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Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Alcohol's Effects on the Lung and Lung Disease
1Department of Internal Medicine, Division of Pulmonary, Critical Care & Sleep, University of Nebraska Medical Center, Omaha, Nebraska Nebraska Food for Health Center, University of Nebraska, Lincoln, Lincoln, Nebraska.
Purpose:
Alcohol misuse is widely accepted as an independent risk factor for a wide variety of lung diseases, such as pneumonia and acute respiratory distress syndrome. Alcohol induces changes in the regulatory mechanisms of the lung, both at a mechanical and immunological level. Understanding these changes might help discover new targets for drugs and therapeutic approaches for the prevention of respiratory disease following alcohol misuse.
Search Methods:
A systematic literature search was conducted on January 25, 2025, in PubMed, Medline, and Embase of manuscripts published between January 2000 and January 2025 using the terms ("alcohol" or "ethanol") AND ("lung," or "respiratory," or "pulmonary") AND ("pneumonia" or "damage" or "leak"). Eligible manuscripts included studies that discussed the effects of ethanol on the lungs.
Search Results:
A total of 962 publications were identified; after excluding duplicates and research not covering alcohol-related lung effects (e.g., studies investigating liver damage or alcohol-related tissue injury; 814 articles), 148 studies were reviewed. An additional 15 papers from before 2000 were included as historical precedents for the current research cited. Of the 148 studies, 114 were cited in this review; previous review articles and those discussing in utero or prenatal alcohol exposure were excluded (34 articles).
Discussion And Conclusions:
The lungs are particularly susceptible to infections and injury following alcohol misuse. Several key mechanisms by which alcohol misuse drives lung damage have been identified. Alcohol misuse leads to impaired mucus-facilitated clearance of bacterial pathogens, increases the aspiration of microbes from the upper alimentary tract, and suppresses tissue recruitment and function of innate and adaptive immune cells. Alcohol-related reductions in antioxidant levels, trace metals, and metabolites may also contribute to lung disease in people with underlying alcohol misuse. Several regulatory molecules may play crucial roles in alcohol-induced disease processes. Although there are currently no approved therapies to combat the detrimental effects of chronic alcohol consumption on the respiratory system, these molecules may be potential therapeutic targets to guide future investigation. Despite these advancements, limitations and knowledge gaps in the field still exist. For example, few studies have investigated dose- and duration-dependent effects of alcohol on the lung, sex-specific differences in lung responses, and the interaction of alcohol with other coexposures/comorbidities, such as smoking and HIV. In addition, well-defined observational and longitudinal human studies employing robust measures of alcohol use are limited. These gaps represent novel opportunities for more thorough and robust experimental designs of human and animal studies investigating alcohol-associated lung disease.
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