title: Impaired respiratory function and heightened pulmonary inflammation in episodic binge ethanol intoxication and burn injury.
abstract: Clinical data indicate that cutaneous burn injuries covering greater than 10% of the total body surface area are associated with significant morbidity and mortality, in which pulmonary complications, including acute respiratory distress syndrome (ARDS), contribute to nearly half of all patient deaths. Approximately 50% of burn patients are intoxicated at the time of hospital admission, which increases days on ventilators by 3-fold, and doubles the length of hospitalization, compared to non-intoxicated burn patients. The most common drinking pattern in the United States is binge drinking, where an individual rapidly consumes alcoholic beverages (4 for women, 5 for men) in 2 h. An estimated 38 million Americans binge drink, often several times per month. Experimental data demonstrate that a single binge-ethanol exposure, prior to scald injury, impairs innate and adaptive immune responses, thereby enhancing infection susceptibility and amplifying pulmonary inflammation, neutrophil infiltration, and edema, and is associated with increased mortality. Since these characteristics are similar to those observed in ARDS burn patients, our study objective was to determine whether ethanol intoxication and burn injury and the subsequent pulmonary congestion affect physiological parameters of lung function, using non-invasive and unrestrained plethysmography in a murine model system. Furthermore, to mirror young adult binge-drinking patterns, and to determine the effect of multiple ethanol exposures on pulmonary inflammation, we utilized an episodic binge-ethanol exposure regimen, where mice were exposed to ethanol for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. Our analyses demonstrate mice exposed to episodic binge ethanol and burn injury have higher mortality, increased pulmonary congestion and neutrophil infiltration, elevated neutrophil chemoattractants, and respiratory dysfunction, compared to burn or ethanol intoxication alone. Overall, our study identifies plethysmography as a useful tool for characterizing respiratory function in a murine burn model and for future identification of therapeutic compounds capable of restoring pulmonary functionality.
authors.affiliation: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Alcohol Research Program, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Shults
authors.affiliation: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Alcohol Research Program, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Department of Surgery, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Curtis
authors.affiliation: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Alcohol Research Program, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Chen
authors.affiliation: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Alcohol Research Program, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Department of Surgery, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA.
authors.forename: Eileen B
authors.initials: EB
authors.lastname: O'Halloran
authors.affiliation: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Department of Surgery, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Ramirez
authors.affiliation: Burn and Shock Trauma Research Institute, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Alcohol Research Program, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA; Department of Surgery, Loyola University Chicago, Health Sciences Campus, Maywood, IL 60153, USA. Electronic address: ekovacs@luc.edu.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: D000435:Alcoholic Intoxication / Q000150:complications / Q000401:mortality* / Q000473:pathology; D000818:Animals; D063425:Binge Drinking / Q000150:complications / Q000401:mortality* / Q000473:pathology; D002056:Burns / Q000150:complications / Q000473:pathology*; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D010991:Plethysmography; D011014:Pneumonia / Q000150:complications / Q000401:mortality*; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins
keywords: Alcohol; Burn; Cytokines; Lung; Neutrophils; Plethysmography