Exploring the potential neurotoxicity of vaping vitamin E or vitamin E acetate.

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.

Tobacco Use and Respiratory Symptoms Among Adults: Findings From the Longitudinal Population Assessment of Tobacco and Health (PATH) Study 2014-2016.

INTRODUCTION: We examined the relationship between current tobacco use and functionally important respiratory symptoms. METHODS: Longitudinal cohort study of 16 295 US adults without COPD in Waves 2-3 (W2-3, 2014-2016) of the Population Assessment of Tobacco and Health Study. Exposure-Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome-Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders. RESULTS: All tobacco use categories featuring cigarettes (>2/3's of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 [95% CI, 1.92, 2.85] and for worsening symptoms at W3 was 2.80 [2.08, 3.76]. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette-respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 [1.02, 2.59]) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 [1.04, 2.58]). CONCLUSIONS: Past and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for pack-years and symptom severity. IMPLICATIONS: How noncigarette tobacco products affect respiratory symptoms is not clear; some studies implicate e-cigarettes. We examined functionally important respiratory symptoms (wheezing/nighttime cough) among US adults without COPD. The majority of adult tobacco users smoke cigarettes and have higher risk of respiratory symptoms and worsening of symptoms, regardless of other products used with them. Exclusive use of other tobacco products (e-cigarettes, cigars, smokeless, hookah) was largely not associated with functionally important respiratory symptoms and risks associated with their use was significantly lower than for cigarettes. The association for e-cigarettes was greatly attenuated by adjustment for cigarette pack-years and sensitive to how symptoms were defined.

Electronic cigarettes: human health effects.

OBJECTIVE: With the rapid increase in use of electronic nicotine delivery systems (ENDS), such as electronic cigarettes (e-cigarettes), users and non-users are exposed to the aerosol and product constituents. This is a review of published data on the human health effects of exposure to e-cigarettes and their components. METHODS: Literature searches were conducted through September 2013 using multiple electronic databases. RESULTS: Forty-four articles are included in this analysis. E-cigarette aerosols may contain propylene glycol, glycerol, flavourings, other chemicals and, usually, nicotine. Aerosolised propylene glycol and glycerol produce mouth and throat irritation and dry cough. No data on the effects of flavouring inhalation were identified. Data on short-term health effects are limited and there are no adequate data on long-term effects. Aerosol exposure may be associated with respiratory function impairment, and serum cotinine levels are similar to those in traditional cigarette smokers. The high nicotine concentrations of some products increase exposure risks for non-users, particularly children. The dangers of secondhand and thirdhand aerosol exposure have not been thoroughly evaluated. CONCLUSIONS: Scientific evidence regarding the human health effects of e-cigarettes is limited. While e-cigarette aerosol may contain fewer toxicants than cigarette smoke, studies evaluating whether e-cigarettes are less harmful than cigarettes are inconclusive. Some evidence suggests that e-cigarette use may facilitate smoking cessation, but definitive data are lacking. No e-cigarette has been approved by FDA as a cessation aid. Environmental concerns and issues regarding non-user exposure exist. The health impact of e-cigarettes, for users and the public, cannot be determined with currently available data.

Tobacco Product Use and Functionally Important Respiratory Symptoms Among US Adolescents/Young Adults.

OBJECTIVE: The relation between respiratory symptoms and the range of tobacco product use among US adolescents/young adults is not yet clear. This cross-sectional analysis examines tobacco product use and respiratory symptoms in a nationally representative sample of 21,057 adolescents/young adults aged 12-24 years from Wave 4 (2016-17) of the Population Assessment of Tobacco and Health Study. METHODS: Presence of functionally important respiratory symptoms was defined by questions regarding wheezing and nighttime cough at a cutoff score associated with poorer functional health status. Past-30-day tobacco use was analyzed 2 ways: never-tobacco users (reference) versus combustible users, noncombustible-only users, and former users; or frequency of use of cigarettes and/or e-cigarettes. Weighted Poisson regression adjusted for past-30-day marijuana use, secondhand smoke exposure, and asthma. RESULTS: Functionally important respiratory symptoms were present in 10.0% overall: 13.8% of combustible users, 9.0% of noncombustible users, 8.2% of noncurrent users and 9.7% of never users. Functionally important respiratory symptoms were associated with combustible tobacco use (relative risk [RR] = 1.52[95% CI 1.29, 1.80]), marijuana use (RR = 1.54[1.34, 1.77]) and secondhand smoke exposure (RR = 1.04[1.03, 1.05]). Higher cigarette smoking frequency was also associated with functionally important respiratory symptoms for frequency categories >14 days/month (eg, RR = 1.93[1.50, 2.49] for 15-29 days/month). Frequency of e-cigarette use was not associated with functionally important respiratory symptoms. CONCLUSIONS: During 2016-17, smoking cigarettes, marijuana use, and secondhand smoke exposure were cross-sectionally associated with functionally important respiratory symptoms in adolescents/young adults. Risk increased with increased frequency of cigarette use but not e-cigarette use. Given changes to contemporary e-cigarettes and use, findings may not generalize to newer products.

Validation of an Index for Functionally Important Respiratory Symptoms among Adults in the Nationally Representative Population Assessment of Tobacco and Health Study, 2014-2016.

The purpose of this study is to validate the seven-item wheezing module from the International Study of Asthma and Allergies in Children (ISAAC) in the nationally representative Population Assessment of Tobacco and Health Study. Adult participants with complete Wave 2-3 data were selected, including those with asthma but excluding those with COPD and other respiratory diseases (n = 16,295). We created a nine-point respiratory symptom index from the ISAAC questions, assessed the reliability of the index, and examined associations with self-reported asthma diagnosis. Threshold values were assessed for association with functional outcomes. The weighted prevalence for one or more respiratory symptom was 18.0% (SE = 0.5) for adults without asthma, 70.1% (SE = 1.3) for those with lifetime asthma, 75.7% (SE = 3.7) for adults with past-year asthma not on medications, and 92.6% (SE = 1.6) for those on medications. Cronbach's alpha for the respiratory symptom index was 0.86. Index scores of ≥2 or ≥3 yielded functionally important respiratory symptom prevalence of 7-10%, adequate sensitivity and specificity for identifying asthma, and consistent independent associations with all functional outcomes and tobacco use variables. Respiratory symptom index scores of ≥2 or ≥3 are indicative of functionally important respiratory symptoms and could be used to assess the relationship between tobacco use and respiratory health.

Chronic Cough Due to Stable Chronic Bronchitis: CHEST Expert Panel Report.

BACKGROUND: Chronic cough due to chronic bronchitis (CB) causes significant impairment in quality of life, and effective treatment strategies are needed. We conducted a systematic review on the management of chronic cough due to CB to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. METHODS: This systematic review asked three questions: (1) What are the clinical features of the history that suggest a patient's cough-phlegm syndrome is due to CB? (2) Can treatment of stable CB improve or eliminate chronic cough? (3) Can therapy that targets chronic cough due to CB prevent or reduce the occurrence of acute CB exacerbations? Studies of adult patients with CB were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the CHEST organization methodology. RESULTS: The search strategy used an assortment of descriptors and assessments to identify studies of chronic cough due to CB. CONCLUSIONS: The evidence supporting the management of chronic cough due to CB is limited overall and of low quality. This article provides guidance on treatment by presenting suggestions based on the best currently available evidence and identifies gaps in our knowledge and areas for future research.

Biomarkers of Exposure among USA Adult Hookah Users: Results from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2014).

Hookah smoking has become common in the USA, especially among young adults. This study measured biomarkers of exposure to known tobacco product toxicants in a population-based sample of exclusive, established hookah users. Urinary biomarker data from 1753 adults in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study were used to compare geometric mean concentrations of biomarkers of exposure in exclusive, established past 30-day hookah users to never users of tobacco. Geometric mean ratios were calculated comparing hookah user groups with never users adjusting for age, sex, race/ethnicity, education, past 30-day marijuana use, secondhand smoke exposure and creatinine. Past 30-day hookah users (n = 98) had 10.6 times the urinary cotinine level of never tobacco users. Compared to never tobacco users, past 30-day hookah users had 2.3 times the level of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1.3 times higher polycyclic aromatic hydrocarbons (PAHs) 3-hydroxyfluorene and 1-hydroxypyrene, 1.8 times higher levels of acrylonitrile, 1.3 times higher levels of acrylamide, and 1.2 times higher levels of acrolein exposure. These data indicate that hookah use is a significant source of exposure to nicotine, carcinogens, and respiratory toxicants.

Calls to Poison Centers for hookah smoking exposures.

Over the past decade, smoking behaviors have changed in the US. Hookah or waterpipe smoking is increasing, especially among youth and young adults. Social media sites describe the "hookah high" or "buzz", which may be related to nicotine, carbon monoxide, or other inhalants in hookah smoke. Most important is the risk of carbon monoxide poisoning. Case reports include a high number of victims presenting with loss of consciousness from either syncope or seizures. Anaphylaxis and a very rare respiratory hypersensitivity reaction, acute eosinophilic pneumonia, have also been reported from hookah smoking in previously healthy young adults. This article provides background information on hookah smoking, describes hookah-induced acute injuries that could precipitate poison center calls, and offers suggestions for exposure characterization.

Mental Health Problems and Onset of Tobacco Use Among 12- to 24-Year-Olds in the PATH Study.

OBJECTIVE: To examine whether mental health problems predict incident use of 12 different tobacco products in a nationally representative sample of youth and young adults. METHOD: This study analyzed Wave (W) 1 and W2 data from 10,533 12- to 24-year-old W1 never tobacco users in the Population Assessment of Tobacco and Health (PATH) Study. Self-reported lifetime internalizing and externalizing symptoms were assessed at W1. Past 12-month use of cigarettes, electronic nicotine delivery systems (ENDS), traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, other smokeless tobacco, bidis and kreteks (youth only), and dissolvable tobacco was assessed at W2. RESULTS: In multivariable regression analyses, high-severity W1 internalizing (adjusted odds ratio [AOR] = 1.5, 95% CI = 1.3-1.8) and externalizing (AOR = 1.3, 95% CI = 1.1-1.5) problems predicted W2 onset of any tobacco use compared to no/low/moderate severity. High-severity W1 internalizing problems predicted W2 use onset across most tobacco products. High-severity W1 externalizing problems predicted onset of any tobacco (AOR = 1.6, 95% CI = 1.3-1.8), cigarettes (AOR = 1.4, 95% CI = 1.0-2.0), ENDS (AOR = 1.8, 95% CI = 1.5-2.1), and cigarillos (AOR = 1.5, 95% CI = 1.0-2.1) among youth only. CONCLUSION: Internalizing and externalizing problems predicted onset of any tobacco use. However, findings differed for internalizing and externalizing problems across tobacco products, and by age, gender, and race/ethnicity. In addition to screening for tobacco product use, health care providers should screen for a range of mental health problems as a predictor of tobacco use. Interventions addressing mental health problems may prevent youth from initiating tobacco use.

Longitudinal associations between youth tobacco and substance use in waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: While evidence suggests bidirectional associations between cigarette use and substance (alcohol or drug) use, how these associations are reflected across the range of currently available tobacco products is unknown. This study examined whether ever tobacco use predicted subsequent substance use, and ever substance use predicted subsequent tobacco use among 11,996 U.S. youth (12-17 years) from Waves 1 (2013-2014) and 2 (2014-2015) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: Ever use of cigarettes, e-cigarettes, traditional cigars, cigarillos, filtered cigars, pipe, hookah, snus pouches, smokeless tobacco excluding snus pouches, dissolvable tobacco, bidis, kreteks, alcohol, marijuana, prescription drugs, and other drugs (cocaine and other stimulants, heroin, inhalants, solvents, and hallucinogens) was assessed at Wave 1 followed by past 12-month use assessments at Wave 2. The analyses included covariates (demographics, mental health, sensation seeking, prior use) to mitigate confounding. RESULTS: Ever tobacco use predicted subsequent substance use. The magnitude of the associations was lowest for alcohol, higher for marijuana, and highest for other drugs. Ever substance use also predicted subsequent tobacco use. Specifically, ever alcohol, marijuana, and non-prescribed Ritalin/Adderall use predicted tobacco-product use. Ever e-cigarette and cigarette use exclusively and concurrently predicted subsequent any drug (including and excluding alcohol) use. E-cigarette and cigarette use associations in the opposite direction were also significant; the strongest associations were observed for exclusive cigarette use. CONCLUSION: Tobacco and substance use prevention efforts may benefit from comprehensive screening and interventions across tobacco products, alcohol, and drugs, and targeting risk factors shared across substances.

Pharmacologic and Nonpharmacologic Treatment for Acute Cough Associated With the Common Cold: CHEST Expert Panel Report.

BACKGROUND: Acute cough associated with the common cold (CACC) causes significant impairment in quality of life. Effective treatment approaches are needed for CACC. We conducted a systematic review on the management of CACC to update the recommendations and suggestions of the CHEST 2006 guideline on this topic. METHODS: This systematic review of randomized controlled trials (RCTs) asked the question: Is there evidence of clinically relevant treatment effects for pharmacologic or nonpharmacologic therapies in reducing the duration/severity of acute CACC? Studies of adults and pediatric patients with CACC were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on using the American College of Chest Physicians organization methodology. RESULTS: Six systematic reviews and four primary studies identified from updated literature searches for each of the reviews or from hand searching were included and reported data on 6,496 participants with CACC who received one or more of a variety of interventions. The studies used an assortment of descriptors and assessments to identify CACC. CONCLUSIONS: The evidence supporting the management of CACC is overall of low quality. This document provides treatment suggestions based on the best currently available evidence and identifies gaps in our knowledge and areas for future research.

Proposed Mode of Action for Acrolein Respiratory Toxicity Associated with Inhaled Tobacco Smoke.

This article presents a mode of action (MOA) analysis that identifies key mechanisms in the respiratory toxicity of inhaled acrolein and proposes key acrolein-related toxic events resulting from the inhalation of tobacco smoke. Smoking causes chronic obstructive pulmonary disorder (COPD) and acrolein has been previously linked to the majority of smoking-induced noncancer respiratory toxicity. In contrast to previous MOA analyses for acrolein, this MOA focuses on the toxicity of acrolein in the lower respiratory system, reflecting the exposure that smokers experience upon tobacco smoke inhalation. The key mechanisms of acrolein toxicity identified in this proposed MOA include (1) acrolein chemical reactivity with proteins and other macromolecules of cells lining the respiratory tract, (2) cellular oxidative stress, including compromise of the important anti-oxidant glutathione, (3) chronic inflammation, (4) necrotic cell death leading to a feedback loop where necrosis-induced inflammation leads to more necrosis and oxidative damage and vice versa, (5) tissue remodeling and destruction, and (6) loss of lung elasticity and enlarged lung airspaces. From these mechanisms, the proposed MOA analysis identifies the key cellular processes in acrolein respiratory toxicity that consistently occur with the development of COPD: inflammation and necrosis in the middle and lower regions of the respiratory tract. Moreover, the acrolein exposures that occur as a result of smoking are well above exposures that induce both inflammation and necrosis in laboratory animals, highlighting the importance of the role of acrolein in smoking-related respiratory disease.

Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report.

BACKGROUND: We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic. METHODS: We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology. RESULTS: The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate. CONCLUSIONS: Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.

Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report.

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators. METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology. RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48). CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.