A great deal of evidence indicates that neutrophil elastase participates in the lung destruction which results in pulmonary emphysema. Many drugs which are currently available for human use are known to reduce neutrophil chemotaxis and lysosomal enzyme release. The purpose of this research is to test the hypothesis that the neutrophil elastase lead in the lungs of patients with emphysema can be reduced with currently available drugs and that reduced elastase loads will reduce elastin catabolism in the lungs. The investigators will measure variables which reflect the load of neutrophil elastase in the lungs of patients with chronic obstructive pulmonary diseases (COPD) and will attempt to reduce this elastase load with drugs which affect neutrophil function. Drugs which reduce chemotaxis or enzyme release by neutrophils or which reduce the secretion of the chemotactic factors and enzyme releasing factors by human alveolar macrophages will be selected for study. We will carry out controlled clinical trails to determine if any of these drugs or any safe combination of these drugs reduces the load of neutrophil elastase in the lungs of these patients. In vitro studies will be used to help select drugs which will be studied in the clinical trials.
