Comparison of Airway and Systemic Malondialdehyde Levels for Assessment of Oxidative Stress in Cystic Fibrosis

Introduction Oxidative stress plays a pivotal role in the pathogenesis of cystic fibrosis (CF). In this study, airway and systemic oxidative stress was investigated in CF using malondialdehyde (MDA), an established by-product of polyunsaturated fatty acid peroxidation. Methods Exhaled breath condensate (EBC), sputum, and plasma were collected from 40 stable CF patients during routine clinical visits and from 25 healthy controls. MDA was measured by high-performance liquid chromatography. Results MDA levels in sputum (279.8 +/- 14.7 vs. 92.7 +/- 9.2 nmol/L, p < 0.0001), EBC (139.9 +/- 6.7 vs. 71.5 +/- 4.3 nmol/L, p < 0.0001), and plasma (176.1 +/- 15.9 vs. 129.6 +/- 12.9 nmol/L, p < 0.05) were increased in patients with CF compared to healthy controls. MDA measurement in sputum [area under receiver operating characteristic curve (AUC): 0.977, p < 0.0001] or EBC (AUC: 0.94, p < 0.0001) discriminated between patients and controls with greater accuracy than in plasma (AUC: 0.677, p < 0.05). Sputum and EBC MDA levels were elevated in patients with severe pulmonary dysfunction [forced expiratory volume in 1 s (FEV1) < 50 % predicted] compared to those with mild-to-moderate functional impairment (FEV1 >= 50 % predicted) (p < 0.05). MDA concentrations in CF patients colonized either with Pseudomonas aeruginosa or with other bacteria were similar (p = NS). The intra-and inter-assay repeatabilities of MDA measurements was similar in all the three types of samples, while the between-visit variability was higher in plasma. Conclusions MDA is a potential new airway marker of oxidative stress in patients with CF. Sputum MDA differentiates best between patients and healthy subjects.