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Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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4

The Effects of Tobacco Use on Health

The scope of the burden of disease and death that cigarette smoking imposes on the public’s health is extensive. Cigarette smoking is the major focus of this chapter because it is the central public health problem, but the topics of secondhand smoke exposure, smoking of other combustible tobacco products, smokeless tobacco, and electronic nicotine delivery systems (ENDS) are also considered. The magnitude of the public health threat posed by cigarette smoking stems from two factors: (1) the prevalence of cigarette smoking is so high, and (2) smoking causes so many deleterious health effects. A policy change that reduces the prevalence of cigarette smoking will result in a commensurate reduction in the population burden of disease and death caused by cigarette smoking. The associations between cigarette smoking and the adverse health effects caused by smoking are dose-dependent (HHS, 2014). Thus, a public health benefit would be realized if a policy change led to reduced exposure to cigarette smoke via means other than reducing the prevalence of smoking. For example, additional reduction in the population burden of smoking-caused disease and death will be generated if the policy also results in delayed initiation of cigarette smoking. The population health benefit from delayed initiation, although potentially large, will be less than the benefit from a commensurate reduction in smoking prevalence because delayed initiation is associated with reduced exposure to cigarette smoking rather than with the complete prevention of the exposure. A decrease in the prevalence of cigarette smoking will have additional downstream benefits by reducing the potential for nonsmokers to be exposed to secondhand tobacco smoke.

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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TIME HORIZON FOR THE HEALTH EFFECTS OF CIGARETTE SMOKING

Cigarette smoking causes chronic diseases that appear at older ages, such as lung cancer, as well as adverse health effects that occur in the short run. The immediate and short-term adverse health effects of cigarette smoking are less likely to be directly fatal than the long-term health effects. Nevertheless, they are important public health indicators because they lead to suboptimal health status throughout the life course in smokers and because many of the short-term physiologic effects mechanistically contribute to the etiology of smoking-caused diseases that usually do not become clinically apparent until later adulthood.

The short-term adverse health effects caused by cigarette smoking can be observed in smokers immediately or soon after they begin smoking. The health effects of cigarette smoking thus begin at or near the age of initiation of cigarette smoking, which is usually in adolescence. To highlight the immediacy of the adverse impact of smoking on health, this report uses a life-course perspective by considering health effects of smoking according to the various stages of life, which include childhood, adolescence, and young adulthood as well as middle and late adulthood, when most of the chronic disease burden imposed by smoking occurs. A particularly vulnerable time during the life course is pregnancy (for both mother and fetus) and the months following birth (for the infant); for this reason, this stage of life is considered separately. In this report, the term “immediate health effects” refers to effects that occur within days of cigarette smoking, while “long-term health effects” refers to the clinical morbidity and mortality that occur primarily in middle and late adulthood, and the term “intermediate health effects” is used to refer broadly to the health outcomes that occur between the immediate and long-term health effects.

SPECTRUM OF HEALTH EFFECTS

Cigarette smoke contains more than 7,000 chemicals (HHS, 2010). Inhaling cigarette smoke exposes the cigarette smoker to these numerous toxins, which include the various tobacco constituents and the products of pyrolysis. As summarized below, exposure to this complex chemical mixture causes immediate adverse physiologic effects shortly after the exposure occurs (HHS, 2010).

The ultimate harm caused by exposure to the toxic agents in cigarette smoke is determined in large part by the extent of the exposure, and most adult cigarette smokers tend to smoke many cigarettes per day for decades (HHS, 2014). This repeated inhalation of the complex mixture of cigarette smoke toxicants at high daily doses, often sustained over the course of

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

TABLE 4-1 Immediate Adverse Health Outcomes Causally Associated with Cigarette Smoking Based on Surgeon General’s Reports

Stage of Life

Health Outcome Childhood/ Adolescence Young Adulthood Middle Adulthood Older Adulthood
Oxidative Stress
Depletion of Antioxidant Micronutrients
Increased Inflammation
Compromised Immune Status
Altered Lipid Metabolism
Lower Self-Rated Health Status
Respiratory Symptoms (coughing, phlegm, wheezing, dyspnea)
Nicotine Addiction

NOTE: The health outcomes are organized in Tables 4-1 through 4-3 according to whether they are immediate, intermediate, or long term and by the stages of life affected.

many years, causes a broad spectrum of short-term and long-term health effects that affect most major organ systems (see Tables 4-1 through 4-3). In the short run, cigarette smoking causes the smoker to have overall diminished health status as measured by a diverse array of indices, including biomarkers of physiologic disadvantage, lower self-reported health, susceptibility to acute illnesses and respiratory symptoms, and absence from school and work. Among the long-term health effects are smoking-caused diseases that are the major causes of death in middle- and upper-income nations: coronary heart disease, cancer, and chronic obstructive pulmonary disease, or COPD (HHS, 2014).

The net result of the broad spectrum of short-term and long-term deleterious health effects caused by cigarette smoking and the substantial prevalence of smoking is that cigarette smoking is the single most important cause of preventable disease and premature mortality in the United States

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

TABLE 4-2 Intermediate Adverse Health Outcomes Causally Associated with Cigarette Smoking Based on Surgeon General’s Reports

Stage of Life

Health Outcome Childhood/ Adolescence Young Adulthood Middle Adulthood Older Adulthood
Increased Absence from Schoola/Work
Increased Use of Medical Services
Subclinical Atherosclerosis
Impaired Lung Development/ Function

Impaired lung growth

Accelerated lung function decline

Increased Risk of Lung Infections (tuberculosis, pneumonia)
Diabetes
Periodontitis
Exacerbation of Asthma
Subclinical Organ Injury
Adverse Surgical Outcomes

aHealth outcome not included in the 2014 Surgeon General’s report.

and in many other high-income nations (Thun et al., 2012). For example, in the United States cigarette smoking is estimated to account for at least 480,000 deaths per year (HHS, 2014). The magnitude of this burden is a direct function of two key facts: (1) cigarette smoking causes an incredibly broad spectrum of short-term and long-term deleterious health effects, and (2) a large proportion of the population is exposed (i.e., the prevalence of smoking is very high).

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

TABLE 4-3 Long-Term Adverse Health Outcomes Causally Associated with Cigarette Smoking Based on Surgeon General’s Reports

Stage of Life

Health Outcome Childhood/ Adolescence Young Adulthood Middle Adulthood Older Adulthood
Cancer (colorectal, liver, lung, bladder, cervical, esophageal, kidney, laryngeal, pancreatic, gastric, oral, and pharynx; acute myeloid leukemia)
Precancerous Lesions (colorectal adenomatous polyps)
Cardiovascular Disease (coronary heart disease, stroke, abdominal aortic aneurysm)
Respiratory Diseases (COPD)
Eye Disease (age-related macular degeneration, nuclear cataracts)
Rheumatoid Arthritis
Reduced Effectiveness of Tumor Necrosis Factor-Alpha Inhibitors
Bone Health (hip fractures, low bone density in postmenopausal women)

In assessing the potential public health impact of enacting a new tobacco policy such as raising the minimum age of legal access to tobacco products (MLA), it is worth keeping in mind that this lengthy catalogue of well-established consequences of cigarette smoking will continue to expand as scientific knowledge advances and more definitive evidence is generated

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

concerning additional health outcomes. Thus, the characterization of the potential impact of a policy change that reduces exposure to cigarette smoke is a conservative estimate of the true public health impact. For example, in addition to the many adverse health outcomes established as causally related to tobacco smoke and summarized in Tables 4-1, 4-2, and 4-3, Tables 4-4 and 4-5 summarize health outcomes for which the evidence summarized in the 2014 Surgeon General’s report is currently considered strong enough to be considered suggestive of a causal association but not yet strong enough to be rated as causal. These are outcomes for which the currently existing body of evidence falls short of being definitive, but the association between cigarette smoking and these outcomes remains under active investigation.

MORBIDITY

Tables 4-1 through 4-3 summarize the preclinical health effects and morbidity caused by cigarette smoking, organized according to whether the effects occur in the immediate, intermediate, or long-term time horizon and by the stages of life usually affected by the health outcome.

Immediate Health Effects

Cigarette smoking causes a constellation of subclinical health effects that occur shortly after initiation of smoking. As described below, these immediate adverse health effects include increased oxidative stress; depletion of selected bioavailable antioxidant micronutrients; increased inflammation; impaired immune status; altered lipid profiles; poorer self-rated health status; respiratory symptoms, including coughing, phlegm, wheezing, and dyspnea; and nicotine addiction. Taken in combination, these detrimental effects detract from a smoker’s overall health status and lead to what has been referred to as “diminished health status” (HHS, 2004). Physiologic markers of diminished health status include subclinical outcomes such as increased oxidative stress, reduced antioxidant defenses, increased inflammation, impaired immune status, and altered lipid profiles (see Tables 4-1 through 4-3). Smoking’s impacts on such short-term physiologic outcomes impair the smoker’s overall health status, which in turn renders the smoker more susceptible to various adverse health outcomes, such as developing acute illnesses, respiratory symptoms, and a lessened capacity to heal wounds. One downstream marker of the diminished health status induced by cigarette smoking is that smokers are more likely to miss school and work. In short, soon after the initiation of smoking, an array of smoking-induced short-term deleterious health effects sets in motion a lifelong trajectory that leaves persistent smokers highly disadvantaged com-

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

TABLE 4-4 Intermediate Adverse Health Outcomes with Evidence Suggestive of a Causal Association with Cigarette Smoking Based on Surgeon General’s Reports

Stage of Life

Health Outcome Childhood/ Adolescence Young Adulthood Middle Adulthood Older Adulthood

Behavioral

Substance use (risk factor for use of marijuana and other substances)
Behavioral and learning disorders (disruptive behavioral disorders, attention deficit hyperactivity disorder)

Dental

Dental caries
Root-surface caries
Failure of dental implants

Respiratory

Incidence of asthma
Exacerbation of asthma
Recurrent tuberculosis infectiona
Idiopathic pulmonary fibrosis
Nonspecific bronchial hyper-responsiveness

aHealth outcome not included in the 2014 Surgeon General’s report.

pared to their counterparts who never smoked. By looking at the immediate and intermediate adverse health effects of cigarette smoking, it is clear that cigarette smoking contributes in important ways to suboptimal health beginning shortly after smoking initiation—long before the chronic diseases that smoking causes at older ages become clinically apparent (HHS, 2004).

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

TABLE 4-5 Long-Term Adverse Health Outcomes with Evidence Suggestive of a Causal Association with Cigarette Smoking Based on Surgeon General’s Reports

Stage of Life

Health Outcomes Childhood/ Adolescence Young Adulthood Middle Adulthood Older Adulthood
Cancer (fatal prostate cancer, higher risk of advanced stage cancer, and disease progression in men who have prostate cancer; noncardia gastric cancers; breast cancer)
Bone Health (low bone density in men)
Eye Disease (opthalmopathy associated with Graves’ disease)
Peptic Ulcer Complications

Physiologic Markers of Diminished Health Status

Increased oxidative stress Cigarette smoke contains free radicals and other oxidants in abundance. A single puff of a cigarette exposes the smoker to more than 1015 free radicals in the gas phase and additional radicals and oxidants in the tar phase (Pryor and Stone, 1993).

The biological impacts of the oxidative stress induced by cigarette smoking have been extensively documented in humans (HHS, 2004). These include oxidative injury to proteins, DNA, and lipids. Assaying protein carbonyls is one method of measuring oxidative damage to proteins, and protein carbonyl concentrations have been observed to be significantly higher in smokers than in nonsmokers (Kapaki et al., 2007; Marangon et al., 1999; Padmavathi et al., 2010). One way of quantifying the oxidative damage to DNA is to measure the DNA damage in peripheral white blood cells induced by the hydroxyl radical at the C8 position of guanine, 8-hydroxy-deoxyguanosine (8-OH-dG). Most of the available evidence indicates that current smokers have concentrations of 8-OH-dG in peripheral leukocytes that are at least 20 percent higher than nonsmokers (HHS, 2004). Studies

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

of 8-OH-dG in DNA extracted from urine provide corroborative evidence, with 8-OH-dG concentrations that are 6 to 50 percent higher in smokers than in nonsmokers (Campos et al., 2011; HHS, 2004; Lowe et al., 2009; Seet et al., 2011). Measures of lipid peroxidation include F2-isoprostanes and malondialdehyde (MDA). Many studies have demonstrated that current smokers have substantially higher concentrations of isoprostanes in both plasma and urine than nonsmokers (Bloomer et al., 2008; HHS, 2004; Kocyigit et al., 2011; Ozguner et al., 2005; Seet et al., 2011; Taylor et al., 2008). The results of several studies indicate that MDA concentrations are 30 percent more abundant in current-versus-nonsmokers, suggesting cigarette smoking directly increases MDA concentrations (Bloomer et al., 2008; Jain et al., 2009; Kocyigit et al., 2005; Ozguner et al., 2005). This is further corroborated by evidence from several studies that have found concentrations of thiobarbituric acid–reactive substances (TBARS) found in MDA range from 6 percent to 118 percent more in smokers than in people who have never smoked (HHS, 2004).

Cigarette smoking clearly generates substantial quantities of oxidative stress, as indicated by a consistent body of evidence indicating that cigarette smoking significantly increases biomarkers of oxidative damage to proteins, DNA, and lipids. Cigarette smokers experience measurable and immediate oxidative damage. This oxidative damage, experienced over long periods of time, is one pathway contributing to smoking-caused disease and death (HHS, 2010).

Depletion of circulating antioxidant micronutrient concentrations Cigarette smoking exposes the smoker to potential oxidative damage not experienced by the nonsmoker. One direct result of the exposure to oxidative stress is the depletion of the body’s defenses against oxidative stress. For example, the antioxidant defense system is partly comprised of antioxidant micronutrients (Evans and Halliwell, 2001). Antioxidant status provides a biomarker of health status because oxidative damage is thought to be centrally involved in the aging process as well as in enhanced susceptibility to a wide range of specific diseases. Evidence from a number of studies firmly establishes that smokers have circulating concentrations of ascorbic acid and provitamin A carotenoids such as a-carotene, b-carotene, and cryptoxanthin that are more than 25 percent lower than nonsmokers (Alberg, 2002). Considered in total, a strong and diverse body of evidence consistently implicates oxidative stress from cigarette smoking in the depletion of antioxidant micronutrients in circulation. Furthermore, the results across studies are consistent with a dose–response relationship, with the amount of smoking being inversely related to the circulating concentrations of vitamin C and provitamin A carotenoids (HHS, 2004).

The immediate effects of cigarette smoking on these concentrations

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

have been examined with measurements of circulating micronutrient concentrations taken before and after a smoker stops smoking. One such study, for example, found substantially increased concentrations of vitamin C and provitamin A carotenoids after 84 hours without a cigarette (Brown, 1996). In another study, the exposure of plasma to the equivalent of six puffs of cigarette smoke completely depleted the ascorbic acid present in the serum (Eiserich et al., 1995). In yet another, measurements taken at baseline and 20 minutes after smoking a cigarette found decreased circulating micronutrient concentrations (Yeung, 1976). Results such as these highlight the immediate impact that smoking a cigarette can have on health status. Cigarette smoking causes depletion of antioxidant micronutrients, leading smokers to have lower circulating concentrations of these antioxidant micronutrients than nonsmokers. The direct immediate result on the smoker’s lower concentrations of antioxidant micronutrients such as vitamin C is to reduce the smoker’s antioxidant defenses, and thus the smoker’s cells throughout the body are more prone to the damaging effects of oxidative stress. Oxidative stress is hypothesized to be associated with premature aging and greater risk of disease (Laher, 2014).

Increased inflammation The direct pro-oxidant effects of cigarette smoke are further exacerbated by additional endogenous oxidant formation via the smoking-induced inflammatory-immune response (van der Vaart et al., 2004; Yao and Rahman, 2011). Another measure of smokers’ poorer health is the chronically higher level of inflammatory response experienced by smokers compared to nonsmokers. Chronic inflammation is hypothesized to play a role in the pathogenesis of numerous chronic diseases (Pawelec et al., 2014; Prasad et al., 2012).

For example, cigarette smoking is strongly and consistently associated with higher leukocyte concentrations (HHS, 2004); this suggests that smoking induces a sustained, long-term inflammatory response. Compared to nonsmokers, current smokers have been uniformly found, across many studies, to have approximately 20 percent higher leucocyte counts. Furthermore, leucocyte counts increase with a greater degree of smoking, measured either by the number of cigarettes smoked per day or the depth of inhalation (HHS, 2004). Prospective cohort studies that evaluate how changes in smoking status relate to changes in leucocyte counts provide evidence that eliminating cigarette smoking leads to reductions in leucocyte counts (HHS, 2004). Leucocytes are a marker of chronic inflammation, but cigarette smoking is also associated with markers of the acute inflammatory response, such as C-reactive protein (HHS, 2014).

Impaired immune status The 2014 Surgeon General’s report was the first report of the Surgeon General to review thoroughly the contribution of

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

cigarette smoking to impaired immune status. Cigarette smoking was found to adversely impact the two major immune pathways, innate immunity and adaptive immunity. Recognizing the extreme complexity of the immune system, with its built-in compensatory mechanisms, the conclusion of the Surgeon General’s report was that the evidence is sufficient to infer that cigarette smoking compromises the immune system and compromises immune homeostasis by diminishing both innate and adaptive immunity (HHS, 2014). The impact of the adverse effects on immune status would be to make smokers more susceptible to disease, which in turn contributes to the etiology of acute infectious and chronic diseases above and beyond the way in which cigarette smoking contributes to acute and chronic inflammation.

Altered lipid profiles Cigarette smoking causes altered lipid metabolism (HHS, 2010). The alterations in the lipid profile induced by cigarette smoking create a higher risk profile: Compared with nonsmokers, cigarette smokers have significantly higher serum cholesterol, triglyceride, and low-density lipoprotein (LDL) levels and lower high-density lipoprotein (HDL) levels (Ambrose and Barua, 2004). In a meta-analysis of 54 epidemiologic studies, smokers were found to have serum concentrations of cholesterol, triglycerides, and very low density lipoprotein (VLDL) cholesterol that were 3 percent, 9 percent, and 10 percent higher, respectively, and HDL cholesterol concentrations that were 6 percent lower than nonsmokers (Craig et al., 1989). Furthermore, clear dose–response associations were observed, with these associations growing stronger as the number of cigarettes smoked per day increased. The alteration of the lipid profile in the direction of increased cardiovascular disease risk has been extensively documented not only in adults but also in children and adolescents. In a meta-analysis of studies in which study participants ranged from 8 to 19 years of age, adolescents who smoked cigarettes had serum LDL cholesterol and triglyceride concentrations that were significantly higher than in nonsmokers, whereas smokers had lower serum concentrations of HDL cholesterol than nonsmokers (Craig et al., 1990). These differences are likely due to a direct effect of cigarette smoking. In a cohort of middle school students in Germany, those who initiated smoking had significantly lower HDL cholesterol levels than nonsmokers after 2 years of follow-up despite there having been similar baseline levels of HDL cholesterol in the two groups—those who would remain nonsmokers and those who would go on to begin smoking (Dwyer et al., 1988).

Poorer Self-Rated Health Status

The adverse impact of smoking on health status has been directly measured by comparing self-rated health in smokers versus nonsmokers. Studies

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

of varying design have uniformly shown that smokers tend to rate their overall health status lower than nonsmokers do (HHS, 2004, 2014). The consistent reporting of poorer self-rated health among smokers compared to nonsmokers across numerous dimensions of health status provides direct evidence that smoking impairs the health of cigarette smokers in ways that are perceptible to the smoker even in the absence of clinical disease.

Respiratory Symptoms: Coughing, Phlegm, Wheezing, Dyspnea

The immediate adverse health effects of cigarette smoking are not limited to subclinical measures; they can also result in physical symptoms. In reviewing the evidence separately for children/adolescents and adults, the 2004 Surgeon General’s report concluded that cigarette smoking was causally associated with all major respiratory symptoms in both age groups (HHS, 2004). The specific symptoms caused by cigarette smoking are coughing, phlegm, wheezing, and dyspnea. The consistent presence of the causal association across the life course supports the classification of these symptoms as an immediate health effect based on the definition used in this report.

Nicotine Addiction

Another clinical, immediate adverse health effect of cigarette smoking is nicotine addiction. The 2012 Surgeon General’s report concluded that cigarette smoking was causally associated with nicotine addiction, beginning in adolescence (HHS, 2012). The onset of nicotine addiction begins soon after smoking initiation.

The importance of nicotine addiction as an immediate adverse health effect cannot be underestimated. Nicotine addiction, via its role in propagating sustained smoking, assumes a role as a central determinant of the entire catalogue of downstream health effects of cigarette smoking. The often long-term, sustained addiction to nicotine is the underlying factor driving the long-term, sustained exposure to the toxins in tobacco smoke that drive the adverse health effects of cigarette smoking.

Finding 4-1: Cigarette smoking is causally associated with a broad spectrum of adverse health effects that begin soon after the onset of regular smoking and that, in total, significantly diminish the health status of the smoker compared to nonsmokers.

Intermediate-Term Effects on Morbidity

The health effects included in the category of “intermediate adverse health effects” consist largely of health outcomes that are not dependent on

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

having smoked a cigarette in the immediate past but rather require a more extensive smoking history for the adverse outcome to become manifest. For example, intermediate adverse health effects are often direct sequellae of some of the immediate health effects of smoking, such as absenteeism and medical care utilization, or else they are diagnoses that are precursors of subsequent, more severe disease endpoints, such as type 2 diabetes and subclinical atherosclerosis. Cigarette smoking cessation diminishes the risk of experiencing these intermediate adverse health effects, but individuals with a past history of cigarette smoking still have greater risks than those who never smoked.

Absenteeism

Another indicator of diminished health status is absence from work. Among the many factors that contribute to attendance, health status is clearly a major determinant. Thus, attendance patterns are potential markers of health status (Alberg et al., 2003).

Cigarette smoking is a determinant of absence. A substantial body of evidence on the association in adults between cigarette smoking and absence from work consistently demonstrates that smokers are significantly more likely to have greater workplace absenteeism (HHS, 2004). The likelihood of workplace absence increases with the number of cigarettes smoked per day (HHS, 2004). Furthermore, smoking cessation is associated with reduced absence rates (HHS, 2004). In addition to smokers having more episodes of absence than nonsmokers, smokers tend to stay out longer when they are sick than nonsmokers. Thus, smokers miss more cumulative work time than nonsmokers (HHS, 2004).

A strong and consistent body of evidence demonstrates that cigarette smoking is associated with a greater likelihood of absence from work. This association could be at least partially due to smoking being a marker for other causes of absenteeism, such as mental illness and abuse of other substances. In considering the societal toll of cigarette smoking, attendance is not only a useful marker of diminished health status, but also a marker of other downstream costs. On the individual level, workplace absenteeism can lead to problems on the job and even result in unemployment. At the societal level, absenteeism decreases productivity and is a drain on the economy.

Increased Utilization of Medical Services

Utilization of medical services provides an additional indicator of health status. Despite the complexities inherent in studying the association between cigarette smoking and use of medical services, the evidence reviewed

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

in the 2004 and 2014 Surgeon General’s reports yields a clear signal indicating that cigarette smokers generate higher medical care costs and have more inpatients and outpatient visits than those who do not smoke (HHS, 2004, 2014). Among patients admitted to the hospital, smokers have longer lengths of stay and incur greater expenses per admission than nonsmokers.

Subclinical Atherosclerosis

Atherosclerosis is a cardiovascular disease precursor that begins early in life; it is the underlying pathogenic mechanism that ultimately leads to many cardiovascular disease endpoints. The epidemiologic evidence has been consistent in demonstrating a strong, dose-dependent association between cigarette smoking and subclinical atherosclerosis as measured by carotid intimal–medial thickness. Consequently, cigarette smoking has been established as a cause of atherosclerosis (HHS, 2004). Establishing the link between cigarette smoking and atherosclerosis provides a strong, biologically plausible rationale for the role of cigarette smoking in the pathogenesis of clinical cardiovascular endpoints that occur as a consequence of atherosclerosis.

Impaired Lung Development and Accelerated Decline in Function

In addition to smoking’s long-term health effects on the respiratory system from diseases such as lung cancer and COPD, some adverse respiratory effects experienced by adolescent cigarette smokers manifest themselves shortly after smoking initiation. Compared to nonsmokers, adolescents who smoke cigarettes are more likely to experience impaired lung growth, early onset in the decline of lung function, and asthma-related symptoms (HHS, 2004). Among adults who smoke cigarettes, lung function begins to decline at younger ages, and the age-related decline in lung function occurs faster (HHS, 2004).

Increased Susceptibility to Infectious Lung Diseases

Due at least in part to its adverse impact on immune status, cigarette smoking predisposes the smoker to developing acute infectious respiratory illnesses such as pneumonia. Established effects of cigarette smoking on the immune system provide a clear biological basis for the increased likelihood that has been observed among smokers of developing an infection after exposure to microbes that cause respiratory infections and also of developing a clinically apparent disease once infected (HHS, 2004). Further, impaired cilia function in the trachea and bronchi also contributes to the increased risk of respiratory infections in smokers (Simet et al., 2010). Thus, it is no

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

surprise that cigarette smokers have an increased susceptibility to respiratory infections.

Cigarette smoking is causally associated with an increased risk of pneumonia (HHS, 2004). The 2014 Surgeon General’s report was the first to review the evidence on the association between cigarette smoking and tuberculosis. A strong statistical association has been observed between cigarette smoking and risk of M. tuberculosis infection and also the risk, once infected, of progressing to tuberculosis disease, but showing a clear causal connection between smoking and risk of tuberculosis has been challenging because cigarette smokers often have a much higher risk profile than nonsmokers for these outcomes because of other social determinants of health. These challenges notwithstanding, the evidence has now coalesced to the point that cigarette smoking is causally associated with tuberculosis disease and tuberculosis mortality (HHS, 2014).

Diabetes

Type 2 diabetes mellitus is a leading underlying cause of mortality from cardiovascular disease, and it also leads to other adverse consequences such as kidney failure and blindness (HHS, 2014). Obesity has long been established as a major risk factor for diabetes, but the association between cigarette smoking and diabetes has only more recently been elucidated. The results of a meta-analysis of 51 prospective cohort studies in the 2014 Surgeon General’s report demonstrated that cigarette smokers have a 30–40 percent greater risk of diabetes than nonsmokers and that there is a strong dose–response relationship, with the risk increasing with the number of cigarettes smoked per day (HHS, 2014). In addition to having an increased risk of developing diabetes, evidence also indicates that, among patients with diabetes, cigarette smokers are more likely to suffer cardiovascular complications and to have higher mortality rates. Based on this body of evidence, the 2014 Surgeon General’s report concluded that cigarette smoking is a cause of diabetes (HHS, 2014).

Periodontitis

A synthesis of the evidence in the 2004 Surgeon General’s report revealed a strong, consistent, and dose-dependent relationship between cigarette smoking and the risk of periodontitis. Based on this evidence, cigarette smoking was judged to be causally associated with periodontitis. Approximately one-half of all diagnoses of adult periodontitis are attributable to cigarette smoking (HHS, 2004).

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

Asthma Exacerbation

The fact that cigarette smoking is causally associated with so many outcomes that are relevant to asthma has long raised suspicions that cigarette smoking is a risk factor for asthma. Examples of these asthma-relevant factors are persistent inflammation, diminished immune status, and the respiratory symptoms of coughing, phlegm, wheezing, and dyspnea. At the present time, the evidence is considered suggestive but not sufficient to infer a causal association between cigarette smoking and the risk of developing asthma in adolescents or adults or between smoking and the risk of asthma exacerbations in adolescents (HHS, 2014). However, the 2014 Surgeon General’s report did conclude that cigarette smoking is causally associated with asthma exacerbation in adults (HHS, 2014).

Adverse Surgical Outcomes: Wound Healing and Respiratory Complications

The fact that smoking causes diminished health status by impairing factors such as immune response and lung function provides a strong reason to believe that cigarette smoking could be associated with a worse prognosis after surgical procedures. Based on a large and diverse body of evidence with outcomes that ranged from short- and long-term complications of surgery to survival, the 2004 Surgeon General’s report concluded that cigarette smoking is a cause of adverse surgical outcomes (HHS, 2004).

Finding 4-2: Cigarette smoking causes many adverse health effects classified as “intermediate,” which include increased absence from work, the increased use of medical services, subclinical atherosclerosis, impaired lung development and function, an increased risk of lung infections, diabetes, periodontitis, the exacerbation of asthma in adults, subclinical organ injury, and adverse surgical outcomes.

Long-Term Morbidity

Cigarette smoking contributes to a major portion of the population burden of many of the chronic diseases that typically occur in middle and late adulthood, such as cancer, cardiovascular disease, and COPD (HHS, 2004). As noted below, the full scope of long-term morbidity attributable to cigarette smoking also extends to numerous other disease endpoints. Cessation of cigarette smoking diminishes the risk of experiencing these long-term adverse health effects, but a past history of cigarette smoking is still associated with increased risk compared to never having smoked (HHS, 2014).

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

Cancer

Cigarette smoking is causally associated with 12 different types of malignancy and is responsible for approximately 30 percent of all cancer deaths in the United States (ACS, 2007; HHS, 2014). Cigarette smoking has been known for many years to be a cause of cancers of the lung, oral cavity, larynx, esophagus, bladder, pancreas, kidney, uterine cervix, and stomach, and of acute myeloid leukemia. The conclusions of the 2014 report of the Surgeon General indicate that cigarette smoking is also causally associated with colorectal cancer and liver cancer. Furthermore, cigarette smoking is causally associated with clinical precursors of cancer lesions, such as colorectal adenomatous polyps (HHS, 2014).

Vascular Disease

Cigarette smoking is associated with numerous clinical cardiovascular disease endpoints, including coronary heart disease, stroke, and abdominal aortic aneurism. Coronary heart disease is a leading cause of death in the United States and most high-income countries. Cigarette smoking has been established as a major cause of coronary heart disease for decades. The impact of cigarette smoking is particularly strong among younger age groups, as it causes 40 percent of ischemic heart disease deaths in 35- to 64-year-olds (HHS, 2004).

Cigarette smoking has long been identified as a major cause of cerebrovascular disease. As with coronary heart disease, the impact of cigarette smoking is proportionally larger in relatively younger adults. Among 35- to 64-year-olds, more than 40 percent of all cerebrovascular disease deaths are attributable to cigarette smoking (HHS, 2004).

Cigarette smoking is an established cause of abdominal aortic aneurysm (HHS, 2004). This condition is often fatal and accounts for more than 10,000 deaths per year in the United States.

COPD

The process of inhaling cigarette smoke brings the smoker’s respiratory system into direct contact with heavy doses of tobacco toxins. Given these profound levels of exposure, it is not surprising that cigarette smoking’s deleterious effects on the respiratory system extend well beyond lung cancer. Cigarette smoking is estimated to have caused 7.5 million prevalent cases of COPD in the United States in 2009 (Rostron et al., 2014). More than 138,000 Americans died from COPD in 2010, making it the third leading cause of death in the United States (Heron, 2013). As the predominant

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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cause of COPD, cigarette smoking is responsible for approximately 80 percent of the mortality burden from COPD (HHS, 2004).

Eye Disease: Age-Related Macular Degeneration and Nuclear Cataracts

Cigarette smoking also adversely affects eye health, causing nuclear cataracts (HHS, 2004). The body of evidence linking cigarette smoking with age-related macular degeneration that was accumulated over the past two decades has now been judged to be strong and consistent enough to prove a causal association between the two (HHS, 2014).

Rheumatoid Arthritis

Cigarette smoking also causes joint disease. More than 1 million Americans have been diagnosed with rheumatoid arthritis, a disease linked to immune dysregulation. Enough supportive evidence has been accumulated to indicate a clear link between cigarette smoking and rheumatoid arthritis. The conclusions of the 2014 Surgeon General’s report contained the conclusion that a causal association has been established between cigarette smoking and rheumatoid arthritis (HHS, 2014).

Bone Health: Hip Fractures and Bone Density

Cigarette smoking has adverse consequences for bone health. Cigarette smoking is causally associated with hip fractures. In postmenopausal women, a causal association has been established between cigarette smoking and low bone density (HHS, 2004).

Finding 4-3: Cigarette smoking is causally associated with a broad spectrum of adverse long-term health effects which cause suffering, impaired quality of life, and death.

Maternal/Fetal and Infancy Health Effects

Pregnancy represents a particularly vulnerable time of life for both the mother and the developing fetus, and this critical time window extends into the neonatal period and infancy. Because of the unique features of this period of enhanced vulnerability and its critical public health importance, the topic is considered separately. Cigarette smoking is an established cause of a broad spectrum of health effects to the mother, fetus, and infant, including decreased likelihood of becoming pregnant, increased risk of experiencing adverse pregnancy outcomes, and adverse effects on the newborn that can range from organ impairment to congenital malformations to death,

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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as summarized in Table 4-6. Table 4-6 also includes the immediate physiologic effects of smoking from Table 4-1 to emphasize the point that pregnant women who smoke incur the same short-term adverse health effects incurred by all cigarette smokers. It is estimated that more than 400,000 infants are exposed each year to maternal smoking in utero. Furthermore, recent data indicate that more than 1.2 million births each year in the

TABLE 4-6 Maternal, Fetal, and Infant Adverse Health Outcomes Causally Associated with Cigarette Smoking Based on Surgeon General’s Reports

Health Outcome Maternal Fetal Infant/Child

Immediate Health Effects on All Smokers, Including During Pregnancy (selected)

Oxidative Stress
Depletion of Antioxidant
Micronutrients
Increased Inflammation
Compromised Immune Status
Altered Lipid Metabolism
Lower Self-Rated Health Status

Likelihood of Becoming Pregnant

Reduced Fertility (maternal and paternal)

Pregnancy Complications

Complications of Pregnancy (ectopic pregnancy, premature rupture of the membranes, placenta previa, and placental abruption)
Shortened Pregnancy (pre-term delivery and shortened gestation)

Outcomes of Childbirth and Survival

Impaired Fetal Growth (fetal growth restriction or low birth weight)
Congenital Malformations (orofacial clefts)
Impaired Organ Function (reduced lung function)
Death (stillbirth, infant mortality, sudden infant death syndrome)
Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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United States occur among mothers under 25 years of age. In the United States in 2012, 31 percent of all births were to mothers less than 25 years old (1,225,871/3,952,841); of these, 90,095 were to mothers less than 18 years old, 85,310 were to mothers who were 18 years old, and 1,050,466 were to mothers who were 19–24 years old (Martin et al., 2013).

Decreased Likelihood of Conception

Cigarette smoking is associated with a decreased likelihood of pregnancy because of smoking’s adverse effects on the female and the male reproductive systems. Cigarette smoking is causally associated with reduced fertility in women (HHS, 2004). Further, the 2014 Surgeon General’s report pointed to a diverse body of research evidence supported by a strong biologic rationale to conclude that cigarette smoking is a cause of erectile dysfunction in men.

Pregnancy Complications

Maternal smoking during pregnancy reduces the likelihood of a full-term gestational period with optimal fetal growth. Cigarette smoking by pregnant women adversely affects pregnancy by making it more likely they will experience ectopic pregnancies, complications of pregnancy such as premature rupture of the membranes, placenta previa, and placental abruption. Furthermore, cigarette smoking in expectant mothers causes preterm delivery and shortened gestation (HHS, 2004).

Outcomes: Childbirth, Infancy, and Survival

Maternal cigarette smoking during pregnancy directly harms the fetus and, later, the infant in several ways (HHS, 2004). Cigarette smoking is causally associated with stunted fetal growth and is an important cause of shortened gestation. In combination, stunted fetal growth and premature delivery are major determinants of low birth weight. Cigarette smoking causes congenital malformations, specifically orofacial clefts. Cigarette smoking is also associated with impaired organ function, specifically reduced lung function (HHS, 2014).

Based on these many severe effects, it is logical to infer that cigarette smoking negatively affects the viability of the fetus and child. Specifically, smoking is causally associated with fetal deaths, or stillbirths; furthermore, among live births smoking is an established cause of overall infant mortality. That is, compared with infants of mothers who do not smoke, infants with mothers who smoke during or after pregnancy experience higher rates of death before reaching 1 year of age. One specific cause of increased mor-

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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tality of infants whose mothers smoke is sudden infant death syndrome, which is more likely to strike those infants than infants whose mothers do not smoke (HHS, 2004).

After birth, children who are exposed to secondhand smoke (SHS) via parental smoking suffer numerous adverse health effects as a consequence. In infants, symptoms associated with SHS exposure include increased lower respiratory illnesses, otitis media, middle ear effusion, reduced lung function, and the respiratory symptoms of coughing, phlegm, wheezing, and dyspnea (HHS, 2006). In addition to the increased risk of symptoms, infants of smoking mothers are more likely to experience subclinical immediate adverse health effects of cigarette smoke exposure as well. For example, evidence indicates that infant exposure to parental smoking is associated with physiologic markers of diminished health status, such as increased oxidative damage to DNA and lipids. As noted above, 8-OH-dG can be used as a measure of oxidative damage to DNA, and neonatal levels of urinary 8-OH-dG have been found to be significantly associated with exposure to the toxicants from tobacco smoke due to the mother’s smoking (Hong et al., 2001). Newborns with mothers who smoked had concentrations of 8-OH-dG that were 333 percent higher than newborns whose mothers did not smoke (Hong et al., 2001).

Finding 4-4: Maternal smoking during pregnancy and secondhand smoke exposure during infancy are causally associated with many adverse health outcomes. This not only leaves exposed infants prone to short- and long-term health risks but also can result in death.

Age of Initiation and Health Outcomes

The following four factors were used to assess the effects that the age of initiation had on an individual’s cigarette smoking trajectory and subsequent health effects: (1) nicotine dependence, (2) the number of cigarettes smoked per day (smoking intensity), (3) the likelihood of smoking cessation (or, conversely, the likelihood of remaining a smoker), and (4) health outcomes. These four factors are closely interrelated. Nicotine dependence is associated with smoking intensity (Hu et al., 2006), and both of these measures are in turn associated with the likelihood of remaining a smoker in the long term. The interrelationships among the factors involve both smoking intensity (number of cigarettes per day) and smoking duration (number of years smoked) and hence also the effects of the lifetime cumulative exposure to cigarette smoking. Many of the established deleterious health effects of cigarette smoking are dose-dependent, thus providing a mechanistic explanation for how earlier age of initiation could exert a powerful contribution

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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on smoking-caused health effects that is mediated by leading to increased doses of exposure to cigarette smoke.

In particular, the mechanistic basis for a powerful influence of the age of initiation on smoking-caused adverse health outcomes is grounded in the evidence, reviewed in Chapter 3, that those who start smoking earlier are more likely to (1) have a greater degree of nicotine dependence (Breslau and Peterson, 1996; Buchmann et al., 2013; HHS, 2012; Hu et al., 2006; Lando et al., 1999; Park et al., 2004), (2) smoke cigarettes more frequently (Breslau, 1993; Buchmann et al., 2013; Chen and Millar, 1998; D’Avanzo et al., 1994; Escobedo et al., 1993; Everett et al., 1999; Fernandez et al., 1999; Hu et al., 2006; Lando et al., 1999; Reidpath et al., 2014; Taioli and Wynder, 1991), and (3) remain smokers for longer periods of time (Breslau and Peterson, 1996; Chen and Millar, 1998; D’Avanzo et al., 1994; Eisner et al., 2000; Everett et al., 1999; Khuder et al., 1999). These associations all point toward an association between a younger age of initiation and greater exposure to the toxicants in cigarette smoke, which because of well-established dose–response relationships would therefore be expected to lead to higher risk of smoking-caused disease and death. A further negative consequence of starting to smoke at younger ages is that tissues and organ systems that are still in the growth and maturation phase may be particularly vulnerable to the toxicants in smoke, so that even a given exposure dose to cigarette smoke may be more harmful when exposure occurs during childhood and adolescence than during adulthood.

Younger age of initiation has been found to be associated with one short-term health effect in particular: an increased risk of hospital inpatient stay during the previous year (Lando et al., 1999). Concerning long-term health effects, the lung is exquisitely sensitive to the adverse consequences of cigarette smoke because it is directly exposed to inhaled cigarette smoke and is further exposed to harmful smoke toxicants via the circulation of those toxicants in the blood. In a prospective cohort study, a strong association was observed between an earlier age of smoking initiation and an increased risk of respiratory disease (Kenfield et al., 2008). Compared to people who have never smoked, the relative odds (and 95 percent confidence intervals) of contracting respiratory disease were 7.0 (3.9–12.4) for those who started smoking at 26 years old or older; 8.1 (5.5–11.9) for those who started between 22 and 25; 10.2 (9.9–13.2) for smoking initiation between 18 and 21; and 13.4 (9.8–18.2) for those who started smoking at 17 or younger; the age trend is highly statistically significant (a p-value of 0.001). The same study also observed a statistically significant trend for the risk of lung cancer, which was not grouped under respiratory disease (Kenfield et al., 2008); this finding was also observed in another population-based cohort study (Prizment et al., 2014). The strong association between an earlier age of starting to smoke and increased lung cancer

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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risk was summarized in a meta-analysis of 69 studies, which estimated that the summary odds ratio for lung cancer was 10.3 (95 percent confidence interval of 8.0–13.3) for starting to smoke around the age of 14 years; 7.5 (5.9–9.4) for starting to smoke at approximately 18 years; and 3.9 (3.3–4.6) for starting to smoke at age 26 years (Lee et al., 2012). Thus, an earlier age of initiation is strongly associated with an increased risk of respiratory diseases (primarily COPD) and lung cancer.

The evidence for cardiovascular disease has been mixed. The risk of cardiovascular disease increased significantly with younger age of initiation in the ARIC prospective cohort study (Huxley et al., 2012), but the results of the Nurses’ Health Study did not find a significant effect (Kenfield et al., 2008). In another study, younger age of initiation was significantly associated with peripheral artery disease (Planas et al., 2002).

Overall, the evidence is consistent in finding that the younger the age of initiation, the greater the risk of nicotine dependence, smoking intensity, and persistent smoking/reduced likelihood of cessation. The associations between a younger age of initiation and these outcomes holds true even after accounting for time from first cigarette to first daily smoking. The findings consistently show a dose–response trend, with younger ages of initiation associated with a higher likelihood of nicotine dependence, greater smoking intensity, and reduced likelihood of cessation. The absence of any apparent age threshold on these associations or any diminution of the associations across the age continuum indicates that any delay in initiation, regardless of the ages affected (e.g., late childhood to early adolescence, early to mid-adolescence, or adolescence to young adulthood) would be expected to have measurable benefits in reducing the lifetime consumption of cigarettes and hence in reducing the risk for smoking-caused disease and death. The adverse consequences of a younger age of initiation appear to manifest at young ages and be sustained over the life course.

Finding 4-5: A younger age of initiation is associated with an increased risk of many adverse health outcomes, such as a hospital inpatient stay in the past year and lifetime risk of respiratory disease, especially chronic obstructive pulmonary disease and lung cancer.

Other Tobacco Products and Sources of Exposure

So far, the discussion has focused specifically on cigarette smoking. SHS exposure and other tobacco products and nicotine delivery devices are discussed below.

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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Secondhand Smoke Exposure

The health effects of cigarette smoking are not limited to the adverse health effects on the smoker; they also include the health consequences that exposure to SHS has on nonsmokers (HHS, 2014). SHS exposure has now been linked with a host of adverse health effects in addition to the long-established causal associations with lung cancer and heart disease.

As cigarette smokers, parents who smoke cigarettes increase their personal risk for all of the adverse health outcomes described above. If parents smoke in the presence of their children, they also negatively affect the health of their children by exposing them to SHS. The health effects of SHS exposure are not limited to long-term enhanced susceptibility to chronic diseases, but, as in the case of cigarette smoking, they also include immediate and substantial effects that leave SHS-exposed individuals prone to short-term health risks (see Table 4-7).

Thus, as is the case with cigarette smoking, SHS exposure is associated with diminished health status. Exposure to SHS is associated with increased oxidative damage to DNA and lipids. As noted above, MDA can be used as a measure of lipid peroxidation, and children exposed to SHS have been found to have significantly higher circulating levels of MDA and also significantly lower levels of glutathione peroxidase (Zalata et al., 2007). Concerning antioxidant micronutrients, the evidence for SHS exposure mirrors the evidence for smoking. Compared to nonsmokers not exposed to SHS, nonsmokers exposed to SHS have significantly reduced circulating concentrations of vitamin C and provitamin A carotenoids, indicating that even low-dose cigarette smoke exposures lower circulating antioxidant micronutrient concentrations. Evidence of lowered circulating antioxidant micronutrient concentrations has also been observed in children of smokers (Wilson et al., 2011; Yilmaz et al., 2009; Zalata et al., 2007). Children whose mothers were smokers had 29 percent and 26 percent lower circulating concentrations of vitamin E and vitamin A, respectively, than children whose mothers did not smoke (Yilmaz et al., 2009).

Nonsmokers exposed to SHS have also been found to have lessened immune status (HHS, 2010). The body of evidence firmly indicates that among nonsmokers, SHS exposure is associated with greater oxidative damage, lower circulating antioxidant micronutrient concentrations, and lessened immune status. Given the consistent body of evidence and the clear biological rationale based on the causal associations seen with cigarette smoking these associations are likely to be rated as causal in the future, but the evidence base has not yet reached the standard for these associations to be judged as causal in the Surgeon General’s report.

Consistent with the health effects observed for cigarette smoking, the health effects of SHS exposure also include reduced lung function and the

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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respiratory symptoms of coughing, phlegm, wheezing, and dyspnea. SHS exposure in children causes numerous adverse health effects, including lower respiratory illnesses, otitis media, and middle ear effusion (HHS, 2006).

In adults, SHS exposure is also causally associated with increased risk of long-term chronic diseases, just as in the case of cigarette smoking. These diseases include lung cancer, coronary heart disease, stroke, and inflammatory bowel disease.

As expected, based on the lower-exposure doses of exposure to tobacco toxins that result from secondhand smoke, the health risks of SHS exposure for most health outcomes tend to be less than the risks of cigarette smoking. Nevertheless, the fact that these risks are incurred even at very low doses indicates that there is no safe threshold for exposure to cigarette smoke. The importance of this public health challenge is accentuated by the fact that these health risks are incurred as the result of smoking by others rather by the affected individuals themselves.

Finding 4-6: Secondhand smoke exposure is causally associated with adverse health effects.

It is worth keeping in mind that this lengthy catalogue of well-established consequences of SHS exposure will continue to grow as more definitive evidence coalesces for additional health outcomes. For example, Table 4-8 summarizes health outcomes for which the evidence summarized in the 2014 Surgeon General’s report is currently considered strong enough to be considered suggestive of a causal association but not yet strong enough to be rated as causal.

Smoking of Pipes, Cigars, and Other Combustible Tobacco Products

Combustible tobacco products other than cigarettes are also associated with the same sort of chronic disease outcomes associated with cigarette smoking, such as cancer and cardiovascular disease. Pipe and cigar smoke contain similar profiles of harmful toxins to those found in cigarette smoke (HHS, 2014). A key distinction in the health risks is that the doses of toxins delivered to the smoker are often less for pipes and cigars than for cigarettes because pipes and cigars are usually smoked less frequently and the smoke tends to be inhaled less deeply (HHS, 1998). For example, pipe and cigar smoking pose risks for malignancies of the larynx, oral cavity, and esophagus that are similar to the risks associated with smoking cigarettes (HHS, 1998). Pipes and cigars are causally associated with lung cancer, even though the risks are less than observed for cigarette smoking because compared to cigarette smoking pipes and cigars are smoked on average

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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TABLE 4-7 Adverse Health Outcomes Causally Associated with Secondhand Smoke Exposure Based on Surgeon General’s Reports

Stage of Life

Health Outcome Infancy Childhood/ Adolescence Young Adulthood Middle Adulthood Older Adulthood

Short-Term and Intermediate-Term Health Effects

Maternal/Fetal Development (low birth weight)
Ear
Ear Problems
Middle Ear Disease
Respiratory
Acute Respiratory Infections
Slower Lung Growth
Respiratory Tract Injury
Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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Coughing, Phlegm, Wheezing, Breathlessness
Lower Respiratory Illness
Wheeze Illnesses
Lower Level of Lung Function
Odor Annoyance
Nasal Irritation
Long-Term Health Effects
Inflammatory Bowel Disease (Crohn’s disease)
Cancer (lung)
Cardiovascular
Stroke, Coronary Heart Disease
Endothelial Cell Dysfunctions
Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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TABLE 4-8 Adverse Health Outcomes with Evidence Suggestive of a Causal Association with Secondhand Smoke Exposure Based on Surgeon General’s Reports

Stage of Life

Health Outcome Pregnancy Infancy Childhood Adolescenc Young e Adulthood Middle Adulthood Older Adulthood
Diminished Immune Function (immune activating and suppressive effects)
Maternal/Fetal Development (pre-term delivery)
Dental Carries
Respiratory

Incidence of asthma

Worsening of asthma control and symptoms

Coughing, wheezing, chest tightness, and breathlessness

COPD

Chronic respiratory symptoms

Small decrement in lung function

Cardiovascular (angina, sudden coronary death, stroke, atherosclerosis)
Cancer

Breast cancer

Childhood leukemias

Childhood lymphomas

Childhood brain tumors

Nasal sinus cancer

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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less frequently and the smoke is inhaled less deeply (Alberg et al., 2013). The available evidence indicating that pipe and cigar smoking have similar adverse health effects to cigarette smoking thus supports the conclusion that the impact of a policy change that resulted in lower uptake or delayed initiation of pipes or cigars would have a significant impact on public health but would be expected to be less than a similar reduction in cigarette smoking because of the lower exposure to tobacco toxins due to the manner in which pipes and cigars are smoked.

Another way to smoke tobacco is with a hookah, or waterpipe. From an exposure assessment perspective, the distinctive features of this tobacco smoke delivery system are that the tobacco is sometimes indirectly heated and that the smoke passes through a water column prior to inhalation (Akl et al., 2010). Hookah use is becoming more common throughout the world, including in the United States (Cobb et al., 2010; Jawad et al., 2013). In a study comparing the urinary concentrations of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in cigarette smokers, hookah smokers, and nonsmokers, it was found that hookah smokers had significantly higher NNAL concentrations than nonsmokers but significantly lower concentrations than cigarette smokers (Radwan et al., 2013). In a study in which urine samples were collected from hookah smokers before and after they smoked from the hookah, significant post-smoking increases were noted in the urinary concentrations of nicotine, cotinine, NNAL, and volatile organic compounds (St. Helen et al., 2014). Expired carbon monoxide concentrations (Jacob et al., 2011) and benzene exposure (Jacob et al., 2013) tend to be much higher for hookah smoking than for cigarette smoking. Studies have assessed the association between hookah smoking and selected health outcomes, but there is a paucity of evidence available on this topic, and the body of evidence is generally of low quality (Akl et al., 2010). In a meta-analysis of data from four studies, hookah smoking was significantly associated with an increased lung cancer risk (odds ratio, 2.1; 95 percent confidence interval, 1.3–3.4) (Akl et al., 2010). In this same systematic review, only one study each was identified to assess the association between hookah smoking and cancers of the bladder, esophagus, and nasopharynx, and none of the observed associations were statistically significant (Akl et al., 2010). With respect to pregnancy outcomes, three studies found hookah smoking to be associated with a significantly increased risk of low birth weight (2.1; 1.1–4.2) (Akl et al., 2010). In one study, hookah smoking was found to be associated with a significantly increased risk of respiratory illness (2.3; 1.1–5.1) (Akl et al., 2010). Definitive conclusions on the risks associated with hookah smoking versus cigarette smoking are not possible with the limited quality and quantity of the evidence currently available.

Little evidence on the health effects of newer combustible tobacco prod-

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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ucts has been generated. In attempting to estimate risks, it is important to account for the specific product features. For example, the 2014 Surgeon General’s report points out that when considering the emergence of small cigarette-like cigars, the health risks may more closely parallel those of cigarettes than of the traditional cigar because of the way that small cigarette-like cigars are used (HHS, 2014). This line of reasoning emphasizes that the health risks of tobacco use are directly linked to doses of exposure to disease-causing toxins, which is a function not only of the tobacco product but also of the frequency and duration of and the manner in which the product is smoked, when factors such as depth of inhalation are accounted for. This concept is also critical to thinking about the health risks of dual use or poly-use of combustible tobacco products and ENDS, an exposure pattern that will likely increase in the future but for which data on health risks are needed.

Finding 4-7: Smoking of combustible tobacco products other than cigarettes, such as pipes and cigars, is causally associated with a broad spectrum of adverse health effects.

Smokeless Tobacco Products

The marketplace for smokeless tobacco products has diversified considerably in recent years. In addition to the traditional smokeless tobacco products of chewing tobacco and snuff, a number of new products have been introduced, such as snus and dissolvable tobacco products.

The 1986 Surgeon General’s report examined the evidence concerning smokeless tobacco and concluded that it was a cause of cancer of the oral cavity. Smokeless tobacco use can also lead to oral leukoplakia, gingival recession, and nicotine addiction. A 2007 monograph of the International Agency for Research on Cancer (IARC) that focused on smokeless tobacco concluded that smokeless tobacco is a Group 1 carcinogen, meaning that it is a human carcinogen (IARC, 2007). The IARC review of the evidence led to the conclusion, “Smokeless tobacco causes cancers of the oral cavity and pancreas” (IARC, 2007, p. 370). Smokeless tobacco may also be linked to an increased risk of esophageal cancer (IARC, 2012).

These earlier reviews of the evidence concerning the health effects of smokeless tobacco use were primarily based on evidence related to traditional smokeless tobacco products and did not take into account the newer products. A more recent review of the epidemiologic evidence for Swedish-type snus, a moist snuff, suggests that the use of snus may be less harmful than cigarette smoking (Lee, 2011). How the health risks of Swedish-type snus differ from the more traditional smokeless tobacco products has yet to be precisely characterized; furthermore, direct epidemiologic evidence is

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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not yet available on the health effects of the Swedish-type snus products presently marketed in the United States.

Finding 4-8: The use of smokeless tobacco products is causally associated with oral cancer.

ENDS

The marketplace for tobacco products and devices that deliver nicotine has recently expanded in response to the smoking bans that have increasingly limited the locations where traditional cigarette smoking is allowed (Jawad et al., 2013; Kamerow, 2013; Popova and Ling, 2013; Schuster et al., 2013). Electronic nicotine delivery systems, or ENDS, have experienced a rapid upsurge in use and are now marketed by the major U.S. tobacco companies (Dockrell et al., 2013; Kamerow, 2013; Li et al., 2013; Popova and Ling, 2013).

Monitoring this expansion in products and how the products are used is important to tobacco control. An ENDS product that decreases the delivery of tobacco toxins would ostensibly also reduce the risk of developing smoking-caused disease if current cigarette smokers were to switch from cigarettes to exclusive use of the ENDS. On the other hand, the risk of smoking-caused disease could be increased if the ENDS maintained nicotine addiction and its users continued to smoke cigarettes and to use multiple products that deliver nicotine. Furthermore, these alternative products, particularly those that involve flavorings attractive to adolescents, may serve as a gateway for adolescents to initiate smoking and thus start on a path that eventually leads to tobacco addiction. Currently there is a paucity of data on issues such as these; along with the direct adverse health effects associated with use of these alternative products, these remain important lines of inquiry for future research. Definitive evidence on the long-term health effects of ENDS products will not be available for many years because any long-term health effects associated with these products will take decades to emerge. Furthermore, generating the needed evidence base will be complicated by the facts that there are so many different ENDS products and the products and their contents are evolving.

IMPACT OF CIGARETTE SMOKING ON MORTALITY

Cigarette smoking contributes significantly to the population burden of many of the leading causes of chronic disease deaths that typically occur in middle and late adulthood, such as cancer, cardiovascular disease, and COPD (HHS, 2004).

The combined death toll linked to cigarette smoking is staggering. Cig-

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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arette smoking is estimated to account for approximately 480,000 deaths per year in the United States (HHS, 2014). In 2010 the four leading causes of death in the United States were heart disease (597,700 deaths), cancer (574,700 deaths), chronic lower respiratory diseases (138,100 deaths), and stroke and cerebrovascular disease (129,500) (Heron, 2013). Cigarette smoking is a major cause of all four of these diseases. Furthermore, smoking is also a cause of the seventh (diabetes, 69,000 deaths) and eighth (influenza/pneumonia, 50,100 deaths) leading causes of death (Heron, 2013).

Cancer

As a cause of 12 different types of malignancy, cigarette smoking is responsible for 163,700 cancer deaths per year in the United States (HHS, 2014; NCHS, 2013). Most of this mortality burden (130,700 deaths) is due to lung cancer, but cigarette smoking also caused 36,000 deaths from other malignancies (HHS, 2014).

Cardiovascular Disease

Cigarette smoking is estimated to cause 160,600 cardiovascular disease deaths per year in the United States (HHS, 2014). The majority of the smoking-caused cardiovascular deaths (99,300 deaths) are due to coronary heart disease, but smoking also causes 25,500 deaths from other forms of heart disease. Furthermore, cigarette smoking causes 15,300 deaths from cerebrovascular disease and 11,500 deaths from other forms of vascular disease.

Diabetes

Type 2 diabetes mellitus is a leading underlying cause of mortality from cardiovascular disease, and it also leads to other adverse consequences such as kidney failure and blindness (HHS, 2014). It is the seventh leading cause of death in the United States (Heron, 2013). Cigarette smoking is estimated to cause 9,000 deaths from type 2 diabetes per year in the United States (HHS, 2014).

COPD

More than 138,000 Americans died from COPD in 2010 (Heron, 2013), making it the third leading cause of death in the United States. Cigarette smoking is the predominant cause of COPD. Estimates indicate that 100,600 COPD deaths per year in the United States are attributable to cigarette smoking (HHS, 2014).

Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
×

Increased Susceptibility to Infectious Lung Diseases

Cigarette smoking is causally associated with an increased risk of pneumonia (HHS, 2004) and tuberculosis mortality (HHS, 2014). Cigarette smoking is estimated to cause 12,500 deaths from these infectious diseases per year.

IMPACT OF EXPOSURE TO SECONDHAND SMOKE ON MORTALITY

Due to its causal associations with coronary heart disease and lung cancer, secondhand smoke exposure is estimated to cause more than 41,300 deaths per year in the United States (HHS, 2014). The majority of these (almost 34,000 deaths) are due to coronary heart disease, while more than 7,000 deaths per year are from lung cancer (HHS, 2014). Furthermore, parental smoking is estimated to cause approximately 600 deaths per year from prenatal conditions and 400 deaths per year from sudden infant death syndrome (HHS, 2014).

Finding 4-9: Tobacco use is causally associated with premature mortality from a variety of causes, such as lung infections, chronic obstructive pulmonary disease, coronary heart disease, and a variety of cancers.

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Suggested Citation:"4 The Effects of Tobacco Use on Health." Institute of Medicine. 2015. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products. Washington, DC: The National Academies Press. doi: 10.17226/18997.
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Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products Get This Book
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Tobacco use by adolescents and young adults poses serious concerns. Nearly all adults who have ever smoked daily first tried a cigarette before 26 years of age. Current cigarette use among adults is highest among persons aged 21 to 25 years. The parts of the brain most responsible for cognitive and psychosocial maturity continue to develop and change through young adulthood, and adolescent brains are uniquely vulnerable to the effects of nicotine.

At the request of the U.S. Food and Drug Administration, Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products considers the likely public health impact of raising the minimum age for purchasing tobacco products. The report reviews the existing literature on tobacco use patterns, developmental biology and psychology, health effects of tobacco use, and the current landscape regarding youth access laws, including minimum age laws and their enforcement. Based on this literature, the report makes conclusions about the likely effect of raising the minimum age to 19, 21, and 25 years on tobacco use initiation. The report also quantifies the accompanying public health outcomes based on findings from two tobacco use simulation models. According to the report, raising the minimum age of legal access to tobacco products, particularly to ages 21 and 25, will lead to substantial reductions in tobacco use, improve the health of Americans across the lifespan, and save lives. Public Health Implications of Raising the Minimum Age of Legal Access to Tobacco Products will be a valuable reference for federal policy makers and state and local health departments and legislators.

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