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

^* 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

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 x 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.

Footnotes

Abbreviations: BALF = BAL fluid; RNS = reactive nitrogen species

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by deAndrade, J. A. Articles by Jackson, R. Search for Related Content PubMed Articles by deAndrade, J. A. Articles by Jackson, R.