Together with antichemotactic drugs, many new compounds or classes of compounds are presently in development for the treatment of COPD, such as antioxidants, protease inhibitors, adhesion molecule inhibitors, and new anti-inflammatory drugs.13–14
All of these new approaches have their rationale in cellular and molecular mechanisms of the inflammatory components in COPD that are taken as targets for the proposed treatment, but there are still a number of problems to be solved. For the antichemotactic drugs, the first problem is to identify the important mediators of chemotaxis that drive neutrophils into the airways of COPD patients. Neutrophilic chemotactic factors such as, IL-8, LTB4, and GRO-α have been identified in COPD patients at different levels, in BAL,15–18
and lung tissue.23
There is a need to clearly identify the chemotactic factors that, among many others, may be more important in COPD patients, and/or are more easily inhibited in their functional activity. As an example, Beeh and colleagues observed that the pretreatment of neutrophils with the combination of both of the antichemotactic drugs (ie, anti-IL-8 and anti-LTB4 receptor) reduced the sputum-induced chemotaxis by roughly 45%, which was less than the combined effect of either drug alone, thus suggesting the presence in the sputa of other, yet unidentified, neutrophil chemoattractants.