title: The Role of TGF-β in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome.
abstract: Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF-β with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single-center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF-β and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF-β and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76-5.38) for the most severe form of PGD. TGF-β and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF-β and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF-β biology.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: A
authors.initials: A
authors.lastname: DerHovanessian
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: S S
authors.initials: SS
authors.lastname: Weigt
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: V
authors.initials: V
authors.lastname: Palchevskiy
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: M Y
authors.initials: MY
authors.lastname: Shino
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: D M
authors.initials: DM
authors.lastname: Sayah
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: A L
authors.initials: AL
authors.lastname: Gregson
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: P W
authors.initials: PW
authors.lastname: Noble
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University, Durham, NC.
authors.forename: S M
authors.initials: SM
authors.lastname: Palmer
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA.
authors.forename: M C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: B M
authors.initials: BM
authors.lastname: Kubak
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of California, Los Angeles, CA.
authors.forename: A
authors.initials: A
authors.lastname: Ardehali
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Ross
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: R
authors.initials: R
authors.lastname: Saggar
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: J P
authors.initials: JP
authors.lastname: Lynch
authors.affiliation: Department of Biomathematics, University of California, Los Angeles, CA.
authors.forename: R M
authors.initials: RM
authors.lastname: Elashoff
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Los Angeles, CA.
authors.forename: J A
authors.initials: JA
authors.lastname: Belperio
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival; D006801:Humans; D007124:Immunoenzyme Techniques; D008171:Lung Diseases / Q000601:surgery; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D055031:Primary Graft Dysfunction / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016212:Transforming Growth Factor beta