The Global Tobacco Epidemic

Tobacco use remains the leading preventable cause of premature death in the United States, and the World Health Organization (WHO) has called tobacco use “the single most preventable cause of death in the world today” (WHO 2008, p. 8). Predictions based on large population studies indicate that one-half of all long-term smokers, particularly those who began smoking in adolescence, will eventually die from their use of tobacco. Furthermore, one-half of the deaths caused by smoking will occur in middle age (35 through 69 years), resulting in the loss of 20 to 25 years of normal life expectancy (Peto et al. 1992, 2006; Doll et al. 1994). In the 45 years since the first U.S. Surgeon General’s report on smoking and health was published in 1964 (U.S. Department of Health, Education, and Welfare [USDHEW] 1964), smoking has been the primary underlying cause of more than 12 million U.S. deaths. Each year since 2004, more than 430,000 additional smoking-attributable deaths have been added to the national total (U.S. Department of Health and Human Services [USDHHS] 2004; Bonnie et al. 2007; Centers for Disease Control and Prevention [CDC] 2008a). It has been estimated that worldwide, tobacco use caused 100 million deaths during the twentieth century, and that tobacco use may cause as many as 1 billion deaths in the twenty-first century, unless urgent and effective action is taken (WHO 2008).

Understanding the health consequences and diseases caused by tobacco use has provided the scientific foundation for public health actions aimed at tobacco use prevention, cessation, and protection from secondhand smoke exposure. Since the first Surgeon General’s report, this series has considered research findings on mechanisms of disease production in assessing the biologic plausibility of associations observed in epidemiologic studies. The important contribution of evidence on biologic plausibility and coherence in evaluation of causality has been reviewed in recent reports (USDHHS 2004, 2006). For example, evidence regarding the biologic plausibility of the observed relationship between exposure to secondhand smoke and coronary heart disease (CHD) has been very important in the evaluation of causality (USDHHS 2001, 2006). In initial studies (e.g., Hirayama 1984; Garland et al. 1985), the estimated magnitude of the association between exposure to secondhand smoke and CHD seemed large compared with the association between active smoking and CHD. However, further findings on mechanisms linking tobacco smoke exposure to CHD risk—in particular, the impact of tobacco smoke exposure on platelet aggregation and acute endothelial dysfunction—provided plausible and quantitatively consistent mechanisms for the observed nonlinear relationship with exposure levels to tobacco smoke (Glantz and Parmley 1991, 1995; Law et al. 1997). More recently, the potential effect of active smoking and exposure to secondhand smoke on breast cancer risk is an area for which data on biologic plausibility and mechanisms are critically needed in the evaluation of potential causality (USDHHS 2006; International Agency for Research on Cancer [IARC] 2004; Miller et al. 2007; Phillips and Garte 2008).

Despite the wealth of scientific evidence on the adverse health effects of exposure to tobacco smoke, many gaps remain in our understanding of the molecular and cellular mechanisms of tobacco-induced diseases. It has been suggested that “given the obvious dangers of tobacco and the associated imperative to eliminate it, research undertaken purely to unravel mechanisms of tobacco-related cancer is difficult to justify” (Carlsten and Burke 2006, p. 2481). However, as discussed in Chapter 1, research to further understand the biologic mechanisms by which exposure to tobacco smoke causes disease has several important applications beyond assisting in the determination of causal relationships, including

• developing biomarkers of injury to identify smokers at early stages of disease development;
• providing a basis for preventive therapies that block or reverse the underlying process of injury;
• identifying the contribution of exposure to tobacco smoke to causation of diseases with multiple etiologic factors; and
• assessing tobacco products for their potential to cause injury through a particular mechanism.

Expanding our knowledge of several common molecular and cellular mechanisms underlying seemingly diverse smoking-induced diseases—such as dysregulation of inflammatory and immune processes (including oxidative stress, altered antibody production, endothelial cell dysfunction, suppression of T cells) and the dysregulation of inflammatory cells—could have important implications in the potential development of novel therapeutic targets for various environmentally induced diseases (Wang and Scott 2005). For example, with growing understanding of genetic and epigenetic mechanisms, opportunities are expanding to address the broader applications of disease mechanisms related to exposure to tobacco smoke (Esteller 2008; Herbst et al. 2008; Caporaso et al. 2009; Breton et al. 2009; National Cancer Institute [NCI] 2009). As noted in the 2007–2008 Annual Report of the President’s Cancer Panel, “…even if all current smokers cease using tobacco today and no new smokers take up the habit, the latency of tobacco-caused cancer and other diseases dictates that cancer and other morbidity and mortality from tobacco will still be affecting our population for at least another two decades” (Reuben 2008, p. 57). A list of research priorities identified in this report is provided in Appendix 9.1.

A key feature of tobacco use is the development of nicotine addiction, which often leads to chronic, daily exposure to tobacco that typically persists for many years. As reviewed in Chapter 4 of this report, addiction, or more technically the diseases of dependence and withdrawal, make it essential to ensure that effective behavioral and pharmacological cessation treatments are widely available and accessible to diverse populations of smokers (Zaza et al. 2005; National Institutes of Health [NIH] State-of-the-Science Panel 2006). The various treatments for tobacco use have targeted different aspects of nicotine addiction, such as reinforcement, withdrawal, and cue-associated learning. Pharmacologic treatments have included nicotinic acetylcholine receptor ligands (nicotine replacement, and varenicline, a partial α4β2 agonist) or have involved alterations in signal transduction to stimulate the release of the same neurochemicals that are released by nicotine (e.g., bupropion and nortriptyline). Ideally, those who smoke would find it as easy to access cessation services as they do commercial tobacco products (Fiore et al. 2008).

Effective public health and clinical approaches to increase smoking cessation rates have been developed (USDHHS 2000; Zaza et al. 2005; Bonnie et al. 2007; Reuben 2007; Fiore et al. 2008). These public health strategies and the clinical treatments need to be more fully implemented.

Significant progress has been achieved in the United States during the last 50 years in reducing smoking initiation and increasing smoking cessation (Bonnie et al. 2007; Reuben 2007; Cokkinides et al. 2009). After 30 years of declining rates of smoking, particularly among men, the total U.S. cancer deaths began to decline in the late 1990s, driven largely by a reduction in male lung cancer deaths (Cokkinides et al. 2009). Moreover, the declines in lung cancer death rates among men and women in California declined more rapidly than in the rest of the country after the implementation of a comprehensive and sustained statewide tobacco control program (Barnoya and Glantz 2004; Jemal et al. 2008).

Today, an estimated one-half of all Americans who have ever smoked have quit (CDC 2008a, 2009a), and the benefits of cessation have been documented for smokers of all ages (USDHHS 1990; IARC 2007a). However, as a group, smokers who successfully quit early in life can avoid a large proportion of the excess mortality caused by smoking (USDHHS 1990; IARC 2007a). Data from the British Doctors’ Study have been used to demonstrate the lifetime risks of smoking and the amount of that risk that can be avoided by sustained cessation at various ages (Doll et al. 2004). Figure 9.1 contrasts the cumulative survival curves for all-cause mortality of continuing smokers (blue lines), with never smokers (red lines), and with smokers who quit by various ages (e.g., effect from sustained quitting at ages 35, 40, 50, and 60 years). The survival curves demonstrate that even at older ages, a substantial and important fraction of the excess all-cause mortality due to smoking can be averted by sustained quitting. Nonetheless, smokers who quit after the age of 44 years continue to have excess risk for tobacco-related diseases.

Figure 9.1

Effects on survival of stopping smoking cigarettes at ages 25–34 years (effect from age 35), ages 35–44 years (effect from age 40), ages 45–54 years (effect from age 50), and ages 55–64 years (effect from age 60). Source: (more...)

As noted in Chapter 6, cigarette smoking is a major cause of cardiovascular disease (CVD) and has multiplicative interactions with the other major risk factors for CHD. Importantly, although there is a strong dose-response relationship between the number of cigarettes smoked per day and cardiovascular risk, the relationship is not linear, with those who smoke few cigarettes per day or who do not smoke every day remaining at significantly elevated risk for CVD. It has been estimated that one-fifth of U.S. smokers are intermittent or occasional smokers (CDC 2008a), and this pattern of use is more common among some racial and ethnic groups, including Blacks and Hispanics, and smokers living below the poverty level (Fagan and Rigotti 2009). This emphasizes the importance of increasing our understanding of the process of smoking and quitting and of providing appropriate cessation services to this group of smokers.

The time course of reduction of risk after quitting smoking varies substantially across disease outcomes, with the risk of CHD declining more rapidly than the risk of tobacco-related cancers, particularly among those with a longer duration of smoking before sustained quitting (USDHHS 1990; IARC 2007a). The continued excess risk of lung cancer among former smokers has focused attention on the need to better identify those at greatest risk and to develop effective methods of early detection (Black and Baron 2007; Dubey and Powell 2008; Field and Duffy 2008). More than one-half of all cases of lung cancer are diagnosed at an advanced stage, and the five-year survival rate for lung cancer remains at about 15 percent (Jemal et al. 2008). At present, the efficacy of screening for lung cancer with low-dose computed tomography or other methodologies remains controversial (Black and Baron 2007). A better understanding of the molecular and cellular pathways involved in respiratory carcinogenesis could increase the feasibility of chemoprevention trials or of more cost-effective application of lung cancer screening (Alberg et al. 2005; Dubey and Powell 2008; Field 2008).

Recent advances in the understanding of the molecular origins of lung cancer have focused attention on the possibility that molecular profiling of genes and proteins could lead to the development of biomarkers for defining cancer risk, prognosis, and potentially improved treatment for some of the even more difficult to manage types of lung cancer (Herbst et al. 2008). The evidence reviewed in Chapter 5 on the major established pathways of cancer causation by cigarette smoking identifies important steps along these mechanistic pathways that could be used in potential biomarkers for defining cancer risk, prognosis, and potentially improved treatment. Figure 9.2 graphically presents how molecular profiling and assessments of genes and proteins could influence decisions regarding lung cancer treatment options for individual patients.

Figure 9.2

Molecular-profiling approaches to the development of personalized therapy. Source:Herbst et al. 2008. Reprinted with permission from Massachusetts Medical Society, © 2008. Note: Host profiling involves innate characteristics of the cancer patient. (more...)

Chronic obstructive pulmonary disease (COPD) remains a leading cause of death in the United States, and in 2005, approximately 1 in 20 deaths in the United States had COPD as the underlying cause, with an estimated 75 percent of these COPD deaths attributable to smoking (CDC 2008b). While the U.S. trend in COPD deaths has remained fairly stable from 2000 to 2005 (CDC 2008b), the global burden of COPD is increasing (Mannino and Buist 2007; Barnes 2007). Importantly, the evidence indicates that in the United States, COPD could be almost completely prevented by the elimination of smoking (USDHHS 2004). Although the risks for COPD morbidity and mortality decline with smoking cessation, they may not return to the levels of nonsmokers (USDHHS 2004). The U.S. Lung Health Study documented the benefits of substantially reduced mortality among individuals with asymptomatic airway obstruction who quit smoking (Anthonisen et al. 2005). The U.S. Lung Health Study also documented the benefits of providing an intensive 10-week smoking cessation program to this at-risk population; nearly 22 percent of intervention participants succeeded in quitting smoking compared with only 5.4 percent of participants who received usual care (Anthonisen et al. 2005). These results emphasize that rates of smoking cessation among patients most at risk of COPD could be increased up to fourfold if current available smoking cessation treatment options were delivered more routinely.

Numerous studies have shown that COPD is associated with lung cancer risk; this association may be attributed to shared exposure to cigarette smoke, to shared genetic susceptibility, and/or to facilitation of tumor initiation and promotion by inflammation (Dubey and Powell 2008). The growing global burden of COPD emphasizes the need for research to develop biomarkers of injury to identify smokers at early stages of disease development and to provide a basis for preventive therapies that block or reverse the underlying process of injury, particularly among former smokers. Research in this area may be guided by the evidence reviewed in Chapter 7, which identifies the two major mechanisms underlying the causation of COPD by cigarette smoking, oxidative stress (injury) and protease-antiprotease imbalance, and the strong association between COPD occurrence and a specific genetic disorder: AAT deficiency.

As noted in Chapter 8, health professionals have long known that exposure to tobacco smoke during pregnancy poses serious risks to fetal development. Despite this, approximately 19 percent of women of reproductive age smoke cigarettes, and based on birth certificate data, more than 1 in 10 (11.4 percent) women reported smoking during pregnancy (CDC 2004, 2008a). However, birth certificate data often underreport smoking during pregnancy. In survey data from 2002 to 2005, 17.3 percent of pregnant women reported smoking cigarettes in the month preceding the survey (NSDUH Report 2007). In addition, many pregnant women who do not smoke are exposed to secondhand smoke in workplaces, public places, and in their own homes. Recommendations have been made regarding the types of smoking cessation services that should be provided to all pregnant smokers (Fiore et al. 2008). Despite the documented costs of poor infant outcomes caused by smoking during pregnancy, and the higher prevalence of prenatal tobacco use found among lower income women, in 2006 only 27 states covered tobacco cessation counseling services for pregnant women in their Medicaid populations (CDC 2008e).

Reducing the Risks from Smoking

The benefits of quitting have been shown for smokers of all ages (USDHHS 1990, 2004; IARC 2007a). Smokers who quit completely and permanently early in life have a risk of premature death very similar to lifetime nonsmokers (Figure 9.1) (USDHHS 1990, 2004; IARC 2007a). However, for lung cancer, there is a persistent elevated risk in former smokers compared with lifetime nonsmokers of the same age even after a long abstinence (IARC 2007a). Evidence indicates that lung cancer risk increases far more strongly with each additional year of smoking than it increases for a higher average number of cigarettes smoked per day (Flanders et al. 2003; IARC 2007a). Although sustained smoking cessation at any age produces substantial reductions in risk, significant health benefits (other than for the fetus during pregnancy) from reducing the amount smoked or from short-term cessation have not been demonstrated (Benhamou et al. 1989; Godtfredsen et al. 2002; Anthonisen et al. 2005; Tverdal and Bjartveit 2006; IARC 2007a; Bjartveit and Tverdal 2009). The evidence presented in this report on the biologic mechanisms by which exposure to tobacco smoke causes cancers, cardiovascular and chronic obstructive pulmonary diseases, and reproductive and developmental effects document the importance of smokers quitting completely early in life and avoiding even occasional or infrequent smoking.

As reviewed in Chapter 2, in recent years a range of new products have been introduced and marketed to smokers as an alternative to conventional cigarettes, sometimes accompanied by messages, explicit or implied, that they offer reduced exposure to toxic substances or risk of disease. Evidence reviewed in this and previous reports indicates that five decades of evolving cigarette design have not reduced overall disease risk among smokers, and new designs can be used to undermine prevention and cessation efforts. It is now recognized that substantial risks may be associated with new tobacco products:

1. Smokers who might have otherwise stopped smoking may continue to smoke because of perceived reduction in risk with use of new products.
2. Former smokers may resume smoking because of perceived reduction in risk with use of new products.
3. Nonsmokers, particularly youth, may start to use new products because of their perceived safety.

The evidence reviewed in this report highlights many of the scientific challenges that will be faced in evaluating new cigarette products presented as alternatives to conventional cigarettes, because of the diversity of such products, the multitude of smoking-related diseases, the impact of these products on nonusers, and the dearth of empirical data on their effects. The Institute of Medicine (IOM) Committee to Assess the Science Base for Tobacco Harm Reduction (Stratton et al. 2001) and more recent reviews (Gray et al. 2005; Royal College of Physicians of London 2007; European Commission 2008) have discussed the potential role in tobacco control of a wider range of alternatives to the current cigarette. Several questions need to be carefully considered when proposing novel tobacco products as strategies to reducing smoking-attributable mortality: Do these products decrease individual risk? Do they increase initiation of tobacco use or promote relapse? Do they delay cessation? Do they lead to dual product use? How does their use compare to cessation? As discussed in Chapter 2, in the absence of a sound science base to support such alternative strategies, the primary public health approaches remain prevention and cessation of all forms of tobacco products.

Chapter 4 in this report documents the importance of nicotine as the drug causing the addiction that is the fundamental reason that individuals persist in using tobacco products. However, other constituents in tobacco and tobacco smoke may also be reinforcing or may facilitate the reinforcing effects of nicotine. The factors contributing to the high addiction potential of tobacco products are multiple and complex. Understanding these relationships is critical in developing better treatments for cessation and for determining appropriate strategies to reduce use of tobacco products (Benowitz and Henning-field 1994; Henningfield et al. 1998, 2004; Gray et al. 2005; Benowitz et al. 2006; Royal College of Physicians of London 2007; Benowitz 2008; Zeller et al. 2009).

The evidence on the CVD risks of low levels of tobacco smoke exposure in Chapter 6 of this report clearly demonstrate that the dose response for CVD is not linear, with risk rising rapidly at low doses and then plateauing at relatively low levels of exposure. The data on CVD also demonstrates the potential for dual tobacco product use resulting in a greater risk of disease than either product alone (Teo et al. 2006). Additional research to identify those toxicants in tobacco products that are most responsible for acute cardiac risks is critically needed (Boffetta and Straif 2009).

As reviewed in this and prior reports, the risk of lung and other cancers, as well as COPD, increases dramatically with greater duration of smoking. In addition, dual use of cigarettes along with other tobacco products could not only result in delays in sustained smoking cessation but may also increase the risk of disease more than cigarette smoking alone. If the use of alternative tobacco products hinders tobacco prevention and cessation efforts and results in longer durations of smoking among some smokers, the population burden of tobacco-related morbidity and mortality would be higher than for an approach focused on helping these smokers quit completely. In addition, tobacco products used in places where smoking is not allowed may defeat public health efforts to reduce smoking rates. Thus, there are continuing concerns about the population health impact of tobacco product modification or alternatives to cigarettes (Stratton et al. 2001; European Commission 2008).

Ending the Tobacco Epidemic

Since the health risks of tobacco use were first identified, the public health response has focused on preventing initiation of tobacco use, encouraging cessation among existing users, and more recently, protecting non-smokers from exposure to secondhand smoke. Although the primary focus of previous Surgeon General’s reports has been a review of scientific evidence related to health effects of tobacco use, numerous reports have provided specific recommendations to reduce the use of tobacco and exposure to secondhand smoke (Lynch and Bonnie 1994; USDHHS 2000; Zaza et al. 2005; NIH State-of-the-Science Panel 2006; Bonnie et al. 2007; Reuben 2007; Fiore et al. 2008). Effective public health and clinical approaches to increase smoking cessation rates have been developed and need to be more fully implemented (USDHHS 2000; Zaza et al. 2005; Bonnie et al. 2007; Reuben 2007; Fiore et al. 2008).

The IOM report, Ending the Tobacco Problem: A Blueprint for the Nation, concluded that the ultimate goal is “to reduce smoking so substantially that it is no longer a significant public health problem” (Bonnie et al. 2007, p. 1). The report proposed a two-pronged strategy to accomplish this goal: first, to strengthen and fully implement traditional tobacco control measures known to be effective, and second, to change the regulatory landscape to permit policy innovations such as strong federal regulation of tobacco products and their marketing and distribution (Bonnie et al. 2007). A complete list of the 42 recommendations made by the IOM report is provided in Appendix 9.2. In addition, the President’s Cancer Panel has highlighted the critical importance of reducing tobacco use stating that “ridding the nation of tobacco is the single most important action needed to dramatically reduce cancer mortality and morbidity” (Reuben 2008, p. iii) and that “if the population ceased smoking, this single behavior change would be tantamount to a vaccine against one-third of cancer deaths” (Reuben 2007, p. vi).

In its 2006–2007 Annual Report, the President’s Cancer Panel provided a detailed review of the status of tobacco control efforts in this country to address tobacco use prevention and treatment (Chapter 4) and environmental tobacco smoke exposure (Chapter 5). In this review, the President’s Cancer Panel outlined the important roles in reducing tobacco-caused death and disease that could be undertaken by federal, state, and local governments; nongovernmental organizations and other partners; the educational system; employers, insurance, and the health care system; and individuals and families (Reuben 2007). Many of these actions are very consistent with the 42 recommendations made by IOM (Appendix 9.2) and emphasize the evidence-based methods identified by the 2006 NIH State-of-the-Science consensus conference (NIH State-of-the-Science Panel 2006). The 15 recommendations from the President’s Cancer Panel are provided in Appendix 9.3.

Since the release of the recommendations from IOM (Bonnie et al. 2007) and the President’s Cancer Panel review of the status of tobacco control in this country (Reuben 2007), additional actions have been taken at the federal, state, and local levels. Below is a summary of the status of tobacco control efforts in this country within the WHO MPOWER framework (WHO 2008):

• Monitor tobacco use and prevention policies.
• Protect people from tobacco smoke.
• Offer help to quit tobacco use.
• Warn about the dangers of tobacco use.
• Enforce comprehensive restrictions on tobacco advertising, promotion, and sponsorship.
• Raise taxes on tobacco.

MONITOR. The monitoring of the population pattern of tobacco use and the status of prevention and control policies and programs has been defined as essential in national efforts to counter the tobacco epidemic (WHO 2008; Giovino et al. 2009). Current efforts to monitor the tobacco use epidemic and identify additional steps to optimize measurement of tobacco use and factors influencing use in the United States have been reviewed (Cruz 2009; Delnevo and Bauer 2009; Farrelly 2009; Giovino et al. 2009; Stellman and Djordjevic 2009). These papers provide detailed analysis of national tobacco monitoring, research, and evaluation under the classic Agent, Host, Vector, and Environment framework. These reviews indicate that many of the most important basic elements of a national monitoring system are in place but that several key elements are needed to improve the system.

PROTECT. This report provides additional scientific evidence that there is no risk-free level of exposure to tobacco smoke. Although progress has been made to increase protection of nonsmokers in the United States from secondhand smoke exposure since the release of the 2006 Surgeon General’s report on the health consequences of involuntary exposure to tobacco smoke (CDC 2008f), biomonitoring of exposure indicates that almost one-half of nonsmokers, and more than 60 percent of young children, continue to be exposed (CDC 2008c). Wide geographic, occupational, and demographic disparities remain (CDC 2008c,f). It has been estimated that only about one in three residents of the United States live under state or local laws that make worksites, restaurants, and bars completely smoke-free (CDC 2008f).

OFFER. The U.S. Tobacco Use and Dependence Guideline Panel has identified the most effective interventions to assist tobacco users to successfully quit (Fiore et al. 2008). Moreover, a systematic review and analysis of recommended clinical preventive services has identified clinical smoking cessation services as one of the most successful and cost-effective recommendations (Maciosek et al. 2006). However, data indicate that less than 30 percent of smokers are offered assistance in quitting annually (Partnership for Prevention 2008). Both IOM and the President’s Cancer Panel address this issue in their recommendations (Appendices 9.2 and 9.3).

WARN. WHO recommends that national efforts to warn about the dangers of tobacco should create high levels of awareness of the health risks of tobacco use across age groups, genders, and places of residence so all people understand that the result of tobacco use is often suffering, disfigurement, and early death (WHO 2008). The President’s Cancer Panel noted that the warning labels on tobacco products in many other countries are larger and more graphic than those on U.S. cigarette packages (see figure 17, page 74, Reuben 2007). The Federal Cigarette Labeling and Advertising Act of 1965 (the Cigarette Act) and the Comprehensive Smokeless Tobacco Health Education Act of 1986 (the Smokeless Act), as amended by the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) (2009), require new, stronger warning statements on cigarette and smokeless tobacco packages and advertising and require color graphics depicting the negative health consequences of smoking on cigarette packages and advertising. The Tobacco Control Act further amends the Cigarette Act and the Smokeless Act to give the U.S. Food and Drug Administration the authority to revise the warning label statements and the color graphics for both cigarettes and smokeless tobacco through rulemaking. In addition to potential changes in package warning labels, evidence supports the effectiveness of health communication and countermarketing strategies employing a wide range of efforts, including paid television, radio, billboard, print, and Web-based advertising at the national, state, and local levels; media advocacy through public relations efforts; and efforts to reduce or replace tobacco industry sponsorship and promotions (CDC 2007; NCI 2008). Recommendations 15 and 16 from IOM address the need for a national, youth-oriented, countermarketing campaign as well as increased mass media and other general and targeted public education programs to promote effective cessation programs and activities (Appendix 9.2) (Bonnie et al. 2007).

ENFORCE. Both the 2007 IOM and 2006–2007 President’s Cancer Panel reports have identified the sophisticated strategies used by the tobacco industry to counter policies and programs to reduce tobacco consumption (Bonnie et al. 2007; Reuben 2007). Cigarettes remain one of the most heavily marketed products in the United States, with more than $250 billion (in 2006 dollars) expended between 1940 and 2005 on cigarette advertising and promotion (NCI 2008). The influence of these tobacco industry efforts in shaping tobacco-related knowledge, opinions, attitudes, and behavior was reviewed in detail, and it was concluded that the total weight of evidence demonstrated a causal relationship between tobacco advertising and promotion and increased tobacco use (NCI 2008). The Tobacco Control Act will enable new actions to be taken at the federal, state, and local levels to counteract the influence of tobacco advertising, promotions, and sponsorship.

RAISE. With the increase in the federal excise tax on cigarettes from $0.24 to $1.01 on April 1, 2009, the combined federal and average state cigarette excise tax increased to $2.21 per pack (CDC 2009b). Evidence-based reviews have concluded that increases in the price of cigarettes through excise taxes or other strategies are an effective policy intervention to prevent smoking initiation among adolescents and young adults, reduce cigarette consumption, and increase the number of smokers who quit (USDHHS 2000; Zaza et al. 2005; NIH State-of-the-Science 2006; Bonnie et al. 2007; CDC 2007; Reuben 2007). Additionally, the WHO MPOWER recommendations emphasize the importance of ensuring that the tax rates on tobacco products are adjusted periodically to keep pace with inflation and rise faster than consumer purchasing power. WHO also stresses that implementation of effective strategies to limit smuggling and the availability of untaxed tobacco products is essential to maximizing the effectiveness of higher taxes in reducing tobacco use (WHO 2008).

Concluding Remarks

In 1964, the Surgeon General’s Advisory Committee concluded: “Cigarette smoking is a health hazard of sufficient importance in the United States to warrant appropriate remedial action” (USDHEW 1964, p. 33). Evidence-based recommendations have helped to define appropriate remedial actions, including those from the 2000 Surgeon General’s report on reducing tobacco use (USDHHS 2000), NIH (NIH State-of-the-Science Panel 2006), the Task Force on Community Preventive Services (Zaza et al. 2005), IOM reports (Stratton et al. 2001; Bonnie et al. 2007), and President’s Cancer Panel reports (Reuben 2007, 2008). The specific scientific conclusions from this report may provide further guidance for developing additional remedial actions.

Despite significant progress, tobacco use remains the single most preventable cause of death and disease in the United States. It is worth noting that lung cancer was once a very rare disease. Primary Malignant Growths of the Lungs and Bronchi, published in 1912, reviewed the worldwide scientific literature and was able to identify only 374 verified cases of lung cancer (Adler 1912; Spiro and Silvestri 2005). In stark contrast, lung cancer is today the nation’s leading cause of cancer death among both men and women, killing an estimated 160,000 people in the United States, and an estimated 1.34 million people worldwide each year (Jemal et al. 2008; WHO 2008). An estimated 90 percent of U.S. lung cancer deaths in men and 80 percent of U.S. lung cancer deaths in women are caused by smoking and exposure to secondhand smoke (CDC 2009c). In addition, more than 100,000 deaths from pulmonary diseases and more than 140,000 deaths from heart disease and stroke in the United States are caused each year by active smoking and exposure to secondhand smoke (CDC 2008d).

Since the publication of the 1964 Surgeon General’s report on smoking and health, this series of reports has provided an incontrovertible body of research evidence documenting the burden of sickness and death caused by tobacco use. Faced with these facts, it is appropriate to restate the challenge issued by a former Director-General of WHO, Dr. Gro Harlem Brundtland, at the start of the international negotiations that led to the landmark Framework Convention on Tobacco Control:

If we do not act decisively today, a hundred years from now our grandchildren and their children will look back and seriously question how people claiming to be committed to public health and social justice allowed the tobacco epidemic to unfold unchecked (Brundtland 1999).

Appendix 9.1. Recommendations for Future Research

The evidence reviewed within this report identified important gaps in our scientific knowledge that merit greater attention in future research. Below is a listing of areas of research that can substantially contribute to a better understanding of how tobacco use causes disease.

Nicotine Addiction

With the emerging science base for understanding the physiological, behavioral, and cognitive bases for addiction and for identifying the genetics and other host factors that may moderate the effects of nicotine, new types of interventions are being developed that are expanding the treatment armamentarium, thus providing more effective interventions for those who continue to have difficulty in quitting smoking. For example, pharmacologic treatments are being marketed that target specific nicotinic receptors responsible for the reinforcing effects of nicotine, such as varenicline (Gonzales et al. 2006; Jorenby et al. 2006; Nides et al. 2006; Oncken et al. 2006). Nicotine immunotherapies (vaccines) under development also offer potential treatments for nicotine addiction. Nicotine immunotherapies stimulate the immune system to develop antibodies to nicotine that reduce the level and speed of nicotine entering the brain, potentially changing the pharmacokinetics of nicotine and thereby reducing the reinforcing effects of nicotine (Pentel 2004; Hatsukami et al. 2005). Another area of major development in the treatment of smokers, as with the treatment of other diseases, involves tailoring treatments to the phenotype and genotype of the individuals to select the most efficacious treatments (Lerman and Niaura 2002). All of these treatment developments have been aided by greatly expanded understanding of the mechanisms of dependence and withdrawal during the past two decades.

Valid indicators and biomarkers of addiction are needed to assess future “less addictive” or “less toxic” tobacco products and treatments and to provide a better understanding of the addictive process. Many subjective and behavioral measures and some cognitive measures have been developed and used to test addiction to tobacco. However, fundamental gaps in knowledge exist, and other areas need to be more vigorously pursued.

Biomarkers for Addiction Potential

Table 9.1 summarizes the methods used for animal and human testing to assess the addiction potential of a nicotine product. Most of these methods have been referred to in Chapter 4 of this report. Although there are many subjective and behavioral methods, researchers have devoted little attention to cognitive and neurophysiological measures of addiction through the use of functional magnetic resonance imaging or positron emission tomography. Using more precise tools to assess and better understand learning processes, decision making, and brain changes associated with addiction will lead to the development of measurements in these areas. The limitations and questions associated with the measures listed in Table 9.1 are similar to those concerning the diagnosis of tobacco addiction or, for that matter, biomarkers for disease in general. That is, other than relative terms (e.g., product A has a greater abuse potential than does product B) or the occurrence of addiction, the threshold or criterion that determines the extent of abuse potential is unknown.

Table 9.1

Behavioral indicators of addiction potential of a drug or addiction to a drug.

Future Directions in Understanding Addiction

Several areas of research that can substantially contribute to a better understanding of nicotine addiction include—but are not limited to—the following:

• Improve understanding of the criteria for and measures of nicotine addiction or dependence and how they might differ across various populations, including youth and ethnic minorities.
• Adapt commonly used measures of assessing addiction to cigarettes to other tobacco products as demonstrated by preliminary efforts to develop and validate scales for smokeless tobacco dependence and, most recently, to waterpipe smoking.
• Develop a better understanding of the contribution of the design features of tobacco products and of constituents other than nicotine that play an important role in all aspects of nicotine addiction, including initiation, maintenance, withdrawal, and relapse.
• Use current knowledge of the neurosystems associated with the reinforcement, withdrawal, and conditioning effects of nicotine addiction to develop a strategic road map for future discoveries in this area.
• Move toward a better understanding of the role and neurobiology of associative learning and cognitive processing in the development of and recovery from nicotine addiction.
• Foster an interdisciplinary effort to develop links among genotypes, endophenotypes, phenotypes, and the neurobiologic effects of nicotine.
• Explore the differences between adolescents and adults in their sensitivity to nicotine and to other factors associated with tobacco use, and find out which factors contribute to these differences (e.g., stage of neurodevelopment, sex hormones).
• Increase understanding of the relationship between comorbid disorders and nicotine addiction, including the common neural pathways and psychosocial vulnerabilities, and the mechanisms associated with an increased risk of nicotine addiction.

Appendix 9.2. Ending the Tobacco Problem: A Blueprint for the Nation

Contributors

Appendix 9.3. Promoting Healthy Lifestyles: Policy, Program, and Personal Recommendations for Reducing Cancer Risk

Authors

2006–2007 Annual Report

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