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- W4312428076 abstract "COPD is characterized by frequent airway neutrophilia, chronic airway injury, and deranged epithelial permeability, contributing to increased susceptibility to infections. The neutrophil granular enzyme MPO generates the toxic metabolite hypochlorite which contributes to oxidative stress and inflammation. We aimed to study the potential association of airway MPO with exacerbations, as well as its effects on epithelial permeability. Baseline sputum samples from 285 COPD patients from a prospective UK cohort study, as well as a second sample from 139 subjects, were analysed for MPO concentration and activity. Patients were followed for 6-12 months to evaluate time to first exacerbation. To study the effect of MPO on epithelial permeability, MPO was added to air-liquid interface (ALI) human airway epithelial cell cultures and permeability measured by transepithelial electrical resistance. Sputum MPO levels were highly variable among subjects (39 to 65,000 ng/mL). MPO concentration and activity were highly correlated (log10 r=0.94). Levels in paired samples obtained 4-6 months apart were correlated (log10 r=0.56, p=10-12), suggesting that airway MPO is a relatively stable trait. During follow-up, 282 subjects experienced at least 134 exacerbation events. A proportional hazards regression model indicated that increasing sputum MPO concentrations were associated with an increased risk of exacerbation (log10 hazard ratio 1.38, CI 1.10-1.73, p=0.005). In ALI cultures, treatment with MPO increased epithelial permeability, which was reverted by an MPO inhibitor. Taken together, these results suggest that airway MPO contributes to epithelial damage in COPD and may enhance the risk of exacerbation." @default.
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- W4312428076 date "2022-09-04" @default.
- W4312428076 modified "2023-09-27" @default.
- W4312428076 title "Airway myeloperoxidase (MPO) is associated with increased risk of exacerbations in COPD" @default.
- W4312428076 doi "https://doi.org/10.1183/13993003.congress-2022.2017" @default.
- W4312428076 hasPublicationYear "2022" @default.
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