Glutathione is an important antioxidant in the lungs but its concentration is low in the
airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress
contributes to lowering glutathione is unknown.
We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous
acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass
spectrometry and immunological techniques.
The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis,
whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised
glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous
acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than
controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of
oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage.
The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age.
Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this
deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset
and progression of lung disease in cystic fibrosis