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E-cigarettes containing ‘nicotine salts’ aim to increase smoker’s satisfaction by improving blood nicotine delivery and other sensory properties. Here, we evaluated the pharmacokinetic profiles and subjective effects of nicotine from two e-cigarette device platforms with varying concentrations of nicotine lactate (nicotine salt) e-liquid relative to conventional cigarettes. A randomised, open-label, cross-over clinical study was conducted in 15 healthy US adult smokers. Five different e-cigarette products were evaluated consecutively on different days after use of own brand conventional cigarette. Plasma nicotine pharmacokinetics, subjective effects, and tolerability were assessed following controlled use of the products. The rate of nicotine absorption into the bloodstream was comparable from all e-cigarettes tested and was as rapid as that for conventional cigarette. However, in all cases, nicotine delivery did not exceed that of the conventional cigarette. The pharmacokinetic profiles of nicotine salt emissions were also dependent upon the properties of the e-cigarette device. Subjective scores were numerically highest after smoking a conventional cigarette followed by the myblu 40-mg nicotine salt formulation. The rise in nicotine blood levels following use of all the tested e-cigarettes was quantified as ‘a little’ to ‘modestly’ satisfying at relieving the desire to smoke. All products were well tolerated with no notable adverse events reported. These results demonstrate that, while delivering less nicotine than a conventional cigarette, the use of nicotine salts in e-cigarettes enables cigarette-like pulmonary delivery of nicotine that reduces desire to smoke.

The pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear, but involves loss of alveolar surface area (emphysema) and airway inflammation (bronchitis) as the consequence of cigarette smoke (CS) exposure. Previously, we demonstrated that autophagy proteins promote lung epithelial cell death, airway dysfunction, and emphysema in response to CS; however, the underlying mechanisms have yet to be elucidated. Here, using cultured pulmonary epithelial cells and murine models, we demonstrated that CS causes mitochondrial dysfunction that is associated with a reduction of mitochondrial membrane potential. CS induced mitophagy, the autophagy-dependent elimination of mitochondria, through stabilization of the mitophagy regulator PINK1. CS caused cell death, which was reduced by administration of necrosis or necroptosis inhibitors. Genetic deficiency of PINK1 and the mitochondrial division/mitophagy inhibitor Mdivi-1 protected against CS-induced cell death and mitochondrial dysfunction in vitro and reduced the phosphorylation of MLKL, a substrate for RIP3 in the necroptosis pathway. Moreover, Pink1(-/-) mice were protected against mitochondrial dysfunction, airspace enlargement, and mucociliary clearance (MCC) disruption during CS exposure. Mdivi-1 treatment also ameliorated CS-induced MCC disruption in CS-exposed mice. In human COPD, lung epithelial cells displayed increased expression of PINK1 and RIP3. These findings implicate mitophagy-dependent necroptosis in lung emphysematous changes in response to CS exposure, suggesting that this pathway is a therapeutic target for COPD.

Background It is well established that airway remodeling and inflammation are characteristics for chronic obstructive pulmonary disease (COPD). Moreover, cigarette smoke extract (CSE) promots inflammation, apoptosis and oxidative stress in COPD. And, there is evidence suggested that alantolactone (ALT), a sesquiterpene lactone isolated from Inula helenium , plays an adverse role in inflammation, apoptosis and oxidative stress. However, few studies have investigated the function and mechanism of ALT treatment on the COPD pathological process. Methods The levels of IL-1 β, TNF-α, IL-6 and IFN-γ were examined by ELISA. Cells’ apoptosis and caspase-3 activity were detected by Cell Death Detection PLUS enzyme-linked immunosorbent assay and caspase-Glo 3/7 Assay, respectively. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using MDA and SOD assay kits. Reactive oxygen species (ROS) generation was measured by DCFH-DA assay. Protein expression was assayed by Western blot. Results In the present study, we aimed to observe the protective effects of ALT against inflammation, apoptosis and oxidative stress in human bronchial epithelial Beas-2B and NHBE cells. Our results showed that different doses of CSE exposure induced Beas-2B and NHBE cell inflammatory cytokines IL-1 β, TNF-α, IL-6 and IFN-γ expression, cell apoptosis, caspase-3 activity and mediated oxidative stress markers MDA, ROS and SOD levels, while ALT treatment counteracted the effects of CSE. Further studies suggested that ALT attenuated NF-κB pathway activation. ALT also activated the Nrf2/HO-1 signal pathway through promoting Nrf2 nuclear aggregation and downstream HO-1 protein expression. HO-1 inhibitor tin protoporphyrin IX (SnPP IX) reversed the effects of ALT on Beas-2B and NHBE cell inflammation, apoptosis and oxidative stress. Conclusions The above results collectively suggested that ALT suppressed CSE-induced inflammation, apoptosis and oxidative stress by modulating the NF-ĸB and Nrf2/ HO-1 axis.

This review is an account of how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in chronic obstructive pulmonary disease (COPD). The authors present evidence that autoimmunity has a role in the development of COPD. This review is an account of how pulmonary damage caused by cigarette smoke and other environmental toxins can incite inflammatory and immunologic reactions that culminate in chronic obstructive pulmonary disease (COPD). The authors present evidence that autoimmunity has a role in the development of COPD. Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death throughout the world. It affects about 10% of the general population, 1 but its prevalence among heavy smokers can reach 50%. 2 COPD is the fourth leading cause of death in most industrialized countries, and it is projected to be the third leading cause of death worldwide by 2020. 1 Tobacco smoking is the primary risk factor for the development of COPD, but other factors, such as burning biomass fuels for cooking and heating, are important causes of COPD in many developing countries. 3 , 4 A principal feature of COPD is . . .

Marine debris is a global environmental issue. Smoked cigarette filters are the predominant coastal litter item; 4.5 trillion are littered annually, presenting a source of bioplastic microfibres (cellulose acetate) and harmful toxicants to marine environments. Despite the human health risks associated with smoking, little is known of the hazards cigarette filters present to marine life. Here we studied the impacts of smoked cigarette filter toxicants and microfibres on the polychaete worm Hediste diversicolor (ragworm), a widespread inhabitant of coastal sediments. Ragworms exposed to smoked cigarette filter toxicants in seawater at concentrations 60 fold lower than those reported for urban run-off exhibited significantly longer burrowing times, >30% weight loss, and >2-fold increase in DNA damage compared to ragworms maintained in control conditions. In contrast, ragworms exposed to smoked cigarette filter microfibres in marine sediment showed no significant effects. Bioconcentration factors for nicotine were 500 fold higher from seawater than from sediment. Our results illustrate the vulnerability of organisms in the water column to smoking debris and associated toxicants, and highlight the risks posed by smoked cigarette filter debris to aquatic life.

Alveolar macrophages (AMs) are critical for lung immune defense and homeostasis. They are orchestrators of chronic obstructive pulmonary disease (COPD), with their number significantly increased and functions altered in COPD. However, it is unclear how AM number and function are controlled in a healthy lung and if changes in AMs without environmental assault are sufficient to trigger lung inflammation and COPD. We report here that absence of isthmin 1 (ISM1) in mice (Ism1 −/−) leads to increase in both AM number and functional heterogeneity, with enduring lung inflammation, progressive emphysema, and significant lung function decline, phenotypes similar to human COPD. We reveal that ISM1 is a lung resident anti-inflammatory protein that selectively triggers the apoptosis of AMs that harbor high levels of its receptor cell-surface GRP78 (csGRP78). csGRP78 is present at a heterogeneous level in the AMs of a healthy lung, but csGRP78high AMs are expanded in Ism1 −/− mice, cigarette smoke (CS)-induced COPD mice, and human COPD lung, making these cells the prime targets of ISM1-mediated apoptosis. We show that csGRP78high AMs mostly express MMP-12, hence proinflammatory. Intratracheal delivery of recombinant ISM1 (rISM1) depleted csGRP78high AMs in both Ism1 −/− and CS-induced COPD mice, blocked emphysema development, and preserved lung function. Consistently, ISM1 expression in human lungs positively correlates with AM apoptosis, suggesting similar function of ISM1–csGRP78 in human lungs. Our findings reveal that AM apoptosis regulation is an important physiological mechanism for maintaining lung homeostasis and demonstrate the potential of pulmonary-delivered rISM1 to target csGRP78 as a therapeutic strategy for COPD.

Nicotiana tabacum is a cash crop that originated in America and was introduced to the world by Christopher Colombus. It is now cultivated in many countries with major producers including China, the USA, India, and Brazil. The plant was widely used by the indigenous people of America for different reasons (spiritual, hallucination, and medical). The medicinal usage of the plant was confirmed by many phytochemical and pharmacological studies on different parts of the plant. The plant essentially contains alkaloids (nicotine is the major component) and phenolic compounds such as flavonoids, tannins, and many phenolic acids. Glycosides and terpenes are also present in N. tabacum. These components are responsible for many pharmacological effects. Besides the therapeutic usage of the plant, the leaves of the plant served as a hallucination agent; they were either smoked or chewed. Nowadays tobacco products are universally used. Smokeless tobacco products are numerous and diversified; they can be handmade or manufactured. Unlike the plant, smokeless tobacco products are harmful to health. Many products exist around the world with different compositions and names, such as paan, zarda, toombak, khaini, naswar, loose leaf, moist snuff, snus, and shammah. These products have been confirmed to cause many serious pathological conditions. In addition to being addictive, they can lead to various types of cancer especially oral cancer, hypertension, cardiovascular diseases, fertility issues, and fetal damage when consumed by pregnant women. They also increase the risk of thrombosis and so on. While the harmful effects of some products have been scientifically proven, others (e.g., chemma) have not. This highlights the importance of scientific investigation to confirm their potential risks.

Abstract Rationale Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Human sirtuin (SIRT1), an antiaging and antiinflammatory protein, is a metabolic NAD+-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. Objectives To determine the expression of SIRT1 in lungs of smokers and patients with COPD, and to elucidate the regulation of SIRT1 in response to cigarette smoke in macrophages, and its impact on nuclear factor (NF)-κB regulation. Methods SIRT1 and NF-κB levels were assessed in lung samples of nonsmokers, smokers, and patients with COPD. Human monocyte–macrophage cells (MonoMac6) were treated with cigarette smoke extract (CSE) to determine the mechanism of CSE-mediated regulation of SIRT1 and its involvement in RelA/p65 regulation and IL-8 release. Measurements and Main Results Peripheral lungs of smokers and patients with COPD showed decreased levels of nuclear SIRT1, as compared with nonsmokers, associated with its post-translational modifications (formation of nitrotyrosine and aldehyde carbonyl adducts). Treatment of MonoMac6 cells with CSE showed decreased levels of SIRT1 associated with increased acetylation of RelA/p65 NF-κB. Mutation or knockdown of SIRT1 resulted in increased acetylation of nuclear RelA/p65 and IL-8 release, whereas overexpression of SIRT1 decreased IL-8 release in response to CSE treatment in MonoMac6 cells. Conclusions SIRT1 levels were reduced in macrophages and lungs of smokers and patients with COPD due to its post-translational modifications by cigarette smoke–derived reactive components, leading to increased acetylation of RelA/p65. Thus, SIRT1 plays a pivotal role in regulation of NF-κB–dependent proinflammatory mediators in lungs of smokers and patients with COPD.

The present study investigated the associations of active, passive, and electronic cigarette (E-cigarette) smoking with asthma in Korean adolescents. We used the cross-sectional study of Korea Youth Risk Behavior Web-based Survey conducted in 2011, 2012 and 2013. Active smoking was classified into 4 groups (0 days, 1–5 days, 6–19 days, and ≥20 days a month). Passive smoking was also categorized into 4 groups (0 days, 1–2 days, 3–4 days, and ≥5 days a week). E-cigarette was defined as yes or no in the last 30 days. Age, sex, obesity, region of residence, economic level, and parental educational level were adjusted for as confounders. Smoking variables were adjusted for one another. Adjusted odd ratios (AORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression analysis with complex sampling. In total, 2.3% (4,890/216,056) of participants reported asthma in the past 12 months. Active smoking was significantly associated with asthma (AOR [95% CI] of smoking ≥20 days/month = 1.57 [1.38–1.77], P < 0.001). Passive smoking was also related with asthma (AOR [95% CI] of smoking ≥5 days/week = 1.40 [1.28–1.53], P < 0.001). E-cigarette showed positive relation with asthma, although the effects of past smoking history could not be excluded (AOR [95% CI] = 1.12 [1.01–1.26], P = 0.027).

Cigarette smoke (CS) exposure is the predominant risk factor for the development of chronic obstructive pulmonary disease (COPD) and the third leading cause of death worldwide. We aimed to elucidate whether mitochondrial respiratory inhibition and oxidative stress are triggers in its etiology. In different models of CS exposure, we investigated the effect on lung remodeling and cell signaling of restoring mitochondrial respiratory electron flow using alternative oxidase (AOX), which bypasses the cytochrome segment of the respiratory chain. AOX attenuated CS-induced lung tissue destruction and loss of function in mice exposed chronically to CS for 9 months. It preserved the cell viability of isolated mouse embryonic fibroblasts treated with CS condensate, limited the induction of apoptosis, and decreased the production of reactive oxygen species (ROS). In contrast, the early-phase inflammatory response induced by acute CS exposure of mouse lung, i.e., infiltration by macrophages and neutrophils and adverse signaling, was unaffected. The use of AOX allowed us to obtain novel pathomechanistic insights into CS-induced cell damage, mitochondrial ROS production, and lung remodeling. Our findings implicate mitochondrial respiratory inhibition as a key pathogenic mechanism of CS toxicity in the lung. We propose AOX as a novel tool to study CS-related lung remodeling and potentially to counteract CS-induced ROS production and cell damage.