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

Pro-inflammatory cytokines and cellular airway inflammation are believed to contribute to duration and severity of RV-induced asthma exacerbations 17,18 and secondary bacterial infection is also associated with greater exacerbation severity in RV-induced COPD exacerbations 16 . Having observed associations between concentrations of MUC5AC and airway inflammation, virus load and secondary bacterial infections, we next determined whether airway mucins during exacerbations were related to clinical outcomes during exacerbation. We observed that sputum MUC5AC concentrations correlated with both upper and lower respiratory tract symptom scores ( Fig.2i ) with no significant correlations observed for MUC5B (Supplementary Fig.1h ). Since chronic mucus hypersecretion is associated with long term FEV 1 decline 19 , we also hypothesized that the amplified induction of MUC5AC during RV infection would be related to acute lung function changes during COPD exacerbation. In experimental RV-induced COPD exacerbations, sputum MUC5AC concentrations correlated negatively with the maximal fall from baseline in peak expiratory flow during exacerbation ( Fig. 2j ) with no such correlation observed for MUC5B ( Supplementary Fig.1i ).