MUC5AC drives COPD exacerbation severity through amplification of virus-induced airway inflammation

Aran Singanayagam; Joseph Footitt; Benjamin T Kasdorf; Matthias Marczynski; Michael T Cross; Lydia J Finney; Maria-Belen Trujillo Torralbo; Maria Calderazzo; Jie Zhu; Julia Aniscenko; Thomas B Clarke; Philip L Molyneaux; Nathan W Bartlett; Miriam F Moffatt; William O Cookson; Jadwiga Wedzicha; Christopher M Evans; Oliver Lieleg; Patrick Mallia; Sebastian L Johnston

We have previously reported that rhinovirus infection induces secondary bacterial infection in COPD through neutrophil elastase cleaving the anti-microbial peptides (AMPs) secretory leucocyte proteinase inhibitor (SLPI) and elafin to promote bacterial growth 16 . We found that sputum MUC5AC correlated positively with sputum neutrophil elastase concentrations during infection (Fig.2f) and negatively with the change from baseline in sputum SLPI and elafin concentrations during infection (Fig.2g) , consistent with greater MUC5AC levels during infection being associated with greater induction of neutrophil elastase, and consequent increased degradation of these AMPs. COPD patients with positive bacterial cultures during RV infection also had higher concentrations of sputum MUC5AC during infection and sputum MUC5AC concentrations correlated with bacterial loads determined by 16S qPCR (Fig.2h) . To confirm these latter findings observed in the rhinovirus challenge model, we performed similar analyses in the naturally occurring COPD exacerbation study author/funder. All rights reserved. No reuse allowed without permission.