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European Journal of Applied Physiology Aug 2023Respiratory function has become a global health priority. Not only is chronic respiratory disease a leading cause of worldwide morbidity and mortality, but the COVID-19... (Review)
Review
Respiratory function has become a global health priority. Not only is chronic respiratory disease a leading cause of worldwide morbidity and mortality, but the COVID-19 pandemic has heightened attention on respiratory health and the means of enhancing it. Subsequently, and inevitably, the respiratory system has become a target of the multi-trillion-dollar health and wellness industry. Numerous commercial, respiratory-related interventions are now coupled to therapeutic and/or ergogenic claims that vary in their plausibility: from the reasonable to the absurd. Moreover, legitimate and illegitimate claims are often conflated in a wellness space that lacks regulation. The abundance of interventions, the range of potential therapeutic targets in the respiratory system, and the wealth of research that varies in quality, all confound the ability for health and exercise professionals to make informed risk-to-benefit assessments with their patients and clients. This review focuses on numerous commercial interventions that purport to improve respiratory health, including nasal dilators, nasal breathing, and systematized breathing interventions (such as pursed-lips breathing), respiratory muscle training, canned oxygen, nutritional supplements, and inhaled L-menthol. For each intervention we describe the premise, examine the plausibility, and systematically contrast commercial claims against the published literature. The overarching aim is to assist health and exercise professionals to distinguish science from pseudoscience and make pragmatic and safe risk-to-benefit decisions.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Pandemics; Pseudoscience; COVID-19; Breathing Exercises
PubMed: 36917254
DOI: 10.1007/s00421-023-05166-8 -
Respiratory Research Jan 2024Electronic 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...
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.
Topics: Nicotine; Electronic Nicotine Delivery Systems; Menthol; Interleukin-8; Epithelium; Fibroblasts; Inflammation; Tobacco Products
PubMed: 38200492
DOI: 10.1186/s12931-023-02537-9 -
Frontiers in Pharmacology 2023Cold thermoreceptor neurons detect temperature drops with highly sensitive molecular machinery concentrated in their peripheral free nerve endings. The main molecular... (Review)
Review
Cold thermoreceptor neurons detect temperature drops with highly sensitive molecular machinery concentrated in their peripheral free nerve endings. The main molecular entity responsible for cold transduction in these neurons is the thermo-TRP channel TRPM8. Cold, cooling compounds such as menthol, voltage, and osmolality rises activate this polymodal ion channel. Dysregulation of TRPM8 activity underlies several physiopathological conditions, including painful cold hypersensitivity in response to axonal damage, migraine, dry-eye disease, overactive bladder, and several forms of cancer. Although TRPM8 could be an attractive target for treating these highly prevalent diseases, there is still a need for potent and specific modulators potentially suitable for future clinical trials. This goal requires a complete understanding of the molecular determinants underlying TRPM8 activation by chemical and physical agonists, inhibition by antagonists, and the modulatory mechanisms behind its function to guide future and more successful treatment strategies. This review recapitulates information obtained from different mutagenesis approaches that have allowed the identification of specific amino acids in the cavity comprised of the S1-S4 and TRP domains that determine modulation by chemical ligands. In addition, we summarize different studies revealing specific regions within the N- and C-terminus and the transmembrane domain that contribute to cold-dependent TRPM8 gating. We also highlight the latest milestone in the field: cryo-electron microscopy structures of TRPM8, which have provided a better comprehension of the 21 years of extensive research in this ion channel, shedding light on the molecular bases underlying its modulation, and promoting the future rational design of novel drugs to selectively regulate abnormal TRPM8 activity under pathophysiological conditions.
PubMed: 37388453
DOI: 10.3389/fphar.2023.1213337 -
Nicotine & Tobacco Research : Official... Feb 2024Tobacco product flavors can increase product appeal, adolescent initiation and experimentation, and difficulty quitting. Flavored tobacco products are not restricted in...
INTRODUCTION
Tobacco product flavors can increase product appeal, adolescent initiation and experimentation, and difficulty quitting. Flavored tobacco products are not restricted in Vietnam or the Philippines despite the high smoking prevalence among those 15 years of age and older (24% and 23%, respectively). There are no published reports to our knowledge on the levels of flavor chemicals in the cigarettes sold in these two countries.
METHODS
Cigarettes were purchased in Vietnam (32 brand variants) and the Philippines (19 brand variants) during 2020. Chemical analyses gave the mg/filter, mg/rod, and mg/stick (= mg/(filter + rod)) values for 180 individual flavor chemicals. Values were calculated for menthol, clove-related compounds, and "other flavor chemicals" (OFCs).
RESULTS
Five flavor groupings were found among the brand variants purchased in Vietnam: menthol + OFCs (n = 15), OFCs only (n = 8), nonflavored (n = 7), menthol + OFCs with a clove flavorant (n = 1) and menthol only (n = 1). Three flavor groupings were found among the brand variants purchased in the Philippines: menthol + OFCs (n = 10), nonflavored (n = 5), and menthol only (n = 4).
CONCLUSIONS
A range of flavored cigarette products are being offered by tobacco companies in Vietnam and the Philippines, presumably to maximize cigarette sales. Regulation of flavor chemicals should be considered in these two countries.
IMPLICATIONS
Article 9 of the WHO Framework Convention on Tobacco Control (FCTC), ratified by both Vietnam and the Philippines, states that "there is no justification for permitting the use of ingredients, such as flavoring agents, which help make tobacco products attractive." Flavors increase product appeal, adolescent initiation and experimentation, and difficulty quitting. These analyses found that cigarettes purchased in Vietnam and the Philippines contained menthol and other flavor chemicals. Tobacco companies are offering multiple flavor chemical profiles and nominally nonflavored versions in these countries; regulation of flavor chemicals should be considered in these two countries.
Topics: Adolescent; Humans; Menthol; Philippines; Vietnam; Flavoring Agents; Electronic Nicotine Delivery Systems; Tobacco Products; Brain; Cleft Lip; Cleft Palate
PubMed: 37578845
DOI: 10.1093/ntr/ntad146 -
Research Square Jun 2023Electronic 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...
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 of the cells in a microtissue chip model.
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 (COL1A1), α-smooth-muscle actin (αSMA), and fibronectin as well as decreased gene expression level of αSMA () 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 gene expression of and .
CONCLUSION
Overall, tobacco-flavored e-cig exposure induces inflammation in both epithelium and fibroblasts, and tobacco-flavored e-cig inhibits wound healing ability in fibroblast.
PubMed: 37398084
DOI: 10.21203/rs.3.rs-3037297/v1 -
European Journal of Sport Science Oct 2023We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance,... (Randomized Controlled Trial)
Randomized Controlled Trial
Topical application of isolated menthol and combined menthol-capsaicin creams: Exercise tolerance, thermal perception, pain, attentional focus and thermoregulation in the heat.
We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance, thermal perception, pain, attentional focus and thermoregulation during exercise in the heat. Ten participants cycled at 70% maximal power output until exhaustion in 35°C and 20% relative humidity after application of (i) 5% isolated menthol, (ii) 5% menthol and 0.025% capsaicin co-application or (iii) placebo cream. Thermo-physiological responses were measured during exercise, with attentional focus and pain determined post-exercise on a 0-to-10 scale. Across the three conditions, time to exhaustion was 13.4 ± 4.8 min, mean ± SD infrared tympanic and skin temperature was 37.2 ± 0.6°C and 35.1 ± 1.2°C, respectively, and heart rate was 152 ± 47 bpm, with no changes between conditions (> 0.05). Perceived exertion was lower in the isolated menthol all other conditions (< 0.05, = 0.44). Thermal sensation was higher in menthol-capsaicin co-application isolated menthol (< 0.05, 1.1), while sweat rate was higher for capsaicin and menthol co-application compared to menthol (< 0.05, = 0.85). The median and interquartile range scores for pain were lower (< 0.05) in the menthol condition (8, 7-8) compared to both menthol and capsaicin (10, 9-10) and placebo (9, 9-10), which was coupled with a greater distraction (< 0.05) in the menthol condition (9, 7-10) compared to placebo (6, 5-7). Despite no performance effects for any topical cream application condition, these data reiterate the advantageous perceptual and analgesic role of menthol application and demonstrate no advantage of co-application with capsaicin.Topical application of isolated menthol cream to cold-sensitive areas of the body during exhaustive exercise in the heat, elicited reduced perception of pain and enhanced sensation of cooling.While this reduction in generally unpleasant feelings (i.e. pain and heat) were coupled with lower RPE scores in the menthol condition and could be considered beneficial, there was no apparent ergogenic effect in an exercise tolerance test.Co-application of capsaicin and menthol appeared to inhibit the positive sensory effects elicited by menthol.Isolated menthol can induce changes in cognitive processes related to pain and exertion, while also reducing thermal sensation; however, the decision to use menthol creams must be balanced with the limited performance or thermoregulatory effects reported herein during exercise in hot environments.
Topics: Humans; Body Temperature Regulation; Capsaicin; Exercise Tolerance; Hot Temperature; Menthol; Pain; Pain Perception; Thermosensing; Cross-Over Studies; Male; Female; Adult
PubMed: 37161852
DOI: 10.1080/17461391.2023.2211966 -
Toxics Aug 2023Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in... (Review)
Review
Heated tobacco products (HTPs) are novel products that allow users to inhale nicotine by heating (350 °C) reconstituted tobacco rather than combustion (900 °C) as in conventional cigarettes. HTP sticks containing reconstituted tobacco come in various flavours such as menthol, citrus, etc., like electronic cigarette liquids. Thus, the composition of HTP aerosol will also vary according to the flavouring agents added. Overall, the content of toxic chemicals in HTP aerosol appears to be lower than in cigarette smoke. However, the concentrations of more than twenty harmful and potentially harmful constituents have been reported to be higher in HTP aerosol than in cigarette smoke. Further, several toxic compounds not detected in cigarette smoke are also reported in HTP aerosol. Thus, the risks of HTP use remain unknown. Most of the available data on the composition and health effects of mainstream HTP aerosol exposure are generated by the tobacco industry. Few independent studies have reported short-term pathophysiological effects of HTP use. Currently available HTP toxicity data are mainly on the pulmonary and cardiovascular systems. Moreover, there are no long-term toxicity data and, therefore, the claims of the tobacco industry regarding HTPs as a safer alternative to traditional combustible cigarettes are unsubstantiated. Furthermore, HTP aerosol contains the highly addictive substance nicotine, which is harmful to the adolescent brain, developing foetuses, pregnant women, and also adults. Hence, comprehensive studies addressing the safety profiling related to long-term HTP use are warranted. With this background, the following review summarizes the current state of knowledge on HTP toxicity on four broad lines: composition of mainstream HTP aerosol compared to traditional combustible cigarette smoke, biomarkers of HTP exposure, health effects of HTP exposure, and the harm reduction aspect.
PubMed: 37624172
DOI: 10.3390/toxics11080667 -
Tobacco Control Nov 2023E-cigarettes with cooling flavours have diversified in ways that complicate tobacco control with the emergence of: (1) Ice-hybrid flavours (eg, 'Raspberry Ice') that... (Review)
Review
E-cigarettes with cooling flavours have diversified in ways that complicate tobacco control with the emergence of: (1) Ice-hybrid flavours (eg, 'Raspberry Ice') that combine cooling and fruity/sweet properties; and (2) Products containing non-menthol synthetic cooling agents (eg, Wilkinson Sword (WS), WS-3, WS-23 (termed 'koolada')). This paper reviews the background, chemistry, toxicology, marketing, user perceptions, use prevalence and policy implications of e-cigarette products with ice-hybrid flavours or non-menthol coolants. Scientific literature search supplemented with industry-generated and user-generated information found: (a) The tobacco industry has developed products containing synthetic coolants since 1974, (b) WS-3 and WS-23 are detected in mass-manufactured e-cigarettes (eg, PuffBar); (c) While safe for limited oral ingestion, inhalational toxicology and health effects from daily synthetic coolant exposure are unknown and merit scientific inquiry and attention from regulatory agencies; (d) Ice-hybrid flavours are marketed with themes incorporating fruitiness and/or coolness (eg, snow-covered raspberries); (e) WS-23/WS-3 concentrates also are sold as do-it-yourself additives, (f) Pharmacology research and user-generated and industry-generated information provide a premise to hypothesise that e-cigarette products with ice flavours or non-menthol cooling agents generate pleasant cooling sensations that mask nicotine's harshness while lacking certain aversive features of menthol-only products, (g) Adolescent and young adult use of e-cigarettes with ice-hybrid or other cooling flavours may be common and cross-sectionally associated with more frequent vaping and nicotine dependence in convenience samples. Evidence gaps in the epidemiology, toxicology, health effects and smoking cessation-promoting potential of using these products exist. E-cigarettes with ice flavours or synthetic coolants merit scientific and regulatory attention.
Topics: Adolescent; Humans; Young Adult; Electronic Nicotine Delivery Systems; Flavoring Agents; Menthol; Tobacco Products; Vaping
PubMed: 35483721
DOI: 10.1136/tobaccocontrol-2021-057073