Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025
Impact of long-term elexacaftor/tezacaftor/ivacaftor therapy on oxidative stress in cystic fibrosis: early insights.
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Örlős Zoltán, Barta Imre, Páska Csilla, Halász Adrien, Antus Balázs
Аннотация
BACKGROUND: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to improve clinical outcomes in people with cystic fibrosis (pwCF). Here, we investigated whether these benefits are associated with the modulation of oxidative stress.
METHODS: Levels of oxidative stress markers including 8-isoprostane (8-IP), 8-hydroxy-2'deoxyguanosine (8-OHdG) and protein carbonyls and activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were measured in systemic and airway samples from clinically stable pwCF (n=26) at baseline and 2 or 3 and 6 months after initiation of ETI therapy. For comparison, measurements were also performed in healthy control subjects.
RESULTS: Baseline levels of oxidative stress markers and antioxidant activities were higher in pwCF than in healthy controls (p<0.05). ETI treatment resulted in improvements in a wide range of clinical parameters in pwCF. In addition, one in two patients had ceased producing sputum while receiving ETI treatment. A reduction in the levels of sputum oxidative stress markers was observed 2 or 3 months (for 8-OHdG and protein carbonyls) and 6 months (for 8-IP) after ETI initiation (p<0.05). Sputum SOD activity showed a similar reduction (p<0.05) upon treatment. In contrast, modulator treatment had no effect on the levels of oxidative stress markers and antioxidant activities in plasma. Extrapulmonary manifestations of CF were not improved by ETI therapy either.
CONCLUSIONS: Our data suggest that the beneficial clinical effect of ETI therapy is accompanied by a decrease in airway but not systemic oxidative stress in pwCF.
METHODS: Levels of oxidative stress markers including 8-isoprostane (8-IP), 8-hydroxy-2'deoxyguanosine (8-OHdG) and protein carbonyls and activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were measured in systemic and airway samples from clinically stable pwCF (n=26) at baseline and 2 or 3 and 6 months after initiation of ETI therapy. For comparison, measurements were also performed in healthy control subjects.
RESULTS: Baseline levels of oxidative stress markers and antioxidant activities were higher in pwCF than in healthy controls (p<0.05). ETI treatment resulted in improvements in a wide range of clinical parameters in pwCF. In addition, one in two patients had ceased producing sputum while receiving ETI treatment. A reduction in the levels of sputum oxidative stress markers was observed 2 or 3 months (for 8-OHdG and protein carbonyls) and 6 months (for 8-IP) after ETI initiation (p<0.05). Sputum SOD activity showed a similar reduction (p<0.05) upon treatment. In contrast, modulator treatment had no effect on the levels of oxidative stress markers and antioxidant activities in plasma. Extrapulmonary manifestations of CF were not improved by ETI therapy either.
CONCLUSIONS: Our data suggest that the beneficial clinical effect of ETI therapy is accompanied by a decrease in airway but not systemic oxidative stress in pwCF.