cohort of patients from the Lung Health Study. We have reported that the genetic polymorphism of exon 5 of smokers with GSTP1 is associated with the development of

COPD in smokers. 3 Because the GSTP1/Ile105 genotype is predominantly found in smokers with COPD (72%), but not in smokers without airflow limitation (52%), the GSTP1/Ile105 genotype may be less protective against the xenobiotics in tobacco smoke. Recent data 8 further support the idea that the GSTP1/Ile105 homozygote is associated with an increase in IgE and histamine after challenge with diesel exhaust particles and allergens. Although cigarette smoking is the most important risk factor for the development of COPD, allergic airway inflammation, long-standing asthma, air pollutants, diesel exhaust particles, and xenobiotics also may cause irreversible airflow limitation such as COPD. It has been reported 9 that tunnel workers being exposed to gases and particles from blasting and diesel exhausts are likely to develop COPD. Therefore, subjects exposed to diesel exhaust particles are susceptible to the accelerated decline of lung function, resulting in COPD. There is growing evidence for the role of xenobiotics and antioxidant imbalance in the pathogenesis of airflow obstruction, which is supported by the results of association studies between COPD and variants in epoxide hydrolase and GSTs that detoxify free radicals and other tobacco products. 10–14 Before these associations are generally accepted, they must be subjected to scrutiny with further association studies in terms of ethnicity and COPD phenotypes.