CF patients had significantly higher level of oxidative stress than control subjects, as assessed by protein oxidation from the content of protein carbonyls in their BALF. The highest levels were found in patients with pathologic pulmonary function or with highly elevated neutrophil counts. Compared to control subjects without lung disease, CF patients with normal lung function, defined as FEV1 > 80% of predicted, also had significantly higher protein carbonyl levels. These data show direct a strong association between increased oxidative stress in the lungs and lung function of these patients with CF. The data support the hypothesis that an abundance of ROS may be a major contributor to the progressive pulmonary damage observed in CF patients. Our findings are consistent with the excessive PMN infiltration in the lungs of CF patients.18The relevance of the PMN infiltration for the oxidative damage to proteins is suggested by our observations that the level of protein carbonyls strongly correlated with the number of PMNs in BALF, and that the oxidative damage was higher in the groups with a higher neutrophil counts. Several lines of evidence suggest that CF patients have inadequate antioxidant defenses to cope with the elevated oxidative stress that they regularly experience. Patients with CF have an impaired absorption of antioxidant nutrients, resulting in lower levels of antioxidants together with increased oxidative stress caused by chronic pulmonary infections.19Specifically in the lungs decreased levels of reduced glutathione in the epithelial lining fluid have been linked to an impaired export of glutathione by the epithelial cells due to lack of CF conductance regulator.20It has been suggested that recurring oxidative lung injury can contribute to the decline in pulmonary function in these patients.21–22 In our findings, there was also a weak positive correlation between protein carbonyls and the age of the CF patients (n = 51; rs = 0.32; p = 0.02) but not between age and pulmonary function (n = 51; rs = − 0.22; p = 0.12). This may reflect a decreasing antioxidative capacity with age or declining activity of the proteasome.24 Previously it was demonstrated that the formation of myeloperoxidase-derived oxidizing and possibly nitrating species within the respiratory tract of subjects with CF may contribute to bronchial injury and respiratory failure.9 Nevertheless, this study9 performed on the population of children with CF revealed no correlation between myeloperoxidase activity, neutrophil numbers, and protein carbonylation. Our data directly support the hypothesis that protein oxidation during chronic and excessive neutrophilic inflammation may contribute to the decline of pulmonary function in CF patients. These processes lead to an increase in local concentrations of free oxygen radicals at the sites of inflammation.25–26 This may result in the most effective defense against pathogens. However, if the pathogens cannot be eliminated as in CF, a high concentration of free radicals locally and an attenuation of antiproteolytic activity may result in lung tissue damage.8,27 It is also known that treatment of infective exacerbations in CF patients results in increased plasma levels of some antioxidant vitamins. However, no immediate changes in plasma protein oxidation are observed, while lipid oxidation is decreased.8 Also, local antioxidative treatment of CF patients with inhaled glutathione for 2 weeks did not change the level of oxidized proteins in the lungs.8 This may be due both to an enormously pronounced lung inflammation in CF lungs, which leads to the continuous generation of free radicals by PMNs and consequently to profound oxidative protein damage and an insufficient protective effect of known antioxidants. Based on the correlation between the level of protein carbonyls, neutrophil granulocyte count, and lung function, the carbonylation state of pulmonary proteins may be used as a marker of disease and help to explore pathophysiology of oxidative stress.