Notably, Maestrelli et al.'s clinical study revealed disease-specific HO-1 expression: COPD patients showed significantly increased HO-1-positive alveolar macrophages compared to healthy nonsmokers, whereas smokers (with or without COPD) exhibited no such differences [71], suggesting HO-1 dysregulation is a COPD-specific hallmark rather than a universal smoking response. This evidence concerns the gene HMOX1 and chronic obstructive pulmonary disease.