(From Grolier Multimedia Encyclopedia)

Smoking and Health

Smoking and Health, a topic, within the context of this article, rooted in the various physiological effects of tobacco smoke. Although a number of psychoactive substances, including marijuana and opiate drugs, can be heated and inhaled in vapor form, in most cultures the term smoking refers, as it does in the following text, to the inhalation of tobacco smoke.

History. How and when humankind discovered the psychotropic properties of tobacco are unknown. Europeans were apparently introduced to tobacco smoking when 15th-century Italian explorer Christopher Columbus and his crew observed the practice among the indigenous peoples of the New World. One of the earliest descriptions of tobacco use was written in 1527 by Bartolomé de las Casas, a Spanish bishop who accompanied later Spanish explorers to the Americas. The clergyman noted that "the natives wrap the tobacco in a certain leaf in the manner of musket formed of paper and having lighted one end of it, by the other they suck, absorb, or receive that smoke inside with their breath." Along with their consumption of tobacco in the form of cigars and pipes, the New World's native inhabitants also inhaled tobacco in a ground or finely shredded form that came to be known as snuff.

Over the next century European explorers became a conduit for tobacco use, spreading the practice and bringing tobacco seeds to Europe, Africa, Asia, the Middle East, and islands of the Pacific. Believing tobacco to be an herbal health remedy, Jean Nicot, French ambassador to Portugal, sent tobacco plants to the queen of France, Catherine de Médicis, in 1561. Sir Walter Raleigh, a favorite of Queen Elizabeth I of England, is credited with having popularized smoking in Britain during the second half of the 16th century.

During the 16th and 17th centuries, tobacco was recommended as a cure for coughs, the pain of labor, headaches, rheumatism, inflammations of the nose and air passages, hoarseness, and pains in the stomach, lungs, and breasts as well as for the treatment of gonorrhea, epilepsy, cancer, and plague. However, Queen Elizabeth's successor, James I, tried aggressively to discourage tobacco use. In his now-famous treatise A Counterblaste to Tobacco (1604), James described smoking as "a custom loathsome to the eye, hateful to the nose, harmful to the brain, dangerous to the lung, and in the black stinking fume thereof resembling the horrible stygian smoke of the pit that is bottomless." Despite such royal opposition, however, tobacco use continued to spread, and by the mid-17th century tobacco was being cultivated throughout the world.

Swedish naturalist Carl Linnaeus in 1753 placed the tobacco plant in its own taxonomic genus, Nicotiana, named in honor of Jean Nicot, and identified two of the eight species, specifically, N. tabacum and N. rustica. In 1828 two medical students at Heidelberg, Wilhelm Heinrich Posselt and Ludwig Reimann, first isolated the tobacco alkaloid, which they called nicotine.

The most efficient form of nicotine consumption, the cigarette, was not invented until the l9th century. The first cigarette factories were set up in Cuba in 1853, London in 1856, and the United States in 1860. In 1884 the cigarette industry grew further, owing to the invention of the Bonsack cigarette machine, which, after subsequent improvements, had a daily output equaling that of 50 laborers working by hand, producing about 120,000 cigarettes a day.

Tobacco-grower James Buchanan Duke, in about 1890, bought out four competing cigarette manufacturers to establish the American Tobacco Company. Through corporate mergers Duke's firm soon became the largest privately owned cigarette and tobacco company in the world, although in 1911 the U.S. government, by way of an antitrust action, forced the enterprise to break up into 16 smaller companies, one of which retained the original name. In some countries the production and sale of cigarettes and other forms of tobacco were limited to national monopolies almost from the time tobacco use was introduced. China's monopoly subsequently became the largest, marketing about 1.7 trillion cigarettes in 1993, enough to account for approximately 31% of the global market.

Until the early years of the 20th century, however, tobacco was consumed mainly in pipes and in the form of cigars and chewing tobacco, products that began to lose popularity in about 1913, when the R. J. Reynolds company introduced a milder cigarette. The company incorporated a sweetened form of the specially bred Burley tobacco and employed a new curing (drying) process, flue curing, in which tobacco is dried in heated air without exposure to smoke or odors. Sold under the Camel brand, the product became the archetype of the modern cigarette. The outbreak of World War I also boosted the popularity of cigarettes through their widespread use by soldiers on both sides of the conflict.

Tobacco Products. Several types of tobacco are used commercially around the world, with harvesting and curing methods differing according to variety and intended use. Cigar tobacco, for example, tends to be air cured, with the leaves being dried under natural weather conditions. Other processing methods include curing under direct sunlight, or sun curing, used in Asia and other parts of the world, and fire curing, utilizing heat and smoke from open fires.

Most smoking-related tobacco products are made from N. tabacum, although N. rustica also is used for cigarette and pipe tobacco. In most parts of the world, commercially manufactured cigarettes are the most popular tobacco product, the typical variety being about 2.5 to 5 inches (6 to 12 cm) long and 0.8 to 1 inch (2 to 3 cm) in circumference, with a weight of 0.02 to 0.04 ounce (0.5 to 1.2 grams). Other types of cigarettes are often hand rolled and include clove-flavored varieties, called kreteks, which are smoked in Indonesia, and bidis, popular in India and other parts of Southeast Asia and usually made from a small amount of locally grown tobacco wrapped in a temburni leaf. These alternative types of cigarettes may deliver three times more tar (discussed below) and two to three times more puffs than an ordinary cigarette.

Cigars range widely in size from large, 0.35-ounce (10-gram) cylinders, to cheroots (a type of small cigar), to cigarillos, which are not much larger than cigarettes. Pipe tobaccos are commonly a blend of 20 or more different leaf (loosely packaged) tobaccos, often with added sweetening agents and flavorings.

Smokeless tobaccos include chewing tobacco, pan, and snuff. In dry form, snuff is inhaled through the nose, while moist snuff is often flavored with sweeteners and is held in the mouth between the cheek and gum. Pan, which, like the bidi cigarette, is popular in India and other regions of Southeast Asia, is also known as betel-quid and consists primarily of tobacco, areca nuts, and slaked lime wrapped together in a betel leaf. Areca nuts are the source of arecoline, a drug that acts as a mild stimulant for the central nervous system. Also popular in India is khaini, a mixture of tobacco and slaked lime used much like snuff.

Tobacco is grown in more than 100 countries, with the 25 largest producers accounting for 90% of the world's production. Most tobacco manufacturing is under the control of multinational corporations and the aforementioned state monopolies. In addition to being the world's largest cigarette manufacturer internationally, China also produces more tobacco than any other nation, growing about 38% of the world's tobacco crop.

Smoking Prevalence. The World Health Organization (WHO) has estimated that by 2006 there were about 1.3 billion smokers worldwide, comprising 1 billion men and 300 million women. At the current rate, that number will rise to 1.7 billion by 2025. The world's smokers together consumed some 6.05 × 1012 cigarettes annually, or 9 to 12 × 109 pounds (4.2 to 5.5 × 109 kg) of tobacco. These figures are only estimates, however, since the quality of tobacco-use data varies widely among countries and the information must often be extrapolated from sales and shipments of manufactured cigarettes, even though in some populous countries, such as India, much of the tobacco smoked is in the form of homemade cigarettes. It is also estimated that 15% to 35% of world tobacco consumption is in noncigarette form.

Internationally, WHO figures indicate remarkable variability in the estimated prevalence of smoking among persons over age 15. The numbers range, for example, from more than 60% among males in Korea, the Philippines, the Russian Federation, Turkey, Cambodia, and China to approximately 20% in Finland, the United States, Sweden, and New Zealand. The figures also reveal that little correlation exists between smoking prevalence among men and that among women. While the rates between males and females are almost equal in the United Kingdom, the United States, and Canada, they are dramatically lower among women in the more observant Islamic countries, in China, and in regions around the Pacific Rim.

Nicotine Pharmacology. About 2% to 8% of the N. tabacum plant consists of nicotine, the biological effects of which have been studied for more than 100 years. As early as the turn of the 20th century, researchers suspected that the compound, known chemically as 3-(-methyl-2-pyrolidinyl) pyridine, causes tobacco cravings, but it was not until the 1970s that enough scientific evidence had been gathered to determine that nicotine is indeed responsible for the psychological and behavioral effects as well as many of the physiological changes linked to smoking. For this reason pharmacological research into smoking has become primarily a study of nicotine pharmacology.

The idea that nicotine acts by binding to specific receptors found on the surface of nerve cells is one of the oldest theories in pharmacology, having first been proposed in about 1889. Research has subsequently determined the molecular structure of these linkage areas in the membrane of the nerve cell. Known specifically as neuronal nicotinic cholinergic receptors, these exist widely in the brain and in both the peripheral and the autonomic nervous system.

Nicotinic cholinergic receptors are composed of five subunits, which combine to form a channel. All nicotinic receptors in the brain are not identical, instead varying according to the makeup of their subunits.

When a molecule known as a nicotinic agonist binds to a nicotinic receptor, the channel opens, allowing ions (atoms or molecules with a positive or negative charge)—including those for sodium (Na+), potassium (K+), and calcium (Ca2+)—to flow in or out of the cell. Though the neurotransmitter acetylcholine, released from nerve cells, normally serves as the nervous system's nicotinic receptor ligand (a ligand being a molecule that binds to a receptor), some drugs or poisons, including nicotine, can bind to these receptors instead, either activating the channels or preventing receptor activation. Ligands that induce activation are called agonists, while those that prevent it are antagonists.

Dopamine Release. Owing to the locations of nicotinic receptors, nicotine interacts with neurons in many parts of the central, peripheral, and autonomic nervous systems, including those within a brain-stem region called the ventral tegmental area (VTA). Evidence suggests that nicotine is habit forming because of its effects on the VTA, which is one of the places where the body produces dopamine, a compound that, when released from neurons in the reward circuitry of the brain, can induce feelings of pleasure. Addictive drugs, including morphine and amphetamine, increase dopamine release from the VTA's neurons, producing euphoria. Nicotine also increases dopamine release from these neurons, with daily nicotine use apparently leading to sensitization, meaning that nicotine's ability to promote dopamine secretion is enhanced. This may partially explain why experienced smokers find cigarette use more rewarding than do novice smokers.

Desensitization and Hormone Release. Smokers often say that smoking keeps them alert and calm and aids concentration. Laboratory studies show that nicotine does improve performance on tasks requiring sustained concentration, but the reasons behind this remain unclear. One theory is that repeated exposure to nicotine desensitizes certain neurons, producing a calming effect. The phenomenon may also be related to the stimulation of acetylcholine release in the brain, although the activation of nicotinic receptors releases many substances besides dopamine and acetylcholine. These include the neurotransmitter serotonin and the hormones vasopressin, growth hormone, adrenocorticotropic hormone, cortisol, and, from the adrenal glands, epinephrine, also known as adrenaline. Some researchers assert that tobacco's calming effect simply results from alleviation of the nicotine withdrawal syndrome.

Antidepressant Effect. In addition to its other qualities, nicotine can, for some smokers, relieve depression, although again the cause is uncertain. This action could, however, help to explain findings that clinically depressed individuals are more likely to smoke and may subsequently experience severe depression when attempting to quit. One study has indicated that an unknown component of tobacco smoke seems to decrease the activity of the enzyme monoamine oxidase (MAO) in the brain, the same therapeutic action produced by antidepressant medications known as monoamine oxidase inhibitors. This same action on the MAO may increase nicotine's pleasurable effects because, when the MAO is inhibited, dopamine levels rise in neurons that are normally controlled by the MAO.

Tolerance. Although nonsmokers commonly experience dizziness or nausea from smoking a single cigarette or cigar, such discomfort is rare among regular smokers, who develop a tolerance to many of nicotine's adverse effects. This change may stem from an increase in the number of the brain's nicotinic cholinergic receptors or from decreased sensitivity in these receptors.

As tolerance rises, so, typically, does a smoker's tobacco use, often to between 15 and 40 cigarettes per day. Some aspects of tolerance, however, rapidly wax and wane, which is why even a heavy smoker perceives the first cigarette of the day as far stronger than the rest.

Nicotine Metabolism. Nicotine is readily absorbed by all of the body's tissues, including the skin, the respiratory epithelium, and the mucous membranes of the mouth, nose, and intestines. The compound's absorption through the mouth also depends on the pH level—or, in effect, the acidity—of the saliva present, with a more acidic saliva changing nicotine molecules into an ionic form that is not well absorbed. Similarly, nicotine entering the acidic medium of the stomach cannot easily move across cellular membranes, again reducing absorption, while in the alkaline medium of the small intestine, the molecule reverts to a soluble, nonionic state, easily passing through the intestinal wall. From there nicotine undergoes extensive metabolism in the liver, the resulting products, or metabolites, of this process being primarily cotinine and nicotine n-oxide. Consequently, only about 30% of nicotine from the intestine reaches the bloodstream in unmetabolized form.

In contrast, inhalation of tobacco smoke allows a greater amount of active nicotine to pass into the circulatory system. (As much as 90% of the nicotine inhaled from a cigarette is absorbed into the bloodstream.) From the bloodstream the compound passes to the heart, which pumps a significant portion of the nicotine directly to the brain; the transfer is so rapid, in fact, that nicotine in tobacco smoke reaches the brain more quickly than does nicotine injected directly into the bloodstream through a vein.

After a brief rise, the brain's nicotine concentration quickly falls as the compound is speedily redistributed to other parts of the body. Some researchers believe that the bolus of nicotine in each puff of tobacco inhaled from a cigarette reinforces the nicotine habit in the brain, probably by releasing a small amount of dopamine, so that hundreds of puffs per day reinforces the addiction hundreds of times per day. Nicotine readily crosses the placental barrier as well, resulting in fetal exposure to the compound when women smoke during pregnancy. Additionally, nicotine can pass into breast milk, albeit in very low levels.

Possessing a relatively short duration of action within the body, nicotine has a plasma half-life of between 30 minutes and 2 hours (meaning that half of the blood's nicotine levels disappear within this span of time). In nicotine-dependent cigarette smokers, who typically smoke every 30 to 45 minutes, blood nicotine levels rise cumulatively during the day before leveling off. Peak levels in the arteries, which deliver the drug to the brain, often reach approximately 40 micrograms per milliliter of blood. Although most nicotine in the body is metabolized in the liver, the compound is also eliminated through excretion in urine, passing into it from the bloodstream according to changes in urinary acidity. Lowering of the pH, that is, making the urine more acidic, as happens in stressful situations or through an increased intake of vitamin C, increases nicotine excretion, decreasing the compound's levels more rapidly.

Because cotinine, nicotine's major metabolite, has a much longer half-life than its parent compound, lasting from 10 to 40 hours, its presence in the body is commonly used to determine whether an individual's smoking cessation efforts have been successful.

Titration. As blood nicotine levels decline, the nicotine-dependent smoker begins to experience a sense of craving, this typically being a cue to reach for another cigarette. Because inhaled nicotine is absorbed so rapidly, smokers can adjust (titrate) their blood nicotine levels within a satisfying range not only by controlling the timing and number of cigarettes consumed but also by altering the way in which each cigarette is smoked, that is, the duration of each puff, the depth of smoke inhalation, and the length of time that smoke is held in the lungs. Consequently, although relatively high doses of nicotine may cause dizziness and nausea or, in extreme concentrations, actually prove lethal, smokers are able to titrate their nicotine intake to relatively safe levels and so rarely experience nicotine poisoning.

Such control also permits smokers to intensify their tobacco intake to the point of receiving almost as much tar, nicotine, and carbon monoxide from a cigarette advertised as low in tar and nicotine as from a standard one. The published tar and nicotine content of cigarettes is obtained using machines that mimic the inhalation of cigarette smoke but do not account for variations in smoking habits when nicotine levels in cigarettes are raised or lowered.

Composition of Tobacco Smoke. Tobacco smoke comprises both mainstream smoke, which tobacco users inhale directly into their lungs, and sidestream smoke, which escapes into the air from the end of a burning cigarette, cigar, or pipe. While smokers use tobacco primarily to obtain nicotine, they are inevitably exposed to the more than 4,000 other chemicals, including many toxins, present in gaseous form or as particulate matter (tar) in cigarette smoke.

The tobacco plant itself constitutes a major source of these compounds, with the green tobacco leaf containing approximately 2,500 distinct chemicals, among which are the residues of fertilizers and insecticides. Other compounds are formed through curing or are added during the manufacture of tobacco products. Additionally, through pyrolysis (heat-induced chemical changes), as tobacco enters the vapor (smoke) phase, more compounds are generated. Although most of the known toxic substances exist in the particulate fraction, some of the gaseous chemicals—such as carbon monoxide, nitric oxide, ammonia, benzene, hydrazine, hydrogen cyanide, various aldehydes, and volatile nitrosamines—have also been linked to various adverse health effects. The tobacco-specific nitrosamines, which are found in tar, are particularly potent carcinogens.

According to the National Cancer Institute, some 60 compounds in tobacco smoke have been classified as carcinogens, tumor initiators (chemicals that can irreversibly change normal cells), or tumor promoters (compounds that encourage tumor growth after the initiation of cell changes). These include benzopyrene, nitrosamines, methylpyrene, and fluoranthene. Because it escapes without first passing down the tobacco column and through a filter, sidestream smoke differs in composition from mainstream smoke, containing higher concentrations of a number of constituents, including more than twice as much carbon monoxide, almost twice as much tar, and nearly 3 times as much nicotine, and 10 to 40 times the level of ammonia and volatile nitrosamine. Sidestream smoke—also known as environmental, secondhand, or passive smoke—can prove unhealthy to individuals, even nonsmokers, who unintentionally inhale it while in the vicinity of a smoker.

The composition of cigarettes differs from one country to the next. In general, since the 1950s, when reports of smoking's adverse health effects became widely available, the tar and nicotine content of the average cigarette has declined from about 35 milligrams of tar and 3 milligrams of nicotine to about l5 milligrams of tar and 1 milligram of nicotine. Further, in most developed countries, cigarettes with filter tips have become almost universal. In Japan, for example, 98% of cigarettes are sold with filters. France and Poland are exceptions among developed countries in that unfiltered cigarettes remain quite popular.