Oxidative stress during acute respiratory exacerbations in cystic fibrosis

Background-Patients with cystic fibrosis experience chronic systemic oxidat ive stress. This is coupled with chronic inflammation of the lung involving bronchial polymorphonuclear neutrophil accumulation and activation. We hyp othesised that, during periods of acute respiratory exacerbation, free radi cal activity and consequent damage would be most marked and that intensive treatment of the infection would result in improvement towards values found during stable periods. Methods-Plasma and red blood cells were collected from 12 healthy normal vo lunteers and from 12 patients with cystic fibrosis with an acute respirator y exacerbation (increased respiratory symptoms, reduction in forced expirat ory volume in one second (FEV,) of more than 10%, and a decision to treat w ith intravenous antibiotics). Further samples were collected from patients following two weeks of treatment. Samples were analysed for inflammatory ma rkers, markers of free radical damage, and aqueous and Lipid phase scavenge rs. Results-During respiratory exacerbations FEV1, and forced vital capacity (F VC) were lower than in controls (mean differences -2.82 (95% CI -2.12 to -3 .52) and -3.79 (-3.03 to -4.55) 1, respectively) but improved following tre atment (mean change 0.29 (95% CI 0.18 to 0.40) and 0.33 (0.23 to 0.43) 1, r espectively). Inflammatory markers during exacerbations were significantly higher in patients than in controls with the following mean (95% CI) differ ences: C reactive protein (CRP), 46 (17 to 75)gn; neutrophil elastase alpha (1), antiprotease complexes (NEAPC), 4.4 (1.77 to 7.07)mg/l; white cell cou nt (WCC), 5.3 (4.7 to 5.9) x 10(9)/l. These markers decreased significantly following treatment with the following mean (95% CI) changes: CRP -26 (-10 to -42) g/l; NEAPC -3.1 (-1.3 to -4.9) mg/l; WCC -1.5 (-1.3 to -1.7) x 10( 9)/l. Malondialdehyde (MDA) as a marker of free radical activity was signif icantly higher in patients during exacerbations than in controls with a mea n (95% CI) difference of 193 (107 to 279) which improved with treatment (me an change -56 (95% CI -28 to -84) nmol/mmol cholesterol). Red blood cell po lyunsaturated fatty acids were significantly lower in patients than in cont rols with a mean difference of -4.4(95% CI -2.6 to -6.2) moles percent, but did not improve significantly after treatment. Protein carbonyls during ex acerbations were not different from controls but did increase with treatmen t compared with levels during the exacerbation (mean change 0.39 (95% CI 0. 11 to 0.67) mu mol/g protein). Aqueous and lipid phase scavengers in patien ts during exacerbations were significantly lower than in controls with the following mean (95% CI) differences: ascorbate, -19.0 (-2.7 to -35.3)mu mol /l; sulphydryls, -122 (-77 to -167)mu mol/l; retinol, -237 (-47 to -427)nmo l/mmol cholesterol; B-carotene, -52.8 (-11.8 to -93.8)nmol/mmol cholesterol ; luteine, -50.4 (-10.4 to -90.4) nmol/mmol cholesterol; lycopene, -90.1 (- 30.1 to -150.1) nmol/mmol cholesterol. Treatment resulted in improvement wi th the following mean (95% CI) changes: sulphydryls, 50 (32 to 68) mu mol/l ; retinol, 152 (47 to 257) nmol/mmol cholesterol; alpha- and beta-carotene, 0.6 (0.0 to 1.2) and 7.6 (0.0 to 15.2) nmol/mmol cholesterol, respectively ; alpha-tocopherol, 839 (283 to 1405) nmol/mmol cholesterol; and lycopene, 8.2 (0.0 to 16.2) nmol/mmol cholesterol. Conclusions "Abnormalities of markers of inflammation, free radical activit y, and radical scavengers were significantly more extreme during acute resp iratory exacerbations and showed improvement with treatment. The need to pr ovide protection from inflammation and free radical damage should therefore be dynamic and related to the inflammatory and oxidative processes.