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Principal Investigator: Robert Blair
Organization: TULANE UNIVERSITY OF LOUISIANA
Fiscal Year: 2023
Award: $198,597
Funding agency: NIH Office of the Director
PROJECT SUMMARY
Vaping is a serious public health concern that was associated with outbreaks of hospitalizations and deaths in
2019. These outbreaks of electronic vaping associated lung injury (EVALI) coincided with increased use of
electronic vaping devices by adolescents and young adults. The rapid disease onset of EVALI and the role of
macrophages in its progression, support a role for the innate immune system in the pathogenesis of EVALI.
Despite its rising use little is currently known about the effect of vaping on pulmonary immunology and physiology
highlighting the need for animal models to better understand its effects. Small animal models have shown
pathologic changes following exposure to vaping aerosols; however, they do not recapitulate the pathologic
manifestations of EVALI reported in humans necessitating a more translatable animal model to investigate the
pathogenesis of EVALI. Nonhuman primates (NHPs) are ideally suited for studying respiratory diseases in
humans due to their similarity in both pulmonary anatomy and immunology which provide advantages over other
animal models. Here, we aim to utilize a NHP model to investigate the impact of vaping aerosol exposure on
innate pulmonary defense mechanisms. We will longitudinally assess pulmonary and innate immune function
(immune cell infiltrates, alveolar macrophage phagocytosis, and secretion of cytokines, chemokines, and
defense molecules) over a four-week period of daily vaping aerosol exposure. At the end of the study, correlation
with pathologic changes will occur through rigorous postmortem examination and sampling of the upper and
lower respiratory tract. The data generated from this study will inform on mechanisms by which vaping aerosols
effect innate pulmonary defenses, an important area of investigation in this time of highly infectious respiratory
diseases. Furthermore, this study will provide preliminary data for future investigations evaluating the contribution
of individual constituents within the vaping liquid (nicotine, tetrahydrocannabinol, and vitamin E acetate); and
vaping in the context of comorbid conditions (SARS-CoV-2 and HIV/SIV), areas of special interest supported by
several funding agencies (NIDA, NHLBI, NIAID). This proposed study and Mentored Career Development Plan
will be conducted at the Tulane National Primate Research Center under the guidance of Drs. Ronald Veazey
and Chad Roy. The TNPRC has been a national resource and center of excellence for biomedical research
using nonhuman primates for over 50 years. The TNPRC has a strong commitment to training and mentorship
and provides support (financial and effort-based) to create a rich and diverse training environment for early-stage
investigators. The TNPRC fully supports Dr. Blair in his career goal to develop into an independently funded
private investigator working with NHP models to study diseases of major public health importance. The dedicated
time and additional mentorship provided by this K01 will help Dr. Blair refine his grant writing and project
management skills to ensure the success of his future R01 proposals.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><9-ene-Tetrahydrocannabinol><AIDS Virus><Acceleration><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Acute><Adolescent><Adolescent Youth><Adolescent and Young Adult><Adoption><Aerosols><Affect><Alveolar><Alveolar Macrophages><Anatomic Sites><Anatomic structures><Anatomy><Animal Model><Animal Models and Related Studies><Area><Assay><Autopsy><Bioassay><Biologic Assays><Biological Assay><Body Tissues><Breathlessness><Bronchiolitis><Bronchoalveolar Lavage Fluid><COBRE><COVID-19 virus><COVID19 virus><Cell Body><Cell Isolation><Cell Segregation><Cell Separation><Cell Separation Technology><Cells><Center of Biomedical Research Excellence><Centers of Research Excellence><Cessation of life><Chad><Chemotactic Cytokines><Clinical><CoV-2><CoV2><Data><Death><Dedications><Defense Mechanisms><Defensins><Delta-9-Tetrahydrocannabinol><Development Plans><Devices><Diffuse><Disease><Disease Outbreaks><Disease model><Disorder><Dysfunction><Dyspnea><ELISA><Educational workshop><Ensure><Environment><Enzyme-Linked Immunosorbent Assay><Exposure to><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Foundations><Functional disorder><Funding><Funding Agency><Funding Source><Future><Goals><Grant><HIV><Homologous Chemotactic Cytokines><Hospital Admission><Hospitalization><Human><Human Immunodeficiency Viruses><Immune><Immune infiltrates><Immunes><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Immunology><Individual><Inflammation><Inflammatory><Innate Immune Response><Innate Immune System><Intercrines><Investigation><Investigators><LAV-HTLV-III><Lipids><Liquid substance><Lower respiratory tract structure><Lung><Lung Function Tests><Lung Inflammation><Lung Respiratory System><Lung immune response><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca mulatta><Macrophage><Mentors><Mentorship><Microscopic><Modeling><Modern Man><Mφ><NHLBI><NIAID><NIDA><NIH><National Heart, Lung, and Blood Institute><National Institute of Allergy and Infectious Disease><National Institute of Drug Abuse><National Institute on Drug Abuse><National Institutes of Health><Nicotine><Onset of illness><Outbreaks><Pathogenesis><Pathogenicity><Pathologic><Patients><Phagocytes><Phagocytic Cell><Phagocytosis><Phenotype><Physiology><Physiopathology><Play><Pneumonia><Pneumonitis><Policies><Position><Positioning Attribute><Primates><Primates Mammals><Privatization><Public Health><Pulmonary Inflammation><Pulmonary Macrophages><Pulmonary Pathology><Pulmonary function tests><Radiography><Reporting><Research><Research Personnel><Research Resources><Researchers><Resources><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Rhesus Macaque><Rhesus Monkey><Rodent Model><Roentgenography><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIS cytokines><SIV><Saline><Saline Solution><Sampling><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Simian Immunodeficiency Viruses><Study models><System><TLR protein><Terminal Bronchiole><Testing><Tetrahydrocannabinol><Time><Tissues><Tocopherol acetate><Toll-Like Receptor Family Gene><Toll-like receptors><Training><Trees><United States National Institutes of Health><Upper respiratory tract><Virus-HIV><Vitamin E Acetate><Workshop><Writing><Wuhan coronavirus><aerosolized><airway epithelium inflammation><airway inflammation><alpha-tocopherol acetate><alpha-tocopheryl acetate><amebocyte><career><career development><cell sorting><chemoattractant cytokine><chemokine><co-morbid><co-morbidity><comorbidity><coronavirus disease 2019 virus><coronavirus disease-19 virus><cytokine><d-alpha-Tocopherol acetate><d-alpha-tocopheryl acetate><delta(1)-THC><delta(1)-Tetrahydrocannabinol><delta(9)-THC><delta(9)-Tetrahydrocannabinol><disease onset><disorder model><disorder onset><e-vape><electronic vape><enzyme linked immunoassay><flow cytophotometry><fluid><hCoV19><immune cell infiltrate><improved><innate immune function><innate immune mechanisms><interest><juvenile><juvenile human><liquid><lower respiratory tract><lung function><lung pathology><model of animal><nCoV2><necropsy><non-human primate><nonhuman primate><novel><pathophysiology><postmortem><psychological defense mechanism><pulmonary><pulmonary function><pulmonary immune response><radiologic imaging><radiological imaging><receptor expression><respiratory inflammation><respiratory tract inflammation><response><skills><social role><success><surfactant><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><tocopherolacetate-d-alpha><tocopheryl acetate><upper airway tract><vaping><vaping associated lung injury><vaping induced acute lung injury><vaping product use associated lung injury><vaping-related lung injury><Δ(1)-THC><Δ(1)-tetrahydrocannabinol><Δ(9)-THC><Δ(9)-tetrahydrocannabinol><Δ-9-tetrahydrocannabinol><Δ9-tetrahydrocannabinol>