The combination of roflumilast N-oxide 10 nM and dexamethasone 10 nM synergistically inhibited p38, AP-1, and NF-κB which may explain in part the additive anti-inflammatory effects of roflumilast N-oxide and dexamethasone in HBECs of COPD patients following TLR3 activation. Here, TLR3 is linked to chronic obstructive pulmonary disease.