15-F2t-Isoprostane, a reliable
biomarker of oxidative stress, has been found elevated in exhaled breath condensate (EBC), a non-invasive technique for sampling of airway secretions, in patients with
cystic fibrosis (CF).
Azithromycin has
antioxidant properties in experimental models of CF, but its effects on oxidative stress in CF patients are largely unknown. Primary objective of this pilot, proof-of-concept, prospective, parallel group, pharmacological study, was investigating the potential
antioxidant effects of
azithromycin in CF patients as reflected by EBC
15-F2t-isoprostane. Secondary objectives included studying the effect of
azithromycin on EBC and serum metabolic profiles, and on serum
15-F2t-isoprostane. In CF patients who were on maintenance treatment with oral
vitamin E (200 UI once daily), treatment with oral
azithromycin (250 or 500 mg depending on
body weight) plus
vitamin E (400 UI once daily) (group A) (n = 24) or oral
vitamin E alone (400 UI once daily) (group B) (n = 21) was not associated with changes in EBC
15-F2t-isoprostane concentrations compared with baseline values after 8-weeks treatment or 2 weeks
after treatment suspension. There was no between-group difference in post-treatment EBC
15-F2t-isoprostane. Likewise, no within- or between-group differences in serum
15-F2t-isoprostane concentrations were observed in either study group. NMR spectroscopy-based metabolomics of EBC shows that
suspension of both
azithromycin plus
vitamin E and
vitamin E alone has a striking effect on metabolic profiles in EBC. Between-group comparisons show that EBC metabolite distribution
after treatment and 2 weeks
after treatment suspension is different. Quantitative differences in
ethanol,
saturated fatty acids,
acetate,
acetoin/
acetone, and
methanol are responsible for these differences. Our study was unable to show
antioxidant effect of
azithromycin as add-on treatment with doubling the dose of oral
vitamin E as reflected by
15-F2t-isoprostane concentrations in EBC. Add-on
therapy with
azithromycin itself does not induce EBC metabolite changes, but its
suspension is associated with EBC metabolic profiles that are different from those observed after
vitamin E suspension. The pathophysiological and therapeutic implications of these findings in patients with stable CF are unknown and require further research. Preliminary data suggest that EBC NMR-based metabolomics might be used for assessing the effects of pharmacological treatment
suspension in stable CF patients.