title: The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia.
abstract: BACKGROUND
  Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion.
  
  
  METHODS
  We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD).
  
  
  RESULTS
  There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects.
  
  
  CONCLUSIONS
  Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.
authors: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Joshua M
authors: JM
authors: Diamond
authors: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Mary K
authors: MK
authors: Porteous
authors: Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee.
authors: L Jackson
authors: LJ
authors: Roberts
authors: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, Tennessee.
authors: Nancy
authors: N
authors: Wickersham
authors: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Melanie
authors: M
authors: Rushefski
authors: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.|Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, PA.|Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Steven M
authors: SM
authors: Kawut
authors: Department of Medicine, University of California, San Francisco, California.
authors: Rupal J
authors: RJ
authors: Shah
authors: Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors: Edward
authors: E
authors: Cantu
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
authors: David J
authors: DJ
authors: Lederer
authors: Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, PA.
authors: Shampa
authors: S
authors: Chatterjee
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan.
authors: Vibha N
authors: VN
authors: Lama
authors: Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois.
authors: Sangeeta
authors: S
authors: Bhorade
authors: Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Maria
authors: M
authors: Crespo
authors: Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: John
authors: J
authors: McDyer
authors: Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Keith
authors: K
authors: Wille
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, Maryland.
authors: Jonathan
authors: J
authors: Orens
authors: Division of Pulmonary and Critical Care Medicine, Stanford University, Palo Alto, California.
authors: Ann
authors: A
authors: Weinacker
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
authors: Selim
authors: S
authors: Arcasoy
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, Maryland.
authors: Pali D
authors: PD
authors: Shah
authors: Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: David S
authors: DS
authors: Wilkes
authors: Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Chadi
authors: C
authors: Hage
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Raleigh-Durham, North Carolina.
authors: Scott M
authors: SM
authors: Palmer
authors: Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Raleigh-Durham, North Carolina.
authors: Laurie
authors: L
authors: Snyder
authors: Department of Medicine, University of California, San Francisco, California.|Departments of Medicine and Anesthesia, University of California, San Francisco, California.
authors: Carolyn S
authors: CS
authors: Calfee
authors: Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee.
authors: Lorraine B
authors: LB
authors: Ware
authors: Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.|Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, PA.
authors: Jason D
authors: JD
authors: Christie
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018496:Hyperoxia / Q000097:blood* / Q000209:etiology; D015227:Lipid Peroxidation; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D011183:Postoperative Complications; D055031:Primary Graft Dysfunction / Q000097:blood* / Q000209:etiology; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications*; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D015415:Biomarkers
keywords: F2-isoprostane; ischemia reperfusion; isofuran; lipid peroxidation; lung transplantation; primary graft dysfunction