attributable Periodontitis

Smoking is a major risk Smoking is a major risk factor for periodontitis factor for periodontitis

Current smokers are Current smokers are approximately 4 times as approximately 4 times as likely as persons who have likely as persons who have never smoked to have never smoked to have periodontitisperiodontitis

Periodontal disease is one Periodontal disease is one of the main causes of tooth of the main causes of tooth loss worldwideloss worldwide

Tomar et al. J Periodontol. 2000;71(5):743-751; http://www.cda-adc.ca/en/oral_ health/complications/tobacco/ smokeless.asp. Accessed October 19, 2007.

5.88

5.10

4.72

2.96

2.79

0.0 2.0 4.0 6.0 8.0 10.0

Smoking: Risk of PeriodontitisSmoking: Risk of Periodontitis

aThe ratio of the odds of the development of disease in exposed persons to the odds of development of disease in nonexposed persons. Odds ratio adjusted for sex, age, race/ethnicity, educational attainment, and income:poverty ratio.Tomar et al. J Periodontal. 2000;71(5):743-751.

9 per day

10-19 per day

20 per day

21-30 per day

31 per day

P.000001 for all levels

Odds Ratio Compared With Nonsmokersa

There is a direct doseThere is a direct dose--response relation between number of cigarettes response relation between number of cigarettes smoked and the odds of developing periodontitissmoked and the odds of developing periodontitis

Oral PathologyOral Pathology

Nicotine StomatitisBrown Hairy Tongue

Leukoplakia

Davis. J Contemp Dent Pract. 2005;6:158-166; Lewin et al. Cancer. 1998;82:1367-1375.

Necrotizing Ulcerative Gingivitis

Oral Squamous Cell CarcinomaOral Squamous Cell Carcinoma

Smoking and other types of Smoking and other types of tobacco use are associated with tobacco use are associated with approximately 70% of oral cancer approximately 70% of oral cancer casescases

Symptoms includeSymptoms include– Sores that don’t healSores that don’t heal– A thickening or lump in the neck, A thickening or lump in the neck,

throat, or mouth, that does not go throat, or mouth, that does not go awayaway

– Persistent white or red patch in Persistent white or red patch in the mouththe mouth

– Difficulty chewing or swallowingDifficulty chewing or swallowing– Weight lossWeight loss

PrognosisPrognosis– Overall 5-year survival rate of Overall 5-year survival rate of

less than 50%less than 50%

Davis. J Contemp Dent Pract. 2005;6(3):158-166; Oliver et al. J Oral Maxillofac Surg. 1996;54:949-954; http://www.mediscan.co.uk/cfm/Im_info.cfm?ImageID=000480&mediatype=Image&log=nk. Accessed October 30, 2007.

Summary: Effects of Smoking on the Summary: Effects of Smoking on the Oral CavityOral Cavity

Major risk factor for periodontitisMajor risk factor for periodontitis

Direct dose-response relationship between smoking and Direct dose-response relationship between smoking and the odds of developing periodontitisthe odds of developing periodontitis

Smoking is associated with oral pathologySmoking is associated with oral pathology– Brown hairy tongueBrown hairy tongue– Nicotine stomatitisNicotine stomatitis– LeukoplakiaLeukoplakia– Necrotizing ulcerative gingivitisNecrotizing ulcerative gingivitis

Most oral cancers are malignant and spread rapidly Most oral cancers are malignant and spread rapidly

Associated with approximately 70% of oral cancer casesAssociated with approximately 70% of oral cancer cases

Presentation SummaryPresentation Summary

Smoking Smoking – Risk factor for multiple malignanciesRisk factor for multiple malignancies– Increases patient risk forIncreases patient risk for

• Osteoporosis Osteoporosis • Hip fracture Hip fracture • Thyroid diseaseThyroid disease• Insulin resistanceInsulin resistance• DiabetesDiabetes

– Increases risk of renal dysfunctionIncreases risk of renal dysfunction– Associated with characteristic skin changes, delayed wound Associated with characteristic skin changes, delayed wound

healing, and increased incidence of wound infection healing, and increased incidence of wound infection – Risk factor for various forms of oral pathologyRisk factor for various forms of oral pathology

Tobacco: Drug of AbuseTobacco: Drug of Abuse

SnusSnus

Moist smokeless tobacco, Moist smokeless tobacco, snuffsnuff

Although used worldwide, the Although used worldwide, the highest consumption of snus highest consumption of snus is in Swedenis in Sweden

Associated with an increased Associated with an increased risk of pancreatic cancer risk of pancreatic cancer (RR 2.0; 95% CI, 1.2-3.3(RR 2.0; 95% CI, 1.2-3.3aa))

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Luo et al. Lancet. 2007. Epub ahead of print; http://www.arnestadphotography.com/stock_photos/albums/concept/snuff_tobacco_black.jpg. Accessed October 19, 2007.

Hookah: Waterpipe Tobacco Smoking Hookah: Waterpipe Tobacco Smoking

Shisha, a mixture of tobacco, Shisha, a mixture of tobacco, molasses, and fruit flavors used molasses, and fruit flavors used in the hookah in the hookah

Water in the hookah does not Water in the hookah does not diminish tobacco toxicitydiminish tobacco toxicity

A 1-hour session of hookah smoking A 1-hour session of hookah smoking exposes the user to 100- 200 times exposes the user to 100- 200 times the volume of smoke inhaled from a the volume of smoke inhaled from a single cigarette single cigarette

Smoke produced contains high Smoke produced contains high levels of carbon monoxide, heavy levels of carbon monoxide, heavy metals, and other carcinogensmetals, and other carcinogens

Delivers significant levels of nicotine Delivers significant levels of nicotine

World Health Organization. http://www.who.int/tobacco/global_interaction/tobreg/Waterpipe%20recommendation_Final.pdf; Sajid et al. J Pak Med Assoc. 1993;43(9):179-182.

Smoking: Addictive PotentialSmoking: Addictive Potential Smoked tobacco is one of the most addictive commonly used drugsSmoked tobacco is one of the most addictive commonly used drugs

Anthony et al. Exp Clin Psychopharm. 1994;2:244-268.

Pre

vale

nce

of

Dep

end

ence

Am

on

g U

sers

(%

)

Age Group

50

30

20

10

0

40

15-24 25-34 35-44 45-54

Tobacco Alcohol Cannabis

Cocaine HeroinPsychedelics

Smoking: Chronic Physical HarmSmoking: Chronic Physical Harm When compared with other drugs of abuse, tobacco is associated When compared with other drugs of abuse, tobacco is associated

with the greatest chronic physical harmwith the greatest chronic physical harm

Nutt et al. Lancet. 2007;369:1047-1053.

2.5

2.0 1.9

2.42.1

1.81.6

2.9

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Heroin

Cocain

e

Barbitur

ates

Alcoho

l

Canna

bis

Ampheta

mine

Ecstas

y

Tobac

co

Phys

ical

Har

m

Smoking: Reduced Life ExpectancySmoking: Reduced Life Expectancy

Long-term cigarette smoking Long-term cigarette smoking reduces life expectancy by reduces life expectancy by approximately 10 years approximately 10 years

Cessation at age 60, 50, 40, Cessation at age 60, 50, 40, or 30 years gains or 30 years gains approximately 3, 6, 9, approximately 3, 6, 9, or 10 years of life or 10 years of life expectancy, respectivelyexpectancy, respectively

Doll et al. BMJ. 2004;328:1519-1527.

Su

rviv

al F

rom

Ag

e 60

(%

)

100

80

60

40

20

040 50 60 70 80 90 100

Age (years)

Cigarette Smokers

Nonsmokers

88

65

26

25

71

32

SummarySummaryTobacco: Drug of AbuseTobacco: Drug of Abuse

Smoked tobacco is one of the most addictive commonly Smoked tobacco is one of the most addictive commonly used drugsused drugs

When compared to other drugs of abuse, tobacco is When compared to other drugs of abuse, tobacco is associated with the greatest chronic physical harmassociated with the greatest chronic physical harm

Long-term cigarette smoking reduces life expectancy Long-term cigarette smoking reduces life expectancy by approximately 10 yearsby approximately 10 years