Using a combination of human and mouse models of RV infection in COPD, we demonstrate that MUC5AC and MUC5B are increased during exacerbations, that MUC5AC has better characteristics than MUC5B as a biomarker of COPD exacerbations, and that virus-induced MUC5AC may have a role in driving COPD exacerbation severity. Here, MUC5AC is linked to chronic obstructive pulmonary disease.