Although he cited many articles on candidate gene-association studies and linkage analyses, which have been reported for COPD patients, the pathogenesis of COPD associated with the xenobiotic enzyme has been totally neglected. It has been suggested that genetic polymorphisms in xenobiotic enzymes may have a role in individual susceptibility to oxidant-related lung disease.2–4 The first-pass metabolism of foreign compounds in the lung is an important protective mechanism against oxidative stress. The polymorphisms in the genes for cytochrome P450, microsomal epoxide hydrolase (mEPHX) and glutathione S-transferase (GST) P1, which are the enzymes involved in this protective process, had some bearing on individual susceptibility to the development of COPD.2–4 As shown in Figure 1
, xenobiotics are closely associated with the oxidant-antioxidant imbalance, which is one of the two major hypotheses in the pathogenesis of smoke-related COPD. Further, oxidant-antioxidant imbalance causes the oxidative inactivation of antiproteinases, alveolar epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of proinflammatory mediators.