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Overview

The Primary Care Physician’s Guide to the Systemic Effects of Smoking and the Benefits of Cessation. Overview. Smoking and Malignancy Renal disease Dermatologic effects Effects on the oral cavity Endocrinologic effects. Smoking and Malignancy. Malignancy Lung Pancreas Esophagus

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Overview

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  1. The Primary Care Physician’s Guide to the Systemic Effects of Smoking and the Benefits of Cessation

  2. Overview • Smoking and • Malignancy • Renal disease • Dermatologic effects • Effects on the oral cavity • Endocrinologic effects

  3. Smoking and Malignancy • Malignancy • Lung • Pancreas • Esophagus • Kidney • Bladder • Gastric

  4. Hazard Ratio (95% CI)a Risk of Lung Cancer • Current smokers have a higher risk of developing lung cancer than ex-smokers or nonsmokers 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.

  5. Hazard Ratio (95% CI)a Never Smokers 30 30 to 60 60 Pack/Years Risk of Lung Cancer • The risk of developing lung cancer is directly related to the amount smoked 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.

  6. Risk of Pancreatic Cancer Relative Risk (95% CI)a 3.3 1.7 1.6 1.0 Nonsmokers FemaleSmokers MaleSmokers Males Smoking 40 Cigarettesper Day 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.

  7. Risk of Pancreatic Cancer • Former smokers reduced their risk of developing pancreatic cancer by almost 50% within 3-10 years of quitting, compared with the risk in current smokers 1.2 1.0 0.8 Relative Risk (95% CI)a 0.6 0.4 0.2 0.0 Current 2 3-10 11-15 16 Never Time Since Quitting Smoking (years) 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.

  8. Smokers have an approximately 3-fold increased risk of esophageal squamous cell cancer Ex-smokers have a lower risk of squamous cell esophageal cancer than current smokers Ten years after cessation of smoking, ex-smokers still have a 2-fold increased risk Risk of Esophageal Cancer 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.

  9. Risk of Esophageal and Gastric Cancer • Smokers have an increased risk of developing esophageal, gastric, and distal gastric cancer Never Smokers Current Smokers Odds Ratio (95% CI)a Esophageal Adenocarcinoma(n=222) Gastric Cardia Adenocarcinoma(n=277) Distal Gastric Adenocarcinoma(n=443) 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.

  10. Risk of Esophageal and Gastric Cancer • Increased risk of developing GI cancers is dependent upon the number of years smoked Esophageal adenocarcinoma(n=222) Gastric cardia adenocarcinoma(n=277) Distal gastric adenocarcinoma(n=443) Odds Ratio (95% CI)a 20 21-40 ≥41 Years of Smoking 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.

  11. Smoking is one of the most important risk factors associated with bladder cancer Prevention of cigarette smoking would result in 50% fewer men and 23% fewer women with bladder cancer Current cigarette smokers have an approximately 3-fold greater risk of bladder cancer than nonsmokers Risk of Bladder Cancer Zeegers et al. World J Urol. 2004;21:392-401; Urology channel. http://www.urologychannel.com/bladdercancer/index.shtml. Accessed September 20, 2007

  12. Risk of Renal Cancer • Relative risk for developing renal cancer is increased with greater cigarette consumption Relative Risk (95% CI)a Cigarettes/Day 1-9 20 1-9 20 Men Women 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.

  13. Risk of Renal Cell Cancer Decreases With Longer Duration of Abstinence • Relative risk for developing renal cell cancer decreases with length of time from smoking cessation b Relative Risk (95% CI)a c Short-term Long-term Male Ex-smokers 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.

  14. Summary: Smoking and Cancer • Smoking is associated with an increased risk of developing the following cancers: • Lung – Gastric • Pancreatic – Bladder • Esophageal – Renal • The risk of developing some cancers may be related to the duration and amount smoked • Ex-smokers may have a reduced cancer risk compared with current smokers • Risk of developing cancer may decrease with longer duration of abstinence

  15. Endocrine Effects of Smoking • Osteoporosis • Thyroid disease • Insulin resistance/diabetes

  16. Osteoporosis Risk and Smoking

  17. Epidemiology of Hip Fracture in Smokers • Smoking is a risk factor for hip fracture in postmenopausal women • In current postmenopausal smokers relative to nonsmokers, the risk of hip fracture is 17% greater at age 60, 41% greater at age 70, and 71% greater at age 80 • Of all hip fractures in women, 1 in 8 may be attributable to smoking • Smoking increases the lifetime risk of postmenopausal hip 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 the age of 90 Law et al. BMJ. 1997;315:841-846.

  18. Bone Mineral Density (BMD):Similar in Premenopausal Smokers and Nonsmokers • In premenopausal women, there is little difference in BMD between smokers and nonsmokersa 1.0 0.5 Differences inBone Density (SD)a 0 (0.5) (1.0) 20 30 40 50 55 Age 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.

  19. Bone Mineral Density: Differences Between Postmenopausal Smokers and Nonsmokers • Postmenopausal bone loss is greater in current smokers than nonsmokers • Bone density diminishes by about an additional 2% for every 10-year increase in age, with a difference of 6% at age 80 1.0 0.5 Differences inBone Density (SD)a 0 (0.5) (1.0) 45 50 60 70 80 Age 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.

  20. 0.84 1.02 0.82 1.00 0.80 0.98 0.78 0.96 0.76 0.94 0.74 0.00 0.00 Bone Mineral Density in Elderly Women • Heavy smokers have an increased reduction in bone mineral density (BMD) compared with light and nonsmokers Total Femur Total Body BMD (g/cm2) BMD (g/cm2) a a Nonsmokers Nonsmokers 1 ≥1 Pack/Day 1 ≥1 Pack/Day Cigarettes/Day Current Smokers Cigarettes/DayCurrent Smokers 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.

  21. Relation of Smoking to Thyroid Disease

  22. Smoking as a Risk Factor for Thyroid Dysfunction in Women • Female smokers have an increased risk of Graves’ disease, toxic nodular goiter, and autoimmune hypothyroidism 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.

  23. Increased susceptibility to Graves’ disease Increased incidence and clinical severity of ophthalmopathy Smoking abstinence may result in a decrease in morbidity in women Smoking and Graves’ Disease http://db2.photoresearchers.com/cgi-bin/big_preview.txt?image_iid=10791029. Accessed October 23, 2007; Vestergaard. Eur J Endocrinol. 2002;146:153-161.

  24. Smoking as a Predictor of Graves’ Disease • Women who smoke 25 cigarettes daily have the greatest risk of Graves’ disease • Among women who previously smoked, risk of Graves’ disease decreases with prolonged smoking cessation Hazard Ratio (95% CI)a Nonsmokers Ex-smokers Current Smokers 1-14 15-24 25 Cigarettes/DayCurrent 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, 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.

  25. Smoking: A Risk Factor for Hypothyroidism • Nystrom et al • 12-year follow-up of 1462 randomly selected women in 5 age strata, evaluated longitudinally • Strong association found between smoking at time of initial screening and later development of hypothyroidism • Relative riska for woman smoker to develop hypothyroidism is 3.9 (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.

  26. Insulin Resistance and Smoking

  27. Insulin Resistance Syndrome in Male Smokers • A syndrome in which endogenous insulin fails to produce an adequate physiologic response from fat, muscle, and liver cells • Compared with nonsmoking men of similar age and BMI, smokers had • Insulin resistance • Higher fasting levels of triglycerides • Lower HDL-C • Elevated C-peptide levels, consistent with compensatory increase in insulin release as a result of insulin resistance • Larger adipose mass at the expense of lean body tissue without increased weight • Lipid intolerance Eliasson et al. Atherosclerosis. 1997;129:79-88.

  28. Type 2 Diabetes Mellitus

  29. Risk of Type 2 Diabetes Mellitus: Men • History of current or past smoking is associated with an elevated risk of diabetes mellitus c b Relative Risk (95% CI)a Aged 20-69 Years 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.

  30. Risk of Developing Type 2 Diabetes: Men • Smoking is associated with an increased risk of diabetes Relative Risk (95% CI)a Nonsmokers Light Smokers(1-19/Day) Moderate/Heavy Smokers(20/Day) Cigarettes/DayCurrent Smokers 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.

  31. Smoking Cessation and Risk of Type 2 Diabetes • Risk of developing diabetes decreases with increased duration of cessation Relative Risk (95% CI)a 5 5-10 11-19 20 Time Since Quitting (Years at Screening) 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.

  32. Smoking-Associated Hyperglycemia: Pathophysiology • Increase in free fatty acids might be cause of insulin resistance • Cigarette smoking may release free radicals that could reduce insulin sensitivity • Tobacco use can stimulate epinephrine and norepinephrine • Direct toxic effect on pancreatic cells has been suggested Beziaud et al. Diabetes Metab. 2004;30:161-166.

  33. Summary: Smoking and the Endocrine System • Postmenopausal bone loss is greater in smokers than in nonsmokers • Women who smoke have an increased risk of developing Graves’ disease • Smoking is associated with an increased incidence and clinical severity of Graves’ ophthalmopathy • Male smokers have a higher incidence of insulin resistance than male nonsmokers • Smokers are at increased risk of developing diabetes • Risk of type 2 diabetes decreases with increased duration of smoking abstinence

  34. Smoking and Renal Disease • Chronic kidney disease (CKD) • Decreased renal function • Decreased glomerular filtration rate (GFR) • Increased relative risk of proteinuria

  35. Smoking and Risk of Chronic Kidney Disease • Smoking is associated with an increased risk of chronic kidney disease (CKD) • Compared with current smokers, ex-smokers have a reduced risk of CKD Odds Ratio (95% CI)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 m2. 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.

  36. Risk of Chronic Kidney Disease In Smokers • There is a dose-response relationship between the quantity and duration of smoking and risk of chronic kidney disease (CKD) OR (95% CI)a OR (95% CI)a Packs/Year Current Smokers Duration of Cigarette Smoking (y) 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.

  37. Risk of Proteinuria in Smokers • Current and ex-smokers have an increased risk of proteinuria P=.0009 P=.01 P=.0001 Relative Risk (95% CI)a P=.01 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.

  38. Male Smokers with Type 2 Diabetes: Decline in Renal Function • Smokers are at increased risk for renal insufficiency. Consequently, significantly more smokers experience reductions in GFR than nonsmokers.a P=.03 P=.02 Adjusted Odds Ratio (95% CI)b Patients With a Low e-GFR (%)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.

  39. Summary: Smoking and Renal Disease • Smokers have a higher risk of • Decreased renal function • Decreased glomerular filtration rate (GFR) • Proteinuria • Chronic Kidney Disease (CKD) • Risk of CKD is dose related

  40. Smoking and the Skin • Characteristic signs • Cutaneous manifestations • Squamous cell carcinoma • Adverse effects on wound healing

  41. Characteristic Signs of Smoking Freiman et al. J Cutan Med Surg. 2004;8(6):415-423.

  42. Prominent periorbital lines Gauntness Graying of the skin Plethorica complexion Cutaneous Manifestations of Smoking aPlethoric denotes a red florid complexion.Freiman et al. J Cutan Med Surg. 2004;8(6):415-423.

  43. Discoloration of the nail in smokers Demarcation line in the nail Cutaneous Manifestations of Smoking Freiman et al. J Cutan Med Surg. 2004;8(6):415-423.

  44. Smoking and Cutaneous Squamous Cell Carcinoma (SCC) • Smokers have a 50% greater chance of developing cutaneous SCC than nonsmokers • Current smokers are at higher risk for cutaneous SCC 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.

  45. Adverse Effects of Smoking on Wound Healing • Decreases cutaneous blood flow • Significantly decreases immune response, leading to poor wound healing • Largest risk factor for complications related to wound healing in postoperative arthroplasty study • Delays 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.

  46. Smoking: Postoperative Wound Complications • Manassa et al • 132 postabdominoplasty patients evaluated • Wound-healing complications assesseda • Significantly increased postoperative wound complications • Smokers 47.9% • Nonsmokers 14.8% (P<.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.

  47. Smoking: Postoperative Wound Infection • Smoking • Decreases blood flow to damaged skin resulting in the disruption of repair and response to foreign contaminants • Independent predictor of wound infection in ventral hernia repair • Abstinence from smoking reduces incisional wound infection • Infection rate 12% (continuous smokers) vs 1% (abstainers), P<.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.

  48. Summary: Smoking and Dermatologic Disease • Smoking • Causes characteristic skin changes • Increases the incidence of squamous cell skin cancer • Delays wound healing and increases risk of wound infections

  49. Effects of Smoking on the Oral Cavity • Periodontitis • Stomatitis • Oral cancer

  50. Smoking is a major risk factor for periodontitis Current smokers are approximately 4 times as likely as persons who have never smoked to have periodontitis Periodontal disease is one of the main causes of tooth loss worldwide Smoking-Attributable Periodontitis 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.

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