title: The association between BMI and plasma cytokine levels in patients with acute lung injury.
abstract: BACKGROUND
  Obesity is associated with poor outcomes in many diseases, although recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting because obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in patients who are obese and critically ill or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI.
  
  
  METHODS
  We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor-alpha receptor 1, surfactant protein D [SP-D], soluble intracellular adhesion molecule, von Willebrand factor (vWF), protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1,409 participants in prior National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials. BMI was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFDs), organ failure-free days (OFDs), and mortality were investigated in regression models adjusting for confounders.
  
  
  RESULTS
  In adjusted analyses, plasma IL-6 (P = .052), IL-8 (P = .001), and SP-D (P < .001) were inversely related to BMI, whereas vWF (P = .001) and WBC count (P = .042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFDs, or OFDs.
  
  
  CONCLUSIONS
  Patients who are obese and have ALI have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in patients with ALI and a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of patients who are obese. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms.
authors.affiliation: Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Vermont College of Medicine, HSRF 222, Burlington, VT 05405, USA. renee.stapleton@uvm.edu
authors.forename: Renee D
authors.initials: RD
authors.lastname: Stapleton
authors.forename: Anne E
authors.initials: AE
authors.lastname: Dixon
authors.forename: Polly E
authors.initials: PE
authors.lastname: Parsons
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Suratt
mesh_terms: D055371:Acute Lung Injury / Q000097:blood* / Q000453:epidemiology* / Q000628:therapy; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000150:complications; D012189:Retrospective Studies; D012307:Risk Factors; D013851:Thinness / Q000097:blood* / Q000150:complications
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators