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Smoking habit. From the history to present philosophy of prevention and ethical issues.

Smoking habit. From the history to present philosophy of prevention and ethical issues.

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Smoking Habit. Physiopathology and prevention Smoking Habit. Physiopathology and prevention Presentation Transcript

  • SMOKING HABIT PHYSIOPATHOLOGY AND PREVENTION
    • Antonio Liras, Sara Martín, Ianire Maté and Verónica Padilla
    • Department of Physiology, Biology School. Madrid Complutense University. SPAIN
    (June, 2008) Correspondence: Antonio Liras, PhD E-mail: aliras@hotmail.com
    • The first written reference to the use of tobacco
    • dates back to the discovery of the Americas, in
    • the work of Fray Bartolomé de las Casas,
    • ("History of the Indies“), where two Spanish
    • settlers saw Indians smoking.
    • Nicotiana , the generic name of the
    • tobacco plant, originates from
    • Dr. Jean Nicot (1560).
    SMOKING A HISTORY FROM PERMISSIVENESS TO RESTRICTION
  • 16th century
    • Tobacco was believed to be the "panacea grass“, with healing powers against all ailments (even asthma).
    • On the other hand, there were always critics of smoking ( James I of England), with criteria similar to those found today .
    • Tobacco consumption spread to many European and Asian countries.
    • Havana was the great tobacco center.
    James I of England
  • 1 7th century  
    • Tobacco sales at the end of the 16th century were a great business, and tobacco plantations became universal - even exceeding potato crops.
    • The consumption of tobacco became popular, and nicotine was even prescribed for therapeutic purposes.
    • In catholic churches and in the Basilica of the Vatican, tobacco consumption was prohibited.
  • 18th century
    • The nobility of the rococo used to inhale the smoke through the nose.
    • For the first time, in 1761, John Hill
    • associated tobacco with cancer, thanks
    • to the diagnosis of cancerous polyps in
    • heavy snuff consumers.
  • 19th century
    • In 1880, James Bonsack invented a
    • machine for rolling cigarettes.
    • This expanded the tobacco
    • industry, with advertising
    • claiming smoking to be
    • beneficial for health.
    •  
    Bonsack's cigarette rolling machine, as shown on U.S. patent 238,640.
  • 20th century
    • In 1935, Fritz Lickint published a
    • number of studies relating cancer
    • to cigarette smoking.
    • Hoffman in the 1950s established that
    • smoking increases the risk of
    • suffering cancer of the mouth, neck,
    • esophagus, larynx and lungs.
    • Finally, Richard Doll and Bradford Hill, in a
    • rigorous epidemiological study,
    • demonstrated the reality of the relationship
    • between cancer and tobacco.
    • 1970s: Great social concern about the consequences of smoking.
    • 1980s: First evidence that lung cancer increases in women married to smoking men.
    20th century
    • The tobacco industry in its zeal to continue with the business, and in collaboration with national institutes of cancer, designed new formulations (filters, low nicotine cigarettes) to suggest that smoking thus might be less harmful.
    21st century
  • PREVENTIVE LEGISLATION
    • Warsaw Declaration (2002): Politicians and WHO see the need for a "Smoke-Free World".
    • Marco Convention: Approved by 192 countries of the WHO, during the World Health Assembly (Geneva on May 21, 2003)
        • First international public health treaty: It attempts to regulate a product that kills its consumers. The aim is to reach children and young people.
    • Aftercare sanitary measures, regulating the sale, supply, consumption and advertising of tobacco.
    “ It tries to banish the social acceptance of smoking to improve the quality of life of individuals”
  • EVOLUTION OF THE CONCEPT OF SMOKING
    • 1960s
    • Status of the "modern" individual.
    • 1970s
    • Consumption as a "dependency".
    • 1980s
    • Consumption as an "addiction".
    • 1990s
    • “ The clinic of smoking”.
    • XXI Century
    • Smoking is considered “nicotine
    • drug addiction”.
  • Is smoking comparable to the effects of other substances such as alcohol, barbiturates, heroin and cocaine?
  • To answer this question we must differentiate between...
    • Habituation
    • “ Repeated consumption of a particular drug”, which is characterized by:
    • No compulsive desire to continue consuming.
    • Moderate tendency to increase the dose.
    • Some degree of physical dependence but without withdrawal symptoms.
    • Effects that are detrimental to the individual.
    • Addiction
    • On the other hand is characterized by:
    • Compulsive desire to consume.
    • Getting drugs desperately.
    • Physical and psychological dependence caused by drugs.
    • Detrimental effects for the individual and society.
  • CLASSIFICATION OF SMOKING
    • First it was seen as a habit.
    • In 1988 the National Center of Health defined
    • the psychoactive effects of nicotine.
    • Nicotine: Addictive substance that induces
    • pharmacological and behavioral processes
    • similar to those of drugs such as heroin and cocaine.
    • In 1992 the WHO, in its International
    • Classification of Diseases, suggested nicotine
    • dependence.
  • DEPENDENCE
    • Dependence is characterized by at least 3 of the
    • following symptoms for 12 months:
    • 1. The need for increasing amounts of cigarettes
    • (tolerance).
    • 2. The effect decreases with continued consumption
    • (tolerance).
    • 3. Withdrawal symptoms.
    • 4. Smoking is resorted to in order to lessen the syndrome.
  • Physical and psychological dependence
    • Physical dependence
    • 7 seconds pass from inhalation of nicotine until its effects are demonstrated in the brain:
    • Pleasure sensation.
    • Supposed increase in mental
    • concentration.
    • Mental stability.
    • Decreased anxiety.
    • “ Physical dependence is produced by constant exposure of the neurons to nicotine"
    • It is produced when the smoker associates environmental stimulus with the act of smoking.
    • Environmental factors: waiting
    • room, bar, restaurant, car…
    • Emotional factors: stress,
    • anxiety, boredom, loneliness...
    • Social events: festivals,
    • meetings, holidays…
    • This dependence is very related
    • to the concept of automatism:
    • “ repetitive behavior of the
    • smoker”.
    • “ When the act of smoking, the managing of the cigarette, the smell, flavor … becomes agreeable, this is when we talk of psychological dependence"
    PSYCHOLOGICAL DEPENDENCE
  • “ To overcome the desire to smoke is the most difficult thing for the smoker "
    • During dreaming,
    • resensitization is produced
    • to the effects of the nicotine:
    • “ many smokers agree
    • that the best cigarettes are
    • the first ones of the
    • morning”.
    • Physiologically, through the
    • cholinergic receptors,
    • nicotine is responsible for
    • the dependence, tolerance,
    • and w ithdrawal symptoms .
  • Reasons for tolerance
    • 1. Metabolic reasons : Tobacco induces the expression of certain liver enzymes that increase tolerance to certain hydrocarbons in the combustion of some tars.
    • 2. Pharmacological reasons : These explain desensitization of the cholinergic receptors by increasing concentrations of the agonist.
    • 3. Psychological reasons : These explain the adaptive and compensatory responses that would reduce the impact of the nicotine dose.
  • This is characterized by migraine, motion sicknesses, insomnia, irritability, anxiety, an increase in appetite, an increase in weight, loss of mental concentration, loss of memory.
    • The behavioral effects of nicotine are associated to the neuroregulatory actions of this substance upon other neurotransmitters (dopamine, norepinephrine, β-endorphin and acetylcholine).
    “ Withdrawal symptom”
    • This is based on genes of a Mendelian pattern and others characterized by polygenic inheritance.
    • Racial or ethnic factors.
    • Studies with twins in search of environmental factors that influence the same genetic base.
    GENETIC BASES OF TOBACCO DEPENDENCE Two aspects are studied : 1. Influence of genotype upon acquisition of the habit during infancy or youth. 2. Influence of genotype upon the maintenance of consumption during adult life.
  • Effects of nicotine on the CNS
    • Its pleasant effects are related to stimulation of the
    • dopaminergic or catecholaminergic pathways; the most
    • implicated route is the mesolimbic pathway (extending from the
    • ventral tegmental zone to the nucleus accumbens and frontal cortex)
    • Projections reaching this nucleus, the amygdala and the
    • hippocampus, are associated with the effect of nicotine on memory,
    • as well as to the mental changes associated with the withdrawal
    • syndrome .
    • The projections that extend to the cortex in the perfrontal,
    • orbitofrontal and anterior cingular regions are associated with the
    • experiences generated by consumption of the drug and the need to
    • continue consuming.
    Next View
  • Previous
        • " Therefore genes that
        • regulate the flow of dopamine,
        • whose levels are increased
        • with nicotine, stimulating basal
        • ganglia such as the nucleus
        • accumbens, like other drugs
        • (such as cocaine or morphine)
        • are good candidates for induction
        • to the habit “
    Genes...! Salvador Dalí, 1957
  • Cloning of the genes that encode for 5 dopamine receptors (DRD1 to DRD5)
    • One of the alleles of DRD1 is more frequent in smokers that in non-
    • smokers.
    • A polymorphism in the 3' region of the DRD2 gene is associated with
    • lesser availability of dopamine receptors in the striate nucleus.
    • Relationship of the DAT protein. A polymorphism of the SLC6A3 gene
    • is associated with high values of dopamine, with a lesser
    • predisposition to develop the habit, greater ease in abandoning it,
    • and prolonged periods of abstinence.
  • Other routes of study to understand the genetic bases of this habit are the following systems:
    • -Serotonin
    • -Cholinergic
    • -Opioid
    • -Aminoacidergic
    • -Cannabinoid
    • - Routes related to the levels of nitric acid
  • THE SANITARY PROBLEM IN NUMBERS: FROM THE HEALING PROPERTIES OF TOBACCO TO PHYSIOPATHOLOGY
    • Nowadays many scientific and epidemiological studies confirm that "panacea grass" is a "poison".
    • Nonetheless, the denomination of "poison" has been rejected by smokers, tobacco companies and public authorities.
  • 1,300 million smokers in the world
    • Underdeveloped countries : 75% smoking
    • Medical group : 19% smoking
    • Age at start : Less than 13 years
    • 6,000,000,000,000 cigarettes consumed/year
    33% adults 25% women 50% men 29% adolescents
    • The first avoidable cause of death in the world, despite the fact that 33% of all smokers are aware of the close relationship between smoking and cancer.
    • 40% of smokers do not think that abandoning the habit is the best thing for cancer prevention.
    • 43% of smokers continue smoking despite having respiratory and/or carcinogenic disorders.
    1 st cause of avoidable death in the world Some data...
  • More data... 1 st cause of avoidable death in the world Number of tobacco smoker deaths/year Deaths due to AIDS + Deaths due to malaria + Deaths from childhood diseases avoidable with Vaccines 5 million deaths =
    • 20 to 40 fold greater risk in smokers of suffering lung cancer.
    • Life expectancy of a consumer of 20 cigarettes a day for 25 years is 25% less than for a non-smoker.
    • Survival after the diagnosis of lung cancer: 13 months.
    • If the tumor is removed: 50% patient life expectancy at 5 years.
    • 60% non-smokers exposed to environmental tobacco smoke.
    • Smoking is the cause of approximately 30 human diseases (cardio- and cerebrovascular diseases, chronic obstructive pulmonary disease, and cancer).
    1 st cause of avoidable death in the world More and more data...
  • Cardiovascular disease Arterial ischemia Vascular disease Nicotine Smoking  Catecholamines  Carboxyhemoglobin Endothelial damage  Cyclooxygenase  Aggregation, adhesion and platelet viscosity  Plasminogen  Alteration of the form of red blood cells  Oxidative stress Proinflammatory state  Oxygen demand  Supply of oxygen to tissues  Thrombus formation  Thrombolysis Atherosclerosis
    • During pregnancy, smoking causes reduction of weight, height and cranial perimeter in the newborn child, and seriously harms health.
    During pregnancy
  • Cancer and tobacco Chemical composition of cigarettes
      • 60 carcinogenic compounds
      • (polyaromatic hydrocarbons)
    • There is a clear relationship between smoking and cancer of the lung, larynx, pharynx, esophagus, oral cavity, pancreas, bladder and renal pelvis.  
    • Smoking is a conditional factor in colorectal, adrenal, gastric, uterine, cervical and hepatic cancers and in myeloid leukemia.
    • The possibility that smokers do not suffer lung cancer is very
    • small, and is due to very scant genetic protection
    View 87% of deaths from lung cancer 82% of deaths from lung diseases Caused by smoking Smoking people 98% of all cases of lung cancer
  • Next Spanish Association against Cancer Tabacco no, thanks How bad fumes? View
  • SYMPTOMS OF LUNG CANCER
    • Persistent cough that worsens over time
    • Pain in the chest
    • Phlegm with blood
    • Wheezing in the chest and shortness of breath
    • Susceptibility to pneumonia and bronchitis
    • Swelling of the face
    • Loss of weight
    • Related other factors
  • TYPES OF LUNG CANCER (I)
    • Large-cell or macrocytic
    • Types
      • Squamous cells (more related to tobacco)
      • Adenocarcinoma
      • Large-cell carcinoma
    • Treatment
    • Surgery, cryosurgery and (to slow
    • progression of the disease) chemotherapy and radiotherapy
    • More common
    • Slow growth
    • Treatment
    • Less common
    • More rapidly evolving
    • More related to tobacco
    • In many cases metastasis exists,
    • making surgery ineffective
    • Chemotherapy or irradiation
    • targeted to the tumor
    Small-cell or microcytic TYPES OF LUNG CANCER (II)
  • TYPES OF LUNG CANCER (III)
  • RISK FACTORS FOR DEVELOPING CANCER (I)
    • Type of cigarette
    • Without filter or pipe
    • Mentholated:  CO absorption/retention of
    • smoke because restricts ventilation
    • “ Light”:  consumption/inhalation (smoke
    • reaches more distal regions)
    Causes squamous cell lung cancer (8 hours of exposure = to smoke 8 cigarettes a day)
    • Passive smoking
    • (environmental smoke)
    • Time elapsed from
    • cessation
     Number of years elapsed
  • RISK FACTORS FOR DEVELOPING CANCER (II)
    • Smoking starting age, length of smoking period, previous
    • smoking diseases (bronchitis, emphysema, pneumonia),
    • exposure to many other substances such as asbestos, arsenic,
    • radon, etc.
    • Genetic and molecular factors
    Metabolic activity Tobacco carcinogen detoxification Individual predisposition for developing lung cancer
  • Products of carcinogen metabolism Covalent binding to DNA (irreversible) (directly connected to cigarette number) Optimal cellular repair mechanism over time Non functioning of some repair mechanisms Normal levels of damage DNA mutation HOMEOSTASIS No apoptosis Cellular transformation CANCER * Moreover, reactive oxygen species of smoke Oxidative damage DNA mutation
  • LUNG CANCER PATHOGENESIS p53 gene encodes for p53 protein Cell cycle control DNA synthesis DNA repair Cellular differentiation Gene transcription Programmed cell death Benzopyrene p53 mutation G-to-C and T-to-A transversion (more frequent in smoking women) p53 protein alteration and loss of function * Moreover, p53 gene = tumour suppressor gene Its mutation Oncogene activation Tumor suppressor gene inhibition Synergistic effect on the combination of several mutations Increased risk of developing cancer
  • p53 gene related mutations
    • p73 gene
    • MDM2 gene : p53 negative regulator
    • EGFR gene : Encodes for epidermal growth factor receptor
    • HGF and HGFR genes : Encode for hepatocyte growth factor
    • and its receptor, respectively, up-regulated expression of
    • HGF in type II alveolar cells, and HGFR in adenocarcinoma
    • k-ras gene
    • HSP90 gene : Encodes for heat shock protein 90 (hsp90),
    • fundamental for tumor cell survival
  • Other genetic factors
    • Gender
    • The incidence is presently lower in women than in men.
    • Between 1930-1997 in the USA, lung carcinoma increased 600% in women.
    • p53, CYP1A1, GSTM1 and k-ras mutations appear more often in smoking women
    • than in smoking men.
    • Data show a greater susceptibility to lung cancer in smoking women.
    Possible explanations
    • Gender differences in DNA repair mechanism.
    • Dietetic factors.
    • Possible relationship to human papilloma virus (HPV) infection.
    • Increased levels of some growth factors expressed on chromosome X.
    • Hormonal effects: Estrogen treatment in menopausal women increases lung
    • cancer risk (high levels of estrogen receptor in normal and carcinogenic lung
    • cells)
    • Ethnic group
    • Epidemiological data show that Afro-americans and native Hawaiians
    • are more susceptible for lung cancer than Caucasians, Japanese Americans and Latins.
  • PREVENTION, CLINICAL ETHICS AND RESPONSIBILITY, AND SOCIAL CONSCIENCE
    • WHO: “Major avoidable reason of morbidity-mortality in developed
    • countries”
    • Entails high social and sanitary cost
    • AIM : Prevention and control of smoking
    • Therapy of addiction and consequences in the smoker
    • Social conscience
    Avoid smoking
  • Therapy of addiction and consequences in the smoker
    • Therapeutic, pharmacological and psychosocial actions
    • Treatments of proven efficiency
        • Self-help manuals
        • Medical advice
        • Psychological interventions
        • Nicotine-replaced substances (chewing gum, nicotine patch,
        • inhalers, sublingual tablets)
        • Pharmacological treatment with bupropion nortriptyline and
        • clonidine
    • The latest strategy: A nicotine vaccine against antibodies
    • that prevent it from crossing the blood-brain barrier
    • (no sensation of pleasure).
    • Nowadays, no-smoking therapies cost 800 million €.
    • However, the success rate is only 20%.
  • SOCIAL CONSCIENCE (I) Necessities
    • Smoke-free spaces.
    • Elimination of tobacco advertisements and brand sponsorship.
    • Establishment of fiscal politics for tobacco.
    The idea is not to suppress or censure smokers; the aim is to ensure freedom to health among non-smokers: CIVIC CONSCIENCE
  • Who has to establish tobacco's rules? SOCIAL CONSCIENCE (II) To preserve public health THE GOVERMENT AND CIVIL SERVICES To preserve sanitary and medical health PHYSICIANS AND SMOKING TREATMENT AND PREVENTION EXPERTS (CLINICAL ETHICS)
  • CLINICAL ETHICS Difference between apparent freedom of action and truly voluntary decisions The cigarette is lighted by the smoker Apparent voluntary action However, it's not a truly free action but rather a lack of will to refrain from smoking Is the intervention of physicians legitimate? The physician has to advise the cessation of smoking (proposition, not imposition) The main function of the physician here is to educate and instruct rather than to cure. (One of every two smokers dies prematurely)
  • In brief … It's a worldwide public health problem that requires: INTERNATIONAL COOPERATION and SOCIAL CONSCIENCE Smoking habit Sanitary Social Economic Environmental … consequences
  • WEB sites (I)  Tobacco Road: History  Hist ory of t he Indies  Jean Nicot  James I of England  John Hill  Fritz Lickint . The first reports on smoking and lung cancer. Why are they consistently ignored?  Schairer and Schöniger : Lung cancer and tobacco consumption  Richard Doll and Bradford Hill  Final Warsaw Declaration  Framework Convention on Tobacco Control  Nicotine Addiction  Genetic basis of tobacco dependence  Drug Addiction  Smoking and lung cancer
  • WEB sites (II)
    •  Recent trends in the treatment of advanced lung cancer
    •  Types of lung cancer
    •  Passive smoking
    •  Environmental Protection Agency
    •  Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer
    • DNA repair
    • Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking associated cancers
    • Quantitative detection of p53 mutations in plasma DNA from tobacco smokers
    • Lung Cancer in Women: Emerging Differences in Epidemiology, Biology, and Therapy
    • Expression of estrogen receptors alpha and beta in human lung tissue and cell lines
    •  Ethnic and racial differences in the smoking-related risk of lung cancer
    •  Biography: Professor Sir Richard Peto
    •  Tobacco and Cancer: Recent Epidemiological Evidence
    •  Tobacco Vaccine
    •  Clinical Ethics
  • References (I)
    • 1.   Redmond DE. Tobacco and cancer: the first clinical report, 1761. N Engl J Med. 1970;282:18-23.
    • 2.    Cami J, Farre M. Drug addiction. N Engl J Med. 2003; 349:975-86.
    • 3. Saijo N. Recent trends in the treatment of advanced lung cancer. Cancer Sci. 2006;97:448-52.
    • 4. Machida EO, Brock MV, Hooker CM, Nakayama J, Ishida A, Amano J, et al. Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer. Cancer Res. 2006;66:6210-8.
    • 5. Lopez MJ, Nebot M, Salles J, Serrahima E, Centrich F, Juarez O, et al. Measurement of exposure to environmental tobacco smoke in education centers, health centers, transport facilities and leisure places. Gac Sanit. 2004;18:451-7.
    • 6. Simonato L, Agudo A, Ahrens W, Benhamou E, Benhamou S, Boffetta P, et al. Lung cancer and cigarette smoking in Europe: an update of risk estimates and an assessment of inter-country heterogeneity. Int J Cancer. 2001;91:876-87.
    • 7. Cassidy A, Myles JP, Liloglou T, Duffy SW, Field JK. Defining high-risk individuals in a population-based molecular-epidemiological study of lung cancer. Int J Oncol. 2006;28:1295-301.
    • 8. Szymanowska A, Jassem E, Dziadziuszko R, Borg A, Limon J, Kobierska-Gulida G, et al. Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism. Lung Cancer. 2006;52:9-14.
    • 9. Hagiwara N, Mechanic LE, Trivers GE, Cawley HL, Taga M, Bowman ED, et al. Quantitative Detection of p53 Mutations in Plasma DNA from Tobacco Smokers. Cancer Res. 2006;66:8309-17.
    • 10. Schabath MB, Wu X, Wei Q, Li G, Gu J, Spitz MR. Combined effects of the p53 and p73 polymorphisms on lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:158-61.
  • References (II)
    • 11. Zhang X, Miao X, Guo Y, Tan W, Zhou Y, Sun T, et al. Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer. Hum Mutat. 2006;27:110-7.
    • 12.   Yokoyama T, Kondo M, Goto Y, Fukui T, Yoshioka H, Yokoi K, et al. EGFR point mutation in non-small cell lung cancer is occasionally accompanied by a second mutation or amplification. Cancer Sci. 2006;97:753-9.
    • 13.   Chen JT, Lin TS, Chow KC, Huang HH, Chiou SH, Chiang SF, et al. Cigarette smoking induces over-expression of hepatocyte growth factor in type II pneumocytes and lung cancer cells. Am J Respir Cell Mol Biol. 2006;34:264-73.
    • 14.   Aviel-Ronen S, Blackhall FH, Shepherd FA, Tsao MS. K-ras mutations in non-small-cell lung carcinoma: a review. Clin Lung Cancer. 2006;8:30-8.
    • 15.    Senju M, Sueoka N, Sato A, Iwanaga K, Sakao Y, Tomimitsu S, et al. Hsp90 inhibitors cause G2/M arrest associated with the reduction of Cdc25C and Cdc2 in lung cancer cell lines. J Cancer Res Clin Oncol. 2006;132:150-8.
    • 16.    Thomas L, Doyle LA, Edelman MJ. Lung Cancer in Women: Emerging Differences in Epidemiology, Biology, and Therapy. Chest. 2005;128;370-81 .
    • 17.   Mollerup S, Jorgensen K, Berge G, Haugen A. Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer. 2002;37:153-9.
    • 18.   Haiman CA, Stram DO, Wilkens LR, Pike MC, Kolonel LN, Henderson BE, et al. Ethnic and racial differences in the smoking-related risk of lung cancer. N Engl J Med. 2006;354:333-42.
    • 19.    Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst. 2004;96:99-106 .