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Principal Investigator: Todd A Wyatt
Organization: OMAHA VA MEDICAL CENTER
Fiscal Year: 2024
Funding agency: Veterans Affairs
Pneumonia is one of the leading causes of morbidity and mortality, particularly in older individuals. Importantly,
alcohol misuse has been associated with increased pneumonia for over 200 years. While the role of alcohol in
bacterial pneumonia susceptibility and severity remains to be fully understood, it is essential to define the at-
risk conditions and unique needs of those who misuse alcohol and to do so immediately in order to optimize
clinical care. Common in both active-duty and the veterans’ population, those with alcohol use disorders (AUD)
can be characterized by heavy cigarette smoking leading to pre-existing lung diseases such as chronic
obstructive pulmonary disease (COPD), a major co-morbidity for pneumonia. Our knowledge about how such
characteristics impact this pathogenesis is limited. However, results from our previous lung alcohol research
have already demonstrated that AUD are associated with cilia dysfunction. Our results also demonstrate that
AUD results in decreased surfactant anti-microbial action. Surfactant protein D has been documented to
specifically bind to and aggregate bacteria for optimal microbicidal action. We hypothesize that altered innate
lung defense at the level of mucociliary clearance and anti-microbial surfactants will negatively impact
susceptibility and pathogenesis of bacterial pneumonia, placing individuals with AUD particularly in harm’s
way. Our assembled team of investigators include a VA Research Career Scientist with 26 years’ experience in
the impact of alcohol on lung injury and repair, a VA pulmonologist whose expertise is on characterizing
primary human lung clinical samples, experienced alcohol liver injury researchers, and a junior investigator
who is already an expert in working with alcohol and bacterial infections. Our established expertise in mouse
models of alcohol injury combined with our existing biobank of human lung cells and tissues, we propose to
address our hypothesis by identifying any differences in S. pneumoniae infection responses due to alcohol
and/or cigarette smoking. We will specifically identify in these groups any changes in cilia beat controlling
clearance, surfactant protein D structure/function, and the role of reactive aldehydes generated by liver-derived
extracellular vesicles. Such studies will be performed for the first time in animal and cell models relevant to
AUD. Defining the modalities of risk will also empower clinicians to make informed preventive care decisions in
the context of alcohol misuse.
Terms: <3-D><3-Dimensional><3D><Acetaldehyde><Address><Adhesions><Alcohol Chemical Class><Alcohol Drinking><Alcohol abuse><Alcohol consumption><Alcohol dehydrogenase><Alcohol-NAD+ Oxidoreductase><Alcohols><Aldehydes><Animal Feed><Animal Model><Animal Models and Related Studies><Bacteria><Bacterial Infections><Bacterial Model><Bacterial Pneumonia><Binding><Body Tissues><COPD><Cell Body><Cell model><Cells><Cellular model><Cessation of life><Characteristics><Chronic Obstruction Pulmonary Disease><Chronic Obstructive Lung Disease><Chronic Obstructive Pulmonary Disease><Cigarette Smoker><Cilia><Clinical><Collagenous Lectins><Collectins><Cytochromes><D pneumoniae><D. pneumoniae><Death><Defensins><Diplococcus pneumoniae><Disease><Disorder><Dysfunction><Enzyme Gene><Enzymes><Epithelial Cells><Epithelium><EtOH abuse><EtOH drinking><EtOH use><Ethanal><Functional disorder><Hepatic Cells><Hepatic Parenchymal Cell><Hepatocyte><Human><Impairment><In Vitro><Individual><Infection><Injury><Injury to Liver><Innate Immune System><Intervention><Intervention Strategies><Investigators><Knowledge><Lead><Literature><Liver><Liver Cells><Lung><Lung Diseases><Lung Protein D><Lung Respiratory System><Lung damage><Lung infections><Macrophage><Malonaldehyde><Malondialdehyde><Malonylaldehyde><Malonyldialdehyde><Mediating><Mice><Mice Mammals><Modality><Modeling><Modern Man><Molecular Interaction><Morbidity><Morbidity - disease rate><Mucociliary Clearance><Mucociliary Transport><Murine><Mus><Mφ><Older Population><Organoids><Pathogenesis><Pb element><Phagocytosis><Physiopathology><Pneumococcus><Pneumonia><Predisposing Factor><Predisposition><Preventative care><Preventive care><Production><Propanedial><Proteins><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Surfactant Protein D><Pulmonary Surfactant-Associated Protein D><Research><Research Personnel><Researchers><Respiratory Epithelium><Risk><Role><S pneumoniae><S. pneumoniae><SP-D><Sampling><Scientist><Severities><Smoke><Smoker><Smoking><Source><Streptococcus pneumoniae><Structure><Structure of respiratory epithelium><Surfactant Protein D><Surfactant-Associated Glycoprotein D><Susceptibility><Testing><Time><Tissues><active duty><active service><adduct><airway epithelium><alcohol co-abuse><alcohol exposed><alcohol exposure><alcohol ingestion><alcohol intake><alcohol misuse><alcohol problem><alcohol product use><alcohol related research><alcohol research><alcohol use><alcohol use disorder><alcoholic beverage consumption><alcoholic drink intake><animal food><anti-microbial><antimicrobial><bacteria infection><bacteria pneumonia><bacterial disease><biobank><biorepository><career><chronic obstructive pulmonary disorder><cigarette smoke><cigarette smoking><cigarette use><clinical care><co-morbid><co-morbidity><comorbidity><cost><disease of the lung><disorder of the lung><empowerment><ethanol abuse><ethanol consumption><ethanol drinking><ethanol exposed><ethanol exposure><ethanol ingestion><ethanol intake><ethanol misuse><ethanol product use><ethanol research><ethanol use><ethanol use disorder><experience><exposed to alcohol><exposed to ethanol><exposure to alcohol><exposure to ethanol><extracellular vesicles><hazardous alcohol use><heavy metal Pb><heavy metal lead><hepatic body system><hepatic damage><hepatic injury><hepatic organ system><in vivo><in vivo Model><inflammatory lung disease><injuries><interventional strategy><liver damage><liver injury><lung development><lung disorder><lung function><lung injury><lung pathogen><lung repair><lung tissue repair><microbicidal><microbicide><military veteran><model of animal><mortality><mouse model><murine model><older groups><older individuals><older person><pathophysiology><problem alcohol use><problem drinking><problematic alcohol consumption><problematic alcohol use><pulmonary><pulmonary damage><pulmonary function><pulmonary infections><pulmonary injury><pulmonary pathogen><pulmonary repair><pulmonary tissue damage><pulmonary tissue injury><respiratory tract epithelium><response><social role><surfactant><three dimensional><translational impact><unhealthy alcohol use><veteran population>