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Increased nitrotyrosine in exhaled breath condensate in cystic fibrosis

¹ Dept of Thoracic Medicine and ² Dept of Cystic Fibrosis, Imperial College School of Medicine at the National Heart and Lung Institute

CORRESPONDENCE: P.J. Barnes, Dept of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse Street, London, SW3 6LY, UK. Fax: 44 2073515675

Keywords: cystic fibrosis, exhaled nitric oxide, nitrate, nitrite, nitrotyrosine, oxidative stress

Received: August 16, 2000
Accepted February 25, 2001

This study was supported by the Hungarian Respiratory Society, Foundation for Patients with Lung & Heart Diseases (Hungary) and the British Lung Foundation (NHLI, UK).

Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species.

Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO (F_eno), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay.

Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3±1.5 versus 6.3±0.8 ng·mL^–1, p<0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease. F_eno levels were significantly lower in CF patients than in normal subjects (4.4±0.3 versus 5.6±0.4 (parts per billion), p<0.05). No correlation was found between nitrotyrosine and F_eno levels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals.

The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.