Tobacco smoking and vascular biology and function: evidence from human studies.

Tobacco cigarette smoking is among the most complex and least understood health risk factors. A deeper insight into the pathophysiological actions of smoking exposure is of special importance as smoking is a major cause of chronic non-communicable diseases, in particular of cardiovascular disease as well as risk factors such as atherosclerosis and arterial hypertension. It is well known that smoking exerts its negative effects on cardiovascular health through various interdependent pathophysiological actions including hemodynamic and autonomic alterations, oxidative stress, inflammation, endothelial dysfunction, thrombosis, and hyperlipidemia. Importantly, impaired vascular endothelial function is acknowledged as an early key event in the initiation and progression of smoking-induced atherosclerosis. Increasing evidence from human studies indicates that cigarette smoke exposure associates with a pathological state of the vascular endothelium mainly characterized by reduced vascular nitric oxide bioavailability due to increased vascular superoxide production. In the present overview, we provide compact evidence on the effects of tobacco cigarette smoke exposure on vascular biology and function in humans centered on main drivers of adverse cardiovascular effects including endothelial dysfunction, inflammation, and oxidative stress.

Role of cytoglobin in cigarette smoke constituent-induced loss of nitric oxide bioavailability in vascular smooth muscle cells.

Cytoglobin (Cygb) has been identified as the major nitric oxide (NO) metabolizing protein in vascular smooth muscle cells (VSMCs) and is crucial for the regulation of vascular tone. In the presence of its requisite cytochrome B5a (B5)/B5 reductase-isoform-3 (B5R) reducing system, Cygb controls NO metabolism through the oxygen-dependent process of NO dioxygenation. Tobacco cigarette smoking (TCS) induces vascular dysfunction; however, the role of Cygb in the pathophysiology of TCS-induced cardiovascular disease has not been previously investigated. While TCS impairs NO biosynthesis, its effect on NO metabolism remains unclear. Therefore, we performed studies in aortic VSMCs with tobacco smoke extract (TSE) exposure to investigate the effects of cigarette smoke constituents on the rates of NO decay, with focus on the alterations that occur in the process of Cygb-mediated NO metabolism. TSE greatly enhanced the rates of NO metabolism by VSMCs. An initial increase in superoxide-mediated NO degradation was seen at 4 h of exposure. This was followed by much larger progressive increases at 24 and 48 h, accompanied by parallel increases in the expression of Cygb and B5/B5R. siRNA-mediated Cygb knockdown greatly decreased these TSE-induced elevations in NO decay rates. Therefore, upregulation of the levels of Cygb and its reducing system accounted for the large increase in NO metabolism rate seen after 24 h of TSE exposure. Thus, increased Cygb-mediated NO degradation would contribute to TCS-induced vascular dysfunction and partial inhibition of Cygb expression or its NO dioxygenase function could be a promising therapeutic target to prevent secondary cardiovascular disease.

A systematic review of smoking-related epigenetic alterations.

The aim of this study is to provide a systematic review of the known epigenetic alterations caused by cigarette smoke; establish an evidence-based perspective of their clinical value for screening, diagnosis, and treatment of smoke-related disorders; and discuss the challenges and ethical concerns associated with epigenetic studies. A well-defined, reproducible search strategy was employed to identify relevant literature (clinical, cellular, and animal-based) between 2000 and 2019 based on AMSTAR guidelines. A total of 80 studies were identified that reported alterations in DNA methylation, histone modifications, and miRNA expression following exposure to cigarette smoke. Changes in DNA methylation were most extensively documented for genes including AHRR, F2RL3, DAPK, and p16 after exposure to cigarette smoke. Likewise, miR16, miR21, miR146, and miR222 were identified to be differentially expressed in smokers and exhibit potential as biomarkers for determining susceptibility to COPD. We also identified 22 studies highlighting the transgenerational effects of maternal and paternal smoking on offspring. This systematic review lists the epigenetic events/alterations known to occur in response to cigarette smoke exposure and identifies the major genes and miRNAs that are potential targets for translational research in associated pathologies. Importantly, the limitations and ethical concerns related to epigenetic studies are also highlighted, as are the effects on the ability to address specific questions associated with exposure to tobacco/cigarette smoke. In the future, improved interpretation of epigenetic signatures will lead to their increased use as biomarkers and/or in drug development.

Differences in acute reinforcement across reduced nicotine content cigarettes.

RATIONALE: The smallest difference in nicotine that can change a smoker's cigarette preference is not clearly known. OBJECTIVE: A procedure to efficiently identify the difference in nicotine needed to change cigarette preference could help inform research to gauge effects of a nicotine reduction policy. METHODS: Using a within-subject design, we assessed preference for research cigarettes varying in nicotine contents (NIC; 18.7, 10.8, 5.3, 2.3, and 1.3 mg/g of tobacco), relative to a very low nicotine cigarette (VLNC; 0.4 mg/g), in 17 adult-dependent non-menthol smokers abstinent overnight. Only one NIC was compared vs. the VLNC per session, with order of the five NIC contents randomized across sessions on five separate days. Preference for each NIC vs. VLNC was determined by validated forced choice procedure, with those NIC chosen more than VLNC indicating greater reinforcement due to greater nicotine per se. Secondarily, less preference for lower NIC (vs. VLNC), relative to choice for the highest NIC, 18.7 mg/g (vs. VLNC), indexed reduced reinforcement. RESULTS: Overall, NIC choices increased as their nicotine increased, as anticipated. Relative to the 0.4 mg/g VLNC, choice was greater for NIC ≥ 5.3 mg/g but not ≤ 2.3 mg/g. Correspondingly, relative to choice for 18.7 mg/g, choice was less for NIC ≤ 2.3 mg/g but not ≥ 5.3 mg/g. CONCLUSIONS: Although replication with larger samples and longer access is needed, results indicate that nicotine reduction to ≤ 2.3 mg/g in cigarettes would attenuate reinforcement. This choice procedure may efficiently inform future clinical trials to assess relative reinforcing effects of smoking reduced nicotine cigarettes.

Optimistic bias in young adults for cancer, cardiovascular and respiratory diseases: A pilot study on smokers and drinkers.

Optimistic bias defines the tendency for human beings to underrate risk when it pertains to themselves compared with their view of risk pertaining to other people in the same conditions. The aim of this work is to investigate the optimistic bias in risk perception and health-related behaviours for three specific conditions in a young adult sample: cancer, respiratory disorders and cardiovascular diseases. Young adults showed an optimistic bias related to cancer, and to cardiovascular diseases. Our findings suggest that optimistic bias is linked to specific behavioural patterns, largely widespread in young adults, such as tobacco cigarette smoking and alcohol consumption.

Pediatric Blood Cancer Survivors and Tobacco Use across Adolescence and Emerging Adulthood: A Narrative Review.

Scholars underline the pivotal role of tobacco cigarette smoking in carcinogenesis process for blood tumors. A controversial debate is represented by the diffusion of tobacco use in young cancer survivors that had a previous diagnosis of blood tumor during the childhood. Compared with their peers, scientific evidence highlights that pediatric survivors have more difficult to give-up cigarette smoking. Furthermore, tobacco-smoking is frequently linked with others risk behaviors as drinking or substance abuse. In reviewing the main knowledge on this topic, authors affirm the need for increasing research on blood cancer survivors in order to depict psychological characteristics of pediatric blood cancer survivors. Improving health decision-making skills in young survivors could reduce the risk to adopt un-healthy behaviors and increase psychological wellbeing. Furthermore, authors propose tailored antismoking interventions based on the knowledge of the psychological and cognitive factors that support smoking during the transition toward emerging-adulthood.

Assessing 30-day quantity-frequency of U.S. adolescent cigarette smoking as a predictor of adult smoking 14 years later.

BACKGROUND: To improve measures of monthly tobacco cigarette smoking among non-daily smokers, predictive of future non-daily monthly and daily smoking. METHODS: Data from United States National Longitudinal Study of Adolescent to Adult Health, tracking adolescents, ages 12-21, over 14 years were analyzed. At baseline, 6501 adolescents were assessed; 5114 individuals provided data at waves 1 and 4. Baseline past 30-day non-daily smokers were classified using quantity-frequency measures: cigarettes smoked/day by number of days smoked in the past 30 days. RESULTS: Three categories of past 30-day non-daily smokers emerged using cigarettes/month (low:1-5, moderate: 6-60, high: 61+) and predicted past 30-day smoking at follow-up (low: 44.5%, moderate: 60.0%, high: 77.0%, versus 74.2% daily smokers; rτ=-0.2319, p<0.001). Two categories of non-smokers plus low, moderate and high categories of non-daily smokers made up a five-category non-daily smoking index (NDSI). High NDSI (61+ cigs/mo.) and daily smokers were equally likely to be smoking 14 years later (High NDSI OR=0.97, 95% CI=0.53-1.80 [daily as reference]). Low (1-5 cigs/mo.) and moderate (6-60 cigs/mo.) NDSI were distinctly different from high NDSI, but similar to one another (OR=0.21, 95% CI=0.15-0.29 and OR=0.22, 95% CI=0.14-0.34, respectively) when estimating future monthly smoking. Among those smoking at both waves, wave 1 non-daily smokers, overall, were less likely than wave 1 daily smokers to be smoking daily 14 years later. CONCLUSIONS: Non-daily smokers smoking over three packs/month were as likely as daily smokers to be smoking 14-years later. Lower levels of non-daily smoking (at ages 12-21) predicted lower likelihood of future monthly smoking. In terms of surveillance and cessation interventions, high NDSI smokers might be treated similar to daily smokers.