skip to main content

Explore Research Products in the NSF-PAR

Title: Menthol in electronic cigarettes causes biophysical inhibition of pulmonary surfactant
With an increasing prevalence of electronic cigarette (e-cigarette) use, especially among youth, there is an urgent need to better understand the biological risks and pathophysiology of health conditions related to e-cigarettes. A majority of e-cigarette aerosols are in the submicron size and would deposit in the alveolar region of the lung, where they must first interact with the endogenous pulmonary surfactant. To date, little is known whether e-cigarette aerosols have an adverse impact on the pulmonary surfactant. We have systematically studied the effect of individual e-cigarette ingredients on an animal-derived clinical surfactant preparation, bovine lipid extract surfactant, using a combination of biophysical and analytical techniques, including in vitro biophysical simulations using constrained drop surfactometry, molecular imaging with atomic force microscopy, chemical assays using carbon nuclear magnetic resonance and circular dichroism, and in silico molecular dynamics simulations. All data collectively suggest that flavorings used in e-cigarettes, especially menthol, play a predominant role in inhibiting the biophysical function of the surfactant. The mechanism of biophysical inhibition appears to involve menthol interactions with both phospholipids and hydrophobic proteins of the natural surfactant. These results provide novel insights into the understanding of the health impact of e-cigarettes and may contribute to better regulation of e-cigarette products.  more » « less
Award ID(s):
2011317 1920304
NSF-PAR ID:
10351137
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Date Published:
Journal Name:
American Journal of Physiology-Lung Cellular and Molecular Physiology
Volume:
323
Issue:
2
ISSN:
1040-0605
Page Range / eLocation ID:
L165 to L177
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ( , PLOS ONE)
    Jeyaseelan, Samithamby (Ed.)
    Introduction E-cigarette (EC) and vaping use continue to remain popular amongst teenage and young adult populations, despite several reports of vaping associated lung injury. One of the first compounds that EC aerosols comes into contact within the lungs during a deep inhalation is pulmonary surfactant. Impairment of surfactant’s critical surface tension reducing activity can contribute to lung dysfunction. Currently, information on how EC aerosols impacts pulmonary surfactant remains limited. We hypothesized that exposure to EC aerosol impairs the surface tension reducing ability of surfactant. Methods Bovine Lipid Extract Surfactant (BLES) was used as a model surfactant in a direct exposure syringe system. BLES (2ml) was placed in a syringe (30ml) attached to an EC. The generated aerosol was drawn into the syringe and then expelled, repeated 30 times. Biophysical analysis after exposure was completed using a constrained drop surfactometer (CDS). Results Minimum surface tensions increased significantly after exposure to the EC aerosol across 20 compression/expansion cycles. Mixing of non-aerosolized e-liquid did not result in significant changes. Variation in device used, addition of nicotine, or temperature of the aerosol had no additional effect. Two e-liquid flavours, menthol and red wedding, had further detrimental effects, resulting in significantly higher surface tension than the vehicle exposed BLES. Menthol exposed BLES has the highest minimum surface tensions across all 20 compression/expansion cycles. Alteration of surfactant properties through interaction with the produced aerosol was observed with a basic e-liquid vehicle, however additional compounds produced by added flavourings appeared to be able to increase inhibition. Conclusion EC aerosols alter surfactant function through increases in minimum surface tension. This impairment may contribute to lung dysfunction and susceptibility to further injury. 
    more » « less
  2. ; ; ; ; ; ; ; ; ( , Cancers)
    Electronic cigarettes (E-cigs) generate nicotine containing aerosols for inhalation and have emerged as a popular tobacco product among adolescents and young adults, yet little is known about their health effects due to their relatively recent introduction. Few studies have assessed the long-term effects of inhaling E-cigarette smoke or vapor. Here, we show that two months of E-cigarette exposure causes suppression of bone marrow hematopoietic stem and progenitor cells (HSPCs). Specifically, the common myeloid progenitors and granulocyte-macrophage progenitors were decreased in E-cig exposed animals compared to air exposed mice. Competitive reconstitution in bone marrow transplants was not affected by two months of E-cig exposure. When air and E-cig exposed mice were challenged with an inflammatory stimulus using lipopolysaccharide (LPS), competitive fitness between the two groups was not significantly different. However, mice transplanted with bone marrow from E-cigarette plus LPS exposed mice had elevated monocytes in their peripheral blood at five months post-transplant indicating a myeloid bias similar to responses of aged hematopoietic stem cells (HSC) to an acute inflammatory challenge. We also investigated whether E-cigarette exposure enhances the selective advantage of hematopoietic cells with myeloid malignancy associated mutations. E-cigarette exposure for one month slightly increased JAK2V617F mutant cells in peripheral blood but did not have an impact on TET2−/− cells. Altogether, our findings reveal that chronic E-cigarette exposure for two months alters the bone marrow HSPC populations but does not affect HSC reconstitution in primary transplants. 
    more » « less
  3. ; ; ; ; ; ( , Nicotine and Tobacco Research)
    Abstract Introduction

    Certain subpopulations in the United States are highly vulnerable to tobacco initiation and addiction, and elimination of disparities among those groups is crucial to reducing the burden of tobacco use.

     Aims and Methods

    This study evaluated the racial and ethnic differences in smoking initiation of menthol flavored cigarettes and cigars among never-users, and in subsequent tobacco use among new users of menthol-flavored products, using longitudinal data from waves 1–4 of the Population Assessment of Tobacco and Health Study. The outcomes of interest were new use of menthol-flavored products, and subsequent past 30-day and past 12-month cigarette and cigar smoking, irrespective of flavors, after initiation.

     Results

    The percentages of new users of menthol-flavored cigarettes and cigars at waves 2–4 were disproportionately higher in non-Hispanic black and Hispanic than in non-Hispanic white people. Adjusting for age and sex, black people who first used any menthol cigars had higher risk of past 30-day use of the same cigar category at the subsequent wave (adjusted risk ratio, aRR 1.48; 95% confidence interval [CI] 1.11 to 1.96) and past 12 months (aRR 1.74; 95% CI 1.55 to 2.63) compared to non-Hispanic white smokers. Black people who first used menthol-flavored cigarettes had marginally higher risk of subsequent past 30-day cigarette use (aRR 1.44; 95% CI 0.99 to 2.10) compared with their non-Hispanic white counterparts.

     Conclusions

    This study shows that racial and ethnic differences exist in both initiation of menthol-flavored tobacco products and product-specific subsequent use after first using menthol-flavored products; black and Hispanic people have higher rates of initiation; black people also have higher rates of subsequent use.

     Implications

    Use of menthol flavors in tobacco products is confirmed to be a contributor to large disparities in tobacco use; black and Hispanic people are more likely to maintain smoking through use of mentholated products than non-Hispanic white people. The findings suggest educational and regulatory actions on menthol-flavored tobacco products including restricting the selective marketing to vulnerable communities and banning characterizing flavors in cigarettes and cigars may reduce tobacco-related disparities and inform the Food And Drug Administration’s evidence-based rulemaking process.

     
    more » « less
  4. ; ; ; ; ; ( , American Journal of Physiology-Heart and Circulatory Physiology)
    null (Ed.)
    Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective cohort of patients with PH is associated with improved survival. Here, we utilized losartan (an ARB specific for angiotensin II type 1 receptor) to further explore nicotine-induced PH. Male C57BL/6 mice received nicotine vapor for 12 h/day, and exposure was assessed using serum cotinine to achieve levels comparable to human smokers or electronic cigarette users. Mice were exposed to nicotine for 8 wk and a subset was treated with losartan via an osmotic minipump. Cardiac function was assessed using echocardiography and catheterization. Although nicotine exposure increased angiotensin II in the RV and lung, this finding was nonsignificant. Chronic, inhaled nicotine significantly increased RV systolic pressure and RV free wall thickness versus air control. These parameters were significantly lower in mice receiving both nicotine and losartan. Nicotine significantly increased RV internal diameter, with no differences seen between the nicotine and nicotine-losartan group. Neither nicotine nor losartan affected left ventricular structure or function. These findings provide the first evidence that antagonism of the angiotensin II type 1 receptor can ameliorate chronic, inhaled nicotine-induced PH and RV remodeling. NEW & NOTEWORTHY Chronic, inhaled nicotine causes pulmonary hypertension and right ventricular remodeling in mice. Treatment with losartan, an angiotensin II type 1 receptor antagonist, ameliorates nicotine-induced pulmonary hypertension and right ventricular remodeling. This novel finding provides preclinical evidence for the use of renin-angiotensin system-based therapies in the treatment of pulmonary hypertension, particularly in patients with a history of tobacco-product use. 
    more » « less
  5. ; ; ; ( , International Journal of Molecular Sciences)
    Electronic cigarettes are frequently viewed as a safer alternative to conventional cigarettes; however, evidence to support this perspective has not materialized. Indeed, the current literature reports that electronic cigarette use is associated with both acute lung injury and subclinical dysfunction to the lung and vasculature that may result in pathology following chronic use. E-cigarettes can alter vascular dynamics, polarize innate immune populations towards a proinflammatory state, compromise barrier function in the pulmonary endothelium and epithelium, and promote pre-oncogenic phenomena. This review will summarize the variety of e-cigarette products available to users, discuss current challenges in e-cigarette study design, outline the range of pathologies occurring in cases of e-cigarette associated acute lung injury, highlight disease supporting tissue- and cellular-level changes resulting from e-cigarette exposure, and briefly examine how these changes may promote tumorigenesis. Continued research of the mechanisms by which e-cigarettes induce pathology benefit users and clinicians by resulting in increased regulation of vaping devices, informing treatments for emerging diseases e-cigarettes produce, and increasing public awareness to reduce e-cigarette use and the onset of preventable disease. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email