The aim of this study is to investigate the mechanisms whereby lung function is decreased in COPD. The hypothesis is that in diseases such as COPD, inflammatory cells including neutrophils, macrophages and lymphocytes migrate to the lung and release either more or different types of inflammatory mediators and/or destructive enzymes compared to subjects without COPD. We aim to investigate these separate cell types in the blood of subjects with COPD and identify which genes are more highly expressed when compared to cells obtained from patients without COPD. We will also investigate the lung macrophages from these subjects to identify whether the same or different genes are expressed in these cells. We will isolate different leukocyte populations from the blood and extract ribonucleic acid (RNA) from these samples. The type and quantity of RNA in these samples is a reflection of the specific genes expressed in these cells. This RNA will be sent to Gene Logic and this company will test these samples to identify which genes have been expressed. Similar experiments will be performed using macrophages obtained following bronchoalveolar lavage of these subjects. We would aim to examine the responses of leukocytes from three groups of subjects, namely (i) non-smoking controls (ii) smokers without clinical or histological signs of COPD and (iii) smokers with COPD. The isolated leukocytes will either be immediately solubilized in solutions to purify RNA or we will then use these isolated cells in vitro and following stimulation investigate whether different genes are expressed or at a differential rate in the disease state. The objective is to identify which genes are specifically expressed in patients with COPD with a view to identify novel targets for drug therapy. We will examine both leukocytes derived from peripheral blood and macrophages obtained from bronchoalveolar lavage with the aim to determine whether differences attributable to disease can be identified in both circulating cells and those at the site of disease. This is a preliminary study to determine the profile of inflammatory mediator expression from leukocytes and as such power calculations to determine the number of subjects is not appropriate.