Clinical Resource for Lung and Alcohol Investigations

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DESCRIPTION (provided by applicant): Pneumonia is a common and serious medical condition among individuals with alcohol use disorders (AUDs) in the US. Despite numerous intriguing observations in animal models and small scale human investigations, none have progressed forward into clinical trials aimed at decreasing the incidence of pneumonia in those with AUDs. To promote innovation in the field, investigators at the University of Colorado Denver (UCD) are seeking support to lead a consortium comprised of 4 premier sites in alcohol- related pneumonia research, including Emory University (EU), Louisiana State University (LSU), Loyola University (LUMC), and the University of Nebraska (UNMC) to investigate the effect of AUDs on susceptibility for pneumonia in human subjects. We will utilize this resource to test the hypothesis that alcohol-related alterations on pulmonary oxidative stress, the cytokine milieu, and endogenous proteins lead to an increased susceptibility to pneumonia through their influence on alveolar macrophage and bronchial airway epithelial cell function, and their influence on the respiratory tract microbiome. With this R24 support, we will expand an established resource at UCD by obtaining additional samples and data from subjects with AUDs and matched controls from EU and LSU, and from burned patients at LUMC and UCD. Support from biopreservation experts at the University of Minnesota will provide assistance in appropriate sample processing and storage to ensure quality experimental results. Specific aims will include determining the mechanisms whereby AUDs increase the predisposition to pneumonia via effects on (1)alveolar macrophage enterocytosis, apoptosis, and maturation and their relationship to zinc deficiency and pulmonary oxidative stress; (2)bronchial airway epithelial cell function, including expression of toll-like receptor-2, ciliary function, and response to protein adducts formed in the setting of AUDs and smoking; (3)respiratory tract microbial ecology, and its relationship to alterations in antimicrobial protein composition/function in the alveolar space, and alterations in pulmonary/systemic cytokine milieu in the presence and absence of burn injury. RELEVANCE: Alcohol-related pneumonias are a significant health care burden to the US. Research in this field has been hampered previously by the lack of an established infrastructure to conduct translational investigations in individuals with alcohol use disorders. Creating a consortium to share clinical samples and data relevant to the study of alcohol-associated pneumonias with committed investigators will promote discovery in this field.