In addition, although we eliminated the gender interference in HE4 expression levels between COPD patients or CS-exposed mice and controls by ensuring the ratio of male to female with no difference, whether different genders have an effect on the expression of HE4 in the airway of COPD patients and whether it is related to the level of estrogen remains to be investigated. This evidence concerns the gene WFDC2 and chronic obstructive pulmonary disease.