Profiling endogenous airway proteases and antiproteases and modeling proteolytic activation of Influenza HA using in vitro and ex vivo human airway surface liquid samples.

Imbalance of airway proteases and antiproteases has been implicated in diseases such as COPD and environmental exposures including cigarette smoke and ozone. To initiate infection, endogenous proteases are commandeered by respiratory viruses upon encountering the airway epithelium. The airway proteolytic environment likely contains redundant antiproteases and proteases with diverse catalytic mechanisms, however a proteomic profile of these enzymes and inhibitors in airway samples has not been reported.

E-Cigarette Use, Cigarette Smoking, and Sex Are Associated With Nasal Microbiome Dysbiosis.

Introduction: Previous research suggests that e-cigarettes can alter immune function, including in the nasal mucosa, in unique ways. The respiratory microbiome plays a key role in respiratory host defense, but the effects of e-cigarettes on the respiratory or nasal microbiome, are not well understood.

Aims And Methods: Using 16S rRNA gene sequencing on nasal samples from adult e-cigarette users, smokers, and nonsmokers, we determined that e-cigarette use and cigarette smoking are associated with differential respiratory microbiome dysbiosis and substantial sex-dependent differences in the nasal microbiome, particularly in e-cigarette users.

Understanding the Relationship Between Neutrophil Function and Demographic Variables.

Neutrophils play a crucial role in the body's defense against respiratory pathogens, and dysregulation is linked to airway diseases. The study presented here explores the association between demographic factors (age, BMI, and sex) and functional phenotypes (oxidative burst and bioenergetics) of neutrophils. We measured PMA-stimulated oxidative burst (Seahorse XF) and phagocytosis (pHrodo red ) of human peripheral blood neutrophils and determined whether there were significant demographic associations with cellular function.

A pilot randomized clinical trial of γ-tocopherol supplementation on wood smoke-induced neutrophilic and eosinophilic airway inflammation.

Background: Air pollutants, including particulates from wood smoke, are a significant cause of exacerbation of lung disease. γ-Tocopherol is an anti-inflammatory isoform of vitamin E that has been shown to reduce allergen-, ozone-, and endotoxin-induced inflammation.

Objective: The objective of this study was to determine whether γ-tocopherol would prevent experimental wood smoke-induced airway inflammation in humans.

SARS-CoV-2 mRNA vaccination induces an intranasal mucosal response characterized by neutralizing antibodies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced systemic antibody profiles are well characterized; however, little is known about whether intranasal mucosal antibodies are induced or can neutralize virus in response to mRNA vaccination.

Objective: We sought to evaluate intranasal mucosal antibody production with SARS-CoV-2 mRNA vaccination.

Methods: SARS-CoV-2-specific IgG and IgA concentrations and neutralization activity from sera and nasal mucosa via nasal epithelial lining fluid (NELF) collection were measured in SARS-CoV-2 mRNA-vaccinated healthy volunteers (N = 29) by using multiplex immunoassays.

Development of LC-HRMS untargeted analysis methods for nasal epithelial lining fluid exposomics.

Background: The nasal mucosa, as a primary site of entry for inhaled substances, contains both inhaled xenobiotic and endogenous biomarkers. Nasal mucosa can be non-invasively sampled (nasal epithelial lining fluid "NELF") and analyzed for biological mediators. However, methods for untargeted analysis of compounds inhaled and/or retained in the nasal mucosa are needed.

Biomarkers of Airway Immune Homeostasis Differ Significantly with Generation of E-Cigarettes.

Numerous studies have demonstrated that e-cigarettes can impact respiratory immune homeostasis; however, the extent of these effects remains an active area of investigation, and most previous studies were conducted with model systems or subjects exposed to third-generation e-cigarettes, such as vape pens and box mods. Given the rise in popularity of nicotine-salt-containing pods and disposable e-cigarettes (fourth generation), we set out to better understand the respiratory effects of these newer e-cigarettes and compare their effects to early-generation devices. We collected induced sputum samples from a cohort of nonsmokers, smokers, third-generation e-cigarette users, and fourth-generation e-cigarette users ( = 20-30 per group) and evaluated the cellular and fluid-phase composition for markers of inflammation, host defense, and lung injury.

Cytokine signature clusters as a tool to compare changes associated with tobacco product use in upper and lower airway samples.

Inhalation exposure to cigarette smoke and e-cigarette aerosol is known to alter the respiratory immune system, particularly cytokine signaling. In assessments of health impacts of tobacco product use, cytokines are often measured using a variety of sample types, from serum to airway mucosa. However, it is currently unclear whether and how well cytokine levels from different sample types and the airway locations they represent are correlated, making comparing studies that utilize differing sample types challenging.

Discovery of Acyl-sulfonamide Na1.7 Inhibitors GDC-0276 and GDC-0310.

Na1.7 is an extensively investigated target for pain with a strong genetic link in humans, yet in spite of this effort, it remains challenging to identify efficacious, selective, and safe inhibitors. Here, we disclose the discovery and preclinical profile of GDC-0276 () and GDC-0310 (), selective Na1.

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial.

Inhalation of tobacco smoke has been linked to increased risk of viral infection, such as influenza. Inhalation of electronic-cigarette (e-cigarette) aerosol has also recently been linked to immune suppression within the respiratory tract, specifically the nasal mucosa. We propose that changes in the nasal mucosal immune response modify antiviral host-defense responses in e-cigarette users.

SARS-CoV-2 Seroprevalence among a Southern U.S. Population Indicates Limited Asymptomatic Spread under Physical Distancing Measures.

Characterizing the asymptomatic spread of SARS-CoV-2 is important for understanding the COVID-19 pandemic. This study was aimed at determining asymptomatic spread of SARS-CoV-2 in a suburban, Southern U.S.

Short course gamma tocopherol did not mitigate effects of ozone on airway inflammation in asthmatics.

Introduction:: Exposure to elevated ambient ozone levels has been associated with exacerbation of asthma, likely mediated by oxidative stress. We have shown that supplementation with the antioxidant vitamin E isoform, gamma tocopherol, mitigates the inflammatory effects of inhaled endotoxin exposure, a key component of ambient air particulate matter.

Objective:: The objective of the current study was to assess the efficacy of gamma tocopherol for mitigating pulmonary effects of ozone, using an abbreviated dosing regimen that could be rapidly begun when high ozone days are anticipated.

Identification of Selective Acyl Sulfonamide-Cycloalkylether Inhibitors of the Voltage-Gated Sodium Channel (Na) 1.7 with Potent Analgesic Activity.

Herein, we report the discovery and optimization of a series of orally bioavailable acyl sulfonamide Na1.7 inhibitors that are selective for Na1.7 over Na1.

Selective Na1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain.

Selective block of Na1.7 promises to produce non-narcotic analgesic activity without motor or cognitive impairment. Several Na1.

Low-level ozone has both respiratory and systemic effects in African American adolescents with asthma despite asthma controller therapy.

In a cohort of African American adolescents with persistent asthma on guidelines-based daily controller therapies, short–term elevation of low ozone levels below the National Ambient Air Quality Standard of 70 ppb were associated with lung function decrements and elevated lipid levels.

Design of Conformationally Constrained Acyl Sulfonamide Isosteres: Identification of N-([1,2,4]Triazolo[4,3- a]pyridin-3-yl)methane-sulfonamides as Potent and Selective hNa1.7 Inhibitors for the Treatment of Pain.

The sodium channel Na1.7 has emerged as a promising target for the treatment of pain based on strong genetic validation of its role in nociception. In recent years, a number of aryl and acyl sulfonamides have been reported as potent inhibitors of Na1.

Zoos and public health: A partnership on the One Health frontier.

Today, accredited zoos are not just places for entertainment, they are actively involved in research for conservation and health. During recent decades in which the challenges for biodiversity conservation and public health have escalated, zoos have made significant changes to address these difficulties. Zoos increasingly have four key areas of focus: education, recreation, conservation, and research.

Diesel exposure suppresses natural killer cell function and resolution of eosinophil inflammation: a randomized controlled trial of exposure in allergic rhinitics.

Exposure to diesel exhaust (DE) is known to exacerbate allergic inflammation, including virus-induced eosinophil activation in laboratory animals. We have previously shown that in human volunteers with allergic rhinitis a short-term exposure to DE prior to infection with the live attenuated influenza virus (LAIV) increases markers of allergic inflammation in the nasal mucosa. Specifically, levels of eosinophilic cationic protein (ECP) were significantly enhanced in individuals exposed to DE prior to inoculation with LAIV and this effect was maintained for at least seven days.

Treatment of dyslipidemia with statins by primary care providers in Veterans with and without chronic Hepatitis C.

Objective: The purpose of this study was to describe the current use of statins in United States (US) veterans at W. G. Hefner Veterans Affairs Medical Center (VA Salisbury) with chronic hepatitis C virus (HCV) compared to those without chronic HCV and to examine why statin use may be avoided in this population.

Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study.

Unlabelled: Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV) as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH) reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells.