However, in this study, among COPD patients (13 subjects), there were three former smokers who had a hypoxemia and moderate COPD with an impairment of eNOS activity (low concentration of nitrate and cGMP), which suggests that besides harmful effect of cigarette smoke, there are also other intrinsic factors which may be involved in the impairment of eNOS expression and activity in patients with COPD. This evidence concerns the gene NOS3 and chronic obstructive pulmonary disease.