Publications by authors named "Ira Advani"

5 Publications

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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.

Front Physiol 2021 31;12:649604. Epub 2021 May 31.

Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, United States.

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 reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses 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.
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http://dx.doi.org/10.3389/fphys.2021.649604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194307PMC
May 2021

Assessing the potential impact of age and inhalant use on sleep in adolescents.

J Clin Sleep Med 2021 May 24. Epub 2021 May 24.

Pulmonary Critical Care Section, Veterans Affairs (VA) San Diego Healthcare System, La Jolla, CA 92161.

Study Objectives: Targeted marketing has caused a recent surge in teen e-cigarette usage. In all-age surveys, we isolated adolescent data (13-20 years) to assess age alongside e-cigarettes, traditional tobacco, and dual usage of both with sleep quality and cough. Based on existing adult literature, we hypothesized an association between dual usage and increased sleep latency.

Methods: Participants were recruited to complete surveys via social media sites. We performed three surveys: Survey 1 (n=47) in 2018, Survey 2 (n=1198) in 2019, Survey 3 (n=564) in 2020. Surveys 1 and 2 had three sections: past and current inhalant use, Pittsburgh Sleep Quality Index (PSQI), and Leicester Cough Questionnaire (LCQ). Survey 3 did not include the LCQ, instead the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire (PHQ9). The adolescent data were isolated (n=609).

Results: Adolescents reported longer sleep duration with increasing age by one-way ANOVA. By Tukey's multiple comparisons test, females slept more at ages 19 and 20 than at age 14 (p<0.01). Female dual users slept more than nonsmokers, (p=0.01; mean difference 43.8 minutes; CI=0.11 to 1.36). We observed an association between dual use and sleep latency versus nonsmokers (p=0.0008; mean difference 6.27 minutes; CI=1.40 to 11.13). We saw no correlation between inhalant use and cough.

Conclusions: In females, we observed a peak in sleep hours at age 19. College-aged females may wake later than younger adolescent females. The data also raised concern for sleep disruption and nicotine-induced wakefulness. Further data are required in order to define public health strategies.
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http://dx.doi.org/10.5664/jcsm.9414DOI Listing
May 2021

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

Clin Infect Dis 2021 May 14. Epub 2021 May 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Background: Increased 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.

Methods: Blood 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.

Results: Elevations 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.

Conclusions: Literature 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.
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http://dx.doi.org/10.1093/cid/ciab437DOI Listing
May 2021

Is Increased Sleep Responsible for Reductions in Myocardial Infarction During the COVID-19 Pandemic?

Am J Cardiol 2020 09 20;131:128-130. Epub 2020 Jun 20.

Pulmonary Critical Care Section, Veterans Affairs (VA) San Diego Healthcare System, La Jolla, California; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, California. Electronic address:

The COVID-19 pandemic caused by the highly contagious SARS-CoV-2 virus has had devastating consequences across the globe. However, multiple clinics and hospitals have experienced a decrease in rates of acute myocardial infarction and corresponding cardiac catheterization lab activations, raising the question: Has the risk of myocardial infarction decreased during COVID? Sleep deprivation is known to be an independent risk factor for myocardial infarction, and sleep has been importantly impacted during the pandemic, possibly due to the changes in work-home life leading to a lack of structure. We conducted a social media-based survey to assess potential mechanisms underlying the observed improvement in risk of myocardial infarction. We used validated questionnaires to assess sleep patterns, tobacco consumption and other important health outcomes to test the hypothesis that increases in sleep duration may be occurring which have a beneficial impact on health. We found that the COVID-19 pandemic led to shifts in day/night rhythm, with subjects waking up 105 minutes later during the pandemic (p <0.0001). Subjects also reported going to sleep 41 minutes later during the pandemic (p <0.0001). These shifts led to longer duration of sleep during the COVID-19 pandemic. Before the pandemic, subjects reported sleeping 6.8 hours per night, which rose to 7.5 hours during the pandemic, a 44 minute or 11% increase (p <0.0001). We acknowledge the major negative health impact of the global pandemic but would advocate for using this crisis to improve the work and sleep habits of the general population, which may lead to overall health benefits for our society.
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http://dx.doi.org/10.1016/j.amjcard.2020.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305870PMC
September 2020