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Reactive Nitrogen Species, Airway Inflammation, and Fibrosis in Lung Transplant

Joao A. deAndrade, MD; John Crow, PhD; Liliana Viera, PhD; C. Bruce Alexander, MD, FCCP; K. Randall Young, MD, FCCP; David McGiffin, MD; George Zorn, MD, FCCP; Sadis Matalon, PhD; Robert Jackson, MD
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*From the Department of Veterans Affairs Medical Center and the University of Alabama at Birmingham, Birmingham AL.

Correspondence to: Joao A. de Andrade, MD, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, 215 Tinsley Harrison Tower, 1900 University Blvd, Birmingham, AL 35294-0006



Chest. 2001;120(1_suppl):S58-S59. doi:10.1378/chest.120.1_suppl.S58-a
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We investigated the association of reactive nitrogen species (RNS) metabolites in serum and BAL fluid (BALF) with development of airway inflammation and fibrosis in lung transplant patients. In a preliminary study (n = 29), the percentage of nitration (nitrotyrosine/total tyrosine × 100) of tyrosines in BALF proteins was as follows: transplant patients, 0.01% (0.00 to 0.12%); (median [25th to 75th % confidence interval]); control subjects, 0.01% (0.00 to 0.02%). In a larger, follow-up study (n = 82), nitrotyrosine was detected by enzyme-linked immunosorbent assay in BALF: patients, 9 pmol/mg protein (0 to 41 pmol/mg protein); control patients, 28 pmol/mg (26 to 33 pmol/mg). Total nitrite (NO2 plus NO3) levels in patients’ BALF (3.3 μmol/L [1.9 to 5.1]) significantly exceeded those in control subjects (1.3 μmol/L [0.8 to 1.3]; p = 0.0133). Serum nitrite level also was significantly higher in patients (37 μmol/L [26 to 55]) than control subjects (19 μmol/L [17 to 20]; p = 0.0037). Airway inflammation and fibrosis in transplant transbronchial biopsy specimens (quantified as the “B” score) correlated with nitrotyrosine in BALF (p = 0.0369). Our most recent study investigates clinical implications of RNS metabolites as markers of airway inflammation in a third group of lung transplant patients (n = 40). Total nitrite (NO2 plus NO3) levels in BALF and serum were 3.8 ± 0.2 μmol/L (mean ± SE) and 49 ± 5 μmol/L, respectively. Serum total nitrite correlated (Pearson product moment correlation) with percentage of neutrophils in BALF (r = 0.650; p < 0.0001), myeloperoxidase (r = 0.431; p = 0.0055), change in FEV1 from baseline (r = − 0.348; p = 0.0298), and days after transplantation (r = 0.345; p = 0.0294). Univariate analysis of airway inflammation as a categorical outcome showed it was associated with BALF neutrophils, change in FEV1 from baseline, and serum total nitrite. RNS metabolites are increased in lung transplants, and serum nitrite level appears to correlate with airway inflammation and fibrosis due to rejection.

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