title: Alcohol and lung injury and immunity.
abstract: Annually, excessive alcohol use accounts for more than $220 billion in economic costs and 80,000 deaths, making excessive alcohol use the third leading lifestyle-related cause of death in the US. Patients with an alcohol-use disorder (AUD) also have an increased susceptibility to respiratory pathogens and lung injury, including a 2-4-fold increased risk of acute respiratory distress syndrome (ARDS). This review investigates some of the potential mechanisms by which alcohol causes lung injury and impairs lung immunity. In intoxicated individuals with burn injuries, activation of the gut-liver axis drives pulmonary inflammation, thereby negatively impacting morbidity and mortality. In the lung, the upper airway is the first checkpoint to fail in microbe clearance during alcohol-induced lung immune dysfunction. Brief and prolonged alcohol exposure drive different post-translational modifications of novel proteins that control cilia function. Proteomic approaches are needed to identify novel alcohol targets and post-translational modifications in airway cilia that are involved in alcohol-dependent signal transduction pathways. When the upper airway fails to clear inhaled pathogens, they enter the alveolar space where they are primarily cleared by alveolar macrophages (AM). With chronic alcohol ingestion, oxidative stress pathways in the AMs are stimulated, thereby impairing AM immune capacity and pathogen clearance. The epidemiology of pneumococcal pneumonia and AUDs is well established, as both increased predisposition and illness severity have been reported. AUD subjects have increased susceptibility to pneumococcal pneumonia infections, which may be due to the pro-inflammatory response of AMs, leading to increased oxidative stress.
authors: Department of Medicine, Emory University and Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA.
authors: Samantha M
authors: SM
authors: Yeligar
authors: Burn and Shock Trauma Research Institute, Alcohol Research Program, Integrative Cell Biology Program, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.
authors: Michael M
authors: MM
authors: Chen
authors: Department of Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors: Elizabeth J
authors: EJ
authors: Kovacs
authors: Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Joseph H
authors: JH
authors: Sisson
authors: Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors: Ellen L
authors: EL
authors: Burnham
authors: Department of Pediatrics, Emory University, Atlanta, GA 30322, USA. Electronic address: lbrow03@emory.edu.
authors: Lou Ann S
authors: LA
authors: Brown
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000276:immunology*; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology
chemical_list: D000431:Ethanol
keywords: Airway cilia; Alcohol; Alveolar macrophage; Gut-liver-lung axis; Lung immunity; Lung injury