title: Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome.
abstract: OBJECTIVE
  Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation.
  
  
  METHODS
  Prospective, randomized, double-blind, controlled clinical trial.
  
  
  METHODS
  Intensive Care Unit of the Ohio State University Medical Center.
  
  
  METHODS
  A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome.
  
  
  METHODS
  A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days.
  
  
  RESULTS
  Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4.
  
  
  CONCLUSIONS
  This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.
authors.affiliation: Pulmonary and Critical Care Division, Ohio State University Medical Center, Columbus, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Pacht
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeMichele
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Nelson
authors.forename: Judy
authors.initials: J
authors.lastname: Hart
authors.forename: Ann K
authors.initials: AK
authors.lastname: Wennberg
authors.forename: James E
authors.initials: JE
authors.lastname: Gadek
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004750:Enteral Nutrition; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000276:immunology* / Q000628:therapy*; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D018836:Inflammation Mediators; D011506:Proteins; D017965:gamma-Linolenic Acid; D015118:Eicosapentaenoic Acid