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.

Public Health 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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects (R24)
Project #
5R24AA019661-04
Application #
8715656
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Jung, Kathy
Project Start
2011-08-01
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Aurora
State
CO
Country
United States
Zip Code
80045
Afshar, Majid; Burnham, Ellen L; Joyce, Cara et al. (2017) Cut-Point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a Mixed Cohort Including Critically Ill Patients. Alcohol Clin Exp Res 41:1745-1753
Ruan, Sanbao; Cai, Yang; Ramsay, Alistair J et al. (2017) B cell and antibody responses in mice induced by a putative cell surface peptidase of Pneumocystis murina protect against experimental infection. Vaccine 35:672-679
Aschner, Yael; Burnham, Ellen L (2017) Adjuvant Therapies for ARDS: Not Ready for Prime Time? Ann Am Thorac Soc 14:14-16
Frankel, John H; Boe, Devin M; Albright, Joslyn M et al. (2017) Age-related immune responses after burn and inhalation injury are associated with altered clinical outcomes. Exp Gerontol :
Sapkota, Muna; Burnham, Ellen L; DeVasure, Jane M et al. (2017) Malondialdehyde-Acetaldehyde (MAA) Protein Adducts Are Found Exclusively in the Lungs of Smokers with Alcohol Use Disorders and Are Associated with Systemic Anti-MAA Antibodies. Alcohol Clin Exp Res 41:2093-2099
Fini, Mehdi A; Gaydos, Jeanette; McNally, Alicia et al. (2017) Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity. Am J Physiol Lung Cell Mol Physiol 313:L1047-L1057
Abdul-Muneer, P M; Alikunju, Saleena; Mishra, Vikas et al. (2017) Activation of NLRP3 inflammasome by cholesterol crystals in alcohol consumption induces atherosclerotic lesions. Brain Behav Immun 62:291-305
Jolley, Sarah E; Alkhafaf, Qasim; Hough, Catherine et al. (2016) Presence of an Alcohol Use Disorder is Associated with Greater Pneumonia Severity in Hospitalized HIV-Infected Patients. Lung 194:755-62
Gaydos, Jeanette; McNally, Alicia; Guo, Ruixin et al. (2016) Alcohol abuse and smoking alter inflammatory mediator production by pulmonary and systemic immune cells. Am J Physiol Lung Cell Mol Physiol 310:L507-18
Moazed, Farzad; Burnham, Ellen L; Vandivier, R William et al. (2016) Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation. Thorax 71:1130-1136

Showing the most recent 10 out of 40 publications