FOS and chronic obstructive pulmonary disease: Several molecular pathways are involved in steroid resistance and lead to the downregulation of GR, and these pathways include the PIK3CD/Akt, AP-1, P38 MAPK, and JNK pathways (Barnes, 2010), whose activity and expression are upregulated in the lungs of smokers or patients with COPD (Kirkham and Barnes, 2013; Barnes et al., 2015; Fischer et al., 2015).