title: Broncho-alveolar lavage matrix metalloproteases as a sensitive measure of bronchiolitis obliterans.
abstract: Bronchiolitis obliterans (BO) is a survival-limiting factor in lung transplantation. There are no common BO markers in use. Since BO is associated with extracellular matrix remodeling, we asked whether matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) could serve as BO markers. In 72 lung transplant patients (34 BO syndrome (BOS) 0, 15 BOS 0-p, and 23 BOS 1) serum and broncho-alveolar lavage (BAL) MMP and TIMP levels were examined by ELISA. The BAL cell counts were additionally analyzed. The serum MMP-2, MMP-8, MMP-9 and TIMP-2 levels were not different in all groups. In contrast, the BAL MMP-8, -9 and TIMP-1 levels were significantly elevated in BOS 0-p (p = 0.003; p = 0.007; p = 0.0003, respectively) and BOS 1 (p = 0.003; p = 0.001; p = 0.0004, respectively) as compared to BOS 0 patients. The BAL MMP-8, -9 and TIMP-1 levels were significant predictors of BOS 0-p (p = 0.01; p = 0.01; p = 0.01, respectively) and BOS-1 (p = 0.007; p = 0.01; p = 0.006, respectively) in receiver operating characteristic analysis. Except for BAL macrophages that were significantly decreased in BOS 0-p versus BOS 0 patients; other cell counts were not different between the groups. BAL MMP-8, -9 and TIMP-1 might be useful markers to detect BO in lung transplant patients.
authors.affiliation: Department of Cardio-Thoracic Surgery, Vienna Medical University, Waehringer Guertel, Austria.
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Taghavi
authors.forename: Katharina
authors.initials: K
authors.lastname: Krenn
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000201:enzymology* / Q000209:etiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008171:Lung Diseases / Q000097:blood / Q000201:enzymology* / Q000628:therapy; D016040:Lung Transplantation / Q000009:adverse effects*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9