Effects of Prolonged E-cigarette Exposures on Lung Physiology and Asthmatic Response in a Murine Model.

In the last decade, e-cigarettes (e-cigs) have grown in popularity among the youth leading to increased cases of E-cigarette Vapor Associate Lung Injury, EVALI. At the time of this study, according to the CDC, there have been 68 deaths and 2,800 hospitalizations due to e-cig use. The e-cig market is constantly changing and relevant research on the effects of the devices are absent, therefore creating a niche for a study that analyzes the popular devices at a dosage similar to general population usage. We exposed mice to either mango or mint JUUL vapor for one hour three times a day for a month and three months. The exposed mice illustrated trends that demonstrated changes in the lung physiology hinting that prolonged use leads to increase in airway resistance and compliance. Our findings illustrate that at a dosage similar to human usage JUUL can negatively impact the lung physiology of mice. Future experiments would be to test the effects of e-cigs in an animal that is more closely related to humans, potentially rhesus macaque

Effects of Prolonged E-cigarette Exposures on Lung Physiology and Asthmatic Response in a Murine Model.

In the last decade, e-cigarettes (e-cigs) have grown in popularity among the youth leading to increased cases of E-cigarette Vapor Associate Lung Injury, EVALI. At the time of this study, according to the CDC, there have been 68 deaths and 2,800 hospitalizations due to e-cig use. The e-cig market is constantly changing and relevant research on the effects of the devices are absent, therefore creating a niche for a study that analyzes the popular devices at a dosage similar to general population usage. We exposed mice to either mango or mint JUUL vapor for one hour three times a day for a month and three months. The exposed mice illustrated trends that demonstrated changes in the lung physiology hinting that prolonged use leads to increase in airway resistance and compliance. Our findings illustrate that at a dosage similar to human usage JUUL can negatively impact the lung physiology of mice. Future experiments would be to test the effects of e-cigs in an animal that is more closely related to humans, potentially rhesus macaque

Abrogation of neutrophil inflammatory pathways and potential reduction of neutrophil-related factors in COVID-19 by intravenous immunoglobulin

Pathogenesis of lung injury in COVID-19 is not completely understood, leaving gaps in understanding how current treatments modulate the course of COVID-19. Neutrophil numbers and activation state in circulation have been found to correlate with COVID-19 severity, and neutrophil extracellular traps (NETs) have been found in the lung parenchyma of patients with acute respiratory distress syndrome (ARDS) in COVID-19. Targeting the pro-inflammatory functions of neutrophils may diminish lung injury in COVID-19 and ARDS. Neutrophils were isolated from peripheral blood of healthy donors, treated ex vivo with dexamethasone, tocilizumab and intravenous immunoglobulin (IVIG) and NET formation, oxidative burst, and phagocytosis were assessed. Plasma from critically ill COVID-19 patients before and after clinical treatment with IVIG and from healthy donors was assessed for neutrophil activation-related proteins. While dexamethasone and tocilizumab did not affect PMA- and nigericin-induced NET production ex vivo, IVIG induced a dose-dependent abrogation of NET production in both activation models. IVIG also reduced PMA-elicited reactive oxygen species production, but did not alter phagocytosis. COVID-19 patients were found to have elevated levels of cell-free DNA, neutrophil elastase and IL-8 as compared to healthy controls. Levels of both cell-free DNA and neutrophil elastase were lower 5 days after 4 days of daily treatment with IVIG. The lack of impact of dexamethasone or tocilizumab on these neutrophil functions suggests that these therapeutic agents may not act through suppression of neutrophil functions, indicating that the door might still be open for the addition of a neutrophil modulator to the COVID-19 therapeutic repertoire

Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2

Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated with several inflammatory lung disorders, including the recent e-cigarette or vaping product use-associated lung injury (EVALI) epidemic, and recent studies have suggested that vaping alters host susceptibility to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the impact of vaping on lung inflammatory pathways, including the angiotensin-converting enzyme 2 (ACE2) receptor known to be involved in SARS-CoV-2 infection, mice were exposed to e-cigarette aerosols for 60 min daily for 1-6 months and underwent gene expression analysis. Hierarchical clustering revealed extensive gene expression changes occurred in the lungs of both inbred C57BL/6 mice and outbred CD1 mice, with 2,933 gene expression changes in C57BL/6 mice, and 2,818 gene expression changes in CD1 mice (>abs 1.25-fold change). Particularly, large reductions in IgA and CD4 were identified, indicating impairment of host responses to pathogens via reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses via decreased neutrophils and/or monocytes in the lungs. Gene set enrichment (GSE) plots demonstrated upregulation of gene expression related to cell activation specifically in neutrophils. As neutrophils are a potential driver of acute lung injury in COVID-19, increased neutrophil activation in the lungs suggests that vapers are at higher risk of developing more severe forms of COVID-19. The receptor through which SARS-CoV-2 infects host cells, ACE2, was found to have moderate upregulation in mice exposed to unflavored vape pens, and further upregulation (six-fold) with JUUL mint aerosol exposure. No changes were found in mice exposed to unflavored Mod device-generated aerosols. These findings suggest that specific vaping devices and components of e-liquids have an effect on ACE2 expression, thus potentially increasing susceptibility to SARS-CoV-2. In addition, exposure to e-cigarette aerosols both with and without nicotine led to alterations in eicosanoid lipid profiles within the BAL. These data demonstrate that chronic, daily inhalation of e-cigarette aerosols fundamentally alters the inflammatory and immune state of the lungs. Thus, e-cigarette vapers may be at higher risk of developing infections and inflammatory disorders of the lungs

Dual use of e-cigarettes with conventional tobacco is associated with increased sleep latency in cross-sectional Study.

The health effects of e-cigarettes remain relatively unknown, including their impact on sleep quality. We previously showed in a pilot study that females who smoke both conventional tobacco and vape e-cigarettes (dual users) had decreased sleep quality (measurement of how well an individual is sleeping) and increased sleep latency (amount of time to fall asleep), suggesting an influence by gender. Cough is also known to adversely impact sleep quality and may be caused by inhalant use. As a result, we undertook this study to assess the impact of e-cigarette, conventional tobacco, and dual use on sleep quality, sleep latency, cough, and drug use. Participants (n = 1198) were recruited through online surveys posted to social media sites with a monetary incentive. Participants were grouped by inhalant use, with 8% e-cigarette users, 12% conventional tobacco users, 30% dual users, and 51% non-smokers/non-vapers. Dual use of e-cigarettes and conventional tobacco was associated with increased sleep latency relative to non-smokers/non-vapers by multivariable linear regression (mean difference of 4.08; 95% CI: 1.12 to 7.05, raw p = 0.007, adjusted p = 0.042); however, dual usage was not significantly associated with sleep quality relative to non-smokers/non-vapers (mean difference 0.22, 95%CI: (-0.36, 0.80), raw p = 0.452, adjust p = 0.542). Dual use was also associated with a higher reporting of cough (p = 0.038), as well as increased marijuana (p < 0.001) and cocaine (p < 0.001) usage. This study demonstrates that  dual use is associated with longer sleep latency, and suggests that the shared component of nicotine may be a driver. Because sleep broadly impacts multiple aspects of human health, defining the associations of e-cigarettes and vaping devices on sleep is critical to furthering our understanding of their influence on the body

Vaping-induced metabolomic signatures in the circulation of mice are driven by device type, e-liquid, exposure duration and sex.

Each type of vaping device (vape pen, box Mod and JUUL), as well as nicotine and flavourings, induces a disparate metabolite profile or signature, such that each device and liquid is likely to lead to its own set of health effects https://bit.ly/3eExKzi

Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice

While health effects of conventional tobacco are well defined, data on vaping devices, including one of the most popular e-cigarettes which have high nicotine levels, are less established. Prior acute e-cigarette studies have demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies have demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated the impact of inhalation of aerosols produced from pod-based, flavored e-cigarettes (JUUL) aerosols three times daily for 3 months on inflammatory markers in the brain, lung, heart, and colon. JUUL aerosol exposure induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens in the central nervous system. Inflammatory gene expression increased in the colon, while gene expression was more broadly altered by e-cigarette aerosol inhalation in the lung. Cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-specific findings were detected across these studies. Our findings suggest that daily e-cigarette use may cause neuroinflammation, which may contribute to behavioral changes and mood disorders. In addition, e-cigarette use may cause gut inflammation, which has been tied to poor systemic health, and cardiac inflammation, which leads to cardiovascular disease

Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice

While health effects of conventional tobacco are well defined, data on vaping devices, including one of the most popular e-cigarettes which have high nicotine levels, are less established. Prior acute e-cigarette studies have demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies have demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated the impact of inhalation of aerosols produced from pod-based, flavored e-cigarettes (JUUL) aerosols three times daily for 3 months on inflammatory markers in the brain, lung, heart, and colon. JUUL aerosol exposure induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens in the central nervous system. Inflammatory gene expression increased in the colon, while gene expression was more broadly altered by e-cigarette aerosol inhalation in the lung. Cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-specific findings were detected across these studies. Our findings suggest that daily e-cigarette use may cause neuroinflammation, which may contribute to behavioral changes and mood disorders. In addition, e-cigarette use may cause gut inflammation, which has been tied to poor systemic health, and cardiac inflammation, which leads to cardiovascular disease

Increased Peripheral Blood Neutrophil Activation Phenotypes and Neutrophil Extracellular Trap Formation in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series and Review of the Literature.

BackgroundIncreased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.MethodsBlood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English.ResultsElevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1β, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death.ConclusionsLiterature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature.

BackgroundIncreased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.MethodsBlood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.ResultsElevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.ConclusionsLiterature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst