Another lesson to be learned from AAT research is the use of AAT as an antiinflammatory and antiapoptotic molecule in the treatment of COPD unrelated to AAT deficiency. In other words, exogenous AAT could be thought of as a therapeutic agent, not only as a replacement as in AAT deficiency. There is growing evidence for this paradigm. Human AAT inhibits the inflammatory activity of human monocytes in vitro, and this effect is still seen with modified forms of AAT that lack antiprotease effects.21 With respect to the antiapoptotic actions of AAT, it has been shown in a mouse model18 that AAT inhibits apoptosis-dependent lung destruction that is not caused by AAT deficiency, and a recent article22 has also demonstrated that AAT attenuates cigarette smoke-induced apoptosis in vitro. In addition to these antiapoptotic actions in vitro and in animal models of lung disease, AAT appears to have broad antiinflammatory effects in humans. Thus, the treatment of patients with cystic fibrosis with aerosol AAT has been reported23 to reduce sputum neutrophil numbers, interleukin-8 concentrations, and unopposed elastase activity. As a serine protease inhibitor, it is not surprising that inhaled AAT attenuated free elastase activity in the lung. More significant was the effect of AAT on interleukin-8, which is a chemoattractant for neutrophils, and on neutrophil recruitment to the lung. Inasmuch as neutrophils are thought to have a major role in the pathogenesis of COPD, one might consider exploring the clinical benefit of AAT in COPD. Currently, only IV administered AAT is available for the purpose of augmentation therapy in patients with AAT deficiency. IV AAT is hardly a therapeutic option in patients with generic COPD. However, with the likelihood that aerosol AAT will soon become available for clinical use, the idea of treating cystic fibrosis and COPD with AAT to prevent disease progression may not be far fetched.