Alpha-1-antitrypsin and the pathogenesis of emphysema

The review examines the relationship between alpha₁-antitrypsin (α ₁AT) and emphysema. Although other defects occur in subjects with alpha₁-antitrypsin deficiency, it seems likely that a reduction in inhibition due to loss of this inhibitor explains their emphysema. There is a great deal of controversy, however, concerning the role of alpha₁-antitrypsin in subjects without inherited deficiency. There is uncertainty about the presence and function of other elastase inhibitors in the peripheral lung. The function of lungα ₁AT and the presence of elastase activity are dependent upon the techniques used and this probably accounts for different results between research groups. In addition, other relevant factors such as which enzymes cause lung elastolysis, control of neutrophil chemotaxis, and mechanisms of elastin synthesis and repair are less well studied. The overall conclusion is that many aspects of the elastase/antielastase hypothesis of emphysema are poorly understood. Without further information the true role ofα ₁AT will remain largely speculative.