SenNet recommendations for detecting senescent cells in different tissues.

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung.

BACKGROUND: Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) aerosolize an e-liquid composed of propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with tobacco-derived nicotine (TDN) composed of S-nicotine, and tobacco-free/synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently, there is limited knowledge of the potential differences in the toxicity of TFN versus TDN. We hypothesized that exposure of TFN and TDN salts to C57BL/6J mice would result in a differential response in lung inflammation and protease/ antiprotease imbalance. METHODS: Five-week-old male and female C57BL/6J mice were exposed to air, PG/VG, PG/VG with TFN salts (TFN), or PG/VG with TDN salts (TDN) by nose-only exposure. Lung inflammatory cell counts, cytokine/chemokine levels, and matrix metalloproteinase (MMP) protein abundance and activity levels were determined by flow cytometry, ELISA, immunoblotting, and gel zymography, respectively. RESULTS: Exposure to the humectants (PG/VG) alone increased cytokine levels- IL-6, KC, and MCP-1 in the BALF and KC levels in lung homogenate of exposed mice. While no change was observed in the cytokine levels in lung homogenate of TDN aerosol exposed mice, exposure to TFN aerosols resulted in an increase in KC levels in the lungs of these mice compared to air controls. Interestingly, exposure to TDN aerosols increased MMP-9 protein abundance in the lungs of female mice, while exposure to TFN aerosol showed no change. The metabolism of nicotine or the clearance of cotinine for TFN exposure may differ from that for TDN. CONCLUSION: Exposure to humectants, PG/VG alone, induces an inflammatory response in C57BL/6J mice. TFN and TDN salts show distinct changes in inflammatory responses and lung proteases on acute exposures. These data suggest variable toxicological profiles of the two forms of nicotine in vivo. Future work is thus warranted to delineate the harmful effects of synthetic/natural nicotine with humectants to determine the potential toxicological risks for users.

Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium.

BACKGROUND: Electronic cigarette (e-cig) vaping has increased in the past decade in the US, and e-cig use is misleadingly marketed as a safe cessation for quitting smoking. The main constituents in e-liquid are humectants, such as propylene glycol (PG) and vegetable glycerine (VG), but different flavoring chemicals are also used. However, the toxicology profile of flavored e-cigs in the pulmonary tract is lacking. We hypothesized that menthol and tobacco-flavored e-cig (nicotine-free) exposure results in inflammatory responses and dysregulated repair in lung fibroblast and epithelium. METHOD: We exposed lung fibroblast (HFL-1) and epithelium (BEAS-2B) to Air, PG/VG, menthol flavored, or tobacco-flavored e-cig, and determined the cytotoxicity, inflammation, and wound healing ability in 2D cells and 3D microtissue chip models. RESULTS: After exposure, HFL-1 showed decreased cell number with increased IL-8 levels in the tobacco flavor group compared to air. BEAS-2B also showed increased IL-8 secretion after PG/VG and tobacco flavor exposure, while menthol flavor exposure showed no change. Both menthol and tobacco-flavored e-cig exposure showed decreased protein abundance of type 1 collagen α 1 (COL1A1), α-smooth-muscle actin (αSMA), and fibronectin as well as decreased gene expression level of αSMA (Acta2) in HFL-1. After tobacco flavor e-cig exposure, HFL-1 mediated wound healing and tissue contractility were inhibited. Furthermore, BEAS-2B exposed to menthol flavor showed significantly decreased tight junction gene expressions, such as CDH1, OCLN, and TJP1. CONCLUSION: Overall, tobacco-flavored e-cig exposure induces inflammation in both epithelium and fibroblasts, and tobacco-flavored e-cig inhibits wound healing ability in fibroblasts.

A review of the toxicity of ingredients in e-cigarettes, including those ingredients having the FDA's "Generally Recognized as Safe (GRAS)" regulatory status for use in food.

INTRODUCTION: Some firms and marketers of electronic cigarettes (e-cigarettes; a type of electronic nicotine delivery system (ENDS)) and refill liquids (e-liquids) have made claims about the safety of ingredients used in their products based on the term "GRAS or Generally Recognized As Safe" (GRAS). However, GRAS is a provision within the definition of a food additive under section 201(s) (21 U.S.C. 321(s)) of the U.S. Federal Food Drug and Cosmetic Act (FD&C Act). Food additives and GRAS substances are by the FD&C Act definition intended for use in food, thus safety is based on oral consumption; the term GRAS cannot serve as an indicator of the toxicity of e-cigarette ingredients when aerosolized and inhaled (i.e., vaped). There is no legal or scientific support for labeling e-cigarette product ingredients as "GRAS". This review discusses our concerns with the GRAS provision being applied to e-cigarette products and provides examples of chemical compounds that have been used as food ingredients but have been shown to lead to adverse health effects when inhaled. The review provides scientific insight into the toxicological evaluation of e-liquid ingredients and their aerosols to help determine the potential respiratory risks associated with their use in e-cigarettes. IMPLICATIONS: The rise in prevalence of e-cigarette use and emerging evidence of adverse effects, particularly on lung health, warrant assessing all aspects of e-cigarette toxicity. One development is manufacturers' stated or implied claims of the safety of using e-cigarette products containing ingredients determined to be "Generally Recognized As Safe" (GRAS) for use in food. Such claims, typically placed on e-cigarette product labels and used in marketing, are unfounded, as pointed out by the United States Food and Drug Administration (FDA)1 and the Flavor and Extract Manufacturers Association (FEMA)2. Assessment of inhalation health risks of all ingredients used in e-liquids, including those claimed to be GRAS, is warranted.

Chemical and physiological interactions between e-liquid constituents: cause for concern?

Studies of Electronic Nicotine Delivery Systems (ENDS) toxicity have largely focused on individual components such as flavour additives, base e-liquid ingredients (propylene glycol, glycerol), device characteristics (eg, model, components, wattage), use behaviour, etc. However, vaping involves inhalation of chemical mixtures and interactions between compounds can occur that can lead to different toxicities than toxicity of the individual components. Methods based on the additive toxicity of individual chemical components to estimate the health risks of complex mixtures can result in the overestimation or underestimation of exposure risks, since interactions between components are under-investigated. In the case of ENDS, the potential of elevated toxicity resulting from chemical reactions and interactions is enhanced due to high operating temperatures and the metallic surface of the heating element. With the recent availability of a wide range of e-liquid constituents and popularity of do-it-yourself creation of e-liquid mixtures, the need to understand chemical and physiological impacts of chemical combinations in ENDS e-liquids and aerosols is immediate. There is a significant current knowledge gap concerning how specific combinations of ENDS chemical ingredients result in synergistic or antagonistic interactions. This commentary aims to review the current understanding of chemical reactions between e-liquid components, interactions between additives, chemical reactions that occur during vaping and aerosol properties and biomolecular interactions, all of which may impact physiological health.

Novel Δ8-Tetrahydrocannabinol Vaporizers Contain Unlabeled Adulterants, Unintended Byproducts of Chemical Synthesis, and Heavy Metals.

Cannabis e-cigarettes containing Δ8-tetrahydrocannabinol (Δ8-THC) produced synthetically from hemp-derived cannabidiol (CBD) have recently risen in popularity as a legal means of cannabis consumption, but questions surrounding purity and unlabeled additives have created doubts of their safety. Herein, NMR, GC-MS, and ICP-MS were used to analyze major components of 27 products from 10 brands, and it was determined none of these had accurate Δ8-THC labeling, 11 had unlabeled cutting agents, and all contained reaction side-products including olivetol, Δ4(8)-iso-tetrahydrocannabinol, 9-ethoxyhexahydrocannabinol, Δ9-tetrahydrocannabinol (Δ9-THC), heavy metals, and a novel previously undescribed cannabinoid, iso-tetrahydrocannabifuran.

Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment.

Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model. Measurements and Main Results: Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin's protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (-0.92%; 95% confidence interval [CI], -1.7% to -0.14%; P = 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P = 0.01). Conclusions: Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study.

BACKGROUND: Oral nicotine pouches are a new form of tobacco-free nicotine products launched in recent years with a variety of flavors. OBJECTIVE: This study aims to examine the public perceptions and discussions of oral nicotine pouches on Reddit, a popular social media platform for sharing user experiences. METHODS: Between February 15, 2019, and February 12, 2021, a total of 2410 Reddit posts related to oral nicotine pouches were obtained over a 2-year period. After the removal of unrelated or commercial posts, 653 Reddit posts related to oral nicotine pouches remained. Topics and sentiments related to oral nicotine pouches on Reddit were hand coded. RESULTS: The number of Reddit posts related to oral nicotine pouches increased during the study period. Content analysis showed that the most popular topic was "sharing product information and user experience" (366/653, 56%), in which sharing oral nicotine pouch products and user experiences were dominant. The next popular topic was "asking product-related questions" (product properties and product recommendations; 115/653, 17.6%), followed by "quitting nicotine products" such as vaping or smoking through use of oral nicotine pouches or quitting the oral nicotine pouches themselves (83/653, 12.7%) and "discussing oral nicotine pouch-related health" symptoms or concerns related to oral nicotine pouches (74/653, 11.3%). The least popular topic was "legality and permissions" related to oral nicotine pouches (15/653, 2.3%). In addition, a greater number of Reddit posts described positive attitudes compared to negative attitudes toward oral nicotine pouches (354/653, 54.2% vs 101/653, 15.5%; P<.001). CONCLUSIONS: Reddit posts overall had a positive attitude toward oral nicotine pouches and users were actively sharing product and user experiences. Our study provides the first insight on up-to-date oral nicotine pouch discussions on social media.

Recent updates on biomarkers of exposure and systemic toxicity in e-cigarette users and EVALI.

Electronic nicotine delivery systems (ENDS), or e-cigarettes, are emerging tobacco products that produce aerosols by heating e-liquids, which most often consist of propylene glycol and vegetable glycerin along with various flavoring compounds, bypassing the combustion that occurs in the use of traditional tobacco cigarettes. These products have seen a drastic increase in popularity in recent years both as smoking cessation devices as well as among younger generations, due in large part to the widespread perception among consumers that e-cigs are significantly less harmful to health than traditional tobacco cigarettes. Due to the novelty of ENDS as well as their rapidly increasing use, research into biomarkers of e-cig exposure and toxicity have lagged behind their popularity, leaving important questions about their potential toxicity unanswered. Research into potential biomarkers of acute and chronic e-cig use, and e-cigarette- or vaping-associated lung injury is necessary for informing both clinical and regulatory decision-making. We aim to provide an updated review of recent research into potential circulating, genomic, transcriptomic, and epigenetic biomarkers of exposure to and toxicity of e-cigs. We additionally highlight research areas that warrant additional study to gain a better understanding of health risks associated with ENDS use, as well as to provide validation of existing data and methods for measuring and analyzing e-cig-associated biomarkers in human and animal biofluids, tissues, and cells. This review also highlights ongoing efforts within the WNY Center for Research on Flavored Tobacco for research into novel biomarkers in extracellular vesicles that may be associated with short- and long-term ENDS use.

Cannabis Vaping: Existing and Emerging Modalities, Chemistry, and Pulmonary Toxicology.

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.

Acute Effects of Heated Tobacco Product (IQOS) Aerosol Inhalation on Lung Tissue Damage and Inflammatory Changes in the Lungs.

INTRODUCTION: Emerging heated tobacco products (HTPs) were designed to reduce exposure to toxicants from cigarette smoke (CS) by avoiding burning tobacco and instead heating tobacco. We studied the effects of short-term inhalation of aerosols emitted from HTP called IQOS, on lung damage and immune-cell recruitment to the lungs in mice. METHODS: Numerous markers of lung damage and inflammation including albumin and lung immune-cell infiltrates, proinflammatory cytokines, and chemokines were quantified in lungs and bronchoalveolar (BAL) fluid from IQOS, CS, or air-exposed (negative control) mice. RESULTS: Importantly, as a surrogate marker of lung epithelial-cell damage, we detected significantly increased levels of albumin in the BAL fluid of both HTP- and CS-exposed mice compared with negative controls. Total numbers of leukocytes infiltrating the lungs were equivalent following both IQOS aerosols and CS inhalation and significantly increased compared with air-exposed controls. We also observed significantly increased numbers of CD4+IL-17A+ T cells, a marker of a T-cell immune response, in both groups compared with air controls; however, numbers were the highest following CS exposure. Finally, the numbers of CD4+RORγt+ T cells, an inflammatory T-cell subtype expressing the transcription factor that is essential for promoting differentiation into proinflammatory Th17 cells, were significantly augmented in both groups compared with air-exposed controls. Levels of several cytokines in BAL were significantly elevated, reflecting a proinflammatory milieu. CONCLUSIONS: Our study demonstrates that short-term inhalation of aerosols from IQOS generates damage and proinflammatory changes in the lung that are substantially similar to that elicited by CS exposure. IMPLICATIONS: Exposure of mice to IQOS, one of the candidate modified-risk tobacco products, induces inflammatory immune-cell accumulation in the lungs and augments the levels of proinflammatory cytokines and chemokines in the BAL fluid. Such an exacerbated pulmonary proinflammatory microenvironment is associated with lung epithelial-cell damage in IQOS-exposed mice, suggesting a potential association with the impairment of lung function.

p16-3MR: A Novel Model to Study Cellular Senescence in Cigarette Smoke-Induced Lung Injuries.

Cellular senescence and lung aging are associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). COPD progresses with aging, and chronic smoking is the key susceptibility factor in lung pathological changes concurrent with mitochondrial dysfunction and biological aging. However, these processes involving cigarette smoke (CS)-mediated lung cellular senescence are difficult to distinguish. One of the impediments to studying cellular senescence in relation to age-related lung pathologies is the lack of a suitable in vivo model. In view of this, we provide evidence that supports the suitability of p16-3MR mice to studying cellular senescence in CS-mediated and age-related lung pathologies. p16-3MR mice have a trimodal reporter fused to the promoter of the p16INK4a gene that enables detection, isolation, and selective elimination of senescent cells, thus making them a suitable model to study cellular senescence. To determine their suitability in CS-mediated lung pathologies, we exposed young (12-14 months) and old (17-20 months) p16-3MR mice to 30 day CS exposure and studied the expression of senescent genes (p16, p21, and p53) and SASP-associated markers (MMP9, MMP12, PAI-1, and FN-1) in air- and CS-exposed mouse lungs. Our results showed that this model could detect cellular senescence using luminescence and isolate cells undergoing senescence with the help of tissue fluorescence in CS-exposed young and old mice. Our results from the expression of senescence markers and SASP-associated genes in CS-exposed young and old p16-3MR mice were comparable with increased lung cellular senescence and SASP in COPD. We further showed alteration in the; (i) tissue luminescence and fluorescence, (ii) mRNA and protein expressions of senescent markers and SASP genes, and (iii) SA-ß-gal activity in CS-exposed young and old p16-3MR mice as compared to their air controls. Overall, we showed that p16-3MR is a competent model for studying the cellular senescence in CS-induced pathologies. Hence, the p16-3MR reporter mouse model may be used as a novel tool for understanding the pathobiology of cellular senescence and other underlying mechanisms involved in COPD and fibrosis.

Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients.

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration. Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets.

Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice.

Electronic-cigarette (e-cig) vaping is a serious concern, as many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on adult offspring, especially on extracellular-matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cig aerosols on the adult offspring of both sexes, with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosols with or without nicotine, throughout gestation, and lungs were collected from adult male and female offspring. Compared with the air-exposed control group, female mice exposed to e-cig aerosols, with or without nicotine, demonstrated increased lung protein abundance of LEF-1 (lymphoid enhancer-binding factor 1), fibronectin, and E-cadherin, whereas altered E-cadherin and PPARγ (peroxisome proliferator-activated receptor γ) levels were observed only in males exposed to e-cig aerosols with nicotine. Moreover, lipogenic and myogenic mRNAs were dysregulated in adult offspring in a sex-dependent manner. PAI-1 (plasminogen activator inhibitor-1), one of the ECM regulators, was significantly increased in females exposed prenatally to e-cig aerosols with nicotine and in males exposed to e-cig aerosols compared with control animals exposed to air. MMP9 (matrix metalloproteinase 9), a downstream target of PAI-1, was downregulated in both sexes exposed to e-cig aerosols with nicotine. No differences in lung histology were observed among any of the treatment groups. Overall, adult mice exposed prenatally to e-cig aerosols could be predisposed to developing pulmonary disease later in life. Thus, these findings suggest that vaping during pregnancy is unsafe and increases the propensity for later-life interstitial lung diseases.

E-cigarette-induced pulmonary inflammation and dysregulated repair are mediated by nAChR α7 receptor: role of nAChR α7 in SARS-CoV-2 Covid-19 ACE2 receptor regulation.

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.

Home smoking and vaping policies among US adults: results from the Population Assessment of Tobacco and Health (PATH) study, wave 3.

We examined the prevalence of home smoking and vaping restrictions among US adults, and compared home policy differences for smoking and vaping among vapers, smokers, and dual users. Secondary data from the Population Assessment of Tobacco and Health (PATH) Study Wave 3 (2015-2016) with 28,148 adults were analyzed using weighted multivariable logistic regression models that account for complex sampling design to compare differences in home policies among non-users, vapers only, smokers only, and dual users. Compared to never-users, current vapers who were ex-smokers and dual users were more likely to allow home vaping (aOR = 11.06, 95% CI: 8.04-15.21; aOR = 6.44, 95% CI: 5.01-8.28) and smoking (aOR = 1.62, 95% CI: 1.19-2.22; aOR = 3.58, 95% CI: 2.88-4.45). Current smokers were more likely to allow vaping (aOR = 3.53, 95% CI: 3.06-4.06) and smoking (aOR = 4.27, 95% CI: 3.73-4.89) inside the home than never-users. Current vapers who never smoked were more likely to allow vaping inside the home than never-users (aOR = 2.45, 95% CI: 1.53-3.93). Vapers reported much lower rates of vape-free home policies relative to both their smoke-free home policies and to vape-free home policies among smokers. Vapers may be using e-cigarettes in hopes of harm reduction, but interpreting "harm reduction" as safe, thus exposing non-users in their homes to second- and thirdhand aerosols. This underscores the need to healthcare providers to extend intervention with vapers to include implementing vape-free home policies.

Use of Electronic Cigarettes and Self-Reported Chronic Obstructive Pulmonary Disease Diagnosis in Adults.

INTRODUCTION: Electronic cigarette (e-cigarette) use (vaping) has increased in recent years. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death associated with smoking. AIMS AND METHODS: Based on 2016 and 2017 Behavioral Risk Factor Surveillance System national survey data on 891 242 adult participants who indicated their smoking and vaping status, the cross-sectional association of vaping with self-reported COPD diagnosis was investigated, using univariable and multivariable weighted logistic regression models. RESULTS: Compared to never users, while dual users showed the highest association with self-reported COPD diagnosis (adjusted odds ratio [aOR] = 4.39; 95% confidence interval [CI] = 3.98 to 4.85), current vapers who were either ex-smokers or never smoked showed significantly higher association with self-reported COPD diagnosis (aOR = 3.24; 95% CI = 2.78 to 3.78 and aOR = 1.47; 95% CI = 1.01 to 2.12, respectively). Current vapers who were ex-smokers showed higher association with self-reported COPD diagnosis than ex-smokers who do not vape (aOR = 1.27; 95% CI = 1.09 to 1.48). Dual users showed higher association with self-reported COPD diagnosis than current smokers who do not vape (aOR = 1.16; 95% CI = 1.05 to 1.27). Ex-smokers showed significantly less association with self-reported COPD diagnosis (aOR = 0.67; 95% CI = 0.64 to 0.71) than current smokers. Current vapers who were either ex-smokers or never smoked had less association with self-reported COPD diagnosis compared to current smokers, with aOR = 0.85 (95% CI = 0.73 to 0.99) and aOR = 0.39 (95% CI = 0.27 to 0.56). CONCLUSIONS: Vaping is significantly associated with self-reported COPD diagnosis in adults, even among vapers who never smoked. Whether there is a benefit for COPD of switching from smoking to vaping requires study of the long-term effects of vaping. IMPLICATIONS: With the increase of e-cigarette use in recent years, the health effects of e-cigarettes need to be investigated. While several studies have examined the association of vaping with respiratory symptoms among adolescents, little is known about the association of vaping with susceptibility to COPD among US adults. Using cross-sectional national survey data in adults, our study showed that vaping was significantly associated with self-reported COPD diagnosis. Although our data did not establish the causal relationship between vaping and self-reported COPD diagnosis, this study raises concerns about the observed association between vaping and self-reported COPD diagnosis.

Cross-Sectional Association Between Exclusive and Concurrent Use of Cigarettes, ENDS, and Cigars, the Three Most Popular Tobacco Products, and Wheezing Symptoms Among U.S. Adults.

INTRODUCTION: This study assessed the association of exclusive and concurrent use of cigarettes, electronic nicotine delivery systems (ENDS), and cigars with ever and past 12-month wheezing symptoms among a nationally representative sample of US adult current tobacco users. METHODS: Cross-sectional data from the Population Assessment of Tobacco and Health (PATH) Study Wave 3 (W3) were used. The weighted prevalence of self-reported ever and past 12-month wheezing symptoms for noncurrent users compared with users of cigarettes, ENDS, cigars, and any combination of these products (polytobacco use of these tobacco products) were presented for 28 082 adults. The cross-sectional association of tobacco use with self-reported wheezing symptoms was assessed using weighted multivariable and ordinal logistic regression with consideration of complex sampling design. RESULTS: Significantly higher odds of ever had wheezing or whistling in the chest at any time in the past were observed among current cigarette (adjusted odds ratio: 2.62, 95% confidence intervals [CI]: 2.35, 2.91), ENDS (1.49, 95% CI: 1.14, 1.95), and polytobacco users (2.67, 95% CI: 2.26, 3.16) compared with noncurrent users. No associations were seen for cigar use. Polytobacco use was associated with a higher odds of ever wheezing when compared with exclusive ENDS (1.61, 95% CI: 1.19, 2.17) and exclusive cigar use (2.87, 95% CI: 1.93, 4.26), but not exclusive use of cigarettes. CONCLUSIONS: Ever wheezing is associated with the use of cigarettes, ENDS, and polytobacco use of cigarettes, ENDS, and/or cigars, but not cigar use. The association of polytobacco use and wheezing appears to be driven by cigarette use. IMPLICATIONS: Cross-sectional associations with ever and past 12-month wheezing symptoms were found to be the strongest among cigarette users, exclusively or in combination. Future longitudinal research is needed to better understand how cigarette use interacts with other tobacco and nicotine products and contributes to respiratory symptoms.

Association of smoking and electronic cigarette use with wheezing and related respiratory symptoms in adults: cross-sectional results from the Population Assessment of Tobacco and Health (PATH) study, wave 2.

BACKGROUND: Wheezing is a symptom of potential respiratory disease and known to be associated with smoking. Electronic cigarette use ('vaping') has increased exponentially in recent years. This study examined the cross-sectional association of vaping with wheezing and related respiratory symptoms and compare this association with smokers and dual users. METHODS: The Population Assessment of Tobacco and Health study wave 2 data collected from October 2014 to October 2015 with 28 171 adults were used. The cross-sectional association of vaping with self-reported wheezing and related respiratory symptoms relative to smokers and dual users of tobacco and electronic cigarettes were studied using multivariable logistic and cumulative logistic regression models with consideration of complex sampling design. RESULTS: Among the 28 171 adult participants, 641 (1.2%) were current vapers who used e-cigarettes exclusively, 8525 (16.6%) were current exclusive smokers, 1106 (2.0%) were dual users and 17 899 (80.2%) were non-users. Compared with non-users, risks of wheezing and related respiratory symptoms were significantly increased in current vapers (adjusted OR (aOR)=1.67, 95% CI: 1.23 to 2.15). Current vapers had significantly lower risk in wheezing and related respiratory symptoms compared with current smokers (aOR=0.68, 95% CI: 0.53 to 0.87). No significant differences were found between dual users and current smokers in risk of wheezing and related respiratory symptoms (aOR=1.06, 95% CI: 0.91 to 1.24). CONCLUSIONS: Vaping was associated with increased risk of wheezing and related respiratory symptoms. Current vapers had lower risk in wheezing and related respiratory symptoms than current smokers or dual users but higher than non-users. Both dual use and smoking significantly increased the risk of wheezing and related respiratory symptoms.

Systemic biomarkers of inflammation, oxidative stress and tissue injury and repair among waterpipe, cigarette and dual tobacco smokers.

BACKGROUND: Waterpipe tobacco (WPT) smoking is associated with deleterious effects on cardio-pulmonary systems which may have adverse repercussions in pathophysiology and progression of chronic lung and cardiovascular diseases. We compared the biomarkers of systemic inflammation, lipid mediators, injury/repair and oxidative stress between groups of non-smokers (NS), exclusive WPT smokers (WPS), exclusive cigarette smokers (CS) and dual WPS and CS (DS). METHODS: Two cohorts were recruited. Cohort I consisted of WPS (n=12), CS (n=26), DS (n=10) and NS (n=25). Cohort II consisted of WPS (n=33) and NS (n=24). Plasma and urine samples were collected and analysed for various systemic biomarkers. RESULTS: Compared with NS, plasma levels of inflammatory mediators (interleukin (IL)-6, IL-8, IL1ß and tumor necrosis factor-α) were significantly higher in WPS and CS, and were further augmented in DS. Endothelial biomarkers (intracellular adhesion molecule-1, prostaglandin E-2 and metalloproteinase-9) were significantly higher in CS. Most notably, pro-resolving lipid mediator (resolvin E1) and biomarkers of immunity, tissue injury, and repair were significantly lower in WPS and CS. Urinary levels of 8-isoprostane were significantly higher in all smoking groups in cohort I, while 8-isoprostane, myeloperoxidase, receptor for advanced glycation end products (RAGE), En-RAGE and matrix metalloproteinase-9 were significantly higher in all smoking groups in cohort II. CONCLUSIONS: Biomarkers of inflammation, oxidative stress, immunity, tissue injury and repair were elevated in WPS and CS groups. Furthermore, concurrent use of WPT and cigarettes is more harmful than cigarette or WPT smoking alone. These data may help inform the public and policy-makers about the dangers of WPT smoking and dual use of tobacco products.