1. Sisteminis rūkymo ir rūkymo metimo poveikis
Dr. Lina Jančaitytė
KMUK Kardiologijos klinika

2. Paskaitos uždaviniai Sisteminis rūkymo poveikis
Laboratorinių rodiklių pokyčiai rūkant ir nerūkant
Rūkymo ir metimo rūkyti įtaka įvairioms organų sistemoms

3. Ar žinote, kad
Rūkymas išlieka antroji didžioji mirties priežastis pasaulyje.
2030 m., išliekant dabartinei situacijai, rūkymas nužudys iki 9 milijonų žmonių.
molecules per puff.7 This oxidative stress can be
registered in several different ways, either by direct
measurements of the oxidative burden (reactive oxygen
species [ROS] production by peripheral blood
cells) or by the effects of oxidative stress on target
molecules (lipid peroxidation products and oxidized
proteins), or as the responses to the oxidative stress
(antioxidant capacity of plasma)8 [Table 1].
Only a few studies9–11 have used ROS production
by blood cells extracted from the circulation of
smokers. Perhaps more important than the presence
of oxidative stress are the effects of this oxidative
stress on a variety of vital target molecules. Numerous
markers for oxidative damage have been proposed,
including oxidation and nitration of proteins.
For example, nitration of tyrosine residues of proteins
leads to the production of 3-nitrotyrosine,
which may be considered as a marker of nitric oxide
(NO)-dependent oxidative damage. Indeed, NOmediated
and peroxynitrite-mediated formation of
3-nitrotyrosine is elevated in plasma and platelets of
chronic smokers.12,13 Furthermore, Pignatelli and
coworkers14 reported significantly higher levels of
nitrated and oxidized fibrinogen, transferrin, plasminogen,
and ceruloplasmin in smokers than in
nonsmokers.
Free radicals from cigarette smoke also cause
peroxidation of the polyunsaturated fatty acids of cell
membranes that amplify oxidative stress during
smoking. The F2-isoprostanes, prostaglandin-like
compounds, are products of free radical-catalyzed
lipid peroxidation of arachidonic acid. Several studies15–
17 have reported an increased level of isoprostane
8-iso-prostaglandin F2 (PGF2) formation in
smokers.

4. Vienas ketvirtadalis visų mirčių tarp rūkančiųjų yra dėl išeminės širdies ligos, kitas ketvirtadalis – dėl plaučių vėžio ir lėtinės obstrukcinės plaučių ligos, kita pusė – dėl neoplastinių ir kvėpavimo ligų.
Lyginant rūkančiuosius ir niekad nerūkiusius asmenis, nustatyta, kad bendras mirštamumas yra didesnis tarp rūkančiųjų 2.77 karto (95% ).

5. Sisteminis rūkymo poveikis
Sisteminis uždegimas
Sisteminis oksidacinis stresas
Poveikis į vazomorinę funkciją ir endotelio funkciją
Systemic Effects of Smoking.
Bill MacNee

6. Sisteminis uždegiminis rūkymo poveikis
Uždegiminių ląstelių aktyvavimas ir atpalaidavimas į cirkuliuojantį kraują, padidėjęs cirkuliuojančių mediatorių kiekis charakterizuoja sisteminį uždegimą.
Sisteminis uždegiminis poveikis pasireiškia hemopoetinės sistemos stimuliavimu, būtent leukocitų ir trombocitų patekimą iš kaulų čiulpų į kraują.
Ilgalaikis rūkymas sukelia leukocitų (neutrofilų) kiekio padidėjimą kraujyje.
Stebimas jaunų leukocitų formų padidėjimas kraujyje. Inflammatory Mediators in Peripheral Blood of
Smokers
Activated inflammatory cells produce a great variety
of inflammatory mediators in response to cigarette
smoke, first of all, acute-phase proteins (APPs)
and cytokines. Conditions that commonly lead to
substantial changes in the plasma concentrations of
APPs and cytokines include infection, trauma, surgery,
burns, tissue infarction, various immunologically
mediated inflammatory conditions, and cancer.
In recent years, these inflammatory mediators have
been studied as potential markers of subtle and
persistent systemic alterations. Many studies have
reported changes in levels of inflammatory mediators
not only in the lungs but also in the circulation of
healthy smokers. Several studies47–49 have reported
strong associations between cigarette smoking and
different APPs such as C-reactive protein (CRP) and
fibrinogen (Table 2).

7. Cirkuliuojantys citokinai tokie, kaip IL 1 ir IL 6 stimuliuoja kaulų čiulpus, sukeldami plaučių uždegimą.
T limfocitai susiję su plaučių ligų, ypač LOPL , vystymųsi.
Daug rūkantiems asmenims stebimas CD4 ląstelių sumažėjimas (T-helperiai) ir CD8 ląstelių (T-ląstelių supresoriai) padidėjimas.

8. Plaučių mikrocirkuliacija ir uždegimas
MacNee et al NEJM 1989

9. Rūkymas ir endotelio funkcija
Rūkymas sutrikdo NO gamybą – rūkančiųjų ji ženkliai sumažėja.
Rūkantiesiems nustatomas MTL padidėjimas.
Pakitusios endotelio ląstelės netenka savo fiziologinės ypatybės nesijungti su cirkuliuojančiomis imuninėmis ląstelėmis (monocitais,makrofagais, T limfocitais, trombocitais).
Rūkymo sukeltas endotelio pažeidimas skatina ir ateromos formavimąsi, kas yra ankstyvas aterogenezės požymis.
However, this hypothesis has to be taken cautiously
because not all smokers acquire one or more of these
diseases. It clearly suggests the existence of other
mechanisms influencing common disease development,
and, beyond doubt, genetic susceptibility is
one of them.86 Different approaches like case-control
and whole-genome association studies, linkage
analysis of extended pedigrees, and affected sibling
pairs are used to dissect genetic component of
complex traits. For genetically complex disease like
cardiovascular diseases, common disease-common
variant hypothesis has been put forward, which
assumes that common disease susceptibility or resistance
variants are expected to be few at each genetic
locus, relatively common in the human population
and enriched in the coding and regulatory sequence
of genes.87 Despite the small effects of such genes
individually, the magnitude of their attributable risk
may be large because they are quite frequent in the
population, making them of public health significance.
However, there is a possibility that many rare
variants, each with small contribution, underlie the
susceptibility to common human disease.88 Nevertheless,
it seems that complete model of complex
disease initiation and progression is based on cooperation
where these multiple genes are likely to
operate through interactions with many environmental
factors where smoking is only one but a very
important variable.

10. Audinių faktorius
Fibrogenezė
Fibrinogenas
Fibrinolizė
Fibrino krešulys
PA inhibitorius
t-PA
Plazminogenas
Plazminas
Fibrino degradacijos
produktai

11. Laboratoriniai rodikliai

16. Rūkymas ir navikai Navikai plaučių kasos stemplės inkstų
šlapimo pūslės
skrandžio
The relationship between smoking and certain cancers, such as lung, bladder, esophageal and pancreatic cancer has been established for many years, while the relationship between smoking and others, such as renal cancer, has only recently been solidified.
A number of studies published over the last few years have sought to further elucidate the effects of smoking on these cancers. Specifically, the effect of cigarette dose and duration of smoking was studied, as well as the effects of smoking cessation and duration of cessation on the reduction of risk.
References
Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States:
data from the First National Health and Nutrition Examination Study. Arch Intern Med. 2003;163:
Lin Y, Tamakoshi A, Kawamura T, et al, for the JACC Study Group. A prospective cohort study of cigarette
smoking and pancreatic cancer in Japan. Cancer Causes Control. 2002:13;
Fuchs CS, Colditz GA, Stampfer MJ, et al. A prospective study of cigarette smoking and the risk of pancreatic cancer.
Arch Intern Med. 1996;156:
Bosetti C, Gallus S, Garavello W, La Vecchia C. Smoking cessation and the risk of oesophageal cancer: an overview
of published studies. Oral Oncol. 2006;42:
Zeegers MPA, Tan FES, Dorant E, van den Brandt PA. The impact of characteristics of cigarette smoking on urinary
tract cancer risk: a meta-analysis of epidemiologic studies. Cancer. 2000;89(3):
Hunt JD, van der Hel OL, McMillan GP, Boffetta P, Brennan P. Renal cell carcinoma in relation to cigarette
smoking: meta analysis of 24 studies. Int J Cancer. 2005;114:

17. Plaučių vėžio rizika Šansų santykis
Hazard Ratio (95% CI)a
Šansų santykis
Key Point
Smoking increases the likelihood of developing lung cancer. Quitting smoking can lower this increased risk.
Participants (noninstitutionalized civilians aged years) in the First National Health and Nutrition Examination Survey ( ) were followed up for a median duration of 17.9 years and analyzed by Mannino et al.
Subjects (N=5402) were analyzed using a proportional hazards model to determine the effect of smoking on the development of lung cancer.
The mean smoke exposure of current and ex-smokers was comparable. Current smokers’ (defined as those smoking at the time of the initial survey) mean smoke exposure was 33.1 (SE: 0.7) pack/years, and the mean smoke exposure of ex-smokers was 33.3 (SE: 1.0) pack/years. Ex-smokers had quit 8.6 (SE: 0.3) years before the initial survey.
Compared with a value of 1.0 for never smokers, the hazard ratio for development of lung cancer was 3.6 (95% CI, ) for ex-smokers and 8.4 (95% CI, ) for current smokers.
Niekada nerūkę Buvę rūkoriai Esami rūkoriai
Mannino et al. Arch Intern Med. 2003;163:
Reference
Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States: data from the First National Health and Nutrition Examination Study. Arch Intern Med. 2003;163:

18. Plaučių vėžio rizika Šansų santykis Niekada nerūkę <30 30-60 >60
Never Smokers
30
30 to 60
60
Pack/Years
Hazard Ratio (95% CI)a
Šansų santykis
Key Point
The risk of developing lung cancer rises with increasing cigarette consumption.
Mannino et al also determined the relationship between the number of cigarettes smoked and the risk of developing lung cancer.
Pack/year was calculated by multiplying the average number of cigarettes smoked daily by the number of years smoked and dividing by 20.
The hazard ratio for development of lung cancer compared with a value of 1.0 for never smokers, was 2.9 for those who smoked <30 pack/years, 9.0 for those who smoked 30 to <60 pack/years, and 19.9 for those who smoked 60 or more pack/years.
Niekada nerūkę < >60
Pakelių per metus
Mannino et al. Arch Intern Med. 2003;163:
Reference
Mannino DM, Aguayo SM, Petty TL, Redd SC. Low lung function and incident lung cancer in the United States: data from the First National Health and Nutrition Examination Study. Arch Intern Med. 2003;163:

19. Males Smoking 40 Cigarettes per Day
Kasos vėžio rizika
Reliatyvi rizika
Relative Risk (95% CI)a
3.3
Key Point
Smoking increases the risk of pancreatic cancer.
Lin et al analyzed data from the Japan Collaborative Cohort Study for the Evaluation of Cancer Risk. The subjects, 99,527 Japanese citizens aged 40 to 79 years with known smoking status and no reported history of cancer, were followed up from the beginning of the study ( ) through 1997.
The RR of death from pancreatic cancer was determined after adjusting for age, body mass index, diabetes, and gallbladder disease. Compared with nonsmokers, male smokers had a RR of 1.6 (95% CI, ), and female smokers had a RR of 1.7 (95% CI, ). There was a trend (P=.59) toward a higher RR (3.3; 95% CI, ) for male smokers who smoked more than 40 cigarettes per day.
1.7
1.6
1.0
Niekada nerūkę Moterys Vyrai Vyrai,
surūkę >40 cig./d.
Nonsmokers
Female Smokers
Male Smokers
Males Smoking 40 Cigarettes per Day
Lin et al. Cancer Causes Control. 2002;13:
Reference
Lin Y, Tamakoshi A, Kawamura T, et al, for the JACC Study Group. A prospective cohort study of cigarette smoking and pancreatic cancer in Japan. Cancer Causes Control. 2002:13;

20. Stemplės vėžio rizika
Rūkantys 3 kartus dažniau serga plokščialąsteliniu stemplės vėžiu.
Buvę rūkoriai serga rečiau nei esami rūkoriai.
Po 10 nerūkymo metų buvę rūkoriai turi 2-kartus didesnę vėžio riziką.
Key Point
Smoking increases the risk of developing esophageal cancer.
Wu et al reported an approximate 3-fold increase in risk of esophageal cancer over that of nonsmokers (see next slide).
Bosetti et al reviewed 20 studies investigating the effect of smoking cessation on increased risk. Many of the studies were in agreement that the risk of esophageal cancer is reduced after smoking cessation, but that there is a lasting effect of smoking on this risk, and even after 10 years or more, the risk of ex-smokers developing this cancer is twice as high as that for nonsmokers.
Nature Clinical Practice. Accessed September 19, Bosetti et al. Oral Oncol. 2006;42: ; Wu et al. Cancer Causes Control. 2001;12:
References
Bosetti C, Gallus S, Garavello W, La Vecchia C. Smoking cessation and the risk of oesophageal cancer: an
overview of published studies. Oral Oncol. 2006;42:
Wu AH, Wan P, Bernstein L. A multiethnic population-based study of smoking, alcohol and body size and risk of
adenocarcinomas of the stomach and esophagus (United States). Cancer Causes Control. 2001;12:

21. Šlapimo pūslės vėžio rizika
Rūkymas yra viena dažniausių priežasčių.
Rūkymo prevencija sumažina vėžio riziką vyrams 50% ir moterims 23%.
Rūkoriai beveik 3-kartus dažniau serga pūslės vėžiu nei nerūkantys.
Key Point
Smoking is one of the most important risk factors associated with bladder cancer.
Bladder cancer is the ninth most frequent cancer in men worldwide (approximately 330,000 new cases per year), and one of the top 5 most frequent cancers in men in the United States. It is more common in men, but there are approximately 60,000 women diagnosed with bladder cancer per year worldwide.
In a meta-analysis of 43 studies, Zeeger et al concluded that cigarette smokers have an approximately 3-fold greater risk of bladder cancer than nonsmokers. Summary ORs compared with nonsmokers were 3.33 (95% CI, ) for smokers and (95% CI, ) for ex-smokers.
Zeegers et al. World J Urol. 2004;21: ; Urology channel. Accessed September 20, 2007
Reference
Zeegers MPA, Kellen E, Buntinx F. The association between smoking, beverage consumption, diet and
bladder cancer: a systematic literature review. World J Urol. 2004;21:

22. Inkstų vėžio rizika Reliatyvi rizika Vyrai Moterys
Relative Risk (95% CI)a
Key Point
Smoking increases the risk of renal cell carcinoma in both men and women in a dose-dependent manner.
Hunt et al conducted a meta-analysis of 19 case-controlled and 5 cohort studies investigating the relationship between smoking and renal cell carcinoma. Smokers were divided into categories based on the extent of their smoking.
All male smokers had an increased risk of developing renal cell carcinoma, and women who smoked more than 10 cigarettes/day (10-20 c/d: RR, 1.38; 95% CI, ) also had an increased risk. The risk for both men and women was dose-dependent.
Cigaretės/dienai
1-9
20
1-9
20
Vyrai Moterys
Men
Women
Hunt et al. Int J Cancer. 2005;114:
Reference
Hunt JD, van der Hel OL, McMillan GP, Boffetta P, Brennan P. Renal cell carcinoma in relation to cigarette smoking: meta analysis of 24 studies. Int J Cancer. 2005;114:

23. Rūkymo poveikis endokrininei sistemai
Osteoporozė
Skydliaukės ligos
Rezistencija insulinui/cukrinis diabetas
In relatively recent years, smoking has been shown to increase the risk of various disorders of the endocrine system. The following section will present a number of studies that clarified the connection between smoking and these disorders.

24. Kaulų tankis vyresnio amžiaus moterims
Šlaunikaulis
Bendras
0.00
0.74
0.76
0.78
0.80
0.82
0.84
0.00
0.94
0.96
0.98
1.00
1.02
tankis (g/cm2)
tankis (g/cm2)
Key Point
Heavy smoking in older women causes a significant reduction in BMD compared with light or no smoking.
Rapuri et al conducted an osteoporotic study in elderly women, including 390 nonsmokers, 33 light smokers (<1 pack/day), and 21 heavy smokers (≥1 pack/day), aged years, measuring bone density at a number of locations in the body.
There was a significant decrease in BMD at the total femur (6%) and total body (4%) in heavy smokers, but not in light smokers. Other sites (lumbar spine, femoral neck) displayed a similar but not significant trend.
nerūkantys 1
≥1 pak./d.
Nerūkantys 1
≥1 pak./d.
Cigaretės/Dienai Rūkantys
Cigaretės/Dienai Rūkantys
Rapuri et al. Bone. 2000;27(3):
Reference
Rapuri PB, Gallagher JC, Balhorn KE, Ryschon KL. Smoking and bone metabolism in elderly women. Bone. 2000;27(3):

25. Rūkymas ir skydliaukės disfunkcija
Liga
Rizika
Graves liga
45%
Mazginis gūžys
28%
Autoimuninis hipotiroidizmas
23%
Key Point
Smoking increases the risk of developing thyroid disease in women.
Vestergaard et al analyzed 617 patients with hyperthyroidism (Graves’ disease) and 408 patients with autoimmune hypothyroidism in Denmark, an area with a high incidence of thyroid disease where smoking is frequent and iodine intake is relatively low. Each subject was age- and sex-matched to a control subject, and each was assessed on the basis of ever smoking and use of hormonal contraceptives or replacement. In each case, 88% to 89% of the subjects were women. Men and women were analyzed separately.
Among the women, the patients were found to have a higher frequency of smoking than the controls.
Using logistic regression to calculate the odds ratios, then calculating percent attributable risk, it was determined that smoking increases the chances of women developing all 3 of the conditions. The greatest effect of smoking was observed in Graves’ disease, where the risk attributed to smoking was 45%.
As in previous studies, smoking was not found to have an effect on thyroid disease in men.
Rūkančios moterys turi didesnę riziką susirgti skydliaukės ligomis.
Vestergaard et al. Thyroid. 2002;12(1):69-75.
Reference
Vestergaard P, Rejnmark L, Weeke J, et al. Smoking as a risk factor for Graves’ disease, toxic nodular goiter, and autoimmune hypothyroidism. Thyroid. 2002;12(1):69-75.

26. Rūkymas ir cukrinis diabetas
Tiriant moteris, sergančias cukriniu diabetu, nustatyta, kad lyginant su niekada nerūkiusiomos mirties rizika metusioms rūkyti yra 1.31 (95% CI, ),
rūkančioms 1-14 cigarečių dienai (95% CI, ),
rūkančioms cigarečių dienai (95% CI, ),
rūkančioms > 35 cigarečių dienai (95% CI, ).
Rūkymas yra susijęs su II tipo cukrinio diabeto atsiradimu – pažeidžiamas rezistentiškumas insulinui, pakinta insulino sekrecija, toksinis poveikis kasai, padidėja adrenalino kiekis.

27. Lyginant su niekada nerūkiusiais II tipo cukrinio diabeto atsiradimas dažnesnis tarp
daug rūkančiųjų (RR 1.61; 95%CI, ),
nedaug rūkančių (RR 1.29; 95% CI, ),
metusių rūkyti (RR 1.23; 95% CI, ).
Rūkantiems ir sergantiems cukriniu diabetu asmenims dažniau stebimos mikrovaskulinės komplikacijos tokios, kaip diabetinė nefropatija, mikroalbuminurija, kurios gali būti grįžtamos metus rūkyti.

28. II tipo cukrinio diabeto rizika
Reliatyvi rizika
Key Point
Smoking can cause an elevated risk of type 2 diabetes in men.
To assess whether there is a relationship between smoking and type 2 diabetes, Beziaud et al conducted a study in France of 27,777 volunteers (12,417 men and 15,360 women), aged years. Smoking and alcohol consumption habits were determined, clinical parameters recorded, and glucose levels measured. Ex-smokers were defined as those who had stopped smoking at least a month before the examination.
The risk of diabetes was calculated based on the subjects’ glucose levels and expressed using odds ratios. Among men 20 to 69 years old, current smokers had an increased risk of diabetes (RR: 1.49; CI ) compared with nonsmokers, and cessation of smoking did not significantly reduce this risk. Interestingly, the effect of smoking on the development of diabetes in women was not conclusive.
Niekada nerūkę Buvę rūkoriai Esami rūkoriai
Aged Years
Beziaud et al. Diabetes Metab. 2004;30:
Reference
Beziaud F, Halimi JM, Lecomte P, Vol S, Tichet J. Cigarette smoking and diabetes mellitus. Diabetes Metab. 2004;30:

29. II tipo CD rizika metus rūkyti
Reliatyvi rizika
Key Point
Risk of diabetes decreases with increased duration of cessation.
Wannamethee et al then studied the effects of smoking cessation on the increased risk of diabetes, finding that the risk of developing diabetes decreased with longer duration of cessation and returns to the nonsmoker level by 20 years after cessation.
However, within the first 5 years, the risk actually increased even when adjusted for BMI. They determined that for those in this group, the length of time they had previously smoked was important. The increased risk was found only for those who had smoked for at least 30 years. The length of time smoked made no difference once a man had stopped smoking for more than 5 years. 5
5-10
11-19
20
Laikas nuo metimo rūkyti (metai)
Wannamethee et al. Diabetes Care. 2001;24(9):
Reference
Wannamethee SG, Shaper AG, Perry IJ. Smoking as a modifiable risk factor for type 2 diabetes in middle-aged men. Diabetes Care. 2001;24(9):

30. Rūkymo neigiamas poveikis inkstų fukcijai
Rūkymas yra nefrotoksinis
senesnio amžiaus pacientams,
pacientams, sergantiems pirmine arterine hipertenzija,
pacientams su beprasidedančia inkstų liga.
Rūkymas, sergantiems glomerulonefritu, policistinių inkstų liga, skatina greitesnį inkstų funkcijos nepakankamumo progresavimą.
Death-censored renal graft survival is
decreased in smokers, indicating that smoking also damages
the renal transplant. We performed a retrospective case-control study to assess
whether smoking increases the risk to progress to ESRF in
patients with IgA-glomerulonephritis or autosomal dominant
polycystic kidney disease (23). Because of the small sample
size and modest average tobacco consumption, the subgroup of
women was excluded from further analysis. After adjustment
for possible confounders, multivariate analysis revealed that
the risk for ESRF was substantially higher in male smokers
with no history of ACE inhibitor treatment (OR, 10.1 [2.3 to
45]; P ). In contrast, the risk for smokers with a history
of ACE inhibitor treatment was not significantly increased
(OR, 1.4 [0.3 to 7.1]; P 0.65). Another case-control study
confirmed that male patients who have glomerulonephritis and
smoke are at increased risk of renal function impairment (24).
In this study, the negative impact of smoking was particularly
marked in elderly hypertensive men.
Effects of Smoking on Systemic and Intrarenal Hemodynamics: Influence on Renal Function
STEPHAN R. ORTH

31. Rūkymas pažeidžia inkstus, ūmiai pažeisdamas hemodinamiką
padidina kraujo spaudimą,
padidina intraglomerulinį spaudimą,
lėtai sutrikdo endotelio ląstelių funkciją.

32. Rūkantiems asmenims dažniau stebima padidinta albumino ekskrecija ir mikroalbuminurija lyginant su nerūkančiais asmenimis.
Pacientams, surūkantiems iki 20 cigarečių per dieną ir surūkantiems virš 20 cigarečių dienai, stebimas skirtingas
albumino koncentracijos šlapime padidėjimas (atitinkamai 1.33 ir 1.98)
skirtingas mikroalbuminurijos dažnis (atitinkamai 1.92 ir 2.15).
Atsiradęs inkstų funkcijos nepakankamumas pats savaime didina širdies ir kraujagyslių ligų riziką.

33. Rūkymas padidina rizika greitai progresuoti terminaliniam inkstų funkcijos nepakankamumui.
Rūkymo nutraukimas sumažina inkstų nepakankamumo progresavimą tiek pacientams su inkstų liga, tiek pacientams su transplantuotu inkstu.
Rūkančiųjų, sergančių cukriniu diabetu ir turinčių transplantuotą inkstą, išgyvenamumas yra labai mažas.
More recent studies using ambulatory BP measurement
clearly document that smokers have higher BP than
nonsmokers, i.e. an increase of approximately 3 to 12 mmHg in
mean arterial pressure (MAP). This has been shown in several
studies including healthy subjects, hypertensive subjects, patients
with type 1 and type 2 diabetes, and patients with
primary renal disease (for review, see reference 7).

34. Rūkymas ir lėtinės inkstų ligos rizika
Šansų santykis (95% CI)a
Key Point
Smoking doubles the risk of chronic kidney disease (CKD). Cessation can greatly reduce this risk.
Shankar et al conducted a study of 4926 people, aged 43 to 86 years, to determine what effect smoking (or alcohol consumption) has on kidney function. Smoking status was determined, serum creatinine measured, and glomerular filtration rate (GFR) calculated. In this study, CKD was defined as an estimated GFR of less than 60 mL/minute per 1.73 m2.
Of the total participants, 324 had CKD, and of the total, 967 were smokers and 1737 were ex-smokers (defined in slide).
Current smokers had double the risk of CKD than nonsmokers. Smoking cessation was able to return the odds to that of nonsmokers. When years since cessation were analyzed, the benefit was apparent in smokers who had stopped smoking for more than 5 years (odds ratio, 0.98; 95% CI, ) as opposed to <5 years (odds ratio, 2.09; 95% CI, ).
Niekada nerūkę Buvę rūkoriai Esami rūkoriai
Shankar et al. Am J Epidemiol. 2006;164(3):
Reference
Shankar A, Klein R, Klein BEK. The association among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol. 2006;164(3):

35. Proteinurijos rizika rūkantiems
Nerūkantys
Rūkę
Rūkantys
P=.0009
P=.01
P=.0001
Reliatyvi rizika
P=.01
Key Point
Current and ex-smokers have an increased risk of proteinuria.
Halimi et al studied a sample from the general French population who had no known renal disease. Information about smoking habits was obtained from 27,777 people aged 20 to 69 years. Ex-smokers were defined as those who had quit smoking at least 1 month prior to the examination.
The presence of proteinuria was determined by measurement from overnight urine samples; 1+ proteinuria was defined as 0.30 g/L and 2+ as 1 g/L.
Unadjusted relative risk was determined to estimate the effect of smoking on proteinuria.
Current and ex-smoking were associated with statistically similar increased risks of proteinuria (1+: approximately 2-fold; 2+: approximately 3-fold).
Halimi et al. Kidney Int. 2000;58:
Reference
Halimi J-M, Giraudeau B, Vol S, et al. Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population. Kidney Int. 2000;58:

36. Rūkymas ir arterinė hipertenzija
Arterinės hipertenzijos dažnis didesnis tarp rūkančiųjų nei tarp nerūkančiųjų (13.5 ir 8.8%; P=0.001).
Hipertenzijos rizika yra didesnė tarp rūkančiųjų nei tarp nerūkančiųjų (ŠS 1.31 [1.13 to 1.52]; P=0.001).
Hipertenzijos rizika priklauso ir nuo per dieną surūkytų cigarečių skaičiaus (ŠS kiekvienoms 10 cigarečių 1.13 [1.05 to 1.21]; P=0.001) ir rūkymo trukmės (ŠS, 0.99 [0.98 to 1.00]; P=0.01).
Pacienti sergantys arterine hipertenzija ir turintys kairiojo skilvelio hpertrofiją, surūkantys 20 cigarečių per dieną, riziką mikroambuminurijos yra 1.6 karto ir makroalbuminurijos rizika yra 3.7 didesnė nei niekada nerūkiūsiųjų.
When body mass index was entered into the model, the risk of
hypertension in former smokers was no longer significant;
current smokers remained at risk for systolic hypertension,
however. Some studies found an increase of BP only during
daytime, which supports the observation that the effect of
smoking on BP is short (lasting approximately 30 min) (7)
There have also been
case reports of an increase in BP as a result of smoking
discontinuation.19 One potential explanation for increased
BP as a result of quitting smoking may be the weight gain
known to accompany quit attempts. Smoking appears to
keep weight down, either through effects on the hypothalamus
or through effects on the basal metabolic rate.
Several studies have indicated that an approximate 5-kg
weight gain often occurs with quitting smoking.24 A
recent review25 of hypertension treatment suggests that
maintaining the ideal body weight is effective in the prevention
or management of hypertension. The same review
states that BP is reduced by an average of 1.6/1.1 mm Hg
for each 1 kg of weight loss.

37. Rūkymas ir širdies ligos
Asmenims, gyvenantiems su rūkančiuoju, IŠL rizika yra 30% didesnė nei gyvenusių tarp nerūkančiųjų.
Pacientų, sergančių IŠL, jei metama rūkyti, bendro mirštamumo rizika sumažėja 36% (RR 0.64; 95% PI, ).
Esant arterinei hipertenzijai, padidintam cholesterolio kiekiui, rūkymui, tikimybė ūmaus išeminio sindromo padidėja iki 8 kartų.
Smoking and Cardiovascular Disease Risk Factors: What a Tangled Web We Weave
By Curtis Handford, MD, CCFP, MHSc

38. Klinikinis atvejis Ligonė V. N. Gimusi 1971.05.15 (37 m.)
Gyvenanti Kaune
Gydyta KMUK I kardiologijos skyriuje nuo iki

39. Nusiskundimai
Skausmas krūtinėje spaudžiančio pobūdžio, stiprus, atsirandęs ramybėje, užtrukęs apie 1 val. laiko.
Minėta simptomatika pirmą kartą gyvenime.

40. Rizikos veiksniai Rūkymas: 20 cig./d. 15 m. Antsvoris
Cukrinis diabetas II tipo, gydomas insulinu.

41. Objektyvūs duomenys Bendra būklė sunki. Liežuvis su apnašu.
Krūtinės ląstos skausmingumas paviršinis. Alsavimas vezikulinis visame plaučių plote.
Širdies veikla ritmiška. ŠSD 91 k/min. Širdies tonai aiškūs. AKS 131/89 mmHg.
Pilvo palpacija neskausminga. Peristaltika normali.

42. EKG (atvykus)

43. Laboratoriniai tyrimai
leuk. 17,6-4,7x10/9,
eritr. 4,46x10/12,
Hb 145 g/l,
tromb. 285x10/9,
troponinas I - 0,19 mcg/l,
glik. 6,74-13,15 mmol/l,
Na 134 mmol/l,
K 4,1 mmol/l,
urea 5 mmol/l,
kreatin. 59 mcmol/l,
BCH 5,1 mmol/l,
DTLCH 1,3 mmol/l,
MTLCH 2,6 mmol/l,
TG 1,53 mmol/l,
GOT 165 U/l,
GPT 97 U/l,
CK 948 U/l,
CRB 5,7 mg/l.

47. Gydymas R - II-III, D - Na, R (-) + CD;
glycerol trinitras 0,5 mg/h į/v AŠP,
heparinas 5000 v.v. -> 1000 v.v./h į/v AŠP;
I kard. sk. –
aspirinas 100 mg x 1,
klopidogrelis 75 mg x 1,
nebivololis 2,5 mg x 1,
ramiprilis 2,5 mg x 1,
rosuvastatinas 10 mg x 1,
KCl 1,5 g per os,
humulin MIX 10 v.v. ryte ir 10 v.v. vakare, humalog 10 v.v. per pietus.

48. CHAMPIX skyrimas 1-3 dienos: 0,5 mg vieną kartą per parą.
4-7 dienos: 0,5 mg du kartus per parą.
Nuo 8 dienos iki gydymo pabaigos:
1 mg du kartus per parą.
Pacientas turi pasirinkti datą, kada mes rūkyti. CHAMPIX reikia pradėti vartoti 1-2 savaitės prieš šią datą.

49. EKG (išvykstant)

50. Rūkymas ir dislipidemija
Rūkymas padidina MTL cholesterolio kiekį kraujyje.
Mesti rūkyti ypač svarbu asmenims su padidintu MTL-Ch kiekiu kraujyje.
Yra stiprus ryšys tarp rūkymo, trigliceridų kiekio ir DTL kiekio kraujyje.
Mažas DTL kiekis bei hipertrigliceridemija yra nepriklausomi IŠL rizikos veiksniai.
CHD and stroke was increased 3-fold, and CV mortality
was markedly increased in subjects with the
metabolic syndrome (P<0.001 for both outcomes).
Perhaps not surprisingly, studies have indicated that
the prevalence of smoking is higher in patients with
the metabolic syndrome than in subjects without the
metabolic syndrome.40 Another study41 established
that cigarette smoking is independently associated
with the metabolic syndrome. However, Masulli et
al36 concluded that this association does not appear to
be related to an insulin-resistance effect of smoking
or an anti-insulin secretion effect of nicotine on pancreatic
beta cells. In a further study, these authors
concluded that the increase in the metabolic syndrome
seen in smokers was largely driven by the higher
prevalence of dyslipidemia.42 Regardless of the
reasons for the association between smoking and
the metabolic syndrome, studies have revealed
that patients with the metabolic syndrome who quit
smoking after an MI had a lower risk of further
cardiac events (HR 0.485; 95% CI, )
compared with those who continued to smoke.

51. Nikotinas stimuliuoja antinksčių žievę, dėl to iš adipocitų mobilizuojamos laivosios riebiosios rūgštys ir skatinama trigliceridų sintezė.
Kita teorija – rūkantys turi mažiau fermentų, skatinančių DTL transportavimą iš periferinių audinių, kas sukelia DTL sumažėjimą plazmoje.

53. Rūkymas ir odos ligos Būdingi požymiai Odos pažeidimai
Plokščialąstelinė adenoma
Žaizdų gijimo sutrikimai
In many cases, to the trained eye, smokers can be identified just by looking at their skin. The following slides illustrate some of the cutaneous manifestations of smoking, and demonstrate smoking’s effect on the development of squamous cell carcinoma. Data on the effect of smoking on wound healing will also be presented.

54. Odos požymiai Gerai matomos periorbitalinės linijos Nuovargio požymiai
Odos pilkumas
Raudonos dėmės
Smoker’s face
Lines or wrinkles on the face, typically radiating at right angles from the upper and lower lips or corners of the eyes, deep lines on the cheeks, or numerous shallow lines on the cheeks and lower jaw
A subtle gauntness of the facial features with prominence of the underlying bony contours
An atrophic, gray appearance of the skin
A plethoric, slightly orange, purple, and red complexion
Freiman et al. J Cutan Med Surg. 2004;8(6):

55. Odos pažeidimai Nagų geltonumas Nagų demarkacinės linijos
Smoker’s nail: yellow pigmentation of the nail plate in chronic smokers.
Freiman et al. J Cutan Med Surg. 2004;8(6):

56. Plokščialąstelinis vėžys
Rūkantys turi 50% didesnę vėžio riziką nei nerūkantys
Esami rūkoriai turi didesnę riziką nei metę rūkyti.
Key Point
Smokers have a greater chance of developing cutaneous squamous cell carcinoma (SCC) than do nonsmokers.
In a study of 107,900 white women, Grodstein et al showed that over an 8-year period, smokers were 50% more likely to develop cutaneous SCC than nonsmokers (RR, 1.5; 95% CI, ).
In a controlled study of people with various forms of carcinoma, De Hertog et al determined that current smokers were 3.3 times more likely (95% CI, ) to develop SCC than nonsmokers, and that cessation of smoking reduced the RR to 1.9 (95% CI, ).
Grodstein et al. J Nat Cancer Inst. 1995; 8714:1061–1066; Hertog et al. J Clin Oncol. 2001; 191:231–238.
Accessed October 19, 2007.
Reference
Grodstein F, Speizer FE, Hunter DJ. A prospective study of incident squamous cell carcinoma of the skin in the nurses health
study. J Nat Cancer Inst 1995; 8714:1061–1066.
Hertog SADe, Wensveen CA, Bastiaens MT, et al. Relation between smoking and skin cancer. J Clin Oncol 2001; 191:231–238. .

57. Žaizdų gijimo sutrikimai
Pablogėja odos kraujotaka
Sumažėja imuninis atsakas, didesnė infekcijos rizika.
Didesnė komplikacijų rizika pooperaciniame periode.
Užtrunka gijimo procesas.
Key Point
Smoking decreases the body’s ability to repair wounds.
It has been known for 40 years that smoking decreases cutaneous blood flow, and this effect has been correlated with impaired wound healing. Dermal fibroblasts have been shown to undergo a significant decrease in activity upon nicotine exposure.
In addition, smoking negatively affects mediators of the immune response, including decreasing interleukin (IL)-1 production, inhibition of early signals for B-cell transduction pathways, lowering natural killer cell cytotoxicity, and causing T-cell anergy.
This, combined with the decreased cutaneous blood flow, has a significant effect on postsurgical healing, and surgeons often refuse to perform cosmetic surgery on patients who smoke and will not quit.
Freiman et al. J Cutan Med Surg. 2004;8(6): ; KCI. Accessed October 23, 2007.
Reference
Freiman A, Bird G, Metelitsa AI, Barankin B, Lauzon GJ. Cutaneous effects of smoking. J Cutan Med Surg. 2004;8(6):

58. Rūkymas ir periodontinės ligos
Rūkymas sutrikdo neutrofilų fukciją, pažeidžia uždegiminį ir imuninį atsaką į periodontinius patogenus.
Rūkymas susijęs su periodontinėmis ligomis tokiomis, kaip dantenų, alveolinio kaulo netekimo, infekcinėmis-uždegiminėmis ligomis.
Effects of Smoking on Periodontal Health: A Review
Patrick Obeid, P. Bercy.

59. Rūkantys beveik 4 kartus nei niekada nerūkę serga periodontitu.
Periodontologinės ligos yra pasaulyje dažniausia dantų netekimo priežastis.
Key Point
Smoking dramatically increases the risk of developing periodontitis.
Cigarette smoking has been reported to increase the risk of periodontitis. Tomar et al conducted a statistical study to determine what proportion of periodontitis in the United States could be attributed to smoking (details on next slide).
They concluded that current smokers are 4 times more likely to develop periodontitis than never smokers, and that 52.8% of periodontitis in the United States is attributable to smoking.
Tomar et al. J Periodontol. 2000;71(5): ; health/complications/tobacco/ smokeless.asp. Accessed October 19, 2007.
Reference
Tomar SL, Asma S. Smoking-attributable periodontitis in the United States: findings from NHANES III. J Periodontol. 2000;71(5):

60. Periodontito rizika 9 per d. P.000001 10-19 per d. 20 per d.
Key Point
Smoking increases the risk of periodontitis in a dose-dependent fashion.
Tomar et al analyzed data from 12,329 participants in the Third National Health and Nutrition Examination Survey (NHANES III). Periodontitis was defined as the presence of one or more periodontal sites that had both a probing depth and loss of clinical attachment of ≥4 mm. Current smokers were defined as those who had smoked at least 100 cigarettes and currently smoked. ex-smokers had smoked at least 100 cigarettes and were not currently smoking. Bivariate analysis and multiple logistic regression was used to determine the link between smoking and periodontitis.
Compared with never smokers, smokers’ risk of periodontitis was increased in a dose-dependent manner over that of nonsmokers, up to almost 6-fold for the heaviest smokers.
Cessation of smoking decreased the risk in a time-dependent fashion. After 11 years of not smoking, the risk was similar to that of a never smoker (not shown).
31 per d.
Šansų santykis lyginant su nerūkančiais
Tomar et al. J Periodontal. 2000;71(5):
Reference
Tomar SL, Asma S. Smoking-attributable periodontitis in the United States: findings from NHANES III. J Periodontol. 2000;71(5):

61. Burnos patologija “Rudų plaukų” liežuvis Nikotininis stomatitas
Key Point
Aside from periodontitis, smoking also causes a number of oral pathologies.
These include:
Brown hairy tongue is condition of defective desquamation of the filiform papillae that results from a number of precipitating factors. Precipitating factors for hairy tongue include poor oral hygiene, the use of medications (especially broad-spectrum antibiotics), tobacco use, coffee or tea drinking and therapeutic radiation of the head and the neck. Bacterial and fungal overgrowth play a role in the color of the tongue.
Leukoplakia is a premalignant white plaque or lesion that cannot be wiped off with a gauze square and cannot be classified as any other disease. They can be white, white yellow, gray, or a mix of white and red. They can be smooth or wrinkled, and appear as cracks, fissures, or fingerlike projections.
Nicotine stomatitis, also known as “smoker’s palate” is a result of heat or trauma from pipes, cigars, or any type of smoked tobacco. Tissue on the palate turns gray.
Necrotizing ulcerative gingivitis, also referred to as trench mouth, is an acute, progressive, painful infection with ulceration, swelling and sloughing off of dead tissue from the mouth and throat due to the spread of infection from the gums marked by ulceration and necrosis of the gum margin, destruction of the interdental papillae, and foul breath.
Leukoplakija
Nekrotizuojantis opinis gingivitas
Davis. J Contemp Dent Pract. 2005;6: ; Lewin et al. Cancer. 1998;82:
References
Black Hairy Tongue. Accessed August 17, 2007.
The American Heritage® Stedman's Medical Dictionary © 2002, 2001, 1995 Houghton Mifflin Company. (Cited by
Davis JM. Tobacco cessation for the dental team: a practical guide part I: background and overview.
J Contemp Dent Pract. 2005;6:

62. Plokščialąstelinė karcinoma
70% burnos vėžio atvejų susiję su rūkymu
Simptomai:
Žaizdos negyjančios
Kaklo, gerklės patinimas
Išliekančios baltos ar raudonos dėmės burnoje
Sunkumas kramtant ar ryjant
Svorio netekimas
Prognozė
5-metų išgyvenamumas mažiau nei 50%
Key Point
Smoking is associated with the majority of cases of SCC.
Oliver et al reviewed the files of 92 primary oral SCC patients from a 7-year period ( ). Seventy-two (80%) of these patients were tobacco users.
In another study (not shown), Lewin et al analyzed 605 SCC cases from the Swedish male population (aged years) from the period of January 1988 to January 1991; 756 control subjects were randomly selected.
Current smokers (those who smoked 1 year prior to interview) had a 6.5-fold RR of head and neck cancer (95% CI, ) compared with never smokers. Ever smokers (men who had ever regularly smoked at least 7 grams of tobacco per week) had a 4-fold (95% CI, ) greater risk.
Davis. J Contemp Dent Pract. 2005;6(3): ; Oliver et al. J Oral Maxillofac Surg. 1996;54: ; Accessed October 30, 2007.
References
Lewin F, Norell SE, Johansson H, et al. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell
carcinoma of the head and neck. Cancer. 1998;82(7):
Oliver AJ, Helfrick JF, Gard D. Primary oral squamous cell carcinoma: a review of 92 cases. J Oral Maxillofac
Surg. 1996;54:

63. Apibendrinimas
Sisteminis rūkymo poveikis pasireiškia uždegimu, oksidaciniu stresu ir endotelio disfunkcija.
Metus rūkyti rodikliai gali susinormalizuoti, skiriasi tik atsistatymo laikas.
Rūkymas gali įtakoti įvairių organų ligas.

64. Ačiū už dėmesį