Tobacco Dependence as a Chronic Disease

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1 Tobacco Dependence as a Chronic Disease Richard D. Hurt, M.D. Professor of Medicine Director, Mayo Clinic Nicotine Dependence Center

2 Per Capita Cigarette Consumption USA Cigarettes (no.) 5,000 4,000 3,000 2,000 1,000 Year of the Camel 1 st Surgeon General s Report Filtered cigarettes 1 st Smoking- Cancer Concern Low tar, low nicotine cigarettes Camel s 75 th birthday Surgeon General s Report on Environmental Tobacco Smoke Minnesota Tobacco Trial Cigarette sales 55-yr low (378 B) CP

3 Cigarettes Tobacco smoke complex mixture of 7,000 chemicals with over 60 known carcinogens Cigarette smoking responsible for 1 in 5 deaths in USA (>450,000 deaths/year) 1965 to 2013 Decline in adult smoking rate, 41% to 18% Recent plateau in youth smoking Lowest consumption of cigarettes in USA in >50 years

4 Tobacco Smoke Constituents Arsenic Benzene Benzo[a]pyrene Cadmium Chromium VI Cresol Formaldehyde Muggli ME et al, AJPH 98:1-8,2008 Lead Nitrosamines Phenol Polonium 210 Polycyclic aromatic hydrocarbons Vinyl chloride

5 The Cigarette Death Epidemic in Perspective in the USA No. (000s) Annual smoking 440,000 Secondhand smoke 50,000 World War II 416,000 Vietnam War 58,000 Annual auto accidents 33,000 AIDS Annual 18,000 Annual murders 15,000 Annual heroin, morphine & cocaine deaths 14,000 CP

6 Smoking Related Mortality USA , , RR* RR* RR* Lung Cancer COPD All Cause Mortality Women Men Women Men Women Men *Relative Risk vs Never Smoke Thun, M et al NEJM 368:351, 2013

7 Cumulative deaths from tobacco (millions) Scenarios for future deaths from Source: Peto et al tobacco Year 520 Trend

8 Cumulative deaths from tobacco (millions) Scenarios: Impact of prevention Source: Peto et al 70 Year 220 Trend If smoking uptake halves by 2020

9 Cumulative deaths from tobacco (millions) Scenarios: Impact of Treatment Source: Peto et al halves by Year Trend 500 If smoking uptake halves by If adult smoking halves by 2020

10 Mortality Smokers vs Nonsmokers Benefits of Stopping US National Health Survey: 113,000 women & 88,000 men All-cause mortality 3X > for smokers vs never smokers Excess mortality due to tobacco-caused diseases Survival for age X > for never smokers vs smokers Stopping smoking years of life gained by 10( age 25-34),9( age 35-44) & 6( age 45-54) Jha, P et al NEJM 368:341, 2013

11 Medical Complications of Tobacco Cancer Cigarette smoking 30% of all cancer deaths Risk of cancer death 2 x higher in smokers and 4 x higher in heavy smokers Smoking causally linked to cancers of lung, larynx, oral cavity, esophagus, pancreas, bladder, kidney, stomach, uterine cervix and acute myeloid leukemia

12 On one point, however, there is nearly complete consensus of opinion, and that is that primary malignant neoplasms of the lungs are among the rarest forms of disease.

15 Nat King Cole

18 Medical Complications of Tobacco Lung Cancer Leading cause of cancer death in men and women in USA. About 15% of smokers will develop lung cancer ,000 new cases Smoking causes 90% of lung cancers and increases risks of all four major cell types Lung cancer causes more deaths than prostate, breast, colon and pancreas cancers combined Cigar and pipe smoking associated with increased risk 5-year survival for non-sclc is 15%. Varies with race and gender Reduced risk with stopping smoking

19 Estimated Cancer Deaths by Site

21 Pancreatic Cancer and Smoking >38,000 deaths/year in USA Male=Female 2.5 X risk among current cigarette smokers 25% of all pancreatic cancers attributable to cigarette smoking risk with pack years of smoking risk with stopping smoking Fuchs, et al. Arch Intern Med 156:2255, 1996

22 Patrick Swayze

23 Bladder Cancer and Smoking ,500 new cases and 14,600 deaths 3X more prevalent in men Lifetime cost of treatment $65,000- $121,000 Population attributable risk for cigarette smoking 46% RR of death in current smokers is 3.3 and in former smokers years after stopping smoking risk of death by 40% Jacobs BL et al CA-Cancer J Clin 60:244, 2010

24 Smoking and Renal Cell CA Current and former smokers risk for RCCa Heavy smokers have highest incidence 845 pts with RCCa: 19% current and 29% former smokers OR for advanced disease 1.5 for current and 1.6 for former smokers Heavier smokers and longer duration associated with more advanced disease Long-term smoking abstinence risk of advanced disease Tsivian, M. et al, J Clin Oncol 15:2027, 2011

Smoking and Colorectal Cancer Smoking nearly doubles the risk of adenomatous polyps (RR 1.82 CI 1.65-2.00) in ever vs.

25 Smoking and Colorectal Cancer Smoking nearly doubles the risk of adenomatous polyps (RR 1.82 CI ) in ever vs. never smokers* Meta-analysis of 26 observational studies with adjusted risk estimates for ever vs. never smokers Risk of colorectal cancer in ever smokers (RR 1.18 CI ) Mortality (RR 1.25 CI ) *Botteri E, et al. Gastroent 134:388, 2008 Botteri E, et al. JAMA 300:2765, 2008

26 Leading Causes of Death in USA Death rates from heart disease (52%), stroke (63%), accidents (41%) Death rates from all types of cancer (2.7%) 2 X in deaths from COPD in deaths from diabetes (45%) Jemal, A et al, JAMA 294:1255, 2005

27 Leading Causes of Death in USA Jemal, A et al, NL JAMA 294:1255, 2005 Jemal, A et al, JAMA 294:1255, 2005

31 Smoking and Pulmonary Infections Smoking s the risk of pulmonary infections by : 1) impeding mucociliary defenses 2) immune responsiveness. Smokers have 2-4 X risk of invasive pneumococcal infections Smokers have risk of influenza In developing countries risk of tuberculosis in smokers is a major problem Arcavi, L and Benowitz, NL Arch. Intern. Med. 164:2206, 2004

32 Smoking and Coronary Artery Disease Leading cause of death in the USA Most of decline in incidence is because of smoking rate ~100,000 CAD deaths due to smoking with >35% before age X risk of sudden death Over 1.6 million coronary procedures/year

33 Tobacco Smoke & Cardiovascular Risk Non-linear Dose Response Pechacek TF & Babb S. BMJ 328:980-3, SOURCE: Pechacek & Babb, British Medical Journal, PubMed Central PMCID: PMC404492

35 Smoking and Recurrent MI Patients (n=2619) who survived to hospital discharge after first MI 34% nonsmokers, 35% former smokers, 31% current smokers Of the 808 current smokers, 449 (57%) stopped during hospitalization or after discharge 50% risk of recurrent MI in continuing smokers Risk in smokers who stopped for 3 years = nonsmokers Rea TD, et al. Ann Intern Med 137:494, 2002

36 Sudden Cardiac Death in CAD Patients Risk of Continued Smoking 3122 patients with known CAD and moderate hypercholesterolemia 8.2 years mean follow-up 12% current smokers, 58% ex-smokers, 30% nonsmokers Current smokers risk of sudden cardiac death (RR 2.47; 95% CI ) Risk for Ex-smokers not different than nonsmokers (RR 1.06; 95% CI ) Goldenberg I, et al. Arch Intern Med 163:2301, 2003

37 Goldenberg I, et al. Arch Intern Med 163:2301, 2003

38 Abdominal Aortic Aneurysm 5% prevalence in older men who ever smoked 13,000 deaths/year US Prev Task Force Rec- abd U/S for ever smoker men age Screening mortality by 43% Screening is cost effective Kravetz JD et al Am J Med 123:899, 2010

40 Heavy Smoking in Midlife and Risk of Dementia Prospective survey of 21,123 patients Diagnosis of dementia, AD, and vascular dementia (VaD) collected from subjects (25.4%) diagnosed as having dementia 1136 with AD & 416 with VaD Heavy Smokers (> 40 CPD) risk of dementia (HR 2.14 CI ), AD (HR 2.57 CI ) and VaD (HR 2.72 CI ) Rusanen, M et al Arch Intern Med 171:333, 2011

41 Skin Effects of Smoking Free Radicals Tobacco smoke contains >10 14 free radicals/puff Free radicals are toxic and highly reactive molecules Deplete antioxidants Promote carcinogenic transformation Damage protein & lipids Alter enzyme activity, membrane receptors, and protein transporters Wolf R. Clin Dermatol 16: , 1998

42 Skin Effects of Smoking Premature Wrinkling 123 nonsmokers, 160 current smokers, and 67 past smokers ages Standardized assessment of crow s feet wrinkling Severe wrinkling current smokers > past smokers > nonsmokers severe wrinkling with pack years of smoking Koh JS. Int J Dermatol 41:21-27, 2002

43 Smoking 52 Y/O Twin Doshi, D. N. et al. Arch Dermatol 2007;143:

44 Nonsmoking 52 Y/O Twin Doshi, D. N. et al. Arch Dermatol 2007;143:

45 Smoking and Macular Degeneration Population-based longitudinal cohort (N=4926) of people age Eye examination every 5 years for 15 years Macular degeneration status determined by stereoscopic color fundus photographs Smokers had risk of age-related macular degeneration (OR 1.47; CI ; p=0.01) and progression (OR 1.43; CI p=0.02) Klein R, et al. Arch Oph. 126:115, 2008

46 Treating Tobacco Dependence in a Medical Setting Best Practices USPHS Guideline ( Behavioral, addictions, pharmacologic treatment, and relapse prevention Neurobiology of tobacco dependence Learning opportunity Telephone quitlines Public policy-taxes and smoke-free workplaces Hurt RD, et al CA 59:314,2009

47 Basic Concepts Treat tobacco dependence for the serious medical problem it is Motivational counseling plus pharmacotherapy Dose response to counseling Higher nicotine patch doses are better Combinations are better Longer treatment is better. This is not strep throat nor a UTI

48 Treating Tobacco Dependence Addictions Therapy Nicotine as drug of dependence Denial and defensiveness Rationalization, preoccupation, loss of control Acceptance of need for intervention Withdrawal symptoms 12-step approach

49 USPHS Clinical Practice Guideline Pharmacotherapy First line nicotine gum nicotine patches nicotine nasal spray nicotine inhaler nicotine lozenge bupropion varenicline Second line clonidine nortriptyline

50 Tailoring Pharmacotherapy Long Acting + Short Acting Long acting Pick 1 or 2 from here Nicotine patch Bupropion Varenicline Short acting Plus 1 or 2 from here Nicotine gum Nicotine inhaler Nicotine lozenge Nicotine nasal spray

51 Treating Tobacco Dependence Relapse Prevention Follow-up visits Support group Telephone counseling Long-term pharmacotherapy

52 Smoking Abstinence at 6 Months in Smokers Receiving Treatment for Tobacco Dependence Croghan IT et al, Addict Behav 34:61, 2009

Smoking Abstinence After Surgery Adjusted Relative Incidence of Quitting 3 2 1 0 No

survey 5,498 US smokers > 50 y/o 1 in 12 quit events associated with surgical procedures

53 Smoking Abstinence After Surgery Adjusted Relative Incidence of Quitting No Surgery Outpatient Surgery Joint Surgery Cancer Surgery Heart surgery Longitudinal survey 5,498 US smokers > 50 y/o 1 in 12 quit events associated with surgical procedures 8-10 million smokers undergo surgery annually in the US Shi and Warner, Anesthesiology 112:102, 2010

54 Smoking Impeds Wound and Bone Healing tissue perfusion tissue oxygenation Impaired neutrophil function Adversely affects fibroblast and osteoblast function

55 Smoking Abstinence Reduces Wound Infections 30% 25% 20% 15% 10% 5% Infection Dehiscence 48 smokers, 30 neversmokers Standardized wounds Smokers randomized to continued smoking or abstinence 0% Continued Smokers Abstinent Smokers Neversmokers Sorensen et al, Ann Surg 238:1, 2003

56 Postoperative Smoking Abstinence Reduces Complications % Control Intervention 105 patients post fracture surgery randomized to tobacco intervention or control (advice only) 10 0 Any Wound castrelated 50% intervention and 17% control patients abstinent from smoking at 2 weeks Complication Nåsell et al, J Bone Joint Surge 92:1335, 2010

Hospitalization Promotes Smoking Abstinence Opportunity to intervene contact with healthcare system forced smoking abstinence in smoke-free hospitals Major

57 Hospitalization Promotes Smoking Abstinence Opportunity to intervene contact with healthcare system forced smoking abstinence in smoke-free hospitals Major medical/surgical events improve smoking abstinence rates Occurs even in the absence of tobacco dependence treatment Improves the effectiveness of tobacco dependence treatment

Tobacco Dependence as a Chronic Disease. Disclosure

Tobacco Dependence as a Chronic Disease David McFadden MD, MPH Mayo Clinic Disclosure I conducted Tobacco Treatment seminars at Pfizer-sponsored conferences in Brazil, Chile and Mexico I did not receive