Disease and Mortality

Tobacco was used in the pre-Columbus Americas for medicinal and religious purposes. Following the first voyage of Columbus, within several centuries of the arrival of tobacco in Europe, as use of tobacco products became prevalent, tobacco was suspected as a cause of disease and mortality. In the 1900s, cigarette smoking became a common and widespread practice among men, probably because of the efficacy of cigarette smoking in delivering nicotine, now known to be addicting, and the powerful marketing of very large corporations. The first indications of the coming epidemic were apparent in the early 1900s as lung cancer death rates began to increase and doctors began to see increasing numbers of cases of this fatal disease.

Lung cancer, now the most common cause of cancer death in the United States, was a relatively rare disease prior to the widespread use of tobacco in developed countries in the first half of the twentieth century. One hypothesis attributed the epidemic increase in lung cancer to worsening environmental pollution from the fumes of motorcars, from industrial plants, from the surface of tarred roads, and from gas works (Doll and Hill 1950). Richard Doll, one of the foremost researchers to link smoking with cancer, later commented, "I was fascinated by the enormous increase in mortality from lung cancer. At first I thought it was more likely to have something to do with motorcars. But I used to go around the wards checking the notes after discharge to see whether the diagnosis [of lung cancer] was confirmed or not and what immediately struck me was that if a person was a nonsmoker the diagnosis was practically never confirmed, but if he or she was a smoker then it was almost always lung cancer" (Bower 1997). Lung cancer was not the only disease to increase during this period; rises were noted for other cancers, and for chronic heart and lung diseases.

These increases were investigated using epidemiology. Epidemiologic studies are designed to uncover the factors that lead one person to develop a disease while some others do not. Epidemiology, defined as the study of the occurrence and causes of disease and death in populations, has been central in tracking the epidemics of diseases related to both active and passive smoking and making the causal linkages to smoking. Typically, an epidemiologic study evaluates the risk for a disease in the exposed persons (smokers) and nonexposed persons (nonsmokers). The "relative risk" refers to the ratio of these two risks. The relative risk can be estimated through two different types of epidemiologic study. A cohort study involves following smokers and nonsmokers over time and comparing disease rates in the two groups. A case-control study involves comparing the smoking habits of people with the disease being studied, for example lung cancer, with smoking habits of similar people without the disease. Epidemiologists gauge the strength of a factor in causing a disease by the size of the relative risk; for lung cancer, they would also examine whether the relative risk is higher for those who have smoked more or longer.

By the early 1950s, landmark epidemiologic investigations provided irrefutable scientific evidence on smoking as a cause of lung cancer, and evidence for causation of other diseases also began to accumulate. To date, numerous scientific publications and summary reports have implicated cigarette smoking as a cause or contributing factor to an ever-lengthening list of diseases: stroke, heart attack, emphysema, chronic bronchitis, pregnancy complications, many types of cancers, and even cataract. Smoking harms nearly every organ of the body, causing not only many specific diseases, but also poorer health in general and a shortened lifespan for smokers as compared to nonsmokers. The scientific research on the many adverse effects of smoking is the largest and best-documented literature linking any behavior and environmental agent to disease in humans. Richard Doll writes, "That so many diseases—major and minor—should be related to smoking is one of the most astonishing findings in medical research in this century; less astonishing perhaps than the fact that so many people have ignored it" (Doll 1999).

Calculating Risk of Lung Cancer from Smoking

I n a cohort study, Richard Doll and Richard Peto tracked British doctors for 20 years. In the study population, death rates from lung cancer in smokers and nonsmokers were 140 and 10 per 100,000 respectively.

To calculate the relative risk of lung cancer:

A relative risk of 14 means that smokers are 14 times more likely to die from lung cancer than nonsmokers.

To calculate the attributable risk, or the total risk of lung cancer in smokers that is attributable to smoking, we would subtract the risk in the unexposed group (nonsmokers) from the risk in the exposed group (smokers).

Attributable risk = Risk of exposed - risk of nonexposed:

140 - 10 = 130 per 100,000

An attributable risk of 130 means that of the 140 lung cancer deaths in smokers, 130 are due to smoking.

To calculate the percent attributable risk, or the percent of lung cancer attributable to smoking, we would divide the attributable risk by the risk in smokers.

A 92.9 percent attributable risk means that of the lung cancer deaths in smokers, 92.9 percent is caused by smoking.

▌ FROM DOLL, RICHARD, AND RICHARD PETO.

"MORTALITY IN RELATION TO SMOKING: TWENTY YEAR'S OBSERVATION ON MALE BRITISH DOCTORS."

BRITISH MEDICAL JOURNAL 2 (1976): 1525–1536.

Health Effects from Active Smoking: A View from Across the Centuries

The extent to which active smoking damages health and causes disease is remarkable. Active smoking results in most of the leading causes of death worldwide: cancers, cardiovascular diseases, chronic respiratory diseases, and respiratory infections. The risks for most of these diseases increase with the number of cigarettes smoked and the length of smoking, and decrease after quitting. Filters on cigarettes do not greatly reduce the risk of smoking, nor are the cigarettes labeled "light" or "mild" any safer than regular cigarettes (NIH 2001). Since 1964 the U.S. Surgeon General has published periodic reviews of the health effects of smoking. The following table lists the diseases that have been linked to smoking and provides the U.S. Surgeon General's highest-level conclusion concerning the causation of the disease by smoking:

Reduced Life Span—Mortality from All Causes

Not surprisingly, smokers have a substantially reduced life span in comparison with people who have never smoked. One of the first studies on the health effects of tobacco was conducted in 1938 by Dr. Raymond Pearl, a biostatistician at the St. Johns Hopkins School of Public Health. Dr. Pearl collected medical histories, complete with smoking habits, of 6,813 men living in Baltimore. He found a sharp decrease in the number of survivors after the age of thirty-five years in male heavy users compared to nontobacco users. Figure 1 shows survival curves for nonsmokers, moderate smokers, and heavy smokers. At the 50 percent point (median) there is an eight-year difference between nonsmokers and heavy smokers. For the time, Pearl offered the controversial conclusion that smoking "is associated with a definite impairment of longevity" (Kluger 1997).

Numerous other studies have also documented reduced life span in smokers compared to nonsmokers. In a study of 34,000 male British physicians tracked for forty years from 1951–1991, the median life expectancy after age thirty-five years was seven and one-half years shorter for smokers compared to nonsmokers (Doll, Peto, and Wheatley 1994). The decrease in survival was inversely related to the length and intensity of smoking: those who smoked more cigarettes per day and over a greater period of years had shorter life spans. Calculations in the 1990 U.S. Surgeon General's Report indicate that for those who quit smoking before the age of fifty, it is possible to avert nearly fifteen years of life lost compared to those who continue to smoke (DHHS 1990). The World Health Organization (WHO) estimates that smoking will prematurely kill half of all lifetime smokers. (WHO 2002).

Today, smoking ranks as the largest cause of avoidable premature death in the developed world. In the United States, smoking deaths that are attributable to tobacco have increased dramatically in both men and women, from 70,000 in 1950 to 440,000 in 2000 (MRC). Each year, smoking contributes to deaths from lung cancer, coronary heart disease, chronic lung disease, stroke, and other cancers (see Figure 2). Even in developing countries, smoking is a major contributor to mortality. Studies in India and China have confirmed findings from earlier studies in the United States and the United Kingdom that overall death rates among tobacco users are about twice those of nonusers (Liu, et al. 1998; Niu, et al. 1998; WHO 2001). In India alone, smoking caused an estimated 700,000 deaths in the year 2000 (Gajalakshmi et al. 2003).

Cancer

In the United States, death rates from lung cancer began increasing rapidly around the mid-twentieth century (see Figure 3). At the time, the causes of many cancers were still unknown and lack of sophisticated treatment options meant that many cancers were fatal. An epidemiological approach—a novel method at the time—was used to look for the underlying causes. Some German studies conducted in the 1930s and 1940s pointed towards tobacco as a factor but the first definitive studies are generally considered to have been published in 1950—five case-control studies.

In one of these studies, Morton Levin at Roswell Park, a cancer hospital, asked his hospital staff to begin collecting data on the smoking habits of every entering patient. Levin compared cancer patients who had smoked to cancer patients who had not smoked. The lung cancer rate in long-term smokers (twenty-five years or more) was 20.7 percent compared to 8.6 percent among nonsmokers (Levin 1950). Using a similar case-control study design, Ernst Wynder, a medical student, and Evarts Graham, a thoracic surgeon, interviewed patients with lung cancer and patients without lung cancer. Smoking histories for all study participants were ranked into 5 categories, ranging from nonsmokers to chain smokers. Wynder recalls, "After twenty or so interviews I knew I had something" (Kluger 1997). The results incriminated smoking as a strong causal factor: 96.5 percent of the 605 lung cancer patients were moderate to heavy chain smokers for several years compared with 73.7 percent of the nonsmoking controls (Wynder and Graham 1950). Also in 1950, Austin Bradford Hill and Richard Doll published results from a smoking study comparing cancer patients in 20 hospitals with noncancer patients. They reported that heavy smokers were 50 times more likely than nonsmokers to contract lung cancer and cautiously concluded "that cigarette smoking is a factor, and an important factor, in the production of carcinoma in the lung." Several animal studies conducted in the 1950s also supported the epidemiologic evidence: cigarette tar applied regularly to the skin of mice over time caused tumors (Wynder et al. 1953).

Together, the combination of the human and animal evidence provided a powerful indication of causation. These studies launched a great variety of follow-up research examining the link between tobacco and disease and sparked substantial media reporting. The tobacco industry was so threatened by the emerging scientific evidence and the resulting drop in cigarette sales that they responded by establishing the Tobacco Industry Research Committee (TIRC), composed of 14 leading tobacco manufacturers and allied groups. The stated objective of the TIRC was to fund independent scientific research about the health effects of smoking. However, tobacco industry documents brought forward from recent litigation show that the TIRC was originally created for the purpose of public relations. The TIRC took out a full page announcement in January 1954 in over 400 newspapers headlined, "A Frank Statement to Cigarette Smokers" aiming to calm consumer fears over the emerging evidence that cigarette smoking is linked to lung cancer. The announcement by the TIRC said that the recent evidence produced was merely statistical and "could be applied with equal force to any one of many aspects of modern life ... We believe the products we make are not injurious to health" (<http://www.tobacco.org> 1998). Despite industry efforts, by the mid-1960s, research on smoking and disease led to major pronouncements on the health hazards of smoking from authorities on both sides of the Atlantic.

Today, it is well accepted that cigarette smoking is without question the most important preventable cause of cancer. Many ingredients in tobacco and tobacco smoke have been found to be carcinogens (cancercausing substances), some added by tobacco manufacturers to enhance flavor and addictiveness (WHO 2001). The 1982 U.S. Surgeon General's Report states, "Cigarette smoking is the major single cause of cancer mortality in the United States." This statement is still true today, not only for the United States, but for many other developed countries. As the above table shows, cigarette smoking has been found to be associated with cancer at many sites. For lung cancer, the risk is particularly great with smokers experiencing an approximately twenty-fold increased risk for lung cancer when compared to lifelong nonsmokers (Doll et al. 1994). Cancers of the larynx, mouth, pharynx, and esophagus are also much more common in smokers than in nonsmokers.

Two Revolutionary Articles

F ive epidemiologic studies were published in 1950 directly associating cigarette smoking with lung cancer. But two studies in particular, from opposite sides of the ocean, caught the attention of the medical research world. Young German-born medical student Ernst L. Wynder and the esteemed surgeon and medical educator, Evarts Graham, reported finding that, of the 605 male patients in their study with bronchogenic carcinoma (lung cancer), 96.5 percent had been heavy smokers (at least 25 cigarettes a day for 20 years), while among male hospital patients without cancer only 73.7 were heavy smokers (at the time, cigarette smoking was much more common among the U.S. population). Their paper, published in the Journal of the American Medical Association, also suggested that men with lung cancer smoked more heavily and for more years than male patients without cancer. In that same year in England, medical professor Richard Doll and famed epidemiologist and statistician Austin Bradford Hill concluded that heavy smokers had a fifty times greater chance of getting lung cancer than nonsmokers. Their influential paper, which appeared in the British Medical Journal, described in detail how they collected information from patients about their smoking history in a way that was reliable and unbiased. Although cigarettes were previous suspects as a link to cancer, the diligence and level of expertise connected with these two studies, in addition to the convincing findings, resonated volumes within the medical community.

▌ DONALD LOWE

Cardiovascular Disease

Reports on the links between smoking and cardiovascular disease date back to the beginning of the twentieth century. Today, the epidemiologic evidence on smoking and cardiovascular diseases is massive. Cardiovascular disease encompasses heart diseases such as coronary heart disease, "heart attack," stroke, arteriosclerosis, and diseases of the blood vessels. The burden of cardiovascular disease is enormous: Together heart disease and stroke account for approximately 40 percent of all deaths annually in the United States (CDC 2004).

Framingham, Massachusetts, has been called the town that changed America's heart. In 1948, 5,000 study participants from Framingham were enrolled in a large-scale cohort study to investigate why cardiovascular disease, in particular coronary heart disease and stroke, had become the nation's number one killer. By tracking disease progression over time in study participants, the Framingham Heart Study uncovered some of the biological and environmental determinants of heart disease and gave public health experts leads for establishing prevention guidelines. The Framingham study examined some key lifestyle behaviors that were possibly contributing to heart disease including diet, physical activity, and smoking. Results soon demonstrated that smokers were at increased risk of having myocardial infarction (sudden death) and coronary heart disease, and the risk was found to be related to the number of cigarettes smoked each day (DHHS 1990). The study showed that modifying lifestyle habits, such as smoking, physical inactivity, and diet could significantly alter disease progression and reduce disease severity: smoking cessation was found to promptly halve the risk compared to those who continued to smoke.

A Nation's Emerging Awareness of Tobacco Dangers

T he public's attention on the dangers of smoking was captured in the 1950s through the media. In 1952, Reader's Digest, one of the most popular magazines in the United States and the United Kingdom, published an article titled "Cancer by the Carton."The article described the dangers of smoking, detailing the risks of lung cancer and heart disease. The article also accused the tobacco industry of covering up the perils of smoking through its advertising claims of "mildness" and references to reduced health risks. The publication of "Cancer by the Carton" instigated a serious of similar attacks of the tobacco industry in other magazines. Media attention and exposure of the tobacco industry significantly began a shift in society's attitude towards tobacco.

In 1964, the Surgeon General of the United States Public Health Service released a landmark report titled, "Smoking and Health." Although there were earlier statements that had been released in 1957 and 1959, the report was an exhaustive literature review of over 7,000 articles, including 3,000 research reports. Conducted by an independent body of scientists, it was the United States' first widely publicized official recognition that smoking causes cancer and other diseases. After much study, the report committee concluded that smoking caused lung and laryngeal cancer in men, probably caused cancer in women, and was the major cause of chronic bronchitis. The report also highlighted that smokers were much more likely than nonsmokers to contract coronary heart disease. Renowned for its clarity and unassailable review of scientific evidence, the 1964 report of the Surgeon General defined the clear beginning of a national tobacco control agenda in the United States. From the time the report was published to the early 2000s, forty years later, the smoking rate in the United States decreased from 46 percent to 23 percent of adults, a reduction of 50 percent.

Another well-known study, the Nurses' Health Study, which began in 1976 (Stampfer et al. 2000), gave similar and powerful results for women. In the Nurses' Health Study the rate of fatal coronary heart disease among participants who never smoked was 5 per 100,000 person-years (a measurement combining persons and time as the denominator in the rate). This rate increased to 8, 19, and 27 deaths per 100,000 person-years for current smokers who smoked 1–14, 15–24, and >25 cigarettes per day, respectively. For women who smoked >25 cigarettes per day, it was reported that 81 percent of the coronary heart disease deaths among these heavy smokers were attributable to cigarette smoking Willett et al. 1997).

Despite the scientific advances in cardiovascular disease research, heart disease and stroke remain the first and third leading causes of death in the United States, with cancer the second leading killer of Americans. Cigarette smoking has been found to be causally associated and an important risk factor for heart disease, cancer, and stroke—the nation's top three leading killers.

Adverse Effects on Reproduction

The adverse effects of smoking begin even before birth. Maternal smoking reduces fertility and adversely affects pregnancy outcomes. Smoking during pregnancy reduces birth weight by approximately 200 grams on average (DHHS 1990). The degree of birth weight reduction is related to the amount smoked. If a mother who smokes gives up this behavior by the third trimester, much of the weight reduction can be avoided. Smoking also increases rates of other adverse effects on reproduction including spontaneous abortion, and smoking during pregnancy is now considered to be a cause of Sudden Infant Death Syndrome (SIDS). There is more limited evidence suggesting that smoking by the mother may increase risk for congenital defects, especially cleft lip and palate (Scientific Committee on Tobacco and Health, et al. 1998).

Health Effects of Secondhand Smoke

Because a third of the world's population are smokers, the remaining two-thirds, nonsmokers, often inhale secondhand smoke (SHS) involuntarily or passively. SHS is the combination of smoke emitted from the burning tip of a cigarette and smoke components in the air exhaled by smokers. Research on SHS began to accumulate in the 1970s, and today there is consensus in the scientific community that no level of exposure to SHS is safe. The Environmental Protection Agency has classified secondhand smoke as a carcinogen, meaning that it causes cancer in humans. Despite the strength of the evidence, the tobacco industry has devised many strategies for discrediting the science to convince the public that there remains a "controversy" as to whether SHS is dangerous.

The adverse effects of passive smoking begin before birth and extend across the lifespan. Historically, epidemiologic studies first found adverse effects in infants and children in families with smoking parents. In infants and preschool children, most studies have found a significant association between exposure to SHS (especially when the child's mother smokes) and respiratory symptoms (wheezing, coughing, phlegm, and shortness of breath) in children. These associations are consistent throughout different geographic areas, including Japan, Korea, the People's Republic of China, Europe, and North America. A 1999 World Health Organization publication evaluated the findings on passive smoking and the health of children. Exposure to SHS was found to be a cause for slightly reduced birth weight, lower respiratory disease, chronic respiratory symptoms, middle ear infection, and reduced lung function (WHO 2001). There is more limited evidence suggesting that SHS exposure of the mother adversely affects child development and behavior (Eskenazi and Castorina 1999). The following table lists the health effects causally linked with SHS for children and adults:

In adults, lung cancer was the first fatal disease shown to be causally associated to SHS. Subsequent studies have linked SHS to heart disease and other adverse health effects. Published in 1981, Takeshi Hirayama's cohort study in Japan was a landmark in SHS research. Hirayama tracked deaths in over 90,000 nonsmokers and compared mortality in those married to smokers and those married to nonsmokers. He found increased risk for lung cancer in women who had never smoked and were married to smokers compared with women who had never smoked and were married to nonsmokers. The tobacco industries responded by arranging for many scientists to criticize and attempt to discredit the study. However, Hirayama's results have been confirmed by many additional studies, and major international consensus reports have concluded that passive smoking causes lung cancer. To date, the association of SHS with lung cancer has now been evaluated in over 50 epidemiological studies. All told, the increased risk for a nonsmoker married to a smoker is on the order of 20 percent for women and 30 percent for men. (IARC 2002).

Epidemiological data first raised concern that passive smoking may cause coronary heart disease with a study in California conducted in 1985 (Garland et al.1985). Over 20 studies have now been reported on the association between SHS and cardiovascular disease risk. These studies cover a wide range of populations, both geographically and racially. While many of the studies were conducted within the United States, some were also conducted in Europe, Asia, South America, and the South Pacific. Most studies measured the effect of secondhand smoke exposure due to smoking by the spouse; however, some studies also assessed exposures from smoking by other household members, or occurring at work, or in transit. Since the 1985 report, as the evidence has subsequently mounted it has been systematically reviewed by the American Heart Association (1992) and the California Environmental Protection Agency (NCI 1999). These expert groups and others have concluded that heart disease is causally associated with SHS exposure. Evidence also links SHS to other adverse effects, including exacerbation of asthma, reduced lung function, and respiratory symptoms, but SHS has not yet been judged to be a cause of these effects (NCI 1999).

The Global Tobacco Epidemic: A View into the Future

Cigarette addiction has been widespread in many developed countries for over a century and mortality statistics from these countries chart the resulting epidemics of heart disease, lung disease, and cancer. Dr. Gro Harlem Brundtland, the Director-General of WHO, writes, "it is rare, if not impossible, to find examples in history that match tobacco's programmed trail of death and disease" (WHO 2001). Most alarming is that the epidemic is growing. If smoking trends continue along the estimated trajectory, in 2020 tobacco use will be responsible for 10 percent of all disease globally (WHO 2001).

While smoking rates have decreased in the United States, the United Kingdom, and other affluent Western countries since the mid-twentieth century, globally, smoking rates are on the rise along with tobacco related deaths. Today there are an estimated 1.1 billion smokers (World Bank 1999). By 2025 it is estimated that there will be 1.6 billion smokers. Not only are more people smoking, but they are smoking more cigarettes per day than previously (World Bank 1999).

Aggressive marketing tactics by the tobacco industry have extended the tobacco epidemic from the developed to the developing regions of the world. The mortality rates have been projected and they are enormous, especially for developing countries. By 2025, there will be an estimated 10 million tobacco deaths globally, of which 70 percent will be in current developing countries (see Figure 4). This is in contrast to the 1 million tobacco deaths globally in 1965, of which only 100,000 were in developing countries (Bollinger and Fagerstroüm 1997). Half of those who die will be middle–aged, losing 20–25 years of life (Peto and Lopez 2000).

If current smoking patterns persist, developing countries will face enormous epidemics of premature death. The tobacco epidemic in China is a case in point. China has the highest cigarette consumption per capita in the world. One out of every three cigarettes smoked in the world today is smoked in China by its 300 million smokers. In 2000, annual smoking deaths in China were estimated at 1 million. In 2050, China is anticipated to face 3 million tobacco deaths per year. Not surprisingly, many other countries that have high smoking rates, such as India and Russia, face a similar epidemic if preventive action is not taken. Future tobacco deaths can be avoided through two means: increasing the rate of smoking cessation (quitting) and decreasing smoking uptake (starting) by young adults (Peto and Lopez 2000).

Tobacco deaths are preventable and can be averted through public health action. The challenge remains for governments to accelerate public health action to protect the health of their populations. If appropriate policy and program responses are not implemented today, the prediction of 10 million deaths a year by 2030 will become a tragic reality.

See Also Doctors; Insurance; Toxins.

▌ MAI-ANH HOANG

▌ JONATHAN M. SAMET

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epidemiology a branch of medicine that investigates the causes and contributing factors of disease.

epidemiological pertaining to epidemiology, that is, to seeking the causes of disease.

tar a residue of tobacco smoke, composed of many chemical substances that are collectively known by this term.

carcinogen a substance or activity that can cause cancer. Cigarette smoking has been proven to be carcinogenic, that is, cancer causing.