• To determine whether 12 weeks of selenium supplementation increases GPx-1 levels compared with placebo
  

• To determine whether selenium affects respiratory symptoms and function, and measures of inflammatory and infections markers.
  

Patients with chronic obstructive pulmonary disease (COPD) are at high risk for atherosclerotic heart disease, in part because of their nearly universal exposure to heavy smoking, and in part to other incompletely understood mechanisms which may include inflammation and anti-oxidant status.

Smoking markedly affects both circulating inflammatory markers concentrations, and the anti-oxidant glutathione peroxidase-1 (GPx-1). We hypothesize that smoking-related inflammation and anti-oxidant consumption lead to both cardiovascular (CV) and respiratory disease. In a recent study, we (Blankenberg et al) found that higher levels of GPx-1 were associated with lower rates af future CV events and death. GPx-1 levels were lower among smokers, and the combination of current smoking and GPx-1 levels below the median was strongly (HR=5.6) and significantly associated with future CV events and death.

There is a biological and epidemiological rationale to study selenium supplementation for CV protection. GPx-1 is a selenium-dependent enzyme, and data support the hypothesis that selenium supplementation increases GPx activity in various diseases. Furthermore, epidemiologic studies have discovered an inverse association between selenium content in soil and CV incidence and mortality. We hypothesize that selenium supplementation will elevate intra-erythrocytic GPx-1 levels in COPD patients and, ultimately, retard CV progression.

In this study, we will test the first component of this assertion. In a randomized, placebo-controlled trial, we will determine whether 12 weeks of selenium supplementation increases GPx-1 levels among 120 COPD patients. If successful, this study may lead to future large clinical trials to assess whether selenium, an inexpensive and safe mineral, improves clinical outcomes in cardiovascular and respiratory disease.