Because of the limitation of the primary human airway epithelial cells, which prohibits us from performing the functional assays of the Wnt signaling pathway in a condition similar to that in vivo, we could not be certain that the down-regulation of Wnt signaling in healthy smokers and COPD patients is the result of SFRP2 up-regulation, despite the fact that SFRP2 could decrease WNT1-induced activation of Wnt reporter luciferase activity in HEK293 cells (p<0.05, Figure S3). Here, WNT1 is linked to chronic obstructive pulmonary disease.