Our present findings extend intriguing previous observations that the primary epithelial NOX isoform DUOX1 is in fact downregulated within the airways of subjects with COPD (22, 23), and demonstrate a gradual loss of small airway DUOX1 protein expression in patients with COPD in correlation with lung function decline and extracellular matrix remodeling and emphysema. Here, DUOX1 is linked to pulmonary emphysema.