Abstract
An alcohol use disorder (AUD) is associated with an increased susceptibility to respiratory infection and injury and, upon hospitalization, higher mortality rates. Studies in model systems show effects of alcohol on mitochondrial function, lipid metabolism and antioxidant systems. The present study applied high-resolution metabolomics to test for these changes in bronchoalveolar lavage fluid (BALF) of subjects with an AUD. Smokers were excluded to avoid confounding effects and compliance was verified by cotinine measurements. Statistically significant metabolic features, differentially expressed by control and AUD subjects, were identified by statistical and bioinformatic methods. The results show that fatty acid and acylcarnitine concentrations were increased in AUD subjects, consistent with perturbed mitochondrial and lipid metabolism. Decreased concentrations of methyl-donor compounds suggest altered one-carbon metabolism and oxidative stress. An accumulation of peptides suggests proteolytic activity, which could reflect altered epithelial barrier function. Two metabolites of possible microbial origin suggest subclinical bacterial infection. Furthermore, increased diacetylspermine suggests additional metabolic perturbations, which could contribute to dysregulated alveolar macrophage function and vulnerability to infection. Together, the results show an extended metabolic consequence of AUD in the bronchoalveolar space.
Highlights
Alcohol abuse is a major worldwide health issue and is an important contributor to lung disease [1, 2]
alcohol use disorder (AUD) subjects and controls were ineligible for the study if they met any of the following criteria: 1) prior medical history of liver disease, 2) prior medical history of gastrointestinal bleeding, 3) prior medical history of heart disease, 4) prior medical history of renal disease, 5) prior medical history of lung disease defined as an abnormal chest radiograph or spirometry, 6) concurrent illicit drug use defined as a toxicology screen for cocaine, opiates, or methamphetamines, 7) prior history of diabetes mellitus, 8) prior history of HIV, 9) failure of the patient to provide informed consent, 10) pregnancy, 11) age > 55, or 12) abnormal nutritional status
Twenty million U.S citizens suffer from an AUD [32], which is associated with an increased risk of tuberculosis [33] and pneumonia [34,35,36], serious Gram-negative or antibiotic-resistant strains of bacteria [36]
Summary
Alcohol abuse is a major worldwide health issue and is an important contributor to lung disease [1, 2]. Ethanol metabolism generates oxidative stress in the lung, which perturbs the alveolar epithelium
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