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1.  Current and Former Smoking and Risk for Venous Thromboembolism: A Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(9):e1001515.
In a meta-analysis of 32 observational studies involving 3,966,184 participants and 35,151 events, Suhua Wu and colleagues found that current, ever, and former smoking was associated with risk of venous thromboembolism.
Please see later in the article for the Editors' Summary
Smoking is a well-established risk factor for atherosclerotic disease, but its role as an independent risk factor for venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis to summarize all published prospective studies and case-control studies to update the risk for VTE in smokers and determine whether a dose–response relationship exists.
Methods and Findings
We performed a literature search using MEDLINE (source PubMed, January 1, 1966 to June 15, 2013) and EMBASE (January 1, 1980 to June 15, 2013) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-two observational studies involving 3,966,184 participants and 35,151 VTE events were identified. Compared with never smokers, the overall combined relative risks (RRs) for developing VTE were 1.17 (95% CI 1.09–1.25) for ever smokers, 1.23 (95% CI 1.14–1.33) for current smokers, and 1.10 (95% CI 1.03–1.17) for former smokers, respectively. The risk increased by 10.2% (95% CI 8.6%–11.8%) for every additional ten cigarettes per day smoked or by 6.1% (95% CI 3.8%–8.5%) for every additional ten pack-years. Analysis of 13 studies adjusted for body mass index (BMI) yielded a relatively higher RR (1.30; 95% CI 1.24–1.37) for current smokers. The population attributable fractions of VTE were 8.7% (95% CI 4.8%–12.3%) for ever smoking, 5.8% (95% CI 3.6%–8.2%) for current smoking, and 2.7% (95% CI 0.8%–4.5%) for former smoking. Smoking was associated with an absolute risk increase of 24.3 (95% CI 15.4–26.7) cases per 100,000 person-years.
Cigarette smoking is associated with a slightly increased risk for VTE. BMI appears to be a confounding factor in the risk estimates. The relationship between VTE and smoking has clinical relevance with respect to individual screening, risk factor modification, and the primary and secondary prevention of VTE.
Please see later in the article for the Editors' Summary
Editors' Summary
Blood normally flows throughout the human body, supplying its organs and tissues with oxygen and nutrients. But, when an injury occurs, proteins called clotting factors make the blood gel (coagulate) at the injury site. The resultant clot (thrombus) plugs the wound and prevents blood loss. Occasionally, a thrombus forms inside an uninjured blood vessel and partly or completely blocks the blood flow. Clot formation inside one of the veins deep within the body, usually in a leg, is called deep vein thrombosis (DVT) and can cause pain, swelling, and redness in the affected limb. DVT can be treated with drugs that stop the blood clot from getting larger (anticoagulants) but, if left untreated, part of the clot can break off and travel to the lungs, where it can cause a life-threatening pulmonary embolism. DVT and pulmonary embolism are collectively known as venous thromboembolism (VTE). Risk factors for VTE include having an inherited blood clotting disorder, oral contraceptive use, prolonged inactivity (for example, during a long-haul plane flight), and having surgery. VTEs are present in about a third of all people who die in hospital and, in non-bedridden populations, about 10% of people die within 28 days of a first VTE event.
Why Was This Study Done?
Some but not all studies have reported that smoking is also a risk factor for VTE. A clear demonstration of a significant association (a relationship unlikely to have occurred by chance) between smoking and VTE might help to reduce the burden of VTE because smoking can potentially be reduced by encouraging individuals to quit smoking and through taxation policies and other measures designed to reduce tobacco consumption. In this systematic review and meta-analysis, the researchers examine the link between smoking and the risk of VTE in the general population and investigate whether heavy smokers have a higher risk of VTE than light smokers. A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis is a statistical method for combining the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 32 observational studies (investigations that record a population's baseline characteristics and subsequent disease development) that provided data on smoking and VTE. Together, the studies involved nearly 4 million participants and recorded 35,151 VTE events. Compared with never smokers, ever smokers (current and former smokers combined) had a relative risk (RR) of developing VTE of 1.17. That is, ever smokers were 17% more likely to develop VTE than never smokers. For current smokers and former smokers, RRs were 1.23 and 1.10, respectively. Analysis of only studies that adjusted for body mass index (a measure of body fat and a known risk factor for conditions that affect the heart and circulation) yielded a slightly higher RR (1.30) for current smokers compared with never smokers. For ever smokers, the population attributable fraction (the proportional reduction in VTE that would accrue in the population if no one smoked) was 8.7%. Notably, the risk of VTE increased by 10.2% for every additional ten cigarettes smoked per day and by 6.1% for every additional ten pack-years. Thus, an individual who smoked one pack of cigarettes per day for 40 years had a 26.7% higher risk of developing VTE than someone who had never smoked. Finally, smoking was associated with an absolute risk increase of 24.3 cases of VTE per 100,000 person-years.
What Do These Findings Mean?
These findings indicate that cigarette smoking is associated with a statistically significant, slightly increased risk for VTE among the general population and reveal a dose-relationship between smoking and VTE risk. They cannot prove that smoking causes VTE—people who smoke may share other unknown characteristics (confounding factors) that are actually responsible for their increased risk of VTE. Indeed, these findings identify body mass index as a potential confounding factor that might affect the accuracy of estimates of the association between smoking and VTE risk. Although the risk of VTE associated with smoking is smaller than the risk associated with some well-established VTE risk factors, smoking is more common (globally, there are 1.1 billion smokers) and may act synergistically with some of these risk factors. Thus, smoking behavior should be considered when screening individuals for VTE and in the prevention of first and subsequent VTE events.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Heart Lung and Blood Institute provides information on deep vein thrombosis (including an animation about how DVT causes pulmonary embolism), and information on pulmonary embolism
The UK National Health Service Choices website has information on deep vein thrombosis, including personal stories, and on pulmonary embolism; SmokeFree is a website provided by the UK National Health Service that offers advice on quitting smoking
The non-profit organization US National Blood Clot Alliance provides detailed information about deep vein thrombosis and pulmonary embolism for patients and professionals and includes a selection of personal stories about these conditions
The World Health Organization provides information about the dangers of tobacco (in several languages), from the US National Cancer Institute, offers online tools and resources to help people quit smoking
MedlinePlus has links to further information about deep vein thrombosis, pulmonary embolism, and the dangers of smoking (in English and Spanish)
PMCID: PMC3775725  PMID: 24068896
2.  Cigarette smoking during pregnancy: chromosome translocations and phenotypic susceptibility in mothers and newborns 
Mutation research  2010;696(1):81-88.
The effects of maternal cigarette smoking during pregnancy on structural chromosome aberrations were evaluated in peripheral lymphocytes from 239 mothers and their 241 newborns to determine whether smoking during pregnancy, genetic susceptibility, and race are associated with chromosome aberrations including translocations. Demographic information and cigarette smoking data were obtained via questionnaire. There were 119 Caucasian Americans, 118 African Americans, and 2 Asian Americans. The average maternal age was 24.9 ± 5.8 (mean ± S.D.) years. Thirty-nine percent of the Caucasian Americans and 45.4% of the African Americans self-reported that they were active smokers during the index pregnancy. The average number of cigarettes smoked per day was 2.65 ± 5.75 and 1.37 ± 3.17 for Caucasian and African American mothers, respectively. Peripheral blood lymphocytes from the mother and from the fetal side of the placenta were evaluated for chromosome aberrations by whole chromosome painting and for genetic susceptibility using an in vitro bleomycin challenge assay. Spontaneous translocation frequencies in both maternal and newborn lymphocytes were not associated with cigarette smoking, socio-economic status, or education. The absence of a smoking effect may be attributable to the low level of cigarette usage in these subjects. The average bleomycin-induced damage in the maternal and newborn populations was 0.37 ± 0.27 and 0.15 ± 0.14 breaks per cell, respectively, a difference that was highly significant (p < 0.0001). In newborns there was a positive association between bleomycin sensitivity and the frequencies of aberrations as measured by chromosome painting: p ≤ 0.0007 for dicentrics and fragments, and p ≤ 0.002 for translocations. Caucasian American newborns demonstrated a significant association between dicentrics and fragments as measured by painting, and bleomycin sensitivity (p ≤ 0.0002), but no such association was observed for African American newborns. The results of this study indicate that while differences were observed between African Americans and Caucasian Americans, race does not appear to be a major contributor to chromosome damage in newborns or their mothers. However, peripheral lymphocytes in pregnant women are more susceptible to genetic damage than peripheral lymphocytes in newborns.
PMCID: PMC3519101  PMID: 20060061
cigarette smoking; pregnancy; newborns; mothers; chromosome translocations; genomic susceptibility
3.  Different measures of smoking exposure and mammographic density in postmenopausal Norwegian women: a cross-sectional study 
Recent cohort studies have suggested an increased risk of breast cancer with long duration of smoking, and with smoking initiation before first birth. Cigarette smoking may have both carcinogenic effects and antiestrogenic effects on the breast tissue. We decided to examine the relationship between different measures of smoking exposure and mammographic density.
Lifetime smoking history was collected through interview and questionnaires among 907 postmenopausal participants in the Tromsø Mammography and Breast Cancer study. The mammograms were obtained from the governmental Norwegian Breast Cancer Screening Program. Mammograms were classified according to the percentage and absolute mammographic densities using a previously validated computer-assisted method.
Sixty-five percent of the women reported having ever smoked cigarettes, while 34% were current smokers. After adjustment for age, age at first birth, parity, age at menopause, postmenopausal hormone therapy use, and body mass index, smoking was inversely associated with both measures of mammographic density (both trends P < 0.01). Both current smokers and former smokers had significantly lower adjusted mean percentage mammographic density compared with never smokers (P = 0.003 and P = 0.006, respectively). An inverse dose–response relationship with mammographic density was found between both the number of cigarettes and the number of pack-years smoked among current smokers. Current smokers who smoked 11 cigarettes or more daily had a 3.7% absolute (36% relative difference) lower percentage mammographic density compared with current smokers who smoked seven cigarettes or less daily (P = 0.008). When former smokers were stratified according to time since smoking cessation, we found that women who had stopped smoking less than 24 years ago had a significantly lower mean percentage mammographic density compared with never smokers (P < 0.001).
We found modest inverse dose–response associations between numbers of cigarettes and of pack-years smoked and both measures of mammographic density among current smokers. Former smokers who had stopped smoking less than 24 years ago also had a statistically significantly lower mean percentage mammographic density when compared with never smokers. These findings are consistent with an antiestrogenic effect of cigarette smoking on the breast tissue.
PMCID: PMC2242671  PMID: 17963507
4.  A cross-sectional study on tobacco use and dependence among women: Does menthol matter? 
Tobacco Induced Diseases  2012;10(1):19.
The question of whether mentholation of cigarettes enhances tobacco dependence has generated conflicting findings. Potential mediating factors in a putative relationship between menthol use and tobacco dependence may include race and gender. While an association between menthol use and dependence is mixed, research on the role of race solely among women smokers is scarce. This study examined whether women menthol smokers have higher tobacco use and dependence than non-menthol smokers. Further, the study investigated differences between White and African American smokers.
A cross-sectional study was conducted among 928 women seeking tobacco dependence treatment in Boston, Massachusetts. Measures obtained included preferred brand and menthol content, dependence markers (cigarettes per day (CPD); time to first cigarette in the morning; number of and longest previous quit attempts) and smoking history (age of initiation; years smoking; menthol or non-menthol cigarette preference). Analysis of variance (ANOVA) was used to detect interactions between menthol preference by race for continuous variables, and Pearson’s chi-squared test was used for analyses with dichotomous variables.
A greater proportion of menthol smokers smoked their first cigarette within five minutes of waking (p < 0.01) and were less likely to have a previous quit attempt longer than 90 days (p < 0.01). ANOVAs revealed no main effects for menthol preferences. However, African American smokers smoked fewer CPD (p<.001), started smoking later in life (p= .04), and had been smoking the same brand for longer (p= .04).
Women menthol smokers showed signs of greater tobacco dependence than non-menthol smokers. African Americans smoked fewer CPD but nevertheless had evidence of greater dependence.
PMCID: PMC3519603  PMID: 23181980
Cigarette smoking; Menthol cigarettes; Tobacco use; Tobacco dependence; Race/Ethnicity; Female Sex/Gender
5.  Lung Cancer Occurrence in Never-Smokers: An Analysis of 13 Cohorts and 22 Cancer Registry Studies  
PLoS Medicine  2008;5(9):e185.
Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions.
Methods and Findings
We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40–69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking.
These comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries.
Michael Thun and colleagues pooled and analyzed comprehensive data on lung cancer incidence and death rates among never-smokers to examine what factors other than active smoking affect lung cancer risk.
Editors' Summary
Every year, more than 1.4 million people die from lung cancer, a leading cause of cancer deaths worldwide. In the US alone, more than 161,000 people will die from lung cancer this year. Like all cancers, lung cancer occurs when cells begin to divide uncontrollably because of changes in their genes. The main trigger for these changes in lung cancer is exposure to the chemicals in cigarette smoke—either directly through smoking cigarettes or indirectly through exposure to secondhand smoke. Eighty-five to 90% of lung cancer deaths are caused by exposure to cigarette smoke and, on average, current smokers are 15 times more likely to die from lung cancer than lifelong nonsmokers (never smokers). Furthermore, a person's cumulative lifetime risk of developing lung cancer is related to how much they smoke, to how many years they are a smoker, and—if they give up smoking—to the age at which they stop smoking.
Why Was This Study Done?
Because lung cancer is so common, even the small fraction of lung cancer that occurs in lifelong nonsmokers represents a large number of people. For example, about 20,000 of this year's US lung cancer deaths will be in never-smokers. However, very little is known about how age, sex, or race affects the incidence (the annual number of new cases of diseases in a population) or death rates from lung cancer among never-smokers. A better understanding of the patterns of lung cancer incidence and death rates among never-smokers could provide useful information about the factors other than cigarette smoke that increase the likelihood of not only never-smokers, but also former smokers and current smokers developing lung cancer. In this study, therefore, the researchers pooled and analyzed a large amount of information about lung cancer incidence and death rates among never smokers to examine what factors other than active smoking affect lung cancer risk.
What Did the Researchers Do and Find?
The researchers analyzed information on lung cancer incidence and/or death rates among nearly 2.5 million self-reported never smokers (men and women) from 13 large studies investigating the health of people in North America, Europe, and Asia. They also analyzed similar information for women taken from cancer registries in ten countries at times when very few women were smokers (for example, the US in the late 1930s). The researchers' detailed statistical analyses reveal, for example, that lung cancer death rates in African Americans and in Asians living in Korea and Japan (but not among Asians living in the US) are higher than those in people of the European continental ancestry group. They also show that men have higher death rates from lung cancer than women irrespective of racial group, but that women aged 40–59 years have a slightly higher incidence of lung cancer than men of a similar age. This difference disappears at older ages. Finally, an analysis of lung cancer incidence and death rates at different times during the past 70 years shows no evidence of an increase in the lung cancer burden among never smokers over time.
What Do These Findings Mean?
Although some of the findings described above have been hinted at in previous, smaller studies, these and other findings provide a much more accurate picture of lung cancer incidence and death rates among never smokers. Most importantly the underlying data used in these analyses are now freely available and should provide an excellent resource for future studies of lung cancer in never smokers.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Cancer Institute provides detailed information for patients and health professionals about all aspects of lung cancer and information on smoking and cancer (in English and Spanish)
Links to other US-based resources dealing with lung cancer are provided by MedlinePlus (in English and Spanish)
Cancer Research UK provides key facts about the link between lung cancer and smoking and information about all other aspects of lung cancer
PMCID: PMC2531137  PMID: 18788891
6.  Electronic Cigarette Use by College Students 
Drug and alcohol dependence  2013;131(3):214-221.
Electronic cigarettes, or ecigarettes, are battery operated devices that deliver nicotine via inhaled vapor. There is considerable controversy about the disease risk and toxicity of ecigarettes and empirical evidence on short- and long-term health effects is minimal. Limited data on e-cigarette use and correlates exist, and to our knowledge, no prevalence rates among U.S. college students have been reported. This study aimed to estimate the prevalence of ecigarette use and identify correlates of use among a large, multi-institution, random sample of college students.
4,444 students from 8 colleges in North Carolina completed a Webbased survey in fall 2009.
Ever use of ecigarettes was reported by 4.9% of students, with 1.5% reporting past month use. Correlates of ever use included male gender, Hispanic or “Other race” (compared to non-Hispanic Whites), Greek affiliation, conventional cigarette smoking and e-cigarette harm perceptions. Although e-cigarette use was more common among conventional cigarette smokers, 12% of ever e-cigarette users had never smoked a conventional cigarette. Among current cigarette smokers, e-cigarette use was negatively associated with lack of knowledge about e-cigarette harm, but was not associated with intentions to quit.
Although e-cigarette use was more common among conventional cigarette smokers, it was not exclusive to them. E-cigarette use was not associated with intentions to quit smoking among a sub-sample of conventional cigarette smokers. Unlike older, more established cigarette smokers, e-cigarette use by college students does not appear to be motivated by the desire to quit cigarette smoking.
PMCID: PMC3760168  PMID: 23746429
electronic cigarettes; young adults; college students; nicotine; smoking; tobacco; cigarettes
7.  Prevalence of tobacco smoking among health-care physicians in Bahrain 
BMC Public Health  2014;14:931.
There is a clear shift in smoking habits among the Middle Eastern population with a recent and alarming increase in the prevalence of waterpipe (shisha) smoking. This phenomenon has not yet been studied sufficiently across the physician population. Therefore, we set out to establish the smoking status of primary healthcare physicians in the kingdom of Bahrain.
A self-administered questionnaire was distributed to a random sample of 175 out of the total 320 primary care physicians. Descriptive analysis was performed on all data and associations between variables were tested using Fishers Exact t test with statistical significance set as P-value < 0.05.
One hundred and fifty two physicians agreed to participate in the study. Sixty seven percent of physicians were females and the mean (SD) age was 45 (10) years. The majority of the physicians were married (93%) and of Bahraini nationality (76%). Ever-smokers were 11% of the population while current smokers corresponded to 8.6%. Waterpipe was the most common method of tobacco smoking followed by cigarettes. Among male physicians, the prevalence of current ‘waterpipe only’ smokers was 12%, followed by 4% and 2% corresponding to ‘cigarette only’ smokers and both, respectively. There were only three female smokers in the population, two ‘waterpipe only’ smokers and one cigar smoker. Of those who smoked waterpipe (n = 9; 6%), 33% smoked daily, 44% smoked weekly and 22% smoked at least once a month. Current smoking status was associated with male gender (P < 0.001) and showed a male to female smoking ratio of (10:1).
Waterpipe smoking rates exceeded cigarette smoking among the population of physicians in Bahrain. Prevalence of smoking remains unacceptably high among male physicians. Assessment of physicians’ knowledge of the harmful effects of waterpipe tobacco smoking is warranted to plan future interventions.
PMCID: PMC4165905  PMID: 25200373
Smoking; Physician; Waterpipe; Shisha; Cigarettes; Doctors; Tobacco; Lifestyle
8.  Cigarette Smoking Impairs Pancreatic Duct Cell Bicarbonate Secretion 
JOP : Journal of the pancreas  2013;14(1):31-38.
To compare pancreatic duct cell function in smokers (current and past) and never smokers by measurement of secretin-stimulated peak bicarbonate concentration ([HCO3−]) in endoscopic collected pancreatic fluid (PF).
This retrospective study was cross-sectional in design, recording demographic information (age, gender, etc.), smoking status (former, current, never), alcohol intake, clinical data (imaging, endoscopy), and laboratory results (peak PF [HCO3−]) from subjects evaluated for pancreatic disease at a tertiary pancreas center. Univariate and multivariate statistical analysis (SAS Version 9.2, Cary, NC, USA) was performed to assess the relationship between cigarette smoking and secretin-stimulated pancreatic fluid bicarbonate concentration.
A total of 131 subjects underwent pancreatic fluid collection (endoscopic pancreatic function test, ePFT) for bicarbonate analysis: 25.2% (33 out of 131) past smokers, 31.3% (41 out of 131) current smokers, and 43.5% (57 out of 131) were never smokers.
Measures of Association
The mean peak PF [HCO3−] in never smokers (81.3±18.5 mEq/L) was statistically higher (indicating better duct cell function) when compared to past smokers (66.8±24.7 mEq/L, P=0.005) and current smokers (70.0±20.2 mEq/L, P=0.005). However, the mean peak [HCO3−] in past smokers was not statistically different from that in current smokers (P=0.575), and therefore, the two smoking groups were combined to form a single “smokers cohort”. When compared to the never smokers, the smokers cohort was older (P=0.037) and had a greater proportion of subjects with definite chronic pancreatitis imaging (P=0.010), alcohol consumption ≥20 g/day (P=0.012), and abnormal peak PF [HCO3-] (P<0.001).
Risk-Based Estimates
Cigarette smoking (risk ratio, RR: 2.2, 95% CI: 1.3–3.5; P<0.001), diagnosis of definite chronic pancreatitis imaging (RR: 2.2, 95% CI: 1.6–3.2; P<0.001) and alcohol consumption ≥20 g/day (RR: 1.6, 95% CI: 1.1–2.4; P=0.033) were all associated with low mean peak PF [HCO3−] (indicating duct cell secretory dysfunction).
Multivariate Analysis
Smoking (odds ratio, OR: 3.8, 95% CI: 1.6–9.1; P=0.003) and definite chronic pancreatitis imaging (OR: 5.7, 95% CI: 2.2–14.8; P<0.001) were determined to be independent predictors of low peak PF [HCO3−], controlling for age, gender, and alcohol intake. Furthermore there was no interaction between smoking status and alcohol intake in predicting duct cell dysfunction (P=0.571).
Measurement of pancreatic fluid bicarbonate in smokers reveals that cigarette smoking (past and current) is an independent risk factor for pancreatic duct cell secretory dysfunction (low PF [HCO3−]). Furthermore, the risk of duct cell dysfunction in subjects who smoked was approximately twice the risk (RR: 2.2) in never smokers. Further in depth, translational research approaches to pancreatic fluid analysis may help unravel mechanisms of cigarette smoking induced pancreatic duct cell injury.
PMCID: PMC4498578  PMID: 23306332
Pancreas; Pancreatic Diseases; Pancreatic Ducts; Pancreatitis; Chronic; Secretin; Smoking
9.  Current cigarette smoking among in-school American youth: results from the 2004 National Youth Tobacco Survey 
Tobacco use is a leading cause of preventable morbidity and mortality. In the developed nations where the burden from infectious diseases is lower, the burden of disease from tobacco use is especially magnified. Understanding the factors that may be associated with adolescent cigarette smoking may aid in the design of prevention programs.
A secondary analysis of the 2004 United States National Youth Tobacco Survey was carried out to estimate the association between current cigarette smoking and selected smoking-related variables. Study participants were recruited from middle and high schools in the United States. Logistic regression analysis using SUDAAN software was conducted to estimate the association between smoking and the following explanatory variables: age, sex, race-ethnicity, peer smoking, living in the same household as a smoker, amount of pocket money at the disposal of the adolescents, and perception that smoking is not harmful to health.
Of the 27727 respondents whose data were analysed, 15.9% males and 15.3% females reported being current cigarette smokers. In multivariate analysis, compared to Whites, respondents from almost all ethnic groups were less likely to report current cigarette smoking: Blacks (OR = 0.52; 95% CI [0.44, 0.60]), Asians (OR = 0.45; 95% CI [0.35, 0.58]), Hispanic (OR = 0.81; 95% CI [0.71, 0.92]), and Hawaii/Pacific Islanders (OR = 0.69; 95% CI [0.52, 0.93]). American Indians were equally likely to be current smokers as whites, OR = 0.98 [95% CI; 0.79, 1.22]. Participants who reported living with a smoker were more than twice as likely to smoke as those who did not live with a cigarette smoker (OR = 2.73; 95% CI [2.21, 3.04]). Having friends who smoked was positively associated with smoking (OR = 2.27; 95% CI [1.91, 2.71] for one friend who smoked, and OR = 2.71; 95% CI [2.21, 3.33] for two or more friends who smoked). Subjects who perceived that it was safe to smoke for one or two years were more likely to smoke than those who thought it was definitely not safe to do so. There was a dose-response relationship between age and the amount of money available to the respondents on one hand, and current smoking status on the other (p-value < 0.001).
We found that White non-Hispanic adolescents were as likely to be current smokers as American Indians but more likely to be smokers than all other racial/ethnic groups. Older adolescents, increase amounts of pocket money, and perception that smoking was not harmful to health. The racial/ethnic differences in prevalence of smoking among America youth deserve particular exploration.
PMCID: PMC2683170  PMID: 19344506
10.  History of Diabetes and risk of head and neck cancer: a pooled analysis from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium 
A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention.
We pooled data from 12 case-control studies including 6,448 cases and 13,747 controls, and estimated odds ratios (OR) and 95% confidence intervals (CI) for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use and body mass index (BMI).
We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI, 0.95–1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI, 1.22–2.07), and no association among ever smokers (OR, 0.96; 95% CI, 0.83–1.11); likelihood ratio test for interaction p=0.001.
A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes.
This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC.
PMCID: PMC3275674  PMID: 22144496
head and neck cancer; head and neck squamous cell carcinoma; diabetes; INHANCE
11.  Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjögren's syndrome? 
OBJECTIVES—Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sjögren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sjögren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG.
METHODS—All living patients with primary Sjögren's syndrome or stomatitis sicca only, who were still in contact with the Sjögren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm2 glandular tissue) into those being normal (focus score ≤ 1) or abnormal (focus score > 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and ⩾ 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely.
RESULTS—The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score ⩽ 1) was decreased in all three age groups (10-45: odds ratio 0.27, 95%CI 0.11 to 0.71; 46-60: odds ratio 0.22, 95%CI 0.08 to 0.59; and ⩾ 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoked per week (p trend 0.00). In the group of former smokers, which included patients that had stopped smoking up to 30 years ago, the results were in between those of the smokers and the historical non-smokers (odds ratio 0.57, 95%CI 0.34 to 0.97, compared with never smokers). Present or past smoking did not correlate with the function of the salivary glands as judged by unstimulated whole sialometry, stimulated whole sialometry or salivary gland scintigraphy. Among former smokers, the median time lapse between the first symptom of primary Sjögren's syndrome and the performance of the lower lip biopsy was approximately half as long as the median time lapse between smoking cessation and biopsy (8 versus 15 years). Hence, symptoms of Sjögren's syndrome are unlikely to have had a significant influence on smoking habits at the time of the biopsy. Among the seroimmunological results only anti-SSA/Ro and anti-SSB/La antibodies reached statistical significance in a manner similar to the way smoking influenced the focus score in lower lip biopsies. On the other hand the level of significance was consistently more pronounced for the influence of smoking on the focus score than for the influence on anti-SSA/Ro and anti-SSB/La autoantibodies.
CONCLUSION—This is believed to be the first report showing that cigarette smoking is negatively associated with focal sialadenitis—focus score >1—in lower lip biopsy in patients with primary Sjögren's syndrome. Furthermore, tobacco seems to decrease the focus score in a dose dependent manner. Smoking may also negatively influence the presence of anti-SSA/Ro and/or anti-SSB/La antibodies in circulating blood. Thus, smoking habits of patients might invalidate the use of both lower lip salivary gland focus score and of anti-SSA/anti-SSB antibodies. It is suggested that the simultaneous performance of other objective tests is required to avoid misdiagnosis of oral involvement in smoking and former smoking patients. Therefore, classification criteria for Sjögren's syndrome that more or less rely on an abnormal focus score and/or presence of anti-SSA/anti-SSB antibodies should be used with great caution.

PMCID: PMC1752994  PMID: 10627428
12.  Smoking and Visual Impairment Among Older Adults With Age-Related Eye Diseases 
Preventing Chronic Disease  2011;8(4):A84.
Tobacco use is the leading preventable cause of death in the United States. Visual impairment, a common cause of disability in the United States, is associated with shorter life expectancy and lower quality of life. The relationship between smoking and visual impairment is not clearly understood. We assessed the association between smoking and visual impairment among older adults with age-related eye diseases.
We analyzed Behavioral Risk Factor Surveillance System data from 2005 through 2008 on older adults with age-related eye diseases (cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy; age ≥50 y, N = 36,522). Visual impairment was defined by self-reported difficulty in recognizing a friend across the street or difficulty in reading print or numbers. Current smokers were respondents who reported having smoked at least 100 cigarettes ever and still smoked at the time of interview. Former smokers were respondents who reported having ever smoked at least 100 cigarettes but currently did not smoke. We used multivariate logistic regressions to examine the association and to adjust for potential confounders.
Among respondents with age-related eye diseases, the estimated prevalence of visual impairment was higher among current smokers (48%) than among former smokers (41%, P < .05) and respondents who had never smoked (42%, P < .05). After adjustment for age, sex, race/ethnicity, education, and general health status, current smokers with age-related eye diseases were more likely to have visual impairment than respondents with age-related eye diseases who had never smoked (odds ratio, 1.16, P < .05). Furthermore, respondents with cataract who were current smokers were more likely to have visual impairment than respondents with cataract who had never smoked (predictive margin, 44% vs 40%, P = .03), and the same was true for respondents with age-related macular degeneration (65% of current smokers vs 57% of never smokers, P = .02). This association did not hold true among respondents with glaucoma or diabetic retinopathy.
Smoking is linked to self-reported visual impairment among older adults with age-related eye diseases, particularly cataract and age-related macular degeneration. Longitudinal evaluation is needed to assess smoking cessation's effect on vision preservation.
PMCID: PMC3136979  PMID: 21672408
13.  Gender and racial Differences in Smoking of Long/Ultra-long and King size Cigarettes among U.S. adult Smokers, NHANES 1999–2012 
Drug and alcohol dependence  2013;136:28-35.
Cigarette rod length as a design feature may play a specific role in harm perception and tobacco use. Internal tobacco industry documents have shown targeting of females with long/ultra-long cigarettes. This study assessed trends and differences in smoking of long/ultra-long cigarettes among U.S. smokers aged ≥20 years during 1999 through 2012.
Data were obtained from the 1999/2000 through 2011/2012 National Health and Nutrition Examination Survey. The proportion of current smokers who reported using long/ultra-long cigarettes during each survey year was calculated and compared using χ2 statistics. Linear and quadratic trends during 1999 through 2012 were assessed using binary logistic regression (p<0.05). Multi-variable analyses were performed to assess current disparities in smoking of long/ultra-long cigarettes.
Despite overall declines in current smoking of long/ultra-long cigarettes during the 1999 through 2012 period (p<0.001 for both linear and quadratic trends), the proportion of smokers of long/ultra-long brands increased in recent years, with over a third (38.7%) of current smokers reporting smoking of long/ultra-long cigarettes during 2011/2012. Current smokers of long/ultra-long cigarettes were more likely to be female compared to males (aOR=3.09; 95%C.I:2.09–4.58), of black race compared to whites (aOR=2.07; 95%C.I:1.30–3.28), or aged 45–64, or ≥65 years (aOR=2.39 and 5.27 respectively), compared to 18–24 year olds.
Specific gender, age and race/ethnic characteristics of smokers of long/ultra-long cigarettes were noted, hence potentially contributing to the widening of health disparities. Cigarette rod length should be considered an important aspect of cigarette engineering/design in regulatory efforts to reduce the burden of tobacco-related disease.
PMCID: PMC3935845  PMID: 24417962
Slim; long; design; cigarettes; tobacco; abuse liability; product appeal
14.  Lysophosphatidylcholine and Carotid Intima-Media Thickness in Young Smokers: A Role for Oxidized LDL-Induced Expression of PBMC Lipoprotein-Associated Phospholipase A2? 
PLoS ONE  2013;8(12):e83092.
Although cigarette smoking has been associated with carotid intima-media thickness (CIMT) the mechanisms are yet not completely known. Lysophosphatidylcholine (lysoPC), a main product of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, appears to be a major determinant of the pro-atherogenic properties of oxidized LDL (oxLDL) and to induce proteoglycan synthesis, a main player in intimal thickening. In this study we assessed whether cigarette smoking-induced oxidative stress may influence plasma Lp-PLA2 and lysoPC and Lp-PLA2 expression in peripheral blood mononuclear cells (PBMC), as well as the relationship between lysoPC and CIMT.
45 healthy smokers and 45 age and sex-matched subjects participated in this study. Smokers, compared to non-smokers, showed increased plasma concentrations of oxLDL, Lp-PLA2 and lysoPC together with up-regulation of Lp-PLA2 (mRNA and protein) expression in PBMC (P<0.001). Plasma Lp-PLA2 positively correlated with both lysoPC (r=0.639, P<0.001) and PBMC mRNA Lp-PLA2 (r=0.484, P<0.001) in all subjects. Moreover CIMT that was higher in smokers (P<0.001), positively correlated with lysoPC (r=0.55, P<0.001). Then in in vitro study we demonstrated that both oxLDL (at concentrations similar to those found in smoker’s serum) and oxidized phospholipids contained in oxLDL, were able to up-regulate mRNA Lp-PLA2 in PBMC. This effect was likely due, at least in part, to the enrichment in oxidized phospholipids found in PBMC after exposure to oxLDL. Our results also showed that in human aortic smooth muscle cells lysoPC, at concentrations similar to those found in smokers, increased the expression of biglycan and versican, two main proteoglycans.
In smokers a further effect of raised oxidative stress is the up-regulation of Lp-PLA2 expression in PBMC with subsequent increase of plasma Lp-PLA2 and lysoPC. Moreover the correlation between lysoPC and CIMT together with the finding that lysoPC up-regulates proteoglycan synthesis suggests that lysoPC may be a link between smoking and intimal thickening.
PMCID: PMC3866188  PMID: 24358251
15.  E-cigarettes and conventional cigarette use among US adolescents: A cross-sectional study 
JAMA pediatrics  2014;168(7):610-617.
E-cigarette use is increasing rapidly among adolescents and e-cigarettes are currently unregulated.
Examine e-cigarette use and conventional cigarette smoking.
Cross-sectional analyses of survey data.
2011 and 2012 National Youth Tobacco Surveys (NYTS)
Representative sample of US middle and high school students in 2011 (n=17,353) and 2012 (n=22,529)
Ever and current e-cigarette use
Main outcome measures
Experimentation with, ever, and current smoking; smoking abstinence
In pooled analyses, among cigarette experimenters (≥1 puff), ever e-cigarette use was associated with higher odds of ever smoking cigarettes (≥100 cigarettes; OR= 6.31, 95% CI [5.39-7.39) and current cigarette smoking (OR=5.96 [5.67-6.27]). Current e-cigarette use was positively associated with ever smoking cigarettes (OR=7.42 [5.63-9.79]) and current cigarette smoking (OR= 7.88 [6.01-10.32]. In 2011, current cigarette smokers who had ever used e-cigarettes were more likely to intend to quit smoking within the next year (OR=1.53 [1.03-2.28]). Among experimenters with conventional cigarettes, ever use of e-cigarettes was also associated with lower 30-day (OR=0.24 [0.21-0.28]), 6-month (OR=0.24 [0.21-0.28]), and 1-year (OR=0.25 [0.21-0.30]) abstinence from cigarettes. Current e-cigarette use was also associated with lower 30-day (OR=0.11 [0.08-0.15]), 6-month (OR=0.11 [0.08-0.15]), and 1-year (OR=0.12 [0.07-0.18]) abstinence. Among ever smokers of cigarettes (≥100 cigarettes), ever e-cigarette use was negatively associated with 30-day (OR=0.61, [0.42-0.89]), 6-month (OR=0.53, [0.33-0.83]) and one-year (OR=0.32 [0.18-0.56) abstinence from conventional cigarettes. Current e-cigarette use was also negatively associated with 30-day (OR=0.35 [0.18-0.69]), 6-month (OR=0.30 [0.13-0.68]), and one-year (OR=0.34 [0.13-0.87]) abstinence.
E-cigarette use was associated with higher odds of ever or current cigarette smoking, higher odds of established smoking, higher odds of planning to quit smoking among current smokers, and, among experimenters, lower odds of abstinence from conventional cigarettes.
Results suggest e-cigarette use does not discourage, and may encourage, conventional cigarette use among US adolescents.
PMCID: PMC4142115  PMID: 24604023
16.  Depressive Symptoms Among Heavy Cigarette Smokers: The Influence of Daily Rate, Gender, and Race 
Nicotine & Tobacco Research  2013;15(10):1714-1721.
Cigarette smokers experience higher levels of depressive symptoms and are more likely to be diagnosed with depressive disorders than nonsmokers. To date, the nature of the smoking–depression relationship has not been adequately studied among heavy smokers, a group at elevated risk for poor health outcomes. In this study, we examined depressive symptom expression among heavy smokers while considering the moderating roles of smoking status, gender, and race. We also explored whether amount of tobacco usually consumed had an impact.
We extracted data from a large, highly nicotine-dependent, nontreatment cigarette smoking study sample (N = 6,158). Participants who consented were screened for major exclusions, and they completed questionnaires.
Smokers reported a higher, clinically meaningful level of depressive symptoms relative to nonsmokers (27.3% of smokers vs. 12.5% of nonsmokers) scored above the clinical cutoff on the Center for Epidemiological Studies Depression (CES-D) scale (p < .001), which differed among race × gender subgroups. Further, amount of daily intake was inversely associated with self-report of depressive symptoms. For every 10-cigarette increment, the likelihood of scoring above the CES-D clinical cutoff decreased by 62% (p < .0001).
These findings improve our understanding of tobacco’s influence on depressive symptom expression among heavy smokers, with implications for tailoring evidence-based tobacco treatments.
PMCID: PMC3768334  PMID: 23569006
17.  Associations between e-cigarette access and smoking and drinking behaviours in teenagers 
BMC Public Health  2015;15:244.
Public health concerns regarding e-cigarettes and debate on appropriate regulatory responses are focusing on the need to prevent child access to these devices. However, little is currently known about the characteristics of those young people that are accessing e-cigarettes.
Using a cross-sectional survey of 14-17 year old school students in North West England (n = 16,193) we examined associations between e-cigarette access and demographics, conventional smoking behaviours, alcohol consumption, and methods of accessing cigarettes and alcohol. Access to e-cigarettes was identified through a question asking students if they had ever tried or purchased e-cigarettes.
One in five participants reported having accessed e-cigarettes (19.2%). Prevalence was highest among smokers (rising to 75.8% in those smoking >5 per day), although 15.8% of teenagers that had accessed e-cigarettes had never smoked conventional cigarettes (v.13.6% being ex-smokers). E-cigarette access was independently associated with male gender, having parents/guardians that smoke and students’ alcohol use. Compared with non-drinkers, teenagers that drank alcohol at least weekly and binge drank were more likely to have accessed e-cigarettes (adjusted odds ratio [AOR] 1.89, P < 0.001), with this association particularly strong among never-smokers (AOR 4.59, P < 0.001). Among drinkers, e-cigarette access was related to: drinking to get drunk, alcohol-related violence, consumption of spirits; self-purchase of alcohol from shops or supermarkets; and accessing alcohol by recruiting adult proxy purchasers outside shops.
There is an urgent need for controls on the promotion and sale of e-cigarettes to children. Findings suggest that e-cigarettes are being accessed by teenagers more for experimentation than smoking cessation. Those most likely to access e-cigarettes may already be familiar with illicit methods of accessing age-restricted substances.
PMCID: PMC4379746  PMID: 25886064
Electronic cigarettes; Adolescents; Smoking; Alcohol use
18.  The moderating role of parental smoking on their children's attitudes toward smoking among a predominantly minority sample: a cross-sectional analysis 
In general having a parent who smokes or smoked is a strong and consistent predictor of smoking initiation among their children while authoritative parenting style, open communication that demonstrates mutual respect between child and parent, and parental expectations not to smoke are protective. It has been hypothesized that parental smoking affects their children's smoking initiation through both imitation of the behavior and effects on attitudes toward smoking. The goals of the current analysis were to examine these two potential mechanisms.
In 2003, 1,417 high school students in Houston, Texas, completed a cross-sectional survey as part of the evaluation of an interactive smoking prevention and cessation program delivered via CD-ROM. To assess the relationship between number of parents who currently smoke and children's smoking status, we completed an unconditional logistic regression. To determine whether the attitudes that children of smokers hold toward smoking are significantly more positive than the attitudes of children of non-smokers we examined whether the parents smoking status moderated the relationship between children's attitudes toward smoking and their ever smoking using unconditional logistic regressions.
Compared to participants whose parents did not currently smoke, participants who reported one or both parents currently smoke, had increased odds of ever smoking (OR = 1.31; 95% CI: 1.03–1.68; Wald χ2 = 4.78 (df = 1) p = 0.03 and OR = 2.16; 95% CI: 1.51–3.10; Wald χ2 = 17.80 (df = 1) p < 0.001, respectively). In addition, the relationship between attitudes and ever smoking was stronger among participants when at least one parent currently smokes (OR = 2.50; 95% CI: 1.96–3.19; Wald χ2 = 54.71 (df = 1) p < 0.001) than among participants whose parents did not smoke (OR = 1.72; 95% CI: 1.40–2.12; Wald χ2 = 26.45 (df = 1) p < 0.001).
Children of smokers were more likely to smoke and reported more favorable attitudes toward smoking compared to children of non-smokers. One interpretation of our findings is that parental smoking not only directly influences behavior; it also moderates their children's attitudes towards smoking and thereby impacts their children's behavior. Our results demonstrate a continued need for primary prevention smoking interventions to be sensitive to the family context. They also underscore the importance of discussing parental smoking as a risk factor for smoking initiation, regardless of ethnicity, and of tailoring prevention messages to account for the influence that parental smoking status may have on the smoking attitudes and the associated normative beliefs.
PMCID: PMC2490678  PMID: 18625061
19.  No effect of cigarette smoking dose on oxidized plasma proteins 
Environmental research  2007;106(2):219-225.
Cigarette smoking is a major source of oxidative stress. Protein carbonyls have been used as a biomarker of oxidative stress because of the relative stability of carbonylated proteins and the high protein concentration in blood. Increased levels of carbonyl groups have been found in serum proteins of smokers compared to nonsmokers. However, neither the dose effect of current cigarette smoke nor other predictors of oxidative stress have been studied. Hence, we used an ELISA (Enzyme-Linked Immunosorbent Assay) to evaluate plasma protein carbonyls in smokers recruited in the Early Lung Cancer Action Project (ELCAP) program. The lung cancer screening program enrolled current and former smokers age 60 years and over without a prior cancer diagnosis. A total of 542 participants (282 men and 260 women) completed a baseline questionnaire and provided blood samples for the biomarker study. Protein oxidation was measured by derivatization of the carbonyl groups with 2,4-dinitrophenylhydrazine (DNPH) and ELISA quantitation of the DNPH group. Current smoking status was confirmed with urinary cotinine. The mean (± SD) protein carbonyl level was 17.9 ± 2.9 nmol carbonyls/ml plasma. Protein carbonyls did not differ significantly by gender. Carbonyl levels were higher among current than former smokers, but these differences did not attain statistical significance, nor did differences by urine cotinine levels, pack-years, pack/day among current smokers, and smoking duration. In a multiple regression analysis, higher protein carbonyl levels were independently associated with increasing age (0.59 nmol/ml increase per 10 years, 95% CI 0.14, 1.05, p = 0.01), African-American vs. white race/ethnicity, (1.30 nmol/ml, 95% CI 0.4, 2.19, p =0.008), and lower educational attainment (0.75 nmol/ml, 95% CI 0.12, 1.38, p = 0.02). Although we found no significant difference between current versus past cigarette smoking and protein carbonyls in this older group of smokers, associations were found for age, ethnicity and educational attainment. Our results indicate that the measurement of plasma carbonyls by this ELISA technique is still an easy and suitable method for studies of diseases related to oxidative stress.
PMCID: PMC2268894  PMID: 17996865
Oxidative stress; Cigarette smoking; Protein carbonyls; Biomarker; ELCAP
20.  Cigarette Smoking Blocks the Protective Expression of Nrf2/ARE Pathway in Peripheral Mononuclear Cells of Young Heavy Smokers Favouring Inflammation 
PLoS ONE  2009;4(12):e8225.
Cigarette smoking is an important risk factor for atherosclerosis, a chronic inflammatory disease. However the underlying factors of this effect are unclear. It has been hypothesized that water-soluble components of cigarette smoke can directly promote oxidative stress in vasculature and blood cells. Aim of this study was to study the relationship between oxidative stress and inflammation in a group of young smokers. To do this we evaluated: 1) the oxidation products of phospholipids (oxPAPC) in peripheral blood mononuclear cells (PBMC); 2) their role in causing PBMC reactive oxygen species (ROS) generation and changes in GSH; 3) the expression of the transcription factor NF-E2-related factor 2 (Nrf2) and of related antioxidant genes (ARE); 4) the activation of NF-kB and C-reactive protein (CRP) values. We studied 90 healthy volunteers: 32 non-smokers, 32 moderate smokers (5–10 cigarettes/day) and 26 heavy smokers (25–40 cigarettes/day). OxPAPC and p47phox expression, that reasonably reflects NADPH oxidase activity, were higher in moderate smokers and heavy smokers than in non-smokers (p<0.01), the highest values being in heavy smokers (p<0.01). In in vitro studies oxPAPC increased ROS generation via NADPH oxidase activation. GSH in PBMC and plasma was lower in moderate smokers and heavy smokers than in non-smokers (p<0.01), the lowest values being in heavy smokers (p<0.01). Nrf2 expression in PBMC was higher in moderate smokers than in non-smokers (p<0.01), but not in heavy smokers, who had the highest levels of NF-kB and CRP (p<0.01). In in vitro studies oxPAPC dose-dependently increased NF-kB activation, whereas at the highest concentrations Nrf2 expression was repressed. The small interference (si) RNA-mediated knockdown of NF-κB/p65 increased about three times the expression of Nrf2 stimulated with oxPAPC. Cigarette smoke promotes oxPAPC formation and oxidative stress in PBMC. This may cause the activation of NF-kB that in turn may participate in the negative regulation of Nrf2/ARE pathway favouring inflammation.
PMCID: PMC2784946  PMID: 20011043
21.  The impact of smoking on the clinical outcome of locoregionally advanced nasopharyngeal carcinoma after chemoradiotherapy 
Cigarette smoking is a common risk factor for developing nasopharyngeal carcinoma. However, the relationship between smoking and clinical outcomes remains uncertain.
The patients who participated in this study were drawn from a randomized clinical trial, for which the purpose was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy with that of induction chemotherapy plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. The patients who ever smoked were divided into the following categories of cumulative smoking exposure based on the duration of smoking and the quantity of cigarettes smoked: light, short-term smokers; light, long-term smokers; heavy, short-term smokers; and heavy, long-term smokers. A log-rank test and Cox models were used to assess the association between smoking and the clinical outcomes of overall survival (OS), failure-free survival (FFS), locoregional recurrence failure-free survival (LRFFS) and distant failure-free survival (DFFS).
We found that ever-smokers experienced significantly shorter LRFFS times than never-smokers (5-year LRFFS rates: 85.8% vs. 88.5%, P = 0.022). The amount of smoking was significantly associated with FFS (P = 0.046) and LRFFS (P = 0.001) in the different ever-smoker groups. The amount of smoking was associated with LRFFS [P = 0.002, HR = 2.069 (95% confident interval (CI), 1.298-3.299)] even after a multivariable adjustment.
Smoking increases the risk of locoregional recurrence. Furthermore, the amount of smoking influences the prognosis of smokers, and these effects are dose-dependent.
PMCID: PMC4251838  PMID: 25424191
Nasopharyngeal carcinoma; Prognostic factor; Radiotherapy; Smoking
22.  Smoking and Smoking Cessation in Relation to Mortality 
Smoking causes death in many ways, but the rate of risk reduction after quitting, compared to continuing to smoke, is uncertain. There is inadequate or insufficient evidence to infer the presence or absence of a causal relationship between smoking and ovarian cancer and colorectal cancer.
To assess the relation between cigarette smoking and smoking cessation on total and cause-specific mortality in women.
Design, Setting, and Participants
Prospective observational study of 104,519 female participants in the Nurses’ Health Study followed from 1980 to 2004.
Main Outcome Measure
Hazard ratios for total mortality, further categorized into vascular and respiratory diseases, cancers and other causes.
A total of 12483 deaths occurred in this cohort, 4485 (35.9%) among never smokers, 3602 (28.9%) among current smokers, and 4396 (35.2%) among past smokers. Compared to never smokers, current smokers had an increased risk of total mortality (hazard ratio = 2.81, 95% confidence interval (CI) = 2.68–2.95) and all major cause-specific mortality evaluated. The hazard ratio for cancers classified by the 2004 Surgeon General’s report to be smoking-related was 7.25 (CI:6.43–8.18) and for other cancers, 1.58 (CI:1.45–1.73). The hazard ratio for colorectal cancer was 1.63 (CI:1.29–2.05) for current smokers and 1.23 (CI:1.02–1.49) for former smokers, compared to never smokers. A significant association was not observed for ovarian cancer. Significant trends were observed for earlier age at initiation for total mortality (P=0.003), respiratory disease mortality (P=0.001), and all smoking-caused cancer mortality (P=0.001). The excess risk for all-cause mortality decreases to the level of a never smoker 20 years after quitting, with different timeframes for risk reduction observed across outcomes. Approximately 64% of deaths among current smokers and 28% of deaths among former smokers were attributable to cigarette smoking.
Most of the excess risk of vascular mortality due to smoking can be eliminated rapidly upon cessation and within 20 years for lung diseases. Postponing the age of smoking initiation has a dramatic impact on risk of respiratory disease, lung cancer, and other smoking-caused cancer deaths and little effect on other cause-specific mortality. These data suggest that smoking increases the risk of colorectal cancer mortality but not ovarian cancer mortality.
PMCID: PMC2879642  PMID: 18460664
23.  Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor, and Leptin Levels 
Toxicological Research  2014;30(2):91-97.
This study aimed to identify changes in the level of neuropeptides among current smokers, former smokers, and individuals who had never smoked, and how smoking habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels, anthropometric parameters, and metabolic syndrome diagnostic indices were determined among male workers; 117 of these had never smoked, whereas 58 and 198 were former and current smokers, respectively. The total sample comprised 373 male workers. The results obtained from anthropometric measurements showed that current smokers attained significantly lower body weight, body mass index, waist circumference, and abdominal fat thickness values than former smokers and those who had never smoked. Current smokers’ eating habits proved worse than those of non-smokers and individuals who had never smoked. The level of brain-derived neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was 23.6 ± 9.2 pg/ml, higher than that of current smokers (20.4 ± 6.1) and individuals who had never smoked (22.4 ± 5.8) (F = 6.520, p = 0.002). The level of adiponectin among former smokers was somewhat lower than that of current smokers, whereas leptin levels were higher among former smokers than current smokers; these results were not statistically significant. A relationship was found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660, β value = −0.416, p < 0.01) and smokers (odds ratio = 0.827, β value = −0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio = 1.622, β value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, β value = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette smoking leads to an imbalance of energy expenditure and appetite by changing the concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and influences food intake, body weight, the body mass index, blood pressure, and abdominal fat, which are risk factors for MetS and cardiovascular disease.
PMCID: PMC4112070  PMID: 25071918
Smoking habits; Neuropeptides; Adiponectine; BDNF; Leptin
24.  Predictors of long-term smoking cessation: results from the global adult tobacco survey in Poland (2009–2010) 
BMC Public Health  2012;12:1020.
Expanding the information on determinants of smoking cessation is crucial for developing and implementing more effective tobacco control measures at the national as well as European levels. Data on smoking cessation and its social correlates among adults from middle-income countries of Central and Eastern Europe are still poorly reported in the literature. The aim of the study was to analyze the association of socio-demographic indicators with long term tobacco smoking cessation (quit smoking for at least one year prior to interview) among adults. Moreover, we evaluated motives for giving up smoking from former smokers.
Data on former as well as current smokers’ socio-demographic and smoking-related characteristics were derived from the Global Adult Tobacco Survey (GATS). GATS is a cross-sectional, nationally representative household survey implemented in Poland between 2009 and 2010. GATS collected data on a representative sample of 7,840 individuals including 1,206 individuals who met the criteria of long-term smoking cessation and 2,233 current smokers. Smoking cessation rate was calculated as the number of former smokers divided by the number of ever smokers. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence interval (CI) of the broad number of variables on successful cessation of smoking.
Among females the quit rate was 30.4% compared to 37.9% in males (p < 0.01). Former smokers declared concerns about the health hazard of smoking (60.8%) and the high price of cigarettes (11.6%) as primary reasons for smoking cessation. Older age, high education attainment, awareness of smoking health consequences was associated with long-term quitting among both genders. Also employed males had over twice the probability of giving up smoking compared with unemployed, and being religious did not contribute to successful smoking cessation.
Results indicated that smoking cessation policies focused on younger age groups are vital for curbing tobacco epidemic in Poland and should become a public health main concern. There is also the need for interventions to raise awareness on smoking health risks and quitting benefits are crucial to increase cessation potential among adult smokers. Nevertheless further effort needs to be done to prevent smoking uptake.
PMCID: PMC3563479  PMID: 23173904
Tobacco smoking cessation; Socio-demographic factors; Adults; GATS; Poland
25.  Electronic-cigarette use among young people in Wales: evidence from two cross-sectional surveys 
BMJ Open  2015;5(4):e007072.
To examine the prevalence of electronic(e)-cigarette use, prevalence of e-cigarette and tobacco use by age, and associations of e-cigarette use with sociodemographic characteristics, tobacco and cannabis use among young people in Wales.
Data from two nationally-representative cross-sectional surveys undertaken in 2013–2014. Logistic regression analyses, adjusting for school-level clustering, examined sociodemographic characteristics of e-cigarette use, and associations between e-cigarette use and smoking.
Primary and secondary schools in Wales.
Primary-school children aged 10–11 (n=1601) and secondary-school students aged 11–16 (n=9055).
Primary-school children were more likely to have used e-cigarettes (5.8%) than tobacco (1.6%). Ever use of e-cigarettes remained more prevalent than ever use of tobacco until age 14–15. Overall, 12.3% of secondary-school students (aged 11–16) reported ever using e-cigarettes, with no differences according to gender, ethnicity or family affluence. The percentage of ‘never smokers’ reporting having used e-cigarettes was 5.3% at age 10–11 to 8.0% at age 15–16. The proportion of children who had ever used an e-cigarette and reported currently smoking increased from 6.9% among 10–11 year olds to 39.2% in 15–16 year olds. Only 1.5% (n=125) of 11–16 year-olds, including 0.3% of never smokers, reported regular e-cigarette use (use at least once a month). Current weekly smokers were 100 times more likely than non-smokers to report regular e-cigarette use (relative risk ratio (RRR=121.15; 95% CI 57.56 to 254.97). Regular e-cigarette use was also more likely among those who had smoked cannabis (RRR 53.03; 95% CI 38.87 to 80.65).
Many young people (including never-smokers) have tried e-cigarettes. However, regular use is less common, and is associated with tobacco cigarette use. Longitudinal research is needed to understand age-related trajectories of e-cigarette use and to understand the temporal nature of relationships between e-cigarette and tobacco use.
PMCID: PMC4420942  PMID: 25877272

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