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. The gene discussed is DUOX1; the disease is chronic obstructive pulmonary disease.