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Monday, November 13, 2023

Tobacco smoking

From Wikipedia, the free encyclopedia
A woman smoking a cigarette, the most common method of tobacco smoking

Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed to have begun as early as 5000–3000 BC in Mesoamerica and South America. Tobacco was introduced to Eurasia in the late 17th century by European colonists, where it followed common trade routes. The practice encountered criticism from its first import into the Western world onwards but embedded itself in certain strata of a number of societies before becoming widespread upon the introduction of automated cigarette-rolling apparatus.

Smoking is the most common method of consuming tobacco, and tobacco is the most common substance smoked. The agricultural product is often mixed with additives and then combusted. The resulting smoke is then inhaled and the active substances absorbed through the alveoli in the lungs or the oral mucosa. Many substances in cigarette smoke trigger chemical reactions in nerve endings, which heighten heart rate, alertness and reaction time, among other things. Dopamine and endorphins are released, which are often associated with pleasure.

German scientists identified a link between smoking and lung cancer in the late 1920s, leading to the first anti-smoking campaign in modern history, albeit one truncated by the collapse of Nazi Germany at the end of World War II. In 1950, British researchers demonstrated a clear relationship between smoking and cancer. Evidence continued to mount in the 1960s, which prompted political action against the practice. Rates of consumption since 1965 in the developed world have either peaked or declined. However, they continue to climb in the developing world. As of 2008 to 2010, tobacco is used by about 49% of men and 11% of women aged 15 or older in fourteen low-income and middle-income countries (Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Russia, Thailand, Turkey, Ukraine, Uruguay and Vietnam), with about 80% of this usage in the form of smoking. The gender gap tends to be less pronounced in lower age groups.

Many smokers begin during adolescence or early adulthood. During the early stages, a combination of perceived pleasure acting as positive reinforcement and desire to respond to social peer pressure may offset the unpleasant symptoms of initial use, which typically include nausea and coughing. After an individual has smoked for some years, the avoidance of withdrawal symptoms and negative reinforcement become the key motivations to continue.

A 2009 study of first smoking experiences of seventh-grade students found out that the most common factor leading students to smoke is cigarette advertisements. Smoking by parents, siblings and friends also encourages students to smoke.

History

Use in ancient cultures

Aztec women are handed flowers and smoking tubes before eating at a banquet, Florentine Codex, 16th century.

Smoking's history dates back to as early as 5000–3000 BC, when the agricultural product began to be cultivated in Mesoamerica and South America; consumption later evolved into burning the plant substance either by accident or with intent of exploring other means of consumption. The practice worked its way into shamanistic rituals. Many ancient civilizations – such as the Babylonians, the Indians, and the Chinese – burnt incense during religious rituals. Smoking in the Americas probably had its origins in the incense-burning ceremonies of shamans but was later adopted for pleasure or as a social tool. The smoking of tobacco and various hallucinogenic drugs was used to achieve trances and to come into contact with the spirit world. Also, to stimulate respiration, tobacco smoke enemas were used.

Eastern North American tribes would carry large amounts of tobacco in pouches as a readily accepted trade item and would often smoke it in ceremonial pipes, either in sacred ceremonies or to seal bargains. Adults as well as children enjoyed the practice. It was believed that tobacco was a gift from the Creator and that the exhaled tobacco smoke was capable of carrying one's thoughts and prayers to heaven.

Apart from smoking, tobacco had uses as medicine. As a pain killer it was used for earache and toothache and occasionally as a poultice. Smoking was said by the desert Indians to be a cure for colds, especially if the tobacco was mixed with the leaves of the small Desert sage, Salvia dorrii, or the root of Indian balsam or cough root, Leptotaenia multifida, the addition of which was thought to be particularly good for asthma and tuberculosis.

Popularization

Gentlemen Smoking and Playing Backgammon in a Tavern by Dirck Hals, 1627

In 1612, six years after the settlement of Jamestown, Virginia, John Rolfe was credited as the first settler to successfully raise tobacco as a cash crop. The demand quickly grew as tobacco, referred to as "brown gold", revived the Virginia joint stock company from its failed gold expeditions. In order to meet demands from the Old World, tobacco was grown in succession, quickly depleting the soil. This became a motivator to settle west into the unknown continent, and likewise an expansion of tobacco production.

Frenchman Jean Nicot (from whose name the word nicotine is derived) introduced tobacco to France in 1560, and tobacco then spread to England. The first report of a smoking Englishman is of a sailor in Bristol in 1556, seen "emitting smoke from his nostrils". Like tea, coffee and opium, tobacco was just one of many intoxicants that was originally used as a form of medicine. Tobacco was introduced around 1600 by French merchants in what today is modern-day Gambia and Senegal. At the same time, caravans from Morocco brought tobacco to the areas around Timbuktu, and the Portuguese brought the commodity (and the plant) to southern Africa, establishing the popularity of tobacco throughout all of Africa by the 1650s.

Soon after its introduction to the Old World, tobacco came under frequent criticism from state and religious leaders. James VI and I, King of Scotland and England, produced the treatise A Counterblaste to Tobacco in 1604, and also introduced excise duty on the product. Murad IV, sultan of the Ottoman Empire 1623–40 was among the first to attempt a smoking ban by claiming it was a threat to public morals and health. The Chongzhen Emperor of China issued an edict banning smoking two years before his death and the overthrow of the Ming dynasty. Later, the Manchu rulers of the Qing dynasty, would proclaim smoking "a more heinous crime than that even of neglecting archery". In Edo period Japan, some of the earliest tobacco plantations were scorned by the shogunate as being a threat to the military economy by letting valuable farmland go to waste for the use of a recreational drug instead of being used to plant food crops.

Bonsack's cigarette rolling machine, as shown on U.S. patent 238,640

Religious leaders have often been prominent among those who considered smoking immoral or outright blasphemous. In 1634, the Patriarch of Moscow forbade the sale of tobacco, and sentenced men and women who flouted the ban to have their nostrils slit and their backs flayed. Pope Urban VIII likewise condemned smoking on holy places in a papal bull of 1624. Despite some concerted efforts, restrictions and bans were largely ignored. When James I of England, a staunch smoking opponent and the author of A Counterblaste to Tobacco, tried to curb the new trend by enforcing a 4000% tax increase on tobacco in 1604 it was unsuccessful, as suggested by the presence of around 7,000 tobacco outlets in London by the early 17th century. From this point on for some centuries, several administrations withdrew from efforts at discouragement and instead turned tobacco trade and cultivation into sometimes lucrative government monopolies.

By the mid-17th century most major civilizations had been introduced to tobacco smoking and in many cases had already assimilated it into the native culture, despite some continued attempts upon the parts of rulers to eliminate the practice with penalties or fines. Tobacco, both product and plant, followed the major trade routes to major ports and markets, and then on into the hinterlands. The English language term smoking appears to have entered currency in the late 18th century, before which less abbreviated descriptions of the practice such as drinking smoke were also in use.

Growth in the US remained stable until the American Civil War in 1860s, when the primary agricultural workforce shifted from slavery to sharecropping. This, along with a change in demand, accompanied the industrialization of cigarette production as craftsman James Bonsack created a machine in 1881 to partially automate their manufacture.

Social attitudes and public health

In Germany, anti-smoking groups, often associated with anti-liquor groups, first published advocacy against the consumption of tobacco in the journal Der Tabakgegner (The Tobacco Opponent) in 1912 and 1932. In 1929, Fritz Lickint of Dresden, Germany, published a paper containing formal statistical evidence of a lung cancer–tobacco link. During the Great Depression Adolf Hitler condemned his earlier smoking habit as a waste of money, and later with stronger assertions. This movement was further strengthened with Nazi reproductive policy as women who smoked were viewed as unsuitable to be wives and mothers in a German family. In the 20th century, smoking was common. There were social events like the smoke night which promoted the habit.

The anti-tobacco movement in Nazi Germany did not reach across enemy lines during the Second World War, as anti-smoking groups quickly lost popular support. By the end of the Second World War, American cigarette manufacturers quickly reentered the German black market. Illegal smuggling of tobacco became prevalent, and leaders of the Nazi anti-smoking campaign were silenced. As part of the Marshall Plan, the United States shipped free tobacco to Germany; with 24,000 tons in 1948 and 69,000 tons in 1949. Per capita yearly cigarette consumption in post-war Germany steadily rose from 460 in 1950 to 1,523 in 1963. By the end of the 20th century, anti-smoking campaigns in Germany were unable to exceed the effectiveness of the Nazi-era climax in the years 1939–41 and German tobacco health research was described by Robert N. Proctor as "muted".

A lengthy study conducted in order to establish the strong association necessary for legislative action (US cigarette consumption per person blue, male lung cancer rate brown)

In 1950, Richard Doll published research in the British Medical Journal showing a close link between smoking and lung cancer. Beginning in December 1952, the magazine Reader's Digest published "Cancer by the Carton", a series of articles that linked smoking with lung cancer.

In 1954, the British Doctors Study, a prospective study of some 40 thousand doctors for about 2.5 years, confirmed the suggestion, based on which the government issued advice that smoking and lung cancer rates were related. In January 1964, the United States Surgeon General's Report on Smoking and Health likewise began suggesting the relationship between smoking and cancer.

As scientific evidence mounted in the 1980s, tobacco companies claimed contributory negligence as the adverse health effects were previously unknown or lacked substantial credibility. Health authorities sided with these claims up until 1998, from which they reversed their position. The Tobacco Master Settlement Agreement, originally between the four largest US tobacco companies and the attorneys general of 46 states, restricted certain types of tobacco advertisement and required payments for health compensation; which later amounted to the largest civil settlement in United States history.

Social campaigns have been instituted in many places to discourage smoking, such as Canada's National Non-Smoking Week.

From 1965 to 2006, rates of smoking in the United States declined from 42% to 20.8%. The majority of those who quit were professional, affluent men. Although the per-capita number of smokers decreased, the average number of cigarettes consumed per person per day increased from 22 in 1954 to 30 in 1978. This paradoxical event suggests that those who quit smoked less, while those who continued to smoke moved to smoke more light cigarettes. The trend has been paralleled by many industrialized nations as rates have either leveled-off or declined. In the developing world, however, tobacco consumption continued to rise at 3.4% in 2002. In Africa, smoking is in most areas considered to be modern, and many of the strong adverse opinions that prevail in the West receive much less attention. Today Russia leads as the top consumer of tobacco followed by Indonesia, Laos, Ukraine, Belarus, Greece, Jordan, and China.

Consumption

Methods

Tobacco is an agricultural product processed from the fresh leaves of plants in the genus Nicotiana. The genus contains several species, of which Nicotiana tabacum is the most commonly grown. Nicotiana rustica follows second, containing higher concentrations of nicotine. The leaves are harvested and cured to allow the slow oxidation and degradation of carotenoids in tobacco leaf. This produces certain compounds in the tobacco leaves which can be attributed to sweet hay, tea, rose oil, or fruity aromatic flavors. Before packaging, the tobacco is often combined with other additives in order to increase the addictive potency, shift the product's pH, or improve the effects of smoke by making it more palatable. In the United States these additives are regulated to 599 substances. The product is then processed, packaged, and shipped to consumer markets.

Common methods of consuming tobacco include the following:

Field of tobacco organized in rows extending to the horizon.
Tobacco field in Intercourse, Pennsylvania
 
Powderly stripps hung vertically, slightly sun bleached.
Basma leaves curing in the sun at Pomak village of Xanthi, Thrace, Greece
 
Rectangular strips stacked in an open square box.
Processed tobacco pressed into flakes for pipe smoking
Beedi
Beedis are thin South Asian cigarettes filled with tobacco flakes and wrapped in a tendu leaf tied with a string at one end. They produce higher levels of carbon monoxide, nicotine, and tar than cigarettes typical in the United States.
Tendu Patta (Leaf) collection for Beedi industries
Cigars
Cigars are tightly rolled bundles of dried and fermented tobacco which are ignited so that smoke may be drawn into the smoker's mouth. They are generally not inhaled because of the high alkalinity of the smoke, which can quickly become irritating to the trachea and lungs. The prevalence of cigar smoking varies depending on location, historical period, and population surveyed, and prevalence estimates vary somewhat depending on the survey method. The United States is the top consuming country by far, followed by Germany and the United Kingdom; the US and Western Europe account for about 75% of cigar sales worldwide. As of 2005 it is estimated that 4.3% of men and 0.3% of women smoke cigars in the US.
Cigarettes
Cigarettes, French for "small cigar", are a product consumed through smoking and manufactured out of cured and finely cut tobacco leaves and reconstituted tobacco, often combined with other additives, which are then rolled or stuffed into a paper-wrapped cylinder. Cigarettes are ignited and inhaled, usually through a cellulose acetate filter, into the mouth and lungs.

Hookah
Hookah are a single or multi-stemmed (often glass-based) water pipe for smoking. Originally from India, the hookah was a symbol of pride and honor for the landlords, kings and other such high class people. Now, the hookah has gained immense popularity, especially in the Middle East. A hookah operates by water filtration and indirect heat. It can be used for smoking herbal fruits, tobacco, or cannabis.
Kretek
Kretek are cigarettes made with a complex blend of tobacco, cloves and a flavoring "sauce". It was first introduced in the 1880s in Kudus, Java, to deliver the medicinal eugenol of cloves to the lungs. The quality and variety of tobacco play an important role in kretek production, from which kretek can contain more than 30 types of tobacco. Minced dried clove buds weighing about one-third of the tobacco blend are added to add flavoring. In 2004 the United States prohibited cigarettes from having a "characterizing flavor" of certain ingredients other than tobacco and menthol, thereby removing kretek from being classified as cigarettes.
Pipe smoking
Pipe smoking is done with a tobacco pipe, typically consisting of a small chamber (the bowl) for the combustion of the tobacco to be smoked and a thin stem (shank) that ends in a mouthpiece (the bit). Shredded pieces of tobacco are placed into the chamber and ignited.
Roll-your-own
Roll-your-own or hand-rolled cigarettes, often called "rollies", "cigi" or "Roll-ups", are very popular particularly in European countries and the UK. These are prepared from loose tobacco, cigarette papers, and filters all bought separately. They are usually much cheaper than ready-made cigarettes and small contraptions can be bought making the process easier.
Vaporizer
A vaporizer is a device used to sublimate the active ingredients of plant material. Rather than burning the herb, which produces potentially irritating, toxic, or carcinogenic by-products; a vaporizer heats the material in a partial vacuum so that the active compounds contained in the plant boil off into a vapor. This method is often preferable when medically administering the smoke substance, as opposed to directly pyrolyzing the plant material.

Physiology

A graph that shows the efficiency of smoking as a way to absorb nicotine compared to other forms of intake

The active substances in tobacco, especially cigarettes, are administered by burning the leaves and inhaling the vaporized gas that results. This quickly and effectively delivers substances into the bloodstream by absorption through the alveoli in the lungs. The lungs contain some 300 million alveoli, which amounts to a surface area of over 70 m2 (about the size of a tennis court). This method is not completely efficient as not all of the smoke will be inhaled, and some amount of the active substances will be lost in the process of combustion, pyrolysis. Pipe and Cigar smoke are not inhaled because of its high alkalinity, which are irritating to the trachea and lungs. However, because of its higher alkalinity (pH 8.5) compared to cigarette smoke (pH 5.3), non-ionized nicotine is more readily absorbed through the mucous membranes in the mouth. Nicotine absorption from cigar and pipe, however, is much less than that from cigarette smoke. Nicotine and cocaine activate similar patterns of neurons, which supports the existence of common substrates among these drugs.

The absorbed nicotine mimics nicotinic acetylcholine which when bound to nicotinic acetylcholine receptors prevents the reuptake of acetylcholine thereby increasing that neurotransmitter in those areas of the body. These nicotinic acetylcholine receptors are located in the central nervous system and at the nerve-muscle junction of skeletal muscles; whose activity increases heart rate, alertness, and faster reaction times. Nicotine acetylcholine stimulation is not directly addictive. However, since dopamine-releasing neurons are abundant on nicotine receptors, dopamine is released; and, in the nucleus accumbens, dopamine is associated with motivation causing reinforcing behavior. Dopamine increase, in the prefrontal cortex, may also increase working memory.

When tobacco is smoked, most of the nicotine is pyrolyzed. However, a dose sufficient to cause mild somatic dependency and mild to strong psychological dependency remains. There is also a formation of harmane (an MAO inhibitor) from the acetaldehyde in tobacco smoke. This may play a role in nicotine addiction, by facilitating a dopamine release in the nucleus accumbens as a response to nicotine stimuli. Using rat studies, withdrawal after repeated exposure to nicotine results in less responsive nucleus accumbens cells, which produce dopamine responsible for reinforcement.

Demographics

Percentage of males smoking any tobacco product
 
Percentage of females smoking any tobacco product. Note that there is a difference between the scales used for males and the scales used for females.

As of 2000, smoking was practiced by around 1.22 billion people. At current rates of 'smoker replacement' and market growth, this may reach around 1.9 billion in 2025.

Smoking may be up to five times more prevalent among men than women in some communities, although the gender gap usually declines with younger age. In some developed countries smoking rates for men have peaked and begun to decline, while for women they continue to climb.

As of 2002, about twenty percent of young teenagers (13–15) smoked worldwide. 80,000 to 100,000 children begin smoking every day, roughly half of whom live in Asia. Half of those who begin smoking in adolescent years are projected to go on to smoke for 15 to 20 years. As of 2019 in the United States, roughly 800,000 high school students smoke.

The World Health Organization (WHO) states that "Much of the disease burden and premature mortality attributable to tobacco use disproportionately affect the poor". Of the 1.22 billion smokers, 1 billion of them live in developing or transitional economies. Rates of smoking have leveled off or declined in the developed world. In the developing world, however, tobacco consumption is rising by 3.4% per year as of 2002.

The WHO in 2004 projected 58.8 million deaths to occur globally, from which 5.4 million are tobacco-attributed, and 4.9 million as of 2007. As of 2002, 70% of the deaths are in developing countries. As of 2017, smoking causes one in ten deaths worldwide, with half of those deaths in the US, China, India and Russia.

Psychology

Takeup

Sigmund Freud, whose doctor assisted his suicide because of oral cancer caused by smoking

Most smokers begin smoking during adolescence or early adulthood. Some studies also show that smoking can also be linked to various mental health complications. Smoking has elements of risk-taking and rebellion, which often appeal to young people. The presence of peers that smoke and media featuring high-status models smoking may also encourage smoking. Because teenagers are influenced more by their peers than by adults, attempts by parents, schools, and health professionals at preventing people from trying cigarettes are often unsuccessful.

Children of smoking parents are more likely to smoke than children with non-smoking parents. Children of parents who smoke are less likely to quit smoking. One study found that parental smoking cessation was associated with less adolescent smoking, except when the other parent currently smoked. A current study tested the relation of adolescent smoking to rules regulating where adults are allowed to smoke in the home. Results showed that restrictive home smoking policies were associated with lower likelihood of trying smoking for both middle and high school students.

Behavioural research generally indicates that teenagers begin their smoking habits due to peer pressure, and cultural influence portrayed by friends. However, one study found that direct pressure to smoke cigarettes played a less significant part in adolescent smoking, with adolescents also reporting low levels of both normative and direct pressure to smoke cigarettes. Mere exposure to tobacco retailers may motivate smoking behaviour in adults. A similar study suggested that individuals may play a more active role in starting to smoke than has previously been thought and that social processes other than peer pressure also need to be taken into account. Another study's results indicated that peer pressure was significantly associated with smoking behavior across all age and gender cohorts, but that intrapersonal factors were significantly more important to the smoking behavior of 12- to 13-year-old girls than same-age boys. Within the 14- to 15-year-old age group, one peer pressure variable emerged as a significantly more important predictor of girls' than boys' smoking. It is debated whether peer pressure or self-selection is a greater cause of adolescent smoking.

Psychologist Hans Eysenck (who later was questioned for nonplausible results and unsafe publications) developed a personality profile for the typical smoker. Extraversion is the trait that is most associated with smoking, and smokers tend to be sociable, impulsive, risk taking, and excitement seeking individuals.

Persistence

The reasons given by some smokers for this activity have been categorized as addictive smoking, pleasure from smoking, tension reduction/relaxation, social smoking, stimulation, habit/automatism, and handling. There are gender differences in how much each of these reasons contribute, with females more likely than males to cite tension reduction/relaxation, stimulation and social smoking.

Some smokers argue that the depressant effect of smoking allows them to calm their nerves, often allowing for increased concentration. However, according to the Imperial College London, "Nicotine seems to provide both a stimulant and a depressant effect, and it is likely that the effect it has at any time is determined by the mood of the user, the environment and the circumstances of use. Studies have suggested that low doses have a depressant effect, while higher doses have stimulant effect."

Patterns

A number of studies have established that cigarette sales and smoking follow distinct time-related patterns. For example, cigarette sales in the United States of America have been shown to follow a strongly seasonal pattern, with the high months being the months of summer, and the low months being the winter months.

Similarly, smoking has been shown to follow distinct circadian patterns during the waking day—with the high point usually occurring shortly after waking in the morning, and shortly before going to sleep at night.

Effects

Health

Tobacco smoking is the leading cause of preventable death and a global public health concern. There are 1.1 billion tobacco users in the world. One person dies every six seconds from a tobacco related disease.

head and torso of a male with internal organs shown and labels referring to the effects of tobacco smoking
Common adverse effects of tobacco smoking. The more common effects are in bold face.

Tobacco use leads most commonly to diseases affecting the heart and lungs, with smoking being a major risk factor for heart attacks, strokes, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), emphysema, and various types and subtypes of cancers (particularly lung cancer, cancers of the oropharynx, larynx, and mouth, esophageal and pancreatic cancer). Cigarette smoking increases the risk of Crohn's disease as well as the severity of the course of the disease. It is also the number one cause of bladder cancer. Cigarette smoking has also been associated with sarcopenia, the age-related loss of muscle mass and strength. The smoke from tobacco elicits carcinogenic effects on the tissues of the body that are exposed to the smoke. Regular cigar smoking is known to carry serious health risks, including increased risk of developing various types and subtypes of cancers, respiratory diseases, cardiovascular diseases, cerebrovascular diseases, periodontal diseases, teeth decay and loss, and malignant diseases.

Tobacco smoke is a complex mixture of over 7,000 toxic chemicals, 98 of which are associated with an increased risk of cardiovascular disease and 69 of which are known to be carcinogenic. The most important chemicals causing cancer are those that produce DNA damage, since such damage appears to be the primary underlying cause of cancer. Cunningham et al. combined the microgram weight of the compound in the smoke of one cigarette with the known genotoxic effect per microgram to identify the most carcinogenic compounds in cigarette smoke: acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide, and isoprene. In addition to the aforementioned toxic chemicals, flavored tobacco contains flavorings which upon heating release toxic chemicals and carcinogens such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), furans, phenols, aldehydes (such as acrolein), and acids, in addition to nitrogenous carcinogens, alcohols, and heavy metals, all of which are dangerous to human health. A comparison of 13 common hookah flavors found that melon flavors are the most dangerous, with their smoke containing four classes of hazards in high concentrations.

The World Health Organization estimates that tobacco caused 5.4 million deaths in 2004 and 100 million deaths over the course of the 20th century. Similarly, the United States Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide." Although 70% of smokers state their intention to quit only 3–5% are actually successful in doing so.

The probabilities of death from lung cancer before age 75 in the United Kingdom are 0.2% for men who never smoked (0.4% for women), 5.5% for male former smokers (2.6% in women), 15.9% for current male smokers (9.5% for women) and 24.4% for male "heavy smokers" defined as smoking more than 5 cigarettes per day (18.5% for women). Tobacco smoke can combine with other carcinogens present within the environment in order to produce elevated degrees of lung cancer.

The risk of lung cancer decreases almost from the first day someone quits smoking. Healthy cells that have escaped mutations grow and replace the damaged ones in the lungs. In the research dated December 2019, 40% of cells in former smokers looked like those of people who had never smoked.

Rates of smoking have generally leveled-off or declined in the developed world. Smoking rates in the United States have dropped by half from 1965 to 2006, falling from 42% to 20.8% in adults. In the developing world, tobacco consumption is rising by 3.4% per year.

Smoking alters the transcriptome of the lung parenchyma; the expression levels of a panel of seven genes (KMO, CD1A, SPINK5, TREM2, CYBB, DNASE2B, FGG) are increased in the lung tissue of smokers.

Passive smoking is the inhalation of tobacco smoke by individuals who are not actively smoking. This smoke is known as second-hand smoke (SHS) or environmental tobacco smoke (ETS) when the burning end is present, and third-hand smoke after the burning end has been extinguished. Because of its negative implications, exposure to SHS has played a central role in the regulation of tobacco products. Six hundred thousand deaths were attributed to SHS in 2004. It also has been known to produce skin conditions such as freckles and dryness.

In 2015, a meta-analysis found that smokers were at greater risk of developing psychotic disorder. Tobacco has also been described an anaphrodisiac due to its propensity for causing erectile dysfunction. There is a correlation between tobacco smoking and a reduced risk of Parkinson's disease.

Economic

In countries where there is a universally funded healthcare system, the government covers the cost of medical care for smokers who become ill through smoking in the form of increased taxes. Two broad debating positions exist on this front, the "pro-smoking" argument suggesting that heavy smokers generally do not live long enough to develop the costly and chronic illnesses which affect the elderly, reducing society's healthcare burden, and the "anti-smoking" argument suggests that the healthcare burden is increased because smokers get chronic illnesses younger and at a higher rate than the general population. Data on both positions has been contested. The Centers for Disease Control and Prevention published research in 2002 claiming that the cost of each pack of cigarettes sold in the United States was more than $7 in medical care and lost productivity. The cost may be higher, with another study putting it as high as $41 per pack, most of which however is on the individual and his/her family. This is how one author of that study puts it when he explains the very low cost for others: "The reason the number is low is that for private pensions, Social Security, and Medicare — the biggest factors in calculating costs to society — smoking actually saves money. Smokers die at a younger age and don't draw on the funds they've paid into those systems." Other research demonstrates that premature death caused by smoking may redistribute Social Security income in unexpected ways that affect behavior and reduce the economic well-being of smokers and their dependents. To further support this, whatever the rate of smoking consumption is per day, smokers have a greater lifetime medical cost on average compared to a non-smoker by an estimated $6000 Between the cost for lost productivity and health care expenditures combined, cigarette smoking costs at least 193 billion dollars (Research also shows that smokers earn less money than nonsmokers). As for secondhand smoke, the cost is over 10 billion dollars.

By contrast, some non-scientific studies, including one conducted by Philip Morris in the Czech Republic called Public Finance Balance of Smoking in the Czech Republic and another by the Cato Institute, support the opposite position. Philip Morris has explicitly apologised for the former study, saying: "The funding and public release of this study which, among other things, detailed purported cost savings to the Czech Republic due to premature deaths of smokers, exhibited terrible judgment as well as a complete and unacceptable disregard of basic human values. For one of our tobacco companies to commission this study was not just a terrible mistake, it was wrong. All of us at Philip Morris, no matter where we work, are extremely sorry for this. No one benefits from the very real, serious and significant diseases caused by smoking."

Between 1970 and 1995, per-capita cigarette consumption in poorer developing countries increased by 67 percent, while it dropped by 10 percent in the richer developed world. Eighty percent of smokers now live in less developed countries. By 2030, the World Health Organization (WHO) forecasts that 10 million people a year will die of smoking-related illness, making it the single biggest cause of death worldwide, with the largest increase to be among women. WHO forecasts the 21st century's death rate from smoking to be ten times the 20th century's rate ("Washingtonian" magazine, December 2007).

The tobacco industry is known to be one of the largest global enterprises in the world. The six biggest tobacco companies made a combined profit of $35.1 billion (Jha et al., 2014) in 2010.

Social

Skull with a burning cigarette, by Vincent van Gogh

Famous smokers of the past used cigarettes or pipes as part of their image, such as Jean-Paul Sartre's Gauloises-brand cigarettes; Albert Einstein's, Douglas MacArthur's, Bertrand Russell's, and Bing Crosby's pipes; or the news broadcaster Edward R. Murrow's cigarette. Writers in particular seem to be known for smoking, for example, Cornell Professor Richard Klein's book Cigarettes are Sublime for the analysis, by this professor of French literature, of the role smoking plays in 19th and 20th century letters. The popular author Kurt Vonnegut addressed his addiction to cigarettes within his novels. British Prime Minister Harold Wilson was well known for smoking a pipe in public as was Winston Churchill for his cigars. Sherlock Holmes, the fictional detective created by Sir Arthur Conan Doyle, smoked a pipe, cigarettes, and cigars. The DC Vertigo comic book character John Constantine, created by Alan Moore, is synonymous with smoking, so much so that the first storyline by Preacher creator Garth Ennis centered around John Constantine contracting lung cancer. Professional wrestler James Fullington, while in character as "The Sandman", is a chronic smoker in order to appear "tough".

The problem of smoking at home is particularly difficult for women in many cultures (especially Arab cultures), where it may not be acceptable for a woman to ask her husband not to smoke at home or in the presence of her children. Studies have shown that pollution levels for smoking areas indoors are higher than levels found on busy roadways, in closed motor garages, and during fire storms. Furthermore, smoke can spread from one room to another, even if doors to the smoking area are closed.

The ceremonial smoking of tobacco, and praying with a sacred pipe, is a prominent part of the religious ceremonies of a number of Native American Nations. Sema, the Anishinaabe word for tobacco, is grown for ceremonial use and considered the ultimate sacred plant since its smoke is believed to carry prayers to the spirits. In most major religions, however, tobacco smoking is not specifically prohibited, although it may be discouraged as an immoral habit. Before the health risks of smoking were identified through controlled study, smoking was considered an immoral habit by certain Christian preachers and social reformers. The founder of the Latter Day Saint movement, Joseph Smith, recorded that on 27 February 1833, he received a revelation which discouraged tobacco use. This "Word of Wisdom" was later accepted as a commandment, and faithful Latter-day Saints abstain completely from tobacco. Jehovah's Witnesses base their stand against smoking on the Bible's command to "clean ourselves of every defilement of flesh" (2 Corinthians 7:1). The Jewish Rabbi Yisrael Meir Kagan (1838–1933) was one of the first Jewish authorities to speak out on smoking. In Ahmadiyya Islam, smoking is highly discouraged, although not forbidden. During the month of fasting however, it is forbidden to smoke tobacco. In the Baháʼí Faith, smoking tobacco is discouraged though not forbidden.

Public policy

On 27 February 2005 the WHO Framework Convention on Tobacco Control, took effect. The FCTC is the world's first public health treaty. Countries that sign on as parties agree to a set of common goals, minimum standards for tobacco control policy, and to cooperate in dealing with cross-border challenges such as cigarette smuggling. Currently the WHO declares that 4 billion people will be covered by the treaty, which includes 168 signatories. Among other steps, signatories are to put together legislation that will eliminate secondhand smoke in indoor workplaces, public transport, indoor public places and, as appropriate, other public places.

Taxation

Many governments have introduced excise taxes on cigarettes in order to reduce the consumption of cigarettes. The World Health Organisation finds that:

The structure of tobacco excise taxes varies considerably across countries, with lower income countries more likely to rely more on ad valorem excises and higher income countries more likely to rely more on specific excise taxes, while many countries at all income levels use a mix of specific and ad valorem excises.

Tobacco excise tax systems are quite complex in several countries, where different tax rates are applied based on prices, product characteristics such as presence/absence of a filter or length, packaging, weight, tobacco content, and/or production or sales volume. These complex systems are difficult to administer, create opportunities for tax avoidance, and are less effective from a public health perspective.

Globally, cigarette excise taxes account for less than 45 percent of cigarette prices, on average, while all taxes applied to cigarettes account for just over half of half of price. Higher income countries levy higher taxes on tobacco products and these taxes account for a greater share of price, with both the absolute tax and share of price accounted for by tax falling as country incomes fall.

In 2002, the Centers for Disease Control and Prevention said that each pack of cigarettes sold in the United States costs the nation more than $7 in medical care and lost productivity, around $3400 per year per smoker. Another study by a team of health economists finds the combined price paid by their families and society is about $41 per pack of cigarettes.

Substantial scientific evidence shows that higher cigarette prices result in lower overall cigarette consumption. Most studies indicate that a 10% increase in price will reduce overall cigarette consumption by 3% to 5%. Youth, minorities, and low-income smokers are two to three times more likely to quit or smoke less than other smokers in response to price increases. Smoking is often cited as an example of an inelastic good, however, i.e. a large rise in price will only result in a small decrease in consumption.

Many nations have implemented some form of tobacco taxation. As of 1997, Denmark had the highest cigarette tax burden of $4.02 per pack. Taiwan only had a tax burden of $0.62 per pack. The federal government of the United States charges $1.01 per pack.

Cigarette taxes vary widely from state to state in the United States. For example, Missouri has a cigarette tax of only 17 cents per pack, the nation's lowest, while New York has the highest cigarette tax in the U.S.: $4.35 per pack. In Alabama, Illinois, Missouri, New York City, Tennessee, and Virginia, counties and cities may impose an additional limited tax on the price of cigarettes. Sales taxes are also levied on tobacco products in most jurisdictions.

In the United Kingdom, as of April 2023, a packet of 20 cigarettes has a tax added of 16.5% of the retail price plus £5.89. The UK has a significant black market for tobacco, and it has been estimated by the tobacco industry that 27% of cigarette and 68% of handrolling tobacco consumption is non-UK duty paid (NUKDP).

In Australia total taxes account for 62.5% of the final price of a packet of cigarettes (2011 figures). These taxes include federal excise or customs duty and Goods and Services Tax.

Restrictions

An enclosed smoking area in a Japanese train station. Notice the air vent on the roof.

In June 1967, the US Federal Communications Commission ruled that programmes broadcast on a television station which discussed smoking and health were insufficient to offset the effects of paid advertisements that were broadcast for five to ten minutes each day. In April 1970, the US Congress passed the Public Health Cigarette Smoking Act banning the advertising of cigarettes on television and radio starting on 2 January 1971.

The Tobacco Advertising Prohibition Act 1992 expressly prohibited almost all forms of Tobacco advertising in Australia, including the sponsorship of sporting or other cultural events by cigarette brands.

All tobacco advertising and sponsorship on television has been banned within the European Union since 1991 under the Television Without Frontiers Directive (1989). This ban was extended by the Tobacco Advertising Directive, which took effect in July 2005 to cover other forms of media such as the internet, print media, and radio. The directive does not include advertising in cinemas and on billboards or using merchandising – or tobacco sponsorship of cultural and sporting events which are purely local, with participants coming from only one Member State as these fall outside the jurisdiction of the European Commission. However, most member states have transposed the directive with national laws that are wider in scope than the directive and cover local advertising. A 2008 European Commission report concluded that the directive had been successfully transposed into national law in all EU member states, and that these laws were well implemented.

Some countries also impose legal requirements on the packaging of tobacco products. For example, in the countries of the European Union, Turkey, Australia and South Africa, cigarette packs must be prominently labeled with the health risks associated with smoking. Canada, Australia, Thailand, Iceland and Brazil have also imposed labels upon cigarette packs warning smokers of the effects, and they include graphic images of the potential health effects of smoking. Cards are also inserted into cigarette packs in Canada. There are sixteen of them, and only one comes in a pack. They explain different methods of quitting smoking. Also, in the United Kingdom, there have been a number of graphic NHS advertisements, one showing a cigarette filled with fatty deposits, as if the cigarette is symbolizing the artery of a smoker.

Some countries have also banned advertisement at point of sale. United Kingdom and Ireland have limited the advertisement of tobacco at retailers. This includes storing of cigarettes behind a covered shelf not visible to the public. They do however allow some limited advertising at retailers. Norway has a complete ban of point of sale advertising. This includes smoking products and accessories. Implementing these policies can be challenging, all of these countries experienced resistance and challenges from the tobacco industry. The World Health Organisation recommends the complete ban of all types of advertisement or product placement, including at vending machines, at airports and on internet shops selling tobacco. The evidence is as yet unclear as to the effect of such bans.  

Many countries have a smoking age. In many countries, including the United States, most European Union member states, New Zealand, Canada, South Africa, Israel, India, Brazil, Chile, Costa Rica and Australia, it is illegal to sell tobacco products to minors and in the Netherlands, Austria, Belgium, Denmark and South Africa it is illegal to sell tobacco products to people under the age of 18. On 1 September 2007 the minimum age to buy tobacco products in Germany rose from 16 to 18, as well as in the United Kingdom where on 1 October 2007 it rose from 16 to 18. Underlying such laws is the belief that people should make an informed decision regarding the risks of tobacco use. These laws have a lax enforcement in some nations and states. In China, Turkey, and many other countries usually a child will have little problem buying tobacco products, because they are often told to go to the store to buy tobacco for their parents.

Several countries such as Ireland, Latvia, Estonia, the Netherlands, Finland, Norway, Canada, Australia, Sweden, Portugal, Singapore, Italy, Indonesia, India, Lithuania, Chile, Spain, Iceland, United Kingdom, Slovenia, Turkey and Malta have legislated against smoking in public places, often including bars and restaurants. Restaurateurs have been permitted in some jurisdictions to build designated smoking areas (or to prohibit smoking). In the United States, many states prohibit smoking in restaurants, and some also prohibit smoking in bars. In provinces of Canada, smoking is illegal in indoor workplaces and public places, including bars and restaurants. As of 31 March 2008 Canada has introduced a smoke-free law in all public places, as well as within 10 metres of an entrance to any public place. In Australia, smoke-free laws vary from state to state. In New Zealand and Brazil, smoking is restricted in enclosed public places including bars, restaurants and pubs. Hong Kong restricted smoking on 1 January 2007 in the workplace, public spaces such as restaurants, karaoke rooms, buildings, and public parks (bars which do not admit minors were exempt until 2009). In Romania smoking is illegal in trains, metro stations, public institutions (except where designated, usually outside) and public transport. In Germany, in addition to smoking bans in public buildings and transport, an anti-smoking ordinance for bars and restaurants was implemented in late 2007. A study by the University of Hamburg (Ahlfeldt and Maennig 2010) demonstrates, that the smoking ban had, if any, only short run effects on bar and restaurant revenues. In the medium and long run no negative effect was measurable. The results suggest either, that the consumption in bars and restaurants is not affected by smoking bans in the long run, or, that negative revenue effects by smokers are compensated by increasing revenues through non-smokers.

Ignition safety

An indirect public health problem posed by cigarettes is that of accidental fires, usually linked with consumption of alcohol. Enhanced combustion using nitrates was traditionally used but cigarette manufacturers have been silent on this subject claiming at first that a safe cigarette was technically impossible, then that it could only be achieved by modifying the paper. Roll your own cigarettes contain no additives and are fire safe. Numerous fire safe cigarette designs have been proposed, some by tobacco companies themselves, which would extinguish a cigarette left unattended for more than a minute or two, thereby reducing the risk of fire. Among American tobacco companies, some have resisted this idea, while others have embraced it. RJ Reynolds was a leader in making prototypes of these cigarettes in 1983 and will make all of their U.S. market cigarettes to be fire-safe by 2010. Phillip Morris is not in active support of it. Lorillard (purchased by RJ Reynolds), the US' 3rd-largest tobacco company, seems to be ambivalent.

Health Warnings

‘Individual cigarettes in Canada now carry warnings such as “poison in every puff” and “cigarettes cause impotence” in what the government says is an effort to make it “virtually impossible to avoid health warnings altogether”. 

Gateway drug theory

The relationship between tobacco and other drug use has been well-established, however the nature of this association remains unclear. The two main theories are the phenotypic causation (gateway) model and the correlated liabilities model. The causation model argues that smoking is a primary influence on future drug use, while the correlated liabilities model argues that smoking and other drug use are predicated on genetic or environmental factors. One study published by the NIH found that tobacco use may be linked to cocaine addiction and marijuana use. The study stated that 90% of adults who used cocaine had smoked cigarettes before (this was for people ages 18–34). This study could support the gateway drug theory.

Cessation

Quitting smoking often involves advice from physicians or social workers, cold turkey, nicotine replacement therapy, contingent vouchers, antidepressants, vaping, hypnosis, self-help (mindfulness meditation), and support groups.

In the United States, about 70% of smokers would like to quit smoking, and 50% report having made an attempt to do so in the past year. Without support, 1% of smokers will successfully quit smoking each year. Physician advice to quit smoking increases the rate to 3% per year. Adding first‐line smoking cessation medications (and some behavioral help), increased quit rates to around 20% of smokers in a year.

Message-oriented middleware

From Wikipedia, the free encyclopedia

Message-oriented middleware (MOM) is software or hardware infrastructure supporting sending and receiving messages between distributed systems. MOM allows application modules to be distributed over heterogeneous platforms and reduces the complexity of developing applications that span multiple operating systems and network protocols. The middleware creates a distributed communications layer that insulates the application developer from the details of the various operating systems and network interfaces. APIs that extend across diverse platforms and networks are typically provided by MOM.

This middleware layer allows software components (applications, Enterprise JavaBeans, servlets, and other components) that have been developed independently and that run on different networked platforms to interact with one another. Applications distributed on different network nodes use the application interface to communicate. In addition, by providing an administrative interface, this new, virtual system of interconnected applications can be made fault tolerant and secure.

MOM provides software elements that reside in all communicating components of a client/server architecture and typically support asynchronous calls between the client and server applications. MOM reduces the involvement of application developers with the complexity of the master-slave nature of the client/server mechanism.

Middleware categories

All these models make it possible for one software component to affect the behavior of another component over a network. They are different in that RPC- and ORB-based middleware create systems of tightly coupled components, whereas MOM-based systems allow for a loose coupling of components. In an RPC- or ORB-based system, when one procedure calls another, it must wait for the called procedure to return before it can do anything else. In these synchronous messaging models, the middleware functions partly as a super-linker, locating the called procedure on a network and using network services to pass function or method parameters to the procedure and then to return results.

Advantages

Central reasons for using a message-based communications protocol include its ability to store (buffer), route, or transform messages while conveying them from senders to receivers.

Another advantage of messaging provider mediated messaging between clients is that by adding an administrative interface, you can monitor and tune performance. Client applications are thus effectively relieved of every problem except that of sending, receiving, and processing messages. It is up to the code that implements the MOM system and up to the administrator to resolve issues like interoperability, reliability, security, scalability, and performance.

Asynchronicity

Using a MOM system, a client makes an API call to send a message to a destination managed by the provider. The call invokes provider services to route and deliver the message. Once it has sent the message, the client can continue to do other work, confident that the provider retains the message until a receiving client retrieves it. The message-based model, coupled with the mediation of the provider, makes it possible to create a system of loosely coupled components.

MOM comprises a category of inter-application communication software that generally relies on asynchronous message-passing, as opposed to a request-response architecture. In asynchronous systems, message queues provide temporary storage when the destination program is busy or not connected. In addition, most asynchronous MOM systems provide persistent storage to back up the message queue. This means that the sender and receiver do not need to connect to the network at the same time (asynchronous delivery), and problems with intermittent connectivity are solved. It also means that should the receiver application fail for any reason, the senders can continue unaffected, as the messages they send will simply accumulate in the message queue for later processing when the receiver restarts.

Routing

Many message-oriented middleware implementations depend on a message queue system. Some implementations permit routing logic to be provided by the messaging layer itself, while others depend on client applications to provide routing information or allow for a mix of both paradigms. Some implementations make use of broadcast or multicast distribution paradigms.

Transformation

In a message-based middleware system, the message received at the destination need not be identical to the message originally sent. A MOM system with built-in intelligence can transform messages and route to match the requirements of the sender or of the recipient. In conjunction with the routing and broadcast/multicast facilities, one application can send a message in its own native format, and two or more other applications may each receive a copy of the message in their own native format. Many modern MOM systems provide sophisticated message transformation (or mapping) tools which allow programmers to specify transformation rules applicable to a simple GUI drag-and-drop operation.

Disadvantages

The primary disadvantage of many message-oriented middleware systems is that they require an extra component in the architecture, the message transfer agent (message broker). As with any system, adding another component can lead to reductions in performance and reliability, and can also make the system as a whole more difficult and expensive to maintain.

In addition, many inter-application communications have an intrinsically synchronous aspect, with the sender specifically wanting to wait for a reply to a message before continuing (see real-time computing and near-real-time for extreme cases). Because message-based communication inherently functions asynchronously, it may not fit well in such situations. That said, most MOM systems have facilities to group a request and a response as a single pseudo-synchronous transaction.

With a synchronous messaging system, the calling function does not return until the called function has finished its task. In a loosely coupled asynchronous system, the calling client can continue to load work upon the recipient until the resources needed to handle this work are depleted and the called component fails. Of course, these conditions can be minimized or avoided by monitoring performance and adjusting message flow, but this is work that is not needed with a synchronous messaging system. The important thing is to understand the advantages and liabilities of each kind of system. Each system is appropriate for different kinds of tasks. Sometimes, a combination of the two kinds of systems is required to obtain the desired behavior.

Standards

Historically, there was a lack of standards governing the use of message-oriented middleware that has caused problems. Most of the major vendors have their own implementations, each with its own application programming interface (API) and management tools.

One of the long-standing standards for message oriented middleware is X/Open group's XATMI specification (Distributed Transaction Processing: The XATMI Specification) which standardizes API for interprocess communications. Known implementations for this API is ATR Baltic's Enduro/X middleware and Oracle's Tuxedo.

The Advanced Message Queuing Protocol (AMQP) is an approved OASIS and ISO standard that defines the protocol and formats used between participating application components, so implementations are interoperable. AMQP may be used with flexible routing schemes, including common messaging paradigms like point-to-point, fan-out, publish/subscribe, and request-response (note that these are intentionally omitted from v1.0 of the protocol standard itself, but rely on the particular implementation and/or underlying network protocol for routing). It also supports transaction management, queuing, distribution, security, management, clustering, federation and heterogeneous multi-platform support. Java applications that use AMQP are typically written in Java JMS. Other implementations provide APIs for C#, C++, PHP, Python, Ruby, and other languages.

The High-Level Architecture (HLA IEEE 1516) is an IEEE and SISO standard for simulation interoperability. It defines a set of services, provided through an API in C++ or Java. The services offer publish/subscribe based information exchange, based on a modular Federation Object Model. There are also services for coordinated data exchange and time advance, based on logical simulation time, as well as synchronization points. Additional services provide transfer of ownership, data distribution optimizations and monitoring and management of participating Federates (systems).

The MQ Telemetry Transport (MQTT) is an ISO standard (ISO/IEC PRF 20922) supported by the OASIS organization. It provides a lightweight publish/subscribe reliable messaging transport protocol on top of TCP/IP suitable for communication in M2M/IoT contexts where a small code footprint is required and/or network bandwidth is at a premium.

The Object Management Group's Data Distribution Service (DDS) provides message-oriented Publish/Subscribe (P/S) middleware standard that aims to enable scalable, real-time, dependable, high performance and interoperable data exchanges between publishers and subscribers. The standard provides interfaces to C++, C++11, C, Ada, Java and Ruby.

XMPP

The eXtensible Messaging and Presence Protocol (XMPP) is a communications protocol for message-oriented middleware based on XML (Extensible Markup Language). Designed to be extensible, the protocol has also been used for publish-subscribe systems, signalling for VoIP, video, file transfer, gaming, Internet of Things applications such as the smart grid, and social networking services. Unlike most instant messaging protocols, XMPP is defined in an open standard and uses an open systems approach of development and application, by which anyone may implement an XMPP service and interoperate with other organizations' implementations. Because XMPP is an open protocol, implementations can be developed using any software license; although many server, client, and library implementations are distributed as free and open-source software, numerous freeware and proprietary software implementations also exist. The Internet Engineering Task Force (IETF) formed an XMPP working group in 2002 to formalize the core protocols as an IETF instant messaging and presence technology. The XMPP Working group produced four specifications (RFC 3920, RFC 3921, RFC 3922, RFC 3923), which were approved as Proposed Standards in 2004. In 2011, RFC 3920 and RFC 3921 were superseded by RFC 6120 and RFC 6121 respectively, with RFC 6122 specifying the XMPP address format. In addition to these core protocols standardized at the IETF, the XMPP Standards Foundation (formerly the Jabber Software Foundation) is active in developing open XMPP extensions. XMPP-based software is deployed widely across the Internet, according to the XMPP Standards Foundation, and forms the basis for the Department of Defense (DoD) Unified Capabilities Framework.

The Java EE programming environment provides a standard API called JMS (Java Message Service), which is implemented by most MOM vendors and aims to hide the particular MOM API implementations; however, JMS does not define the format of the messages that are exchanged, so JMS systems are not interoperable.

A similar effort is with the actively evolving OpenMAMA project, which aims to provide a common API, particularly to C clients. However, at the moment (August 2012) it is primarily appropriate for distributing market-oriented data (e.g. stock quotes) over pub-sub middleware.

Message queuing

Message queues allow the exchange of information between distributed applications. A message queue can reside in memory or disk storage. Messages stay in the queue until the time they are processed by a service consumer. Through the message queue, the application can be implemented independently - they do not need to know each other's position, or continue to implement procedures to remove the need for waiting to receive this message.

Trends

  • Advanced Message Queuing Protocol (AMQP) provides an open standard application layer protocol for message-oriented middleware.
  • The Object Management Group's Data Distribution Service (DDS) has added many new standards to the basic DDS specification. See Catalog of OMG Data Distribution Service (DDS) Specifications for more details.
  • XMPP is a communications protocol for message-oriented middleware based on XML (Extensible Markup Language).
  • Streaming Text Oriented Messaging Protocol (STOMP), formerly known as TTMP, is a simple text-based protocol, provides an interoperable wire format that allows STOMP clients to talk with any Message Broker supporting the protocol.
  • An additional trend sees message-oriented middleware functions being implemented in hardware - usually FPGAs or other specialized silicon chips.
  • Non-small-cell lung cancer

    From Wikipedia, the free encyclopedia
    Non-small-cell lung cancer
    Other namesNon-small-cell lung carcinoma
    Micrograph of a squamous carcinoma, a type of non-small-cell lung carcinoma, FNA specimen, Pap stain.
    SpecialtyOncology 

    Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy).

    Types

    Pie chart showing incidences of nonsmall-cell lung cancers as compared to small-cell carcinoma shown at right, with fractions of smokers versus nonsmokers shown for each type

    The most common types of NSCLC are squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma, but several other types occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Non-squamous-cell carcinoma almost occupies the half of NSCLC. In the tissue classification, the central type contains about one-ninth.

    Sometimes, the phrase "not otherwise specified" (NOS) is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small number of malignant cells or tissue in a cytology or biopsy specimen.

    Lung cancer in people who have never smoked is almost universally NSCLC, with a sizeable majority being adenocarcinoma.

    On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors are classified as combined small-cell lung carcinoma (c-SCLC), and are (usually) treated as "pure" SCLC.

    Lung adenocarcinoma

    Adenocarcinoma of the lung is currently the most common type of lung cancer in "never smokers" (lifelong nonsmokers). Adenocarcinomas account for about 40% of lung cancers. Historically, adenocarcinoma was more often seen peripherally in the lungs than SCLC and squamous-cell lung cancer, both of which tended to be more often centrally located. Recent studies, though, suggest that the "ratio of centrally to peripherally occurring" lesions may be converging toward unity for both adenocarcinoma and squamous-cell carcinoma.

    Squamous-cell lung carcinoma

    Photograph of a squamous-cell carcinoma: The tumour is on the left, obstructing the bronchus (lung). Beyond the tumour, the bronchus is inflamed and contains mucus.

    Squamous-cell carcinoma (SCC) of the lung is more common in men than in women. It is closely correlated with a history of tobacco smoking, more so than most other types of lung cancer. According to the Nurses' Health Study, the relative risk of SCC is around 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to "never smokers" (lifelong nonsmokers). The relative risk increases to about 16 with a previous smoking duration of 30 to 40 years, and roughly 22 with more than 40 years.

    Large-cell lung carcinoma

    Large-cell lung carcinoma (LCLC) is a heterogeneous group of undifferentiated malignant neoplasms originating from transformed epithelial cells in the lung. LCLCs have typically comprised around 10% of all NSCLC in the past, although newer diagnostic techniques seem to be reducing the incidence of diagnosis of "classic" LCLC in favor of more poorly differentiated SCCs and adenocarcinomas. LCLC is, in effect, a "diagnosis of exclusion", in that the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer. LCLC is differentiated from SCLC primarily by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin.

    Symptoms

    Many of the symptoms of NSCLC can be signs of other diseases, but having chronic or overlapping symptoms may be a signal of the presence of the disease. Some symptoms are indicators of less advanced cases, while some may signal that the cancer has spread. Some of the symptoms of less advanced cancer include chronic cough, coughing up blood, hoarseness, shortness of breath, wheezing, chest pain, weight loss, and loss of appetite. A few more symptoms associated with the early progression of the disease are feeling weak, being very tired, having trouble swallowing, swelling in the face or neck, and continuous or recurring infections such as bronchitis or pneumonia. Signs of more advanced cases include bone pain, nervous-system changes (headache, weakness, dizziness, balance problems, seizures), jaundice, lumps near the surface of the body, numbness of extremities due to Pancoast syndrome, and nausea, vomiting, and constipation brought on by hypercalcemia. Some more of the symptoms that indicate further progression of the cancer include shortness of breath, superior vena cava syndrome, trouble swallowing, large amounts of mucus, weakness, fatigue, and hoarseness.

    Cause

    Smoking is by far the leading risk factor for lung cancer. Cigarette smoke contains more than 6,000 components, many of which lead to DNA damage (see table of tobacco-related DNA damages in Tobacco smoking).

    Other causes include radon, exposure to secondhand smoke, exposure to substances such as asbestos, chromium, nickel, beryllium, soot, or tar, family history of lung cancer, and air pollution.

    Genetics can also play a role as a family history of lung cancer can contribute to an increased risk of developing the disease. Furthermore, research has revealed specific chromosome regions associated with increased risks of developing lung cancer.

    In general, DNA damage appears to be the primary underlying cause of cancer. Though most DNA damages are repairable, leftover unrepaired DNA damages from cigarette smoke are the likely cause of NSCLC.

    DNA replication past an unrepaired damage can give rise to a mutation because of inaccurate translesion synthesis. In addition, during repair of DNA double-strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can lead to epigenetic gene silencing.

    DNA repair deficiency in NSCLC

    Deficiencies in DNA repair underlie many forms of cancer. If DNA repair is deficient, the frequency of unrepaired DNA damages increases, and these tend to cause inaccurate translesion synthesis leading to mutation. Furthermore, increased damages can elevate incomplete repair, leading to epigenetic alterations.

    Mutations in DNA repair genes occasionally occur in cancer, but deficiencies of DNA repair due to epigenetic alterations that reduce or silence DNA repair-gene expression occur much more frequently in cancer.

    Epigenetic gene silencing of DNA repair genes occurs frequently in NSCLC. At least nine DNA repair genes that normally function in relatively accurate DNA repair pathways are often repressed by promoter hypermethylation in NSCLC. One DNA repair gene, FEN1, that functions in an inaccurate DNA repair pathway, is expressed at an increased level due to hypo-, rather than hyper-, methylation of its promoter region (deficiency of promoter methylation) in NSCLC.

    Epigenetic promoter methylation in DNA repair genes in NSCLC
    Gene Frequency of hyper- (or hypo-) methylation DNA repair pathway
    NEIL1 42% base excision repair
    WRN 38% homologous recombinational repair, nonhomologous end joining, base excision repair
    MGMT 13% - 64% direct reversal
    ATM 47% homologous recombinational repair
    MLH1 48% - 73% mismatch repair
    MSH2 42% - 63% mismatch repair
    BRCA2 42% homologous recombinational repair
    BRCA1 30% homologous recombinational repair
    XRCC5 (Ku80) 20% nonhomologous end joining
    FEN1 100% hypomethylated (increased expression) microhomology-mediated end joining

    The frequent deficiencies in accurate DNA repair, and the increase in inaccurate repair, likely cause the high level of mutation in lung cancer cells of more than 100,000 mutations per genome (see Whole genome sequencing).

    Staging

    Staging is a formal procedure to determine how developed the cancer is, which determines treatment options.

    The American Joint Committee on Cancer and the International Union Against Cancer recommend TNM staging, using a uniform scheme for NSCLC, SCLC, and bronchopulmonary carcinoid tumors. With TNM staging, the cancer is classified based on the size of the tumor and spread to lymph nodes and other organs. As the tumor grows in size and the areas affected become larger, the staging of the cancer becomes more advanced as well.

    Several components of NSCLC staging then influence physicians' treatment strategies. The lung tumor itself is typically assessed both radiographically for overall size and by a pathologist under the microscope to identify specific genetic markers or to see if invasion into important structures within the chest (e.g., bronchus or pleural cavity) has occurred. Next, the patient's nearby lymph nodes within the chest cavity, known as the mediastinum, are checked for disease involvement. Finally, the patient is evaluated for more distant sites of metastatic disease, most typically with brain imaging and or scans of the bones.

    Five-year survival rates

    The survival rates for stages I through IV decrease significantly due to the advancement of the disease. For stage I, the five-year survival rate is 47%, stage II is 30%, stage III is 10%, and stage IV is 1%.

    Treatment

    More than one kind of treatment is often used, depending on the stage of the cancer, the individual's overall health, age, response to chemotherapy, and other factors such as the likely side effects of the treatment. After full staging, the NSCLC patient can typically be classified in one of three different categories: patients with early, nonmetastatic disease (stages I and II, and select type III tumors), patients with locally advanced disease confined to the thoracic cavity (e.g., large tumors, tumors involving critical chest structures, or patients with positive mediastinal lymph nodes), or patients with distant metastasis outside of the thoracic cavity.

    Early/nonmetastatic NSCLC

    NSCLCs are usually not very sensitive to chemotherapy and/or radiation, so surgery (lung resection to remove the tumor) remains the treatment of choice if patients are diagnosed at an early stage.

    If the persons have a small, but inoperable tumor, they may undergo highly targeted, high-intensity radiation therapy. New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Cyberknife and stereotactic body radiation therapy. Certain people who are deemed to be higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy. A number of possible chemotherapy agents can be selected, but most involve the platinum-based chemotherapy drug called cisplatin.

    Other treatments include percutaneous ablation and chemoembolization. The most widely used ablation techniques for lung cancer are radiofrequency ablation (RFA), cryoablation, and microwave ablation. Ablation may be an option for patients whose tumors are near the outer edge of the lungs. Nodules less than 1 cm from the trachea, main bronchi, oesophagus, and central vessels should be excluded from RFA given high risk of complications and frequent incomplete ablation. Additionally, lesions greater than 5 cm should be excluded and lesions 3 to 5 cm should be considered with caution given high risk of recurrence. As a minimally invasive procedure, it can be a safer alternative for patients who are poor candidates for surgery due to comorbidities or limited lung function. A study comparing thermal ablation to sublobar resection as treatment for early stage NSCLC in older people found no difference in overall survival of the patients. It is possible that RFA followed by radiation therapy has a survival benefit due to synergism of the two mechanisms of cell destruction.

    Advanced/metastatic NSCLC

    The treatment approach for people who have advanced NSCLC is first aimed at relieving pain and distress (palliative), but a wide variety of chemotherapy options exists. These agents include both traditional chemotherapies, such as cisplatin, which indiscriminately target all rapidly dividing cells, and newer targeted agents, which are more tailored to specific genetic aberrations found within a person's tumor. When choosing an appropriate chemotherapy approach, the toxicity profile (side effects of the drug) should be taken into account and balanced with the person's comorbidities (other conditions or side effects that the person is experiencing). Carboplatin is a chemotherapy agent that has a similar effect on a person's survival when compared to cisplatin, and has a different toxicity profile from cisplatin. Carboplatin may be associated with a higher risk of thrombocytopenia. Cisplatin may cause more nausea or vomiting when compared to carboplatin treatment. PD‐L1 inhibitors are more effective and lead to longer survival with fewer side effects compared to platinum-based chemotherapy.

    At present, two genetic markers are routinely profiled in NSCLC tumors to guide further treatment decision-making - mutations within epidermal growth factor (EGFR) and anaplastic lymphoma kinase. Also, a number of additional genetic markers are known to be mutated within NSCLC and may impact treatment in the future, including BRAF, HER2/neu, and KRAS. For advanced NSCLC, a combined chemotherapy treatment approach that includes cetuximab, an antibody that targets the EGFR signalling pathway, is more effective at improving a person's overall survival when compared to standard chemotherapy alone.

    Thermal ablations, i.e. RFA, cryoablation, and microwave ablation, are appropriate for palliative treatment of tumor-related symptoms or recurrences within treatment fields. People with severe pulmonary fibrosis and severe emphysema with a life expectancy less than a year should be considered poor candidates for this treatment.

    EGFR mutations

    Roughly 10–35% of people who have NSCLC will have drug-sensitizing mutations of the EGFR. The distribution of these mutations has been found to be race-dependent, with one study estimating that 10% of Caucasians, but 50% of Asians, will be found to have such tumor markers. A number of different EGFR mutations have been discovered, but certain aberrations result in hyperactive forms of the protein. People with these mutations are more likely to have adenocarcinoma histology and be nonsmokers or light smokers. These people have been shown to be sensitized to certain medications that block the EGFR protein known as tyrosine kinase inhibitors specifically, erlotinib, gefitinib, afatinib, or osimertinib. Reliable identification of mutations in lung cancer needs careful consideration due to the variable sensitivity of diagnostic techniques.

    ALK gene rearrangements

    Up to 7% of NSCLC patients have EML4-ALK translocations or mutations in the ROS1 gene; these patients may benefit from ALK inhibitors, which are now approved for this subset of patients. Crizotinib, which gained FDA approval in August 2011, is an inhibitor of several kinases, specifically ALK, ROS1, and MET. Crizotinib has been shown in clinical studies to have response rates around 60% if patients are shown to have ALK-positive disease. Several studies have also shown that ALK mutations and EGFR activating mutations are typically mutually exclusive. Thus, patients who fail crizotinib are not recommended to be switched to an EGFR-targeted drug such as erlotinib.

    Other treatment options

    Micrograph showing a PD-L1-positive NSCLC, PD-L1 immunostain

    NSCLC patients with advanced disease who are not found to have either EGFR or ALK mutations may receive bevacizumab, which is a monoclonal antibody medication targeted against the vascular endothelial growth factor (VEGF). This is based on an Eastern Cooperative Oncology Group study that found that adding bevacizumab to carboplatin and paclitaxel chemotherapy for certain patients with recurrent or advanced NSCLC (stage IIIB or IV) may increase both overall survival and progression-free survival.

    https://doi.org/10.3390/ph13110373
    The main treatment arms of phase 3 clinical trials providing immunotherapy in the first line for patients with non-small cell lung cancer.
    Non-small cell lung cancer (NSCLC) cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system. Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and Pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets Vascular Endothelial Growth Factor (VEGF) in the circulation and functions as an angiogenesis inhibitor.

    NSCLC cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system. Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and Pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets Vascular Endothelial Growth Factor (VEGF) in the circulation and functions as an angiogenesis inhibitor. Multiple phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC were published, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

    In 2015, the US Food and Drug Administration (FDA) approved the anti-PD-1 agent nivolumab for advanced or metastatic SCC.

    In 2015, FDA also approved the anti-EGFR drug necitumumab for metastatic SCC.

    2 October 2015, the FDA approved pembrolizumab for the treatment of metastatic NSCLC in patients whose tumors express PD-L1 and who have failed treatment with other chemotherapeutic agents.[58]

    October 2016, pembrolizumab became the first immunotherapy to be used first line in the treatment of NSCLC if the cancer overexpresses PDL1 and the cancer has no mutations in EGFR or in ALK; if chemotherapy has already been administered, then pembrolizumab can be used as a second-line treatment, but if the cancer has EGFR or ALK mutations, agents targeting those mutations should be used first. Assessment of PDL1 must be conducted with a validated and approved companion diagnostic.

    https://doi.org/10.3390/ph13110373
    Overall survival in non-small cell lung cancer patients treated with protocols incorporating immunotherapy in the first line for advanced or metastatic disease. Nasser NJ, Gorenberg M, Agbarya A. Pharmaceuticals2020, 13(11), 373; https://doi.org/10.3390/ph13110373

    The prognosis of patients with non-small-cell lung cancer improved significantly with the introduction of immunotherapy. People with tumor PDL-1 expressed over half or more of the tumor cells achieved a median overall survival of 30 months with pembrolizumab.

    Mobocertinib (Exkivity) was approved for medical use in the United States in September 2021, and it is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

    Operator (computer programming)

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