Oxidative damage to proteins of bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome: Evidence for neutrophil-mediated hydroxylation, nitration, and chlorination

Objective: To assess the degree, source, and patterns of oxidative damage t o bronchoalveolar ravage proteins as a modification of amino acid residues in patients with acute respiratory distress syndrome (ARDS). Design: Prospective, controlled study. Setting: Adult intensive care unit of a postgraduate teaching hospital. Patients: Twenty-eight patients with established ARDS were studied and comp ared with six ventilated patients without ARDS and 11 normal healthy contro ls. Interventions: Supportive techniques appropriate to ARDS. Measurements and Main Results: Evidence of oxidative modification of bronch oalveolar lavage fluid protein, indicative of the production of specific re active oxidizing species, was sought using a high-performance liquid chroma tography technique. Bronchoalveolar lavage fluid samples from patients with ARDS, ventilated intensive care controls, and normal healthy controls were analyzed. Concentrations of orthotyrosine were significantly higher in the ARDS group than in either control group (7.98 +/- 3.78 nmol/mg for ARDS, 0 .67 +/- 0.67 for ventilated controls, and 0.71 +/- 0.22 for healthy control s; p < .05). Chlorotyrosine concentrations were also significantly increase d in the ARDS group over either control group (4.82 +/- 1.07 nmol/mg for AR DS, 1.55 +/- 1.34 for ventilated controls, and 0.33 +/- 0.12 for healthy co ntrols; p < .05). Nitrotyrosine concentrations were similarly significantly increased in the ARDS groups compared with each control group (2.21 +/- 0. 65 nmol/mg for ARDS, 0.29 +/- 0.29 for ventilated controls, and 0.06 +/- 0. 03 for healthy controls; p < .05). Chlorotyrosine and nitrotyrosine concentrations showed significant correlat ions with myeloperoxidase concentrations in bronchoalveolar lavage fluid, m easured using an enzyme-linked immunosorbent assay in patients with ARDS. T hese findings suggest a possible relationship between inflammatory cell act ivation, oxidant formation, and damage to proteins in the lungs of these pa tients Conclusions: Overall, our data strongly suggest heightened concentrations o f oxidative stress in the lungs of patients with ARDS that lead to signific antly increased oxidative protein damage.