The influence of tobacco load versus smoking status on outcomes following lobectomy for lung cancer in a statewide quality collaborative.

BACKGROUND: Collaborative quality consortia can facilitate implementation of quality measures arising from clinical databases. Our statewide general thoracic surgery (GTS) collaborative investigated the influences of cigarette smoking status on mortality and major morbidity following lobectomy for lung cancer. METHODS: Society of Thoracic Surgeons General Thoracic Surgery Database records were identified from 14 institutions participating in a statewide thoracic surgical quality collaborative between 2012 and 2017. We excluded patients with nonelective procedures, stage 0 tumors, American Society of Anesthesiologists class VI disease, and missing clinical characteristics. Outcomes analysis included the combined mortality and major postoperative morbidity rates and the influence of patient characteristics, including smoking status, on composite rate and on postoperative complications. RESULTS: The study cohort included 2267 patient records for analysis. Overall combined mortality and major morbidity rate was 10.2% (n = 231). Postoperative 30-day mortality was 1.5%, and major morbidity 9.6%. Significant predictors of the combined outcome included male sex (P = .004), body mass index (P < .001), Zubrod score (P = .02), smoking pack-years (P = .03), and thoracotomy (P < .001). Higher American Society of Anesthesiologists disease class and advanced tumor stage were marginally associated with worse combined outcome (P = .06). Smoking status; that is, current, past (no smoking within 30 days), or never smoked, was not associated with worse combined outcome (P = .56) and had no significant influence on major complications. CONCLUSIONS: Smoking status was not associated with worse outcomes; however, smoking dose (pack-years) was associated with worse combined mortality and major morbidity. A statewide quality collaborative provides constructive feedback for participating institutions and surgeons, promoting quality improvement in perioperative patient care strategies and improved outcomes.

Cancer deaths attributable to cigarette smoking in 152 U.S. metropolitan or micropolitan statistical areas, 2013-2017.

PURPOSE: There are limited data on the burden of cancer attributable to cigarette smoking by metropolitan areas to inform local tobacco control policies in the USA. We estimated the proportion of cancer deaths attributable to cigarette smoking (or population attributable fraction [PAF]) in 152 U.S. metropolitan or micropolitan statistical areas (MMSAs). METHODS: Smoking-related PAFs for cancer mortality in ages ≥ 30 years in 2013-2017 were estimated using cross-sectional age-, sex-, and MMSA-specific cigarette smoking prevalence and cancer mortality data obtained from the Behavioral Risk Factor Surveillance System and the U.S. Cancer Statistics Database, respectively. RESULTS: Overall smoking-related PAFs of cancer ranged from 8.8% (95% CI, 6.3-11.9%) to 35.7% (33.3-37.9%); MMSAs with the highest PAFs were in the South region and Appalachia. PAFs also substantially varied across MMSAs within regions or states. In the Northeast, for example, the PAF ranged from 24.2% (23.7-24.7%) to 33.7% (31.3-36.2%). CONCLUSION: The proportion of cancer deaths attributable to cigarette smoking is considerable in each MMSA, with as many as 4 in 10 cancer deaths attributable to smoking in the South region and Appalachia. Broad and equitable implementation and enforcement of proven tobacco control interventions at all government levels could avert many cancer deaths across the USA.

The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group.

OBJECTIVE: To prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS & METHODS: We collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival. RESULTS AND LIMITATIONS: Our final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9-26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16-0.87, p = 0.023, and OR 0.34, 95% CI 0.13-0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02-6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival. CONCLUSIONS: Smoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers.

Spatial Survival Analysis of Initiation Age and Prevalence of Smoking in Iran; Results from a Population Based Study.

BACKGROUND: The initiation age and prevalence of cigarette smoking are two important parameters in any smoking-related policymaking domain. METHODS: Dataset was extracted from STEPs survey, a population-based study conducted in Iran in 2016. A total of 27612 participants were included in the current study. We used a spatial parametric survival mixture rate cure model with doubly censoring to simultaneously assess the initiation age and prevalence of smoking. RESULTS: The entire study population, men and women had the estimated median initiation age of 23.3 (95% CI: 22.2-24.5), 21.9 (95% CI: 21.3-22.5), and 25.5 (95% CI: 22.8-28.7) years, and the prevalence of 10.11% (95% CI: 9.3%-11.0%), 22.3% (95% CI: 21.0%-23.6%), 0.78% (95% CI: 0.62%-0.97%), respectively. The hazard of smoking initiation in men was 66% which was higher than in women (hazard ratio [HR] = 1.66, 95% CI: 1.15-2.48). The odds of smoking in men was 36.5 times greater than that of women (odds ratio [OR] = 36.5, 95% CI: 29.66-45.52). Odds of smoking decreased by 32% in the entire study population and 14% with one level increase in their education (OR = 0.68, 95% CI: 0.65-0.72) and socioeconomic status (OR = 0.86, 95% CI: 0.82-0.94), respectively. The geographical distribution of smoking initiation age varied from 21.5 to 26.37 years for the entire study population, 20.2 to 24.8 years for men, and 23.53 to 28.91 years for women. The geographical distribution of smoking prevalence varied from 5.46% to 14.98% for the entire study population, 12.82% to 30.98% for men, and 0.4% to 1.2% for women. CONCLUSION: The geographical distribution of smoking initiation age and prevalence showed that in different parts of the country, the initiation age and rate of smoking are different which should be considered in any preventative policy making.

Cigarette Smoking and Incident Stroke in Blacks of the Jackson Heart Study.

Background Blacks are disproportionately affected by stroke compared with whites; however, less is known about the relationship between stroke and cigarette smoking in blacks. Therefore, we evaluated the relationship between cigarette smoking and all incident stroke in the JHS (Jackson Heart Study). Methods and Results JHS participants without a history of stroke (n=4410) were classified by self-reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers at baseline (2000-2004). Current smokers were further classified by smoking intensity (number of cigarettes smoked per day [1-19 and ≥20]) and followed up for incident stroke (through 2015). Hazard ratios (HRs) for incident stroke for current and past smoking compared with never smoking were estimated with adjusted Cox proportional hazard regression models. After adjusting for cardiovascular risk factors, the risk for stroke in current smokers was significantly higher compared with never smokers (HR, 2.48; 95% CI, 1.60-3.83) but there was no significant difference between past smokers and never smokers (HR, 1.10; 95% CI, 0.74-1.64). There was a dose-dependent increased risk of stroke with smoking intensity (HR, 2.28 [95% CI, 1.38-3.86] and HR, 2.78 [95% CI, 1.47-5.28] for current smokers smoking 1-19 and ≥20 cigarettes/day, respectively). Conclusions In a large cohort of blacks, current cigarette smoking was associated with a dose-dependent higher risk of all stroke. In addition, past smokers did not have a significantly increased risk of all stroke compared with never smokers, which suggests that smoking cessation may have potential benefits in reducing the incidence of stroke in blacks.

Trends in Active Cigarette Smoking Among Stroke Survivors in the United States, 1999 to 2018.

Background and Purpose- Patients who continue to smoke after a stroke face a higher risk of recurrent stroke. While several effective drugs for smoking cessation became available over the past 2 decades, whether active smoking has decreased among stroke survivors is unknown. We, therefore, evaluated trends in active smoking among stroke survivors during this period. Methods- We performed trends analyses using cross-sectional data collected every 1 to 2 years from 2 US health surveys spanning 1999 to 2018. In the National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) survey, participants were asked about prior stroke and active tobacco smoking. In NHANES, serum cotinine levels were available as a secondary measure of active smoking. We used multivariable logistic regression models for survey data to assess trends in active smoking among participants with and without prior stroke. Results- Among 49 375 participants in NHANES during 1999 to 2016 and 3 621 741 participants in BRFSS during 2011 to 2018, the prevalence of stroke was ≈3%. The overall prevalence of active smoking among stroke survivors was 24% in NHANES and 23% in BRFSS. Among individuals without prior stroke, the odds of smoking decreased over time in both NHANES (odds ratio, 0.95 per 2 years [95% CI, 0.93-0.96]) and BRFSS (odds ratio, 0.96 per year [95% CI, 0.96-0.96]). In contrast, there was no decrease in smoking among stroke survivors in NHANES (odds ratio, 1.00 [95% CI, 0.93-1.07]) or BRFSS (odds ratio, 0.99 [95% CI, 0.98-1.004]). Results were consistent in secondary analysis using biochemical ascertainment of active smoking in NHANES and in sensitivity analyses accounting for potential demographic changes in stroke epidemiology. Conclusions- In contrast to the general population, the prevalence of active smoking among stroke survivors has not decreased during the past 2 decades.

Novel microsimulation model of tobacco use behaviours and outcomes: calibration and validation in a US population.

BACKGROUND AND OBJECTIVE: Simulation models can project effects of tobacco use and cessation and inform tobacco control policies. Most existing tobacco models do not explicitly include relapse, a key component of the natural history of tobacco use. Our objective was to develop, calibrate and validate a novel individual-level microsimulation model that would explicitly include smoking relapse and project cigarette smoking behaviours and associated mortality risks. METHODS: We developed the Simulation of Tobacco and Nicotine Outcomes and Policy (STOP) model, in which individuals transition monthly between tobacco use states (current/former/never) depending on rates of initiation, cessation and relapse. Simulated individuals face tobacco use-stratified mortality risks. For US women and men, we conducted cross-validation with a Cancer Intervention and Surveillance Modeling Network (CISNET) model. We then incorporated smoking relapse and calibrated cessation rates to reflect the difference between a transient quit attempt and sustained abstinence. We performed external validation with the National Health Interview Survey (NHIS) and the linked National Death Index. Comparisons were based on root-mean-square error (RMSE). RESULTS: In cross-validation, STOP-generated projections of current/former/never smoking prevalence fit CISNET-projected data well (coefficient of variation (CV)-RMSE≤15%). After incorporating smoking relapse, multiplying the CISNET-reported cessation rates for women/men by 7.75/7.25, to reflect the ratio of quit attempts to sustained abstinence, resulted in the best approximation to CISNET-reported smoking prevalence (CV-RMSE 2%/3%). In external validation using these new multipliers, STOP-generated cumulative mortality curves for 20-year-old current smokers and never smokers each had CV-RMSE ≤1% compared with NHIS. In simulating those surveyed by NHIS in 1997, the STOP-projected prevalence of current/former/never smokers annually (1998-2009) was similar to that reported by NHIS (CV-RMSE 12%). CONCLUSIONS: The STOP model, with relapse included, performed well when validated to US smoking prevalence and mortality. STOP provides a flexible framework for policy-relevant analysis of tobacco and nicotine product use.

Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults.

PURPOSE: Air pollution and smoking are associated with various types of mortality, including cancer. The current study utilizes a publicly accessible, nationally representative cohort to explore relationships between fine particulate matter (PM2.5) exposure, smoking, and cancer mortality. METHODS: National Health Interview Survey and mortality follow-up data were combined to create a study population of 635,539 individuals surveyed from 1987 to 2014. A sub-cohort of 341,665 never-smokers from the full cohort was also created. Individuals were assigned modeled PM2.5 exposure based on average exposure from 1999 to 2015 at residential census tract. Cox Proportional Hazard models were utilized to estimate hazard ratios for cancer-specific mortality controlling for age, sex, race, smoking status, body mass, income, education, marital status, rural versus urban, region, and survey year. RESULTS: The risk of all cancer mortality was adversely associated with PM2.5 (per 10 µg/m3 increase) in the full cohort (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22) and the never-smokers' cohort (HR 1.19, 95% CI 1.06-1.33). PM2.5-morality associations were observed specifically for lung, stomach, colorectal, liver, breast, cervix, and bladder, as well as Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia. The PM2.5-morality association with lung cancer in never-smokers was statistically significant adjusting for multiple comparisons. Cigarette smoking was statistically associated with mortality for many cancer types. CONCLUSIONS: Exposure to PM2.5 air pollution contributes to lung cancer mortality and may be a risk factor for other cancer types. Cigarette smoking has a larger impact on cancer mortality than PM2.5 , but is associated with similar cancer types.

Association of Silica Dust Exposure and Cigarette Smoking With Mortality Among Mine and Pottery Workers in China.

Importance: The joint association of long-term silica dust exposure and cigarette smoking with mortality has not been well established. Objective: To evaluate the joint association of silica dust exposure and cigarette smoking with mortality in a large cohort of workers at mines and factories in China. Design, Setting, and Participants: This cohort study included 44 708 adults who were employed in 20 metal mines and 9 pottery factories in central and southern China for at least 1 year between January 1, 1960, and December 31, 1974. Participants were retrospectively followed up to January 1, 1960, and prospectively followed up to December 31, 2003. Data analysis was conducted from April 5, 2019, to October 26, 2019. Exposures: Cumulative respirable silica dust exposure was estimated by linking a job-exposure matrix to participants' personal work histories. Cigarette smoking data were collected through participant questionnaires. Main Outcomes and Measures: The main outcome was mortality, with codes from the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) used to categorize diseases associated with mortality. Results: Among 44 708 participants, 38 221 (85.49%) were men, with a mean (SD) age at cohort entrance of 26.9 (8.1) years. A total of 13 700 deaths were observed during 1 534 005 person-years of follow-up, with a median follow-up period of 34.9 years (range, 4.8-43.9 years). Silica exposure was associated with a higher risk of mortality among individuals with all diseases, lung cancer, respiratory tuberculosis, cardiovascular diseases, and diseases of the respiratory system; cigarette smoking was associated with an increased risk of mortality among individuals with all diseases, lung cancer, respiratory tuberculosis, cerebrovascular diseases, and diseases of the respiratory tract. The hazard ratios for the joint association of silica dust exposure and cigarette smoking with mortality were 4.51 (95% CI, 3.23-6.29) for lung cancer, 3.21 (95% CI, 2.53-4.08) for certain infectious and parasitic diseases, 3.93 (95% CI, 2.99-5.15) for respiratory tuberculosis, 6.27 (95% CI, 4.83-8.15) for diseases of the respiratory system, and 12.52 (95% CI, 7.92-19.80) for pneumoconiosis, with a significant additive interaction (P < .001). The proportions of the joint association for the additive interaction of silica dust exposure and cigarette smoking were 21.63% for lung cancer, 42.12% for certain infectious and parasitic diseases, 42.25% for respiratory tuberculosis, 29.55% for diseases of the respiratory system, and 36.46% for pneumoconiosis. Conclusions and Relevance: These findings suggest that cigarette smoking is associated with an increased risk of mortality in individuals exposed to silica dust. Smoking cessation and the control of silica dust concentrations may be important for reducing the risk of mortality among individuals exposed to silica.

Deaths from smoking and from HIV/AIDS among gay and bisexual men in California, 2005-2050.

INTRODUCTION: Deaths from HIV/AIDS have long been of concern to the gay community, but less attention has focused on smoking-attributable deaths despite the relatively high smoking rates among gay and bisexual men. This study compared deaths from HIV/AIDS with smoking-attributable deaths among California gay and bisexual men from 2005 to 2050. METHODS: Smoking-attributable fractions (SAFs) were estimated using smoking prevalence for gay and bisexual men from the 2011-2014 California Health Interview Surveys and published relative risks of death. Smoking-attributable deaths were calculated by multiplying the SAFs by deaths among gay and bisexual men. Deaths from HIV/AIDS among men who have sex with men was obtained from the California Department of Public Health. Future deaths from smoking and HIV/AIDS were projected using regression equations based on time trends. RESULTS: From 2005 to 2014, smoking caused over 6800 deaths among gay and bisexual men, while nearly 9500 died from HIV/AIDS. Mortality from both causes has been falling, but deaths from HIV/AIDS have been falling more rapidly. Projections suggest that in the mid-2040s, more gay/bisexual men will die from smoking than from HIV/AIDS. CONCLUSION: Smoking will surpass HIV/AIDS as a cause of death among gay and bisexual men in California within a few decades. The lesbian, gay, bisexual and transgender (LGBT) community was highly effective in drawing attention and resources to the fight against HIV/AIDS, saving untold lives by hastening effective treatments. Lessons learnt in the fight against AIDS should be used to help fight the tobacco epidemic.

Assessment of Relative Utility of Underlying vs Contributory Causes of Death.

Importance: In etiological research, investigators using death certificate data have traditionally extracted underlying cause of mortality alone. With multimorbidity being increasingly common, more than one condition is often compatible with the manner of death. Using contributory cause plus underlying cause would also have some analytical advantages, but their combined utility is largely untested. Objective: To compare the relative utility of cause of death data extracted from the underlying cause field vs any location on the death certificate (underlying and contributing combined). Design, Setting, and Participants: This study compares the association of 3 known risk factors (cigarette smoking, low educational attainment, and hypertension) with health outcomes based on where cause of death data appears on the death certificate in 2 prospective cohort study collaborations (UK Biobank [N = 502 655] and the Health Survey for England [15 studies] and the Scottish Health Surveys [3 studies] [HSE-SHS; N = 193 873]). Data were collected in UK Biobank from March 2006 to October 2010 and in HSE-SHS from January 1994 to December 2008. Data analysis began in June 2018 and concluded in June 2019. Main Outcomes and Measures: Death from cardiovascular disease, cancer, dementia, and injury. For each risk factor-mortality end point combination, a ratio of hazard ratios (RHR) was computed by dividing the effect estimate for the underlying cause by the effect estimate for any mention. Results: In UK Biobank, there were 14 421 deaths (2.9%) during a mean (SD) of 6.99 (1.03) years of follow up; in HSE-SHS, there were 21 314 deaths (11.0%) during a mean (SD) of 9.61 (4.44) years of mortality surveillance. Established associations of risk factors with death outcomes were essentially the same irrespective of placement of cause on the death certificate. Results from each study were mutually supportive. For having ever smoked cigarettes (vs never having smoked) in the UK Biobank, the RHR for cardiovascular disease was 0.98 (95% CI, 0.87-1.10; P value for difference = .69); for cancer, the RHR was 0.99 (95% CI, 0.93-1.05; P value for difference = .69). In the HSE-SHS, the RHR for cardiovascular disease was 0.94 (95% CI, 0.87-1.01; P value for difference = .09); for cancer, it was 1.01 (95% CI, 0.94-1.10; P value for difference = .75). Conclusions and Relevance: Risk factor-end point associations were not sensitive to the placement of data on the death certificate. This has implications for the examination of the association of risk factors with causes of death where there may be too few events to compute reliable effect estimates based on the underlying field alone.

Impact of baseline cigarette smoking status on clinical outcome after transcatheter aortic valve replacement.

OBJECTIVES: To explore the prevalence of smoking, and its association with clinical and mortality outcome among patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Less data exist regarding the effect of baseline smoking status on clinical and mortality outcome among patients undergoing TAVR. METHODS: Consecutive patients who underwent TAVR at two high volume Dutch centers were included. Smoking status was prospectively questioned by a structured interview at admission. Primary endpoint was 1-year all-cause mortality after TAVR. RESULTS: A total of 913 consecutive patients (80.1 ± 7.6 years; logistic EuroSCORE: 16.5 ± 9.9%) who underwent TAVR for severe aortic valve stenosis were included. There were 47% (n = 432) males, and 57% (n = 522) never-smokers, and 35% (n = 317) prior-smokers, and 8% (n = 74) current-smokers. Smokers (i.e., prior-smokers or current-smokers) were younger compared to never-smokers (78.9 ± 7.9 and 76.4 ± 8.0 vs. 81.3 ± 7.1, P < 0.000, respectively). Median follow-up time was 365 (interquartile range [IQR]: 280-365) days. Overall, prior-smoking was not associated with all-cause mortality at 1-year following TAVR (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.55-1.23). After stratification according to sex, male prior-smokers showed better 1-year survival after TAVR than male never-smokers (12% vs. 20%; P = 0.018, respectively, HR 0.52, 95% CI 0.29-0.89), while this reversed effect was not observed among female prior-smokers versus female never-smokers after TAVR (HR 1.70, 95% CI 0.95-3.05). CONCLUSIONS: Overall, baseline prior-smokers had similar 1-year mortality outcome after TAVR compared with baseline never-smokers. However, there was a reversed association between baseline prior-smoking status and 1-year mortality after TAVR among males, which could partially be explained due to the favorable baseline characteristics.

The effects of cigarette smoking on the associations between sitting time and all-cause mortality: a meta-analysis.

BACKGROUND: Sedentary behavior is recognized as an independent risk factor for mortality, but it remains unclear whether cigarette smoking will aggravate the detrimental effects of prolonged sitting on mortality. This study examined the impact of cigarette smoking on the relationship between sitting time and all-cause mortality in adults. METHODS: Electronic database searches were conducted in PubMed, Web of Science, and the EMBASE up to 1 June 2017. Prospective studies that reported sitting time, percent of current smokers, and all-cause mortality were included. Data were extracted independently by two authors. RESULTS: Ten prospective studies met the inclusion criteria. These studies included 850990 adults who were followed up for 2-15.7 years, during which 64 781 died (7.6%). Generally, during follow-up sitting time showed a dose-response relationship with all-cause mortality, with each 1 h increment of sitting time per day accounting for hazard ratio (HR) of mortality 1.02 (95%CI, 1.02-1.03). The relationship remained significant when stratified by the quartiles of smoking populations (≤8.4%, 8.5%-12.6%, 12.7%-27.9%, and ≥28.0%), and the risk of sitting time-related mortality increased parallel to the increment of the percent of smoking populations, with HRs 1.02 (95%CI, 1.02-1.03), 1.03 (95%CI, 1.02-1.03), 1.04 (95%CI, 1.03-1.04) and 1.06 (95%CI, 1.06-1.06), respectively. The associations between the risk of prolonged sitting-related mortality and the percent of smoking populations were linear (P = 0.032). CONCLUSIONS: Cigarette smoking significantly aggravated the detrimental effects of sitting time on all-cause mortality. Our findings provided further evidence on the harmful effects of smoking combing prolonged sitting on adult health.

Association Between Reductions of Number of Cigarettes Smoked per Day and Mortality Among Older Adults in the United States.

Many smokers do not quit but instead reduce the number of cigarettes they smoke per day (CPD) over their lifetime. Yet the associations of such changes in CPD with health risks are unclear. We examined the association of changes in CPD with subsequent death in the period 2004-2011 among 253,947 participants of the National Institutes of Health-AARP Diet and Health Study. Using a questionnaire assessing responders' history of smoking cigarettes, we identified cigarette smokers who quit, decreased, maintained, or increased their CPD between ages 25-29 and 50-59 years. Hazard ratios and 95% confidence intervals were obtained from multivariable adjusted Cox proportional hazards regression models. Relative to never smokers, smokers who maintained a consistent CPD had 2.93 times (95% confidence interval (CI): 2.82, 3.05) higher all-cause mortality risk, and participants who increased their CPD had still higher risk (hazard ratio (HR) = 3.37, 95% CI: 3.23, 3.52). Death risk was lower among participants who decreased their CPD (HR = 2.38, 95% CI: 2.25, 2.52) or quit smoking (for quitting between ages 30 and 39 years, HR = 1.32, 95% CI: 1.25, 1.39). Similar patterns were observed for smoking-related causes of death, with particularly strong associations for lung cancer and respiratory disease. Reductions in CPD over the lifetime meaningfully decreased death risk; however, cessation provided a larger benefit than even large declines in CPD.

Nicotine stimulates IL-6 expression by activating the AP-1 and STAT-3 pathways in human endothelial EA.hy926 cells.

Interleukin-6 (IL-6), a pleiotropic cytokine, plays a key role in endothelial injury and atherosclerosis. In this study, we investigated the effects of nicotine, a major psychoactive compound in cigarette smoke, on IL-6 expression and EA.hy926 endothelial cell invasion. Nicotine stimulated IL-6 expression via the activator protein 1 (AP-1) transcription factor. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen-activated protein kinase (MAPK) mediated the IL-6-induced upregulation of nicotine in EA.hy926 cells. Furthermore, the antioxidant compound N-acetyl-cysteine eliminated the nicotine-activated production of reactive oxygen species (ROS) and inhibited signal transducer and activator of transcription 3 (STAT-3) phosphorylation; these two mechanisms mediated the upregulation of IL-6 expression by nicotine. In addition, the EA.hy926 cells treated with nicotine displayed markedly enhanced invasiveness due to IL-6 upregulation. Our data demonstrate that nicotine induced IL-6 expression, which, in turn, enhanced the invasiveness of endothelial EA.hy926 cells, via activation of the p38 MAPK/AP-1 and ROS/STAT-3 signaling pathways.

Non-Daily Cigarette Smokers: Mortality Risks in the U.S.

INTRODUCTION: Worldwide, an estimated 189 million adults smoke tobacco "occasionally" but not every day. Yet few studies have examined the health risks of non-daily smoking. METHODS: Data from the 1991, 1992, and 1995 U.S. National Health Interview Surveys, a nationally representative sample of 70,913 U.S. adults (aged 18-95 years) were pooled. Hazard ratios and 95% CIs for death through 2011 were estimated from Cox proportional hazards regression using age as the underlying time metric and stratified by 5-year birth cohorts in 2017. RESULTS: Non-daily smokers reported smoking a median of 15 days and 50 cigarettes per month in contrast to daily smokers who smoked a median of 600 cigarettes per month. Compared with never smokers, lifelong nondaily smokers who had never smoked daily had a 72% higher mortality risk (95% CI=1.36, 2.18): higher risks were observed for cancer, heart disease, and respiratory disease mortalities. Higher mortality risks were observed among lifelong non-daily smokers who reported 11-30 (hazard ratio=1.34, 95% CI=0.81, 2.20); 31-60 (hazard ratio=2.02, 95% CI=1.17, 3.29); and >60 cigarettes per month (hazard ratio=1.74, 95% CI=1.12, 2.72) than never smokers. Median life-expectancy was about 5 years shorter for lifelong non-daily smokers than never smokers. As expected, daily smokers had even higher mortality risks (hazard ratio=2.50, 95% CI=2.35, 2.66) and shorter survival (10 years less). CONCLUSIONS: Although the mortality risks of non-daily smokers are lower than daily smokers, they are still substantial. Policies should be specifically directed at this growing group of smokers.

Adolescent tolerance for deviance, cigarette smoking trajectories, and premature mortality: A longitudinal study.

Cigarette smoking is a well-established cause of excess morbidity and mortality in the United States and globally. The current study builds on the existing literature by examining how smoking trajectories might be a mechanism through which adolescent tolerance for deviance predicts premature all-cause and tobacco-specific mortality. Participants were from a cohort-sequential study conducted in the Midwestern United States of the natural history of cigarette smoking from adolescence through midlife that collected nine waves of data from 1980 to 2011. For the current study, we selected participants who were measured at least once at age 18 or older and who did not die before age 24 (n = 7575). Participants' tolerance for deviance was assessed in adolescence, smoking trajectory group was based on self-reported smoking status during the first six waves of data collection, and cause of death for deceased participants (n = 222) was obtained from the National Death Index. Mediation analyses using the joint significance test were conducted separately for all-cause mortality and tobacco-specific mortality. Adolescent tolerance for deviance significantly predicted smoking trajectory group over and above the influence of covariates. Adolescents with higher tolerance for deviance were more likely to belong to any smoking trajectory group compared to abstainers, and membership in a smoking trajectory group characterized by early onset and heavy, persistent smoking was related to premature all-cause and tobacco-specific mortality. Finally, smoking trajectory group was a significant mediator of the relation between adolescent tolerance for deviance and all-cause mortality.

Cancer mortality attributable to cigarette smoking in 2005, 2010 and 2015 in Qingdao, China.

INTRODUCTION: Cigarette smoking is among the most important public health concerns worldwide and the leading preventable cause of illness and death associated with cancer, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). Although Qingdao, China implemented smoking control measures in 2007 and smoke-free legislation in 2013, smoking-attributable cancer mortality remains at a high level. The present study aimed to facilitate changes in policy-making, intervention implementation, monitoring and evaluation by estimating and comparing the burden of smoking-attributable cancers in Qingdao during 2005, 2010 and 2015. METHODS: This study used the disease list from the Global Burden of Disease (GBD) study to quantify the burden of smoking-related cancer. Sex and age-specific smoking-attributable mortality data were collected from the Qingdao Municipal Center for Disease Control and Prevention using an online reporting system. The population-attributable fractions (PAFs) of smoking and smoking-attributable cancer mortality in 2005, 2010 and 2015 were estimated using the smoking impact ratio (SIR) and relative risks (RRs) and by multiplying the smoking-attributable fraction by total cancer mortality, respectively. RESULTS: The numbers of smoking-attributable cancer deaths increased from 2484 in 2005 to 2999 in 2010 and 4148 in 2015, with corresponding PAFs of 26.41%, 25.76% and 29.13%, respectively. The PAFs were higher among men (vs. women) for all cancers except cervical cancer. In 2005, lung, liver, esophageal and stomach cancers were most frequently associated with smoking-associated cancer mortality, and lung cancer had the greatest PAF, followed by nasopharyngeal, oral and esophageal cancers. Similar patterns were observed in 2010 and 2015. In 2015, 1 in 3 and 1 in 5 cancer deaths in men and women, respectively, were attributable to smoking, and 95% of these deaths were associated with lung, liver, esophageal or stomach cancer. Over time, downward and upward trends in smoking-attributable cancer deaths were respectively observed among people younger than and older than 50 years. CONCLUSIONS: The smoking-attributable cancer burden in Qingdao remains considerable, despite the implementation of tobacco control and smoke-free measures. Tobacco control efforts should remain a major public health priority.

Cigarette Smoking and All-Cause and Cause-Specific Adult Mortality in the United States.

This study illuminates the association between cigarette smoking and adult mortality in the contemporary United States. Recent studies have estimated smoking-attributable mortality using indirect approaches or with sample data that are not nationally representative and that lack key confounders. We use the 1990-2011 National Health Interview Survey Linked Mortality Files to estimate relative risks of all-cause and cause-specific mortality for current and former smokers compared with never smokers. We examine causes of death established as attributable to smoking as well as additional causes that appear to be linked to smoking but have not yet been declared by the U.S. Surgeon General to be caused by smoking. Mortality risk is substantially elevated among smokers for established causes and moderately elevated for additional causes. We also decompose the mortality disadvantage among smokers by cause of death and estimate the number of smoking-attributable deaths for the U.S. adult population ages 35+, net of sociodemographic and behavioral confounders. The elevated risks translate to 481,887 excess deaths per year among current and former smokers compared with never smokers, 14 % to 15 % of which are due to the additional causes. The additional causes of death contribute to the health burden of smoking and should be considered in future studies of smoking-attributable mortality. This study demonstrates that smoking-attributable mortality must remain a top population health priority in the United States and makes several contributions to further underscore the human costs of this tragedy that has ravaged American society for more than a century.