1 Örebro universitet
Enheten för klinisk medicin Medicin C, Examensarbete, 15 hp HT 2014
Presence of postoperative complication in smoking compared to
non-smoking patients who underwent bariatric surgery in Örebro
County: a quality register study.
VERSION 3
Författare: Fátima da Silva Supervisors: Matz Larsson, Chief physician
2
Abstract
Background: Smoking and obesity are two major causes of health problems in the modern
society. Smokers have higher risk for developing cardiovascular disease, cancer, infection, renal and pulmonary disorders. Obesity is correlated to diabetes mellitus type II, coronary heart disease and stroke.
Obese smokers have high morbidity and mortality risks. When facing surgery they may stay longer in the hospital to a higher degree that non-smokers, and show more comprehensive postoperative complications.
Objective: The aim of this paper is to follow up, for a period of two years, and evaluate the
presence of postoperative complication in smokers compared to non-smokers who underwent bariatric surgery in Örebro County.
Method: Patients who underwent bariatric surgery in Örebro County were retrieved from
SOReg, Scandinavian Obesity surgery Registry and followed up for a period of 2 years. OR and CI (95%) were used to estimate the impact of smoking on postoperative complications.
Results: The odds for smokers of developing post-operative complications increase over the
time. At 6 weeks control the OR = 0.88, CI 0.47-1.64; at 1 year the OR = 1.07, CI = 0.59-1.64; at 2 years the OR = 1.85, CI = 1.04-3.32.
In this study 6 weeks control shows no statistical correlation between cigarette smoking, BMI and diabetes. Patients smokers over the age 35 have higher risk of post-operative
complication, OR = 1.23, CI 0.61-2.47. Patients smokers with high blood pressure have higher risk for postoperative complication after bariatric surgery, OR = 1.19, CI 0.40-3.51. One year control shows that smokers patients with BMI less than 30 and over 35 years of age have higher odds of developing post-operative complication, OR= 1.65, CI = 0.83-3.28 respectively OR = 1.8, CI = 0.54-2.55. Diabetic smokers had OR = 1.69, CI = 0.18-15.71. Two years control shows an OR= 2.53, CI = 1.33-4.84 for smokers with a BMI below 30. Smokers under the age of 35 years have higher risk of presenting post-operative
complications, OR = 2.39, CI = 0.94-6.08. Smokers with high blood pressure have higher odds of developing post-operative complications, OR = 2.18, CI = 0.49-9.62.
Conclusion: The findings observed show a tendency for smokers of having a higher risk for
developing postoperative complications than non-smokers. A further nationwide study that involves a bigger set of patients may lead to more conclusive results on the matter.
3
Table of contents
Background ... 4
Objective: ... 7
Material and method ... 7
Study subjects and follow up ... 8
Statistical methods ... 9 Ethics ... 9 Results ... 9 Discussion ... 11 Conclusion ... 12 Acknowledgements ... 12 References ... 13
4
Background
Modern life presents two major health issues: smoking related diseases and obesity.
According to the World Health Organization (WHO) tobacco alone is responsible for almost six million deaths worldwide. Cigarette smoke has more than 7000 different chemical
components of which more than 70 substances are known carcinogens [11]. Smoking can lead to cardiovascular, [11,17], pulmonary [11] and renal diseases [1], as well as inflammation [19,20] and cancer [12-15]. Smoking causes the blood vessels to narrow, prevents oxygen to be delivered to the cells and puts an extra workload on the heart [18]. Not only that, smoking increases insulin resistance and can cause central fat accumulation which in turn raises the risk for metabolic syndrome and diabetes [2,3].
In the face of surgery a smoker has a higher risk for post operational complications such as infection, poor wound healing [36] and thromboembolism [4] .
Obesity is the most common nutritional problem in the Western world. It raises the risk for a person to develop coronary heart disease, stroke [5], metabolic syndrome and diabetes mellitus type II [6] as well as for complications following surgery [30-33]. Obese smokers have high morbidity and mortality risks [7].
Obesity
Obesity is defined as BMI (body mass index) equal to or higher than 30. It is a worldwide growing problem that affects populations of all age groups. In 2008 35 % of the world’s adult population, 20 and older, were overweight and of these 11 % suffered from obesity [8]. Studies show that obesity leads to serious health problems. It interacts negatively with bones and muscles resulting in increased frequency of bone fractures, poor strength and muscle quality [9].
Obesity alters the intestinal microbiome leading to thinner gut mucus which weakens the intestinal lining permitting in this way the penetration of endotoxins [10].
Obese patients tend to have respiratory problems. The complications caused on their
respiratory system are: lowered respiratory compliance, elevated work for breathing, higher demand for ventilation and respiratory muscle inefficiency [11].
Some forms of cancer such as oesophageal adenocarcinoma have been linked to obesity [12]. Obesity is associated with metabolic syndrome which can cause cardiovascular problems [13,14]. Obesity is also a risk factor for many chronic diseases and therefore means higher cost to the healthcare system [15].
History of tobacco smoking
Tobbaco came into the Western World around 16 th Century after Columbus’ discovery of the New World and rapidly became of popular usage.
Six billion cigars and 3.5 billion cigarettes were sold in 1901, however, the consumption of cigarettes exploded with World War I. The tobacco industry developed up and steadily becoming a strong force in the economy which lasts until today [16,17].
5
Chemical components in cigarette smoke
There are more than 7000 different chemicals components in tobacco smoke. In addition to nicotine, it contains among other components polycyclic aromatic hydrocarbon, carbon monoxide nitrosamines, amnonia, benzene, toluene, aldehydes, aromatic amines and heavy metals. Due to the influence of nicotine on the reward system in the brain tobacco smoking is highly addictive [18].
Smoking and health
Scientific reports pointing to the hazardous effects of cigarette smoking began to come out in the 1950’s. Richard Doll was the first to show the relationship between smoking and lung cancer [19]. Other forms of cancer in which smoking is a risk factor are pancreatic, oesophageal, and ovarian cancer [20-22].
Tobacco smoking results in haemostatic dysfunction when used long term and it affects cardiac diastolic functions [23,24] which leads to a higher heart rate. Cigarette smoking is a contributing factor for the development of atherosclerosis [25] and it causes inflammation in patients with COPD (chronic obstructive pulmonary disease) [26,27].
In pregnancy smoking is associated with miscarriage and newborns of smoking mothers have impaired growth in length and weight at birth as well reduced lung compliance [28,29].
Obesity and complications to surgery
Obesity causes a series of changes in the human body. Obese patients have a cardiovascular system functionally and structurally altered resulting in an increased cardiac output and blood volume. Obesity leads to lower lung volumes caused by an altered position of the diaphragm altered due to a rise in abdominal pressure, an increased chest wall resistance and respiratory muscle dysfunction [30]. All of these changes can pose problems for surgery and the
patient’s postoperative recuperation.
Obese patients are at high risk for rhabdomyolysis under surgery as well as for periprosthetic infection [31,32]. Pregnant obese women have higher bleeding rates post partum than non obese [33]. The incidence of adverse respiratory events post surgery is higher among obese patients [34].
Cigarette smoking nd complications to surgery
Tobacco smoking causes a series of physiological effects due to metabolism of its various components, specially carbon monoxide and nicotine.
Nicotine is sympathomimetic alkaloid that causes an increase in heart rate [18]. It is also a vasoconstrictor and promotes platelet aggregation which may result in thrombosis [18,35]. Carbon monoxide binds to hemoglobin causing hypoxia which in turn increases red blood cells production and the higher production of erythrocytes increases blood viscosity [18,35]. Cigarette smoke contains a variety of metals among them zink, nickel, copper, lead, cadmium, mercury and aluminium. The metals induce oxidation of proteins in the cells and this process may alter the endothelial structure leading to endothelial dysfunction and causing separation of endothelial cells from the blood vessels wall [18].
6
Smoking affects the immune system. It causes neutrophils to accumulate in the lungs resulting in a disproportional inflammatory reaction. Nicotine in particular affects the immune system by impairing cytotoxic T lymphocyte memory cell differentiation [36]. Cigarette smokers have a disproportional production of anti- and pro-inflammatory cytokines and a defective NK cytotoxic activity [37].
Tobacco smoking can cause graft necrosis [38]. Smokers have greater complication risks for wound healing which can give leave these patients with aesthetically unpleasing scars [40]. Smokers have also unplanned intubation and mechanical ventilation more often, higher odds of sepsis, sepsis chock and an increased probability of 30-day mortality after surgery [41].
Obese smokers
Obese smokers have increased risk for circulatory diseases, impaired immune system, and decreased life expectancy [42-44].
There is a common believe that cigarette smoking helps to keep body weight under control [45], therefore weight gain is perceived as a problem when quitting smoking is considered [46]. It has been shown that smokers tend to be leaner [47] due to the fact that nicotine is an appetite modulator that acts upon the feeding center of the hypothalamus [48,49]. However researchers point out that smoking may actually contribute to central fat accumulation [47,50].
Cigarette smoking is highly addictive, leads to health problems and can result in
complications under and after surgery. Therefore smokers are advised to stop smoking before an operation. Both food consuming and smoking activate the mesolimbic reward system and therefore it has been proposed that obesity and cigarette smoking may share a common biological ground [51], hence quitting smoking before surgery may impose an extra challenge to obese patients.
Two of the few existing studies that concentrate specifically on obese smokers suggested that there might a tendency for morbidly obese people to be smokers, specially men [52,53]. Swedish patients who smoke are advised by their doctors to stop smoking before surgery and offered special programs to follow if they show the desire to quit.
Different studies have pointed to the detrimental effects of cigarette smoking and obesity on surgery. Obese smokers may stay longer in the hospital to a higher degree that non-smokers [54], and they show more comprehensive postoperative complications [35,55].
Although many studies point to the risks that obese smokers have for many different types of surgery, there is lack of research concerning postoperative problems obese smokers may face when going through a bariatric procedure.
Obesity in Sweden
If on one hand the smoking rates have been lowering in Sweden, overweight and obesity rates on the other hand have been rising over the last 20 years, especially among young people. According to a report from National Board of Health and Wellfare 35% of the Swedish population between ages 16-84 years are overweight and 14% are obese. 133,000 people have
7
a BMI between 35-40 and 48,000 have a BMI of 40 [56]. As well as in other countries obesity in Sweden can lead to a loss of productivity to society as a whole once obese workers may tend to take more sick-leave days [57], as well as going on premature retirement [58] . This group is at higher risks for cancer, heart disease, mental health problems, diabetes type II, and death [56].
Criteria for bariatric surgery in Sweden
Bariatric surgery is one of the methods used to treat people suffering from obesity. In Sweden patients have to meet some specific criteria in order to be eligible for surgery [58]. These criteria are:
- Patients must be 18 years old or older. - BMI higher than 35 kg/m2
- Before surgery the patient must have given an honest chance to other conservative forms of weight loosing.
Objective:
The aim of this paper is to follow up for a period of two years and evaluate the presence of postoperative complication in smokers compared to non-smokers who underwent bariatric surgery in Örebro County.
Material and method
SOReg, Scandinavian Obesity surgery Registry, is a Scandinavian quality register for bariatric surgery. It was established 2007 and comprises all operating units of the country. The main purpose of SOReg is to provide new knowledge around the disease and its treatment as well as to help in the development of effective and high quality bariatric surgery. Individual information is collected from the patients’ journal and a questionnaire is answered by the patients themselves. Those data are then registered in SOReg’s database.
From Örebro County there are 1688 patients registered in the database of which there is information about smoking habits for 1236 subjects (fig 1).
8
Fig. 1 Smoking habit amongst men and women patients who underwent bariatric surgery in Örebro County
Up until 2012 patients were only asked if they were smokers, non-smokers or had quitted smoking at least 6 months before surgery. From 2013 and forward there is a specific question asking if patients have stopped smoking because of the surgery. This study focuses only in two groups of patients and their eventual postoperative complications: smokers and non-smokers.
The postoperative complications observed here are: leakage, incision rupture, stricture, DVT, hernia, bleeding, ileus, stomach ulcus, pulmonary complications, perforation, abcess/deep wound infection, port site infection, cardiovascular complications, urinary infection, and complications of other nature.
Study subjects and follow up
There is information concerning smoking habit for 1236 of the subjects registered in SOReg. 361 patients had quitted smoking 6 months or more prior to surgery, 621 are non-smokers, 233 are smokers and 10 quitted momentarily smoking due to surgery. Excluded from this study are patients who had quitted smoking 6 months or more prior to surgery, as well as patients who quitted smoking due to surgery. The reason is that it would not be possible to evaluate the presence of previous diseases that might had influence on the post-operative outcome for the first group mentioned, as for the second group a follow up of two years cannot be done since it started 2013.
Postoperative data for the group chosen refers to a period of 0-6 weeks, one, and two years after the procedure.
168 442 275 9 329 65 179 86 1 134
Smokers Non-smokers Quitted smoking 6 moths or more prior to surgery Momentarily smoking cessation due to surgery
Missing data for smoking habit
9
Statistical methods
OR and CI (95%) are used to calculate the outcome of the observations. In order to compare the occurrence of post-operative complication among smokers and non-smokers the following variables are included: age, education level, BMI, diabetes and hypertension.
Ethics
Obesity surgery patients were informed about Scandinavian Obesit surgery Registry, SOReg, and its purpose. It was explained to them that the information gathered would be handled confidentially and could be used for research purposes. All of those belonging to the registry receive a number and therefore cannot be identified personally. Patients were also informed that they could abstain from the registry by refusing to participate on it.
Results
The odds for smokers of developing postoperative complications increase over the time. At 6 weeks control the OR = 0.88, CI 0.47-1.64; at 1 year the OR = 1.07, CI = 0.59-1.64; at 2 years the OR = 1.85, CI = 1.04-3.32.
6 weeks control (Table 1) no statistical correlation was observed between cigarette smoking,
BMI and diabetes.
Smoking over the age 35 had higher risk of post-operative complication, OR = 1.23, CI 0.61-2.47.
Smoking with high blood pressure have higher risk for postoperative complication after bariatric surgery, OR = 1.19, CI 0.40-3.51.
The non response rate on smoking habit for this period was 9.20%
Table 1. Smokers and non-smokers, 6 weeks control period. BMI, age at surgery, high blood pressure, diabetes, and educational level
6 weeks control
Smokers with postop complications
N/total %
Non smokers with postop complications N/total % OR CI 14/233 6.00 42/621 6.76 0.88 0.47-1.64 BMI* <35 2/10 20.00 4/18 22.22 0.87 0.13-5.88 >35 12/218 5.50 38/591 6.42 0.84 0.43-1.65 Age at surgery* <35 2/97 2.06 12/213 5.63 0.35 0.07-1.6 >35 12/131 9.16 30/396 7.57 1.23
0.61-10 2.47 High Blood Pressure 5/46 10.86 14/151 9.27 1.19 0.40-3.51 Diabetes 2/28 7.14 11/89 12.35 0.54 0.11-2.62 *Missing data for 5 patients
One year control ( Table 2) shows that smokers with BMI less than 30 and over 35 years of
age have higher odds of developing postoperative complication, OR= 1.65, CI = 0.83-3.28 respectively OR = 1.8, CI = 0.54-2.55.
For diabetic smokers the OR = 1.69, CI = 0.18-15.71. Non response rate on smoking habit was 31.72%
Table 2. Smokers and non-smokers, 1 year control period. BMI, age at surgery, high blood pressure, diabetes, and educational level.
1 year control Smokers with postop complications
N/total %
Non smokers with postop complications N/total % OR CI 17/262 6.48 38/628 6.05 1.07 0.59-1.64 BMI* <30 15/177 8.47 21/396 5.30 1.65 0.83-3.28 >30 2/84 2.38 17/231 7.35 0.30 0.06-1,35 Age at surgery* <35 7/107 6.54 16/206 7.76 0.90 0.35-2.26 >35 10/154 6.49 22/422 5.21 1.18 0.54-2.55 High Blood Pressure 1/30 3.33 10/121 8.26 0.38 *Missing data for one patient
Two years control (Table 3) shows an OR= 2.53, CI = 1.33-4.84 for smokers with a BMI
below 30.
Smokers under the age of 35 years have higher risk of presenting postoperative complications, OR = 2.39, CI = 0.94-6.08.
Smokers with high blood pressure have higher odds of developing postoperative complications, OR = 2.18, CI = 0.49-9.62.
11
Smoking, diabetes and the presence of postoperative complications when correlated to each other show no statistical relevance at this period of the control.
The non response rate concerning smoking habits was the highest of all of control periods, 61.48%.
Table 3. Smokers and non-smokers, 2 years control period. BMI, age at surgery, high blood pressure, diabetes, and educational level.
2 years control
Smokers with postop complications
N/total %
Non smokers with postop complications N/total % OR CI 20/198 10.10 33/579 5.69 1.85 1.04-3.32 BMI <30 19/127 14.96 23/355 6.47 2.53 1.33-4.84 >30 1/71 1.40 10/223 4.48 0.30 0.03-2.41 Age at surgery <35 9/64 9.37 11/172 6.39 2.39 0.94-6.08 >35 11/134 8.20 22/406 5.41 1.56 0.73-3.31 High Blood Pressure 3/37 8.10 5/129 3.87 2.18 0.49-9.62 Diabetes 0/8 0 1/34 2.94 0
Discussion
Smoking and obesity are two detrimental health issues [5-13; 30-33] that combined can lead to postoperative complications [35; 54-55] and therefore pose problems to a patient’s
recuperation.
The purpose of this study was to investigate and evaluate, during a follow up period of two years, the presence of post-operative complications, in patients smokers compared to non smokers who underwent bariatric surgery in Örebro County.
The observation shows that the risk for smokers, who underwent bariatric surgery, of
developing postoperative complications increases over time. Due to the scope of this study it was not possible to investigate further if there were any other aggravating factors such as sex, high cholesterol level, hormone imbalance, excess weight loss or other disease that might have had influence or could explain such development.
Not taking sex differences into consideration means that when correlating the variables it is not possible to see if there is any or how big the variation in postoperative complications between male and female patients is. It is not possible to answer, for instance, if one of the
12
two sexes is more prone to postoperative complications. Therefore, important information may have been lost.
Dividing the BMI measurements into only two groups means that a large variation of values lie between them. This in turn makes it difficult to see if there is a particular value spectrum in which more post-operative complications could be present. The same reasoning is valid for age.
The rate of non response concerning smoking habits is also high, 27% of the total. The low response rate implicates the findings shown here have weak statistical significance, they may, howbeit, be seen as tendency for smokers of having higher odds for developing postoperative complications when compared to non smokers.
Because smoking is negative health factor and because when combined with obesity it can lead to serious problems it is advisable to investigate further what can be done to reach a higher level of answers. The more information the caregiver has the better he/she can help the patient.
The high rate of non response concerning smoking habits, the fact that there was no matching between the groups of patients and that the sample sizes between them were uneven and not adjusted is a weakness in this work. It means that the result may be biased by factors other than smoking such as differences between groups in age, sex, and socio economic factors. However, the findings may suggest a tendency for smokers having higher odds of developing post-operative complications than non smokers.
Conclusion
In spite of the low response rate about smoking habits, the findings presented here suggest a tendency for smokers of having a higher risk for developing postoperative complications than non-smokers patients. A further nationwide study that involves a bigger set of patients may lead to more conclusive results on the matter.
Acknowledgements
I would like to thank my supervisors Matz Larsson and Lars Hagberg for all the support, encouragement and guidance given to me during this work.
I want to thank dr Johan Ottonsson for granting me access to SOReg.
I also would like to express my gratitude to my classmates Sanne Johansson, Johanna Karlsson, Annaclara Ariander, Kristian Westerling, Jonathan Persson, Linnea Hartman and Oscar Smedberg for all the support, help and comfort they gave me when Excel simply refused to work with me, despite the fact that I did follow all the instructions given on Youtube.
13
References
:1. Elihimas Junior UF, Elihimas HC, Lemos VM, Leao MD, Sa MP, Franca EE, et al.
Smoking as risk factor for chronic kidney disease: systematic review. J Bras Nefrol 2014 Dec;36(4):519-528.
2. Slagter SN, van Vliet-Ostaptchouk JV, Vonk JM, Boezen HM, Dullaart RP, Kobold AC, et al. Associations between smoking, components of metabolic syndrome and lipoprotein particle size. BMC Med 2013 Sep 3;11:195-7015-11-195.
3. Tweed JO, Hsia SH, Lutfy K, Friedman TC. The endocrine effects of nicotine and cigarette smoke. Trends Endocrinol Metab 2012 Jul;23(7):334-342.
4. Sweetland S, Parkin L, Balkwill A, Green J, Reeves G, Beral V, et al. Smoking, surgery, and venous thromboembolism risk in women: United Kingdom cohort study. Circulation 2013 Mar 26;127(12):1276-1282.
5. Yatsuya H, Li Y, Hilawe EH, Ota A, Wang C, Chiang C, et al. Global trend in overweight and obesity and its association with cardiovascular disease incidence. Circ J
2014;78(12):2807-2818.
6. Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 2006 Mar 21;47(6):1093-1100.
7. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L, et al. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 2003 Jan 7;138(1):24-32.
8. World Health Organization. Obesity and overweight. 2014; Available at:
http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed 11/18, 2014. 9. Armamento-Villareal R, Napoli N, Waters D, Villareal D. Fat, muscle, and bone
interactions in obesity and the metabolic syndrome. Int J Endocrinol 2014;2014:247076. 10. Bradlow HL. Obesity and the gut microbiome: pathophysiological aspects. Horm Mol
Biol Clin Investig 2014 Jan 1;17(1):53-61.
11. Parameswaran K, Todd DC, Soth M. Altered respiratory physiology in obesity. Can Respir J 2006 May-Jun;13(4):203-210.
12. Long E, Beales IL. The role of obesity in oesophageal cancer development. Therap Adv Gastroenterol 2014 Nov;7(6):247-268.
13. Castro AV, Kolka CM, Kim SP, Bergman RN. Obesity, insulin resistance and comorbidities ? Mechanisms of association. Arq Bras Endocrinol Metabol 2014 Aug;58(6):600-609.
14. Grundy SM. Metabolic Syndrome: Connecting and Reconciling Cardiovascular and Diabetes Worlds. Jornal of the American College of Cardiology 2006;47(6):1093-1100.
14
15. Quesenberry CP,Jr, Caan B, Jacobson A. Obesity, health services use, and health care costs among members of a health maintenance organization. Arch Intern Med 1998 Mar 9;158(5):466-472.
16. Randall V. The History of Tobacco. 1999; Available at:
http://academic.udayton.edu/health/syllabi/tobacco/history.htm. Accessed 11/10, 2014. 17. Young J. The history of tobacco and its growth around the world. Available at:
https://web.stanford.edu/class/e297c/trade_environment/health/htobacco.html. Accessed 11/10, 2014.
18. Centers for Disease Control and Prevention (US), National Center for Chronic Disease Prevention and Health Promotion (US), Office on Smoking and Health (US).
How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 2010.
19. DOLL R, HILL AB. Smoking and carcinoma of the lung; preliminary report. Br Med J 1950 Sep 30;2(4682):739-748.
20. Nakao M, Hosono S, Ito H, Oze I, Watanabe M, Mizuno N, et al. Cigarette smoking and pancreatic cancer risk: a revisit with an assessment of the nicotine dependence
phenotype. Asian Pac J Cancer Prev 2013;14(7):4409-4413.
21. Kamangar F, Chow WH, Abnet CC, Dawsey SM. Environmental causes of esophageal cancer. Gastroenterol Clin North Am 2009 Mar;38(1):27-57, vii.
22. Jordan SJ, Whiteman DC, Purdie DM, Green AC, Webb PM. Does smoking increase risk of ovarian cancer? A systematic review. Gynecol Oncol 2006 Dec;103(3):1122-1129. 23. Ngozi SC, Ernest NE. Long-term smoking results in haemostatic dysfunction in chronic
smokers. Niger Med J 2014 Mar;55(2):121-125.
24. Alshehri AM, Azoz AM, Shaheen HA, Farrag YA, Khalifa MA, Youssef A. Acute effects of cigarette smoking on the cardiac diastolic functions. J Saudi Heart Assoc 2013
Jul;25(3):173-179.
25. Poredos P, Orehek M, Tratnik E. Smoking is associated with dose-related increase of intima-media thickness and endothelial dysfunction. Angiology 1999 Mar;50(3):201-208. 26. Zhang MQ, Wan Y, Jin Y, Xin JB, Zhang JC, Xiong XZ, et al. Cigarette Smoking
Promotes Inflammation in Patients with COPD by Affecting the Polarization and
Survival of Th/Tregs through Up-Regulation of Muscarinic Receptor 3 and 5 Expression. PLoS One 2014 Nov 6;9(11):e112350.
27. Hoonhorst S, Timens W, Koenderman L, Lo Tam Loi AT, Lammers JW, Boezen H, et al. Increased activation of blood neutrophils after cigarette smoking in young individuals susceptible to COPD. Respir Res 2014 Oct 10;15(1):121.
15
28. Pineles BL, Park E, Samet JM. Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy. Am J Epidemiol 2014 Apr 1;179(7):807-823.
29. Milner AD, Marsh MJ, Ingram DM, Fox GF, Susiva C. Effects of smoking in pregnancy on neonatal lung function. Arch Dis Child Fetal Neonatal Ed 1999 Jan;80(1):F8-14. 30. Brown CV, Velmahos GC. The consequences of obesity on trauma, emergency surgery,
and surgical critical care. World J Emerg Surg 2006 Sep 6;1:27.
31. Goodman SM, Figgie M, Green D, Memtsoudis S. Rhabdomyolysis is a Potential
Complication of Total Hip Arthroplasty in the Morbidly Obese. HSS J 2013 Jul;9(2):200-202.
32. Dowsey MM, Choong PF. Obesity is a major risk factor for prosthetic infection after primary hip arthroplasty. Clin Orthop Relat Res 2008 Jan;466(1):153-158.
33. Fyfe EM, Thompson JM, Anderson NH, Groom KM, McCowan LM. Maternal obesity and postpartum haemorrhage after vaginal and caesarean delivery among nulliparous women at term: a retrospective cohort study. BMC Pregnancy Childbirth 2012 Oct 18;12:112-2393-12-112.
34. Mendonca J, Pereira H, Xara D, Santos A, Abelha FJ. Obese patients: respiratory
complications in the post-anesthesia care unit. Rev Port Pneumol 2014 Jan-Feb;20(1):12-19.
35. D. Lindström. The impact of tobacco use on postoperative complications . Stockholm: Karolinska institutet; 2008.
36. Sun Z, Smyth K, Garcia K, Mattson E, Li L, Xiao Z. Nicotine inhibits memory CTL programming. PLoS One 2013 Jul 2;8(7):e68183.
37. Zeidel A, Beilin B, Yardeni I, Mayburd E, Smirnov G, Bessler H. Immune response in asymptomatic smokers. Acta Anaesthesiol Scand 2002 Sep;46(8):959-964.
38. Goldminz D, Bennett RG. Cigarette smoking and flap and full-thickness graft necrosis. Arch Dermatol 1991 Jul;127(7):1012-1015.
39. Chan LK, Withey S, Butler PE. Smoking and wound healing problems in reduction mammaplasty: is the introduction of urine nicotine testing justified? Ann Plast Surg 2006 Feb;56(2):111-115.
40. Rogliani M, Labardi L, Silvi E, Maggiulli F, Grimaldi M, Cervelli V. Smokers: risks and complications in abdominal dermolipectomy. Aesthetic Plast Surg 2006
Jul-Aug;30(4):422-4 discussion 425.
41. Turan A, Mascha EJ, Roberman D, Turner PL, You J, Kurz A, et al. Smoking and perioperative outcomes. Anesthesiology 2011 Apr;114(4):837-846.
16
42. Freedman DM, Sigurdson AJ, Rajaraman P, Doody MM, Linet MS, Ron E. The mortality risk of smoking and obesity combined. Am J Prev Med 2006 Nov;31(5):355-362.
43. O'Shea D, Cawood TJ, O'Farrelly C, Lynch L. Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. PLoS One 2010 Jan 25;5(1):e8660.
44. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L, et al. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med 2003 Jan 7;138(1):24-32.
45. Williamson DF, Madans J, Anda RF, Kleinman JC, Giovino GA, Byers T. Smoking cessation and severity of weight gain in a national cohort. N Engl J Med 1991 Mar 14;324(11):739-745.
46. Levine MD, Kalarchian MA, Courcoulas AP, Wisinski MS, Marcus MD. History of smoking and postcessation weight gain among weight loss surgery candidates. Addict Behav 2007 Oct;32(10):2365-2371.
47. Clair C, Chiolero A, Faeh D, Cornuz J, Marques-Vidal P, Paccaud F, et al.
Dose-dependent positive association between cigarette smoking, abdominal obesity and body fat: cross-sectional data from a population-based survey. BMC Public Health 2011 Jan 11;11:23-2458-11-23.
48. Chen H, Saad S, Sandow SL, Bertrand PP. Cigarette smoking and brain regulation of energy homeostasis. Front Pharmacol 2012 Jul 25;3:147.
49. Martinez de Morentin PB, Whittle AJ, Ferno J, Nogueiras R, Dieguez C, Vidal-Puig A, et al. Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. Diabetes 2012 Apr;61(4):807-817.
50. Yun JE, Kimm H, Choi YJ, Jee SH, Huh KB. Smoking is associated with abdominal obesity, not overall obesity, in men with type 2 diabetes. J Prev Med Public Health 2012 Sep;45(5):316-322.
51. Thorgeirsson TE, Gudbjartsson DF, Sulem P, Besenbacher S, Styrkarsdottir U, Thorleifsson G, et al. A common biological basis of obesity and nicotine addiction. Transl Psychiatry 2013 Oct 1;3:e308.
52. Chatkin R, Mottin CC, Chatkin JM. Smoking among morbidly obese patients. BMC Pulm Med 2010 Nov 24;10:61-2466-10-61.
53. John U, Hanke M, Rumpf HJ, Thyrian JR. Smoking status, cigarettes per day, and their relationship to overweight and obesity among former and current smokers in a national adult general population sample. Int J Obes (Lond) 2005 Oct;29(10):1289-1294. 54. Sadr Azodi O, Bellocco R, Eriksson K, Adami J. The impact of tobacco use and body
mass index on the length of stay in hospital and the risk of post-operative complications among patients undergoing total hip replacement. J Bone Joint Surg Br 2006
17
55. Lindstrom D, Sadr Azodi O, Bellocco R, Wladis A, Linder S, Adami J. The effect of tobacco consumption and body mass index on complications and hospital stay after inguinal hernia surgery. Hernia 2007 Apr;11(2):117-123.
56. Sveriges Kommuner och Landsting. Fetmakirurgi - Behov Kvalitet Likvärdig vård Arbetsprocess och resultat nationella medicinska indikationer och kvalitetskrav på producenter av fetmakirurgi. 2011.Available at www.regionorebrolan.se. Accessed 13/12/2014
57. Neovius K, Neovius M, Kark M, Rasmussen F. Association between obesity status and sick-leave in Swedish men: nationwide cohort study. Eur J Public Health 2012
Feb;22(1):112-116.
58. Socialstyrelsen ,Sveriges Kommuner och Landsting, Svenska Läkarsällskapet. NATIONELLA INDIKATIONER FÖR OBESITAS KIRURGI. 2009. Available at www.sfoak.se/wp-content/niok_2009.pdf. Accessed 10/11/2014
