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Association of Reactive Nitrogen Species Metabolites, Myeloperoxidase, and Airway Inflammation in Lung Transplants
  1. João A. de Andrade,
  2. Jason D. Christie,
  3. C. Bruce Alexander,
  4. K. Randall Young,
  5. David C. McGiffin,
  6. George L. Zorn,
  7. Robert M. Jackson
  1. From the Birmingham Department of Veterans Affairs Medical Center and University of Alabama at Birmingham (J.A.D., C.B.A., K.R.Y., D.C.M., G.L.Z., R.M.J.), Philadelphia
  2. University of Pennsylvania (J.D.C.), Philadelphia.
  1. Address correspondence to: R. Jackson, MD, Division of Pulmonary, Allergy, and Critical Care Medicine, Room 215 Tinsley Harrison Tower, University of Alabama at Birmingham, Birmingham, AL 35294-0006. E-mail rjackson{at}uab.edu
  2. Supported by Veterans Administration Research Service (R.J.), HL 57801, Office of Naval Research (N00014-97-1-03-09) (R.J.), and a Career Investigator Award from the American Lung Association (R.J.).
  3. Abstract presented at American Thoracic Society meeting on May 8, 2000.

Abstract

Background We have previously reported that patients who had single or double lung transplants had higher concentrations than controls of nitrite and nitrate, which are metabolites of reactive nitrogen species (RNS), in bronchoalveolar lavage fluid (BALF) and serum.

Methods This study investigates implications of RNS metabolites as markers of airway inflammation in a distinct group of lung transplant patients (n=40). All patients underwent spirometry, routine surveillance transbronchial lung biopsies, and bronchoalveolar lavage as required by clinical protocol. Four normal controls also had bronchoscopy for measurement of BALF nitrite (NO2 -) and nitrate (NO3 -). BALF NO2 - and NO3 -, myeloperoxidase (MPO), protein, and urea were assayed. Total nitrite (NO2 - plus enzymatically reduced NO3 -) and urea were measured in serum.

Results BALF RNS metabolites were mainly NO3 -. Forced expiratory volume in 1 s (FEV1) obtained near bronchoscopy was compared with best postoperative FEV1. Total nitrite in transplant patients' BALF and serum were 3.8±0.2 and 49±5 μM, respectively. Total nitrite in controls' BALF and serum were 2.2±0.7 and 19±2 μM, respectively (P<0.05 compared with transplant values). Serum total nitrite correlated (Pearson product moment) with percentage of neutrophils in BALF (R=0.650, P<0.0001), MPO (R=0.431, P=0.0055), change in FEV1 from baseline (ΔFEV1) (R=-0.348, P=0.0298), and days after transplantation (R=0.345, P=0.0294). None of the associated variables, airway inflammation (quantified as a score, “B”), ΔFEV1, serum, or BALF total nitrite, were explained by infection. Univariate analysis of airway inflammation in patients showed that it was associated with BALF neutrophils, ΔFEV1, and serum total nitrite.

Conclusions Serum nitrite appears to reflect the degree of airway inflammation in this lung-transplant study group.

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