title: A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment of acute lung injury.
abstract: OBJECTIVE
  Administration of eicosapentaenoic acid and docosahexanoic acid, omega-3 fatty acids in fish oil, has been associated with improved patient outcomes in acute lung injury when studied in a commercial enteral formula. However, fish oil has not been tested independently in acute lung injury. We therefore sought to determine whether enteral fish oil alone would reduce pulmonary and systemic inflammation in patients with acute lung injury.
  
  
  METHODS
  Phase II randomized controlled trial.
  
  
  METHODS
  Five North American medical centers.
  
  
  METHODS
  Mechanically ventilated patients with acute lung injury ≥18 yrs of age.
  
  
  METHODS
  Subjects were randomized to receive enteral fish oil (9.75 g eicosapentaenoic acid and 6.75 g docosahexanoic acid daily) or saline placebo for up to 14 days.
  
  
  RESULTS
  Bronchoalveolar lavage fluid and blood were collected at baseline (day 0), day 4 ± 1, and day 8 ± 1. The primary end point was bronchoalveolar lavage fluid interleukin-8 levels. Forty-one participants received fish oil and 49 received placebo. Enteral fish oil administration was associated with increased serum eicosapentaenoic acid concentration (p < .0001). However, there was no significant difference in the change in bronchoalveolar lavage fluid interleukin-8 from baseline to day 4 (p = .37) or day 8 (p = .55) between treatment arms. There were no appreciable improvements in other bronchoalveolar lavage fluid or plasma biomarkers in the fish oil group compared with the control group. Similarly, organ failure score, ventilator-free days, intensive care unit-free days, and 60-day mortality did not differ between the groups.
  
  
  CONCLUSIONS
  Fish oil did not reduce biomarkers of pulmonary or systemic inflammation in patients with acute lung injury, and the results do not support the conduct of a larger clinical trial in this population with this agent. This experimental approach is feasible for proof-of-concept studies evaluating new treatments for acute lung injury.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Vermont College of Medicine, Burlington, VT, USA. renee.stapleton@uvm.edu
authors.forename: Renee D
authors.initials: RD
authors.lastname: Stapleton
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Martin
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Crowley
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Gundel
authors.forename: Avery B
authors.initials: AB
authors.lastname: Nathens
authors.forename: Saadia R
authors.initials: SR
authors.lastname: Akhtar
authors.forename: John T
authors.initials: JT
authors.lastname: Ruzinski
authors.forename: Ellen
authors.initials: E
authors.lastname: Caldwell
authors.forename: J Randall
authors.initials: JR
authors.lastname: Curtis
authors.forename: Daren K
authors.initials: DK
authors.lastname: Heyland
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Watkins
authors.forename: Polly E
authors.initials: PE
authors.lastname: Parsons
authors.forename: Julie M
authors.initials: JM
authors.lastname: Martin
authors.forename: Mark M
authors.initials: MM
authors.lastname: Wurfel
authors.forename: Teal S
authors.initials: TS
authors.lastname: Hallstrand
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Sims
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Neff
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002452:Cell Count; D018932:Chemokine CCL2 / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004750:Enteral Nutrition; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D016209:Interleukin-8 / Q000032:analysis* / Q000097:blood; D007975:Leukotriene B4 / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D011014:Pneumonia / Q000188:drug therapy; D018467:Positive-Pressure Respiration, Intrinsic; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood; D013990:Tidal Volume / Q000187:drug effects; D014841:von Willebrand Factor / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D037663:Pulmonary Surfactant-Associated Protein D; D014841:von Willebrand Factor; D007975:Leukotriene B4; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid