A neuroglobin-based high-affinity ligand trap reverses carbon monoxide-induced mitochondrial poisoning.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC-treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 µm) and nitric oxide (100 µm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 µm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

Changes in Cigarettes per Day and Biomarkers of Exposure Among US Adult Smokers in the Population Assessment of Tobacco and Health Study Waves 1 and 2 (2013-2015).

INTRODUCTION: Some studies have found some reduction in tobacco exposure and tobacco-related disease risk with decreased numbers of cigarettes smoked per day (CPD), but biomarker of exposure estimates by change in CPD are generally unavailable for the US population. METHODS: We analyzed biomarker of exposure data by smoking status from over 1100 adult exclusive daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study who were either exclusive daily smokers or had quit tobacco use entirely at Wave 2. Wave 1 smoking categories consisted of "very light" (1-4 CPD), "light" (5-9 CPD), "moderate" (10-19 CPD), and "heavy" (20+ CPD), and Wave 2 categories were "quitters" (stopped smoking entirely), exclusive cigarette "reducers" (CPD decreased ≥ 50%), "maintainers" (CPD within 50%-150% of Wave 1 value), and "increasers" (CPD increased ≥ 50%). RESULTS: Complete quitters had significantly lower levels of TNE-2, NNAL, NNN, 2-Fluorene, HPMA, CYMA, and MHB3 at Wave 2 for all Wave 1 CPD categories, and decreases were often large. Moderate "reducers" had lower levels of NNAL and 1-Hydroxypyrene at Wave 2, and heavy "reducers" had lower levels of NNAL, 2-Fluorene, and MHB3. Light "increasers" had higher levels of TNE-2, NNAL, 2-Fluorene, CYMA, and cadmium at Wave 2, and heavy "increasers" had higher levels of NNAL and HPMA. CONCLUSIONS: Smoking "reducers" and "increasers" had changes in some biomarker of tobacco exposure levels, but reductions were much greater and more consistent for complete quitters. IMPLICATIONS: PATH longitudinal cohort study data show that some exclusive daily cigarette smokers increase or decrease CPD over time. These differences may result in moderate changes in the levels of some biomarkers such as NNAL. Even so, however, reductions in biomarker levels are much greater with complete smoking cessation.

US Adult Cigar Smoking Patterns, Purchasing Behaviors, and Reasons for Use According to Cigar Type: Findings From the Population Assessment of Tobacco and Health (PATH) Study, 2013-2014.

Introduction: The US cigar market is diverse, yet until recently most research studies and tobacco surveillance systems have not reported behavioral and related outcomes by cigar type. Methods: The 2013-2014 Population Assessment of Tobacco and Health Study collected data separately for filtered cigars (FCs), cigarillos, and traditional cigars, which were further distinguished as premium or nonpremium. Descriptive statistics for adult established current smokers of each cigar type and cigarettes were calculated for demographic characteristics, tobacco use patterns, purchasing behaviors and reasons for use. Adjusted prevalence ratios (APRs) using a marginal predictions approach with logistic regression assessed correlates of dual cigar and cigarette smoking. Results: Age, sex, race/ethnicity, education level, and poverty status of smokers varied according to cigar type. Daily cigar smoking prevalence and number of cigars smoked per day were higher for FCs (37.3%; median: 1.6 cigars/day, respectively), than all other cigar types (6.7%-25.3%, all p < .01; 0.1-0.4 cigars/day, all p < .01, respectively); daily smoking and cigars per day were similar for nonpremium cigars and cigarillos (p = .11; p = .33, respectively). Cigarette smoking was twice as common among smokers of nonpremium cigars, cigarillos, and FCs (58.0%-66.0%) than among premium cigars (29.9%). Among current cigar smokers, FC smokers (APR = 1.23, 95% confidence interval [CI] = 1.09-1.39), other tobacco product users (APR = 1.27, 95% CI = 1.15-1.41), and those with a GED/high school diploma or less (APR = 1.20, 95% CI = 1.09-1.33) were more likely to also smoke cigarettes. Conclusion: User characteristics, cigar smoking patterns, and dual smoking with cigarettes varied by cigar type highlighting the importance of adequately describing the cigar type studied and, where appropriate, differentiating results by cigar type. Implications: Despite the diversity of the cigar market place, historically many research studies and tobacco surveillance systems have treated cigars as a single product type. This study describes similarities and differences in the user characteristics, tobacco use patterns, and purchasing behaviors of premium, nonpremium, cigarillo, and filtered cigar smokers. To enhance tobacco regulatory science, sufficient descriptions of the cigar type(s) studied and, where appropriate, differentiation of the particular cigar type(s) studied should be undertaken to improve the interpretation of study findings, understanding of cigar use patterns and related behaviors and future approaches to reducing cigar-attributable morbidity and mortality.

Tobacco Product Use Among Adults - United States, 2015.

Tobacco use remains the leading cause of preventable disease and death in the United States (1). Despite declining cigarette smoking prevalence among U.S. adults, shifts in the tobacco product landscape have occurred in recent years (2,3). Previous estimates of tobacco product use among U.S. adults were obtained from the National Adult Tobacco Survey, which ended after the 2013-2014 cycle. This year, CDC and the Food and Drug Administration (FDA) assessed the most recent national estimates of tobacco product use among adults aged ≥18 years using, for the first time, data from the 2015 National Health Interview Survey (NHIS), an annual, nationally representative, in-person survey of the noninstitutionalized U.S. civilian population. The 2015 NHIS adult core questionnaire included 33,672 adults aged ≥18 years, reflecting a 55.2% response rate. Data were weighted to adjust for differences in selection probability and nonresponse, and to provide nationally representative estimates. In 2015, 20.1 % of U.S. adults currently (every day or some days) used any tobacco product, 17.6% used any combustible tobacco product, and 3.9% used ≥2 tobacco products. By product, 15.1% of adults used cigarettes; 3.5% used electronic cigarettes (e-cigarettes); 3.4% used cigars, cigarillos, or filtered little cigars; 2.3% used smokeless tobacco; and 1.2% used regular pipes, water pipes, or hookahs.* Current use of any tobacco product was higher among males; persons aged <65 years; non-Hispanic American Indian/Alaska natives (AI/AN), whites, blacks, and persons of multiple races; persons living in the Midwest; persons with a General Educational Development (GED) certificate; persons with annual household income of <$35,000; persons who were single, never married, or not living with a partner or divorced, separated, or widowed; persons who were insured through Medicaid or uninsured; persons with a disability; and persons who identified as lesbian, gay, or bisexual (LGB). Current use of any tobacco product was 47.2% among adults with serious psychological distress compared with 19.2% among those without serious psychological distress. Proven population-level interventions that focus on the diversity of tobacco product use are important to reducing tobacco-related disease and death in the United States (1).

Tobacco Use Among Middle and High School Students--United States, 2011-2015.

Tobacco use is the leading cause of preventable disease and death in the United States; if current smoking rates continue, 5.6 million Americans aged <18 years who are alive today are projected to die prematurely from smoking-related disease. Tobacco use and addiction mostly begin during youth and young adulthood. CDC and the Food and Drug Administration (FDA) analyzed data from the 2011-2015 National Youth Tobacco Surveys (NYTS) to determine the prevalence and trends of current (past 30-day) use of seven tobacco product types (cigarettes, cigars, smokeless tobacco, electronic cigarettes [e-cigarettes], hookahs [water pipes used to smoke tobacco], pipe tobacco, and bidis [small imported cigarettes wrapped in a tendu leaf]) among U.S. middle (grades 6-8) and high (grades 9-12) school students. In 2015, e-cigarettes were the most commonly used tobacco product among middle (5.3%) and high (16.0%) school students. During 2011-2015, significant increases in current use of e-cigarettes and hookahs occurred among middle and high school students, whereas current use of conventional tobacco products, such as cigarettes and cigars decreased, resulting in no change in overall tobacco product use. During 2014-2015, current use of e-cigarettes increased among middle school students, whereas current use of hookahs decreased among high school students; in contrast, no change was observed in use of hookahs among middle school students, use of e-cigarettes among high school students, or use of cigarettes, cigars, smokeless tobacco, pipe tobacco, or bidis among middle and high school students. In 2015, an estimated 4.7 million middle and high school students were current tobacco product users, and, therefore, continue to be exposed to harmful tobacco product constituents, including nicotine. Nicotine exposure during adolescence, a critical period for brain development, can cause addiction, might harm brain development, and could lead to sustained tobacco product use among youths. Comprehensive and sustained strategies are warranted to prevent and reduce the use of all tobacco products among U.S. youths.

Flavored Tobacco Product Use Among Middle and High School Students--United States, 2014.

The 2009 Family Smoking Prevention and Tobacco Control Act prohibits "characterizing flavors" (e.g., candy, fruit, and chocolate) other than tobacco and menthol in cigarettes; however, characterizing flavors are not currently prohibited in other tobacco products. Analyses of retail sales data suggest that U.S. consumption of flavored noncigarette tobacco products, including flavored cigars and flavored e-cigarettes, has increased in recent years. There is growing concern that widely marketed varieties of new and existing flavored tobacco products might appeal to youths (2) and could be contributing to recent increases in the use of tobacco products, including e-cigarettes and hookah, among youths. CDC and the Food and Drug Administration (FDA) analyzed data from the 2014 National Youth Tobacco Survey (NYTS) to determine the prevalence of past 30 day use (current use) of flavored e-cigarette, hookah tobacco, cigar, pipe tobacco or smokeless tobacco products, and menthol cigarettes among middle and high school students, and the proportion of current tobacco product users who have used flavored products. An estimated 70.0% (3.26 million) of all current youth tobacco users had used at least one flavored tobacco product in the past 30 days. Among current users, 63.3%, (1.58 million) had used a flavored e-cigarette, 60.6%, (1.02 million) had used flavored hookah tobacco, and 63.5% (910,000) had used a flavored cigar in the past 30 days. Given the millions of current youth tobacco users, it is important for comprehensive tobacco prevention and control strategies to address all forms of tobacco use, including flavored tobacco products, among U.S. youths.

Frequency of Tobacco Use Among Middle and High School Students--United States, 2014.

The use of tobacco products during adolescence increases the risk for adverse health effects and lifelong nicotine addiction. In 2014, an estimated 4.6 million middle and high school students were current users of any tobacco product, of whom an estimated 2.2 million were current users of two or more types of tobacco products. Symptoms of nicotine dependence are increased for multiple tobacco product users compared with single-product users. CDC and the Food and Drug Administration (FDA) analyzed data from the 2014 National Youth Tobacco Survey (NYTS) to determine how frequently (the number of days in the preceding 30 days) U.S. middle school (grades 6­8) and high school (grades 9­12) students used cigarettes, e-cigarettes, cigars, and smokeless tobacco products. Among current users (≥1 day during the preceding 30 days) in high school, frequent use (≥20 days during the preceding 30 days) was most prevalent among smokeless tobacco users (42.0%), followed by cigarette smokers (31.6%), e-cigarette users (15.5%), and cigar smokers (13.1%); a similar pattern was observed for those who used during all 30 days. Among current users in middle school, frequent use was greatest among smokeless tobacco users (29.2%), followed by cigarette smokers (20.0%), cigar smokers (13.2%) and e-cigarette users (11.8%). Current use of two or more types of tobacco products was common, even among students who used tobacco products 1­5 days during the preceding 30 days: 77.3% for cigar smokers, 76.9% for cigarette smokers, 63.4% for smokeless tobacco users, and 54.8% for e-cigarettes users. Preventing youths from initiating the use of any tobacco product is important to tobacco use prevention and control strategies in the United States. Monitoring the frequency and patterns of tobacco use among youths, including the use of two or more tobacco products, is important to inform evidence-based interventions to prevent and reduce all forms of tobacco use among youths.

Tobacco use among middle and high school students - United States, 2011-2014.

Tobacco use and addiction most often begin during youth and young adulthood. Youth use of tobacco in any form is unsafe. To determine the prevalence and trends of current (past 30-day) use of nine tobacco products (cigarettes, cigars, smokeless tobacco, e-cigarettes, hookahs, tobacco pipes, snus, dissolvable tobacco, and bidis) among U.S. middle (grades 6-8) and high school (grades 9-12) students, CDC and the Food and Drug Administration (FDA) analyzed data from the 2011-2014 National Youth Tobacco Surveys (NYTS). In 2014, e-cigarettes were the most commonly used tobacco product among middle (3.9%) and high (13.4%) school students. Between 2011 and 2014, statistically significant increases were observed among these students for current use of both e-cigarettes and hookahs (p<0.05), while decreases were observed for current use of more traditional products, such as cigarettes and cigars, resulting in no change in overall tobacco use. Consequently, 4.6 million middle and high school students continue to be exposed to harmful tobacco product constituents, including nicotine. Nicotine exposure during adolescence, a critical window for brain development, might have lasting adverse consequences for brain development, causes addiction, and might lead to sustained tobacco use. For this reason, comprehensive and sustained strategies are needed to prevent and reduce the use of all tobacco products among youths in the United States.

E-Cigarette Market Trends in Traditional U.S. Retail Channels, 2012-2013.

INTRODUCTION: E-cigarette sales continue to increase in the United States. To date, little surveillance research has documented the specific product attributes driving growth. This study uses national market scanner data to describe sales trends in traditional U.S. tobacco retail channels between 2012 and 2013 and identifies product features associated with sales increases. METHODS: Data on e-cigarette sales in convenience stores, drug stores, grocery stores, and mass merchandisers in the United States were obtained from the Nielsen Company. Each product was coded for attributes such as brand, flavor, and unit size. Total sales volume, market share, and percent growth were calculated for various product attributes. RESULTS: E-cigarette sales more than doubled between 2012 and 2013, from $273.6 million to $636.2 million, respectively. Growth was particularly strong in the convenience store channel. Blu eCigs quickly emerged as the best-selling brand and in 2013 constituted nearly half (44.1%) of overall sales. Although fruit-flavored and other flavored products experienced marked growth, unflavored and menthol e-cigarettes overwhelmingly dominated the market. Sales of single unit products (likely disposable e-cigarettes) increased by 216.4%, a much faster rate than multi-unit packs and cartridge refills. CONCLUSIONS: In traditional U.S. retail channels, particularly the convenience store channel, sales of e-cigarettes continue to grow, with brands like blu and disposable products as the likely drivers. Given the rapidly-changing market, expanded surveillance is needed to monitor sales not only in traditional retail locations, but sales online and in specialty "vape shops," as well.

Intentions to smoke cigarettes among never-smoking US middle and high school electronic cigarette users: National Youth Tobacco Survey, 2011-2013.

INTRODUCTION: Electronic cigarette (e-cigarette) use is increasing rapidly, and the impact on youth is unknown. We assessed associations between e-cigarette use and smoking intentions among US youth who had never smoked conventional cigarettes. METHODS: We analyzed data from the nationally representative 2011, 2012, and 2013 National Youth Tobacco Surveys of students in grades 6-12. Youth reporting they would definitely not smoke in the next year or if offered a cigarette by a friend were defined as not having an intention to smoke; all others were classified as having positive intention to smoke conventional cigarettes. Demographics, pro-tobacco advertisement exposure, ever use of e-cigarettes, and ever use of other combustibles (cigars, hookah, bidis, kreteks, and pipes) and noncombustibles (chewing tobacco, snuff, dip, snus, and dissolvables) were included in multivariate analyses that assessed associations with smoking intentions among never-cigarette-smoking youth. RESULTS: Between 2011 and 2013, the number of never-smoking youth who used e-cigarettes increased 3-fold, from 79,000 to more than 263,000. Intention to smoke conventional cigarettes was 43.9% among ever e-cigarette users and 21.5% among never users. Ever e-cigarette users had higher adjusted odds for having smoking intentions than never users (adjusted odds ratio = 1.70, 95% confidence interval = 1.24-2.32). Those who ever used other combustibles, ever used noncombustibles, or reported pro-tobacco advertisement exposure also had increased odds for smoking intentions. CONCLUSION: In 2013, more than a quarter million never-smoking youth used e-cigarettes. E-cigarette use is associated with increased intentions to smoke cigarettes, and enhanced prevention efforts for youth are important for all forms of tobacco, including e-cigarettes.

Preference for flavoured cigar brands among youth, young adults and adults in the USA.

BACKGROUND: While cigarette consumption in the USA continues to decline, cigar consumption has increased. Tobacco-trade publications suggest that flavoured cigars are driving the recent growth in cigar consumption. Limited survey data exist to explore flavoured cigar preferences among youth and adults. METHODS: This study used the 2010-2011 National Survey on Drug Use and Health (NSDUH) and Nielsen market scanner data. The NSDUH sample consisted of 6678 past 30-day cigar smokers who reported smoking a usual brand of cigars. NSDUH contains a measure on usual cigar brand smoked and was merged with Nielsen data to estimate the per cent of each cigar brand's market share that is flavoured. RESULTS: Multivariate analyses indicate that youth, young adults, females, blacks, cigarette smokers, blunt users and daily cigar smokers are significantly more likely to report a usual cigar brand that is flavoured. Preference for a usual brand that produces flavoured cigars decreases significantly with age. CONCLUSIONS: This study finds recent growth in flavoured cigar consumption and preference among youth and young adults for cigar brands that are flavoured. These findings underscore the need to expand monitoring of product attributes as well as individual-level cigar use behaviours captured through population surveillance.

Systematic review of cigar smoking and all cause and smoking related mortality.

BACKGROUND: Cigars are a growing public health concern, given the changes in cigar use patterns in the US and elsewhere since the 1960s. We conducted a systematic review of published studies on current cigar smoking and all-cause and cause-specific mortality risks to inform potential regulatory approaches and future research that would strengthen the body of evidence. METHODS: Using 3 different databases and handsearching, we identified epidemiological studies published prior to June 2014 that examined the association between cigar smoking and all-cause mortality and smoking-related mortality. Detailed study characteristics as well as association-level characteristics, including effect estimates and 95% confidence intervals, were abstracted or calculated from each selected study. RESULTS: A total of 22 studies from 16 different prospective cohorts were identified. Primary cigar smoking (current, exclusive cigar smoking with no history of previous cigarette or pipe smoking) was associated with all cause-mortality, oral cancer, esophageal cancer, pancreatic cancer, laryngeal cancer, lung cancer, coronary heart disease (CHD), and aortic aneurysm. Strong dose trends by cigars per day and inhalation level for primary cigar smoking were observed for oral, esophageal, laryngeal, and lung cancers. Among primary cigar smokers reporting no inhalation, relative mortality risk was still highly elevated for oral, esophageal, and laryngeal cancers. CONCLUSIONS: In summary, cigar smoking carries many of the same health risks as cigarette smoking. Mortality risks from cigar smoking vary by level of exposure as measured by cigars per day and inhalation level and can be as high as or exceed those of cigarette smoking. The body of evidence would be strengthened by future studies that focus on the health effects of primary cigar smoking and incorporate more contemporary and diverse study populations to better reflect the current patterns of cigar use in the US. Ideally, these studies would also collect detailed information on cigar type, exposure level, and biomarkers of exposure and potential harm.

Little filtered cigar, cigarillo, and premium cigar smoking among adults--United States, 2012-2013.

The burden of death and disease from tobacco use in the United States has been caused overwhelmingly by cigarettes and other smoked tobacco products. In the United States, cigarette consumption declined during 2000-2011; however, consumption of cigars more than doubled during the same period. The cigar market includes diverse product types manufactured with a variety of shapes and sizes, filters, tips, flavors, and prices. Although national estimates of cigar consumption have been reported previously, data characterizing who smokes different cigar types are limited. A recent analysis from the 2012-2013 National Adult Tobacco Survey (NATS) found that more than one in 20 U.S. adults smoke cigars "every day," "someday," or "rarely". This report expands upon those findings, using data from the 2012-2013 NATS to further characterize cigar smokers by the usual type of cigar smoked using the following categories: little filtered cigars (LFCs), cigarillos/other mass market cigars (cigarillos/MMCs), and premium cigars. The findings indicate that among U.S. adults who smoke cigars, 61.8% usually smoke cigarillos/MMCs, 19.9% usually smoke premium cigars, and the remainder, 18.4%, usually smoke LFCs. These data can help to inform public health interventions to reduce the burden of adverse health effects caused by cigar smoking in the United States, including regulation.

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)-dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α-dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)-specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

Correlates of tobacco product initiation among youth and young adults between waves 1-4 of the population assessment of tobacco and Health (PATH) study (2013-2018).

INTRODUCTION: While risk factors for cigarette smoking among youth and young adults are well-documented, less is known about the correlates of initiation of other tobacco products. This study aims to provide estimates and correlates of initiation among U.S. youth and young adults. METHODS: Data on youth aged 12-17 (n = 10,072) and young adults aged 18-24 (N = 5,727) who provided information on cigarettes, electronic nicotine delivery systems (ENDS), cigars, pipe, hookah and smokeless tobacco use in Wave 1 (W1: 2013-2014)-Wave 4 (W4: 2016-2018) of the nationally-representative PATH Study were used to calculate ever use initiation and correlates of initiation by W4. RESULTS: Nearly 6 million youth and 2.5 million young adults used tobacco for the first time between W1-W4. Approximately one quarter of youth and young adult ENDS never users initiated ENDS between W1-W4 of the PATH Study. Among youth, use of other tobacco products, ever substance use, and high externalizing problems were associated with initiation of most products. Among young adults, use of other tobacco products and ever substance use were associated with initiation of most products. In both youth and young adults, Hispanics were more likely to initiate hookah use than their non-Hispanic White counterparts. While male sex was a risk factor for most tobacco product initiation across both age groups, it was not associated with hookah initiation. CONCLUSIONS: Cigarette and non-cigarette products shared many correlates of initiation, although there are noteworthy demographic differences. Findings can help tailor product specific interventions to reach populations at risk during preliminary stages of use.

Cigar smoking prevalence and morbidity among US adults, 2000-2015.

Cigar smoking causes many of the same health conditions as cigarettes, but less information is available on prevalence of use trends and the disease burden of cigar smoking in the US. To examine these issues, we analyzed cigar use and health condition data from the National Health Interview Survey from 2000, 2005, 2010, and 2015, estimating prevalence of use by year and over time. We also estimated the number of, and adjusted disease prevalence ratios for, US adults aged ≥35 years with self-reported history of heart disease, stroke, or cancer attributable to cigar smoking. We found that prevalence of current cigar smoking has remained generally stable at around 2.3% among US adults aged ≥18 years between 2000 and 2015 but has increased among female and non-Hispanic black adults. Former exclusive cigar smokers were more likely to report having had heart conditions (aPR = 1.33, 95% CI = 1.03-1.72), stroke (aPR = 2.42, 95% CI = 1.57-3.75), and cancer (aPR = 1.44, 95% CI = 1.09-1.88) than never cigar smokers. It is estimated that nearly 200,000 cardiovascular conditions and cancer cases among US adults are attributable to former exclusive cigar smoking. This analysis shows that prevalence of current cigar smoking has remained stable among US adults but has increased among certain demographic groups. Former exclusive cigar use is associated with increased prevalence of heart disease, stroke, and cancer, which may result in part from smoking cessation following disease onset.

Associations of Cigarettes Smoked Per Day with Biomarkers of Exposure Among U.S. Adult Cigarette Smokers in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

BACKGROUND: The dose-response relationships between number of cigarettes smoked per day (CPD) and health outcomes, such as cancer and heart disease, are well established, but much less is known about the relationships between CPD and biomarkers of exposure. METHODS: We analyzed biomarker data by CPD from more than 2,700 adult daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health Study. Tobacco use categories consisted of exclusive cigarette smokers, dual cigarette and e-cigarette users, and dual cigarette and smokeless tobacco users. RESULTS: Biomarker concentrations consistently increased with CPD for each tobacco user group, although concentrations tended to level off at high smoking levels, such as those at and above 20 CPD. Dual cigarette and e-cigarette users had higher levels of some biomarkers such as Total Nicotine Equivalents-2 (P = 0.0036) than exclusive cigarette smokers, and dual cigarette and smokeless tobacco users had higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (P < 0.0001) and N'-nitrosonornicotine (P = 0.0236) than exclusive cigarette smokers. CONCLUSIONS: Among daily smokers, exposure to tobacco toxicants and constituents exhibits a dose-response relationship by number of cigarettes smoked, but the relationship is not necessarily linear in form. Dual users of cigarettes with either e-cigarettes or smokeless tobacco are exposed to higher levels of certain toxicants and carcinogens than exclusive cigarette smokers. IMPACT: Availability of biomarker data by CPD may aid in comparisons between cigarette smoking and use of new and potentially reduced exposure tobacco products, which may result in different levels of constituent and toxicant exposure.

Platelet bioenergetics correlate with muscle energetics and are altered in older adults.

BACKGROUND: Physical function decreases with age, and though bioenergetic alterations contribute to this decline, the mechanisms by which mitochondrial function changes with age remains unclear. This is partially because human mitochondrial studies require highly invasive procedures, such as muscle biopsies, to obtain live tissue with functional mitochondria. However, recent studies demonstrate that circulating blood cells are potentially informative in identifying systemic bioenergetic changes. Here, we hypothesize that human platelet bioenergetics reflect bioenergetics measured in muscle biopsies. METHODS & RESULTS: We demonstrate that maximal and ATP-linked respiratory rate measured in isolated platelets from older adults (86-93 years) correlates significantly with maximal respiration (r = 0.595; P = 0.003) measured by muscle biopsy respirometry and maximal ATP production (r = 0.643; P = 0.004) measured by 31P-MRS respectively, in the same individuals. Comparison of platelet bioenergetics in this aged cohort to platelets from younger adults (18-35 years) shows aged adults demonstrate lower basal and ATP-linked respiration. Platelets from older adults also show enhanced proton leak, which is likely due to increased protein levels of uncoupling protein 2, and correlates with increased gate speed in this cohort (r = 0.58; P = 0.0019). While no significant difference in glycolysis was observed in older adults compared to younger adults, platelet glycolytic rate correlated with fatigability (r = 0.44; P = 0.016). CONCLUSIONS: These data advance the mechanistic understanding of age-related changes in mitochondrial function. Further, they suggest that measuring platelet bioenergetics provides a potential supplement or surrogate for muscle biopsy measurement and may be a valuable tool to study mitochondrial involvement in age-related decline of physical function.

Biomarkers of Exposure among U.S. Adult Cigar Smokers: Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

BACKGROUND: Given the diverse cigar market and limited data on biomarker patterns by cigar type, we compared biomarkers of nicotine and tobacco toxicants among cigar smokers and other groups. METHODS: Using Wave 1 urinary biomarker data from 5,604 adults in the Population Assessment of Tobacco and Health (PATH) Study, we compared geometric mean concentrations among cigar-only smokers (all cigars and separately for traditional, cigarillo, and filtered cigars), cigarette-only smokers, dual cigar/cigarette smokers, and never users of tobacco. We calculated geometric mean ratios comparing groups with never users adjusting for sex, age, race/ethnicity, education and creatinine. RESULTS: Some day cigar-only smokers had lower biomarker concentrations than every day cigar-only smokers, but higher than never users. Every day cigar-only smokers (n = 61) had lower TNE-2 (cotinine+trans-3'-hydroxycotinine) compared to every day cigarette-only (n = 2217; P < 0.0001) and dual cigar/cigarette smokers (n = 601; P < 0.0001). Several biomarkers, including NNAL (NNK metabolite) and CYMA (metabolite of acrylonitrile), were comparable in these groups. In exploratory analyses, every day filtered cigar-only (n = 7) smokers had higher biomarker concentrations compared with every day traditional cigar-only smokers (n = 12) and cigarillo-only smokers (n = 24). Every day smokers of each cigar type were similar to exclusive cigarette smokers. For some biomarkers, particularly for every day filtered cigar-only smokers, concentrations were higher. CONCLUSIONS: For some biomarkers, every day cigar-only smokers were comparable with every day cigarette-only smokers. Exploratory analyses suggest that biomarkers vary by cigar type with every day filtered cigar-only smokers having the highest concentrations. IMPACT: High exposure to harmful constituents among cigar smokers is a continuing health issue.