ABSTRACT
The hypothesis that an increased protease burden in the lung was the biochemical basis of emphysema emerged in the early 1960s. This followed the observation that (a) a deficiency of α-1 antitrypsin (AAT; also called α-1 proteinase inhibitor, the major serum inhibitor of neutrophil elastase) is associated with early development of emphysema [1] and (b) papain, a proteinase with high elastinolytic activity, induced emphysema when instilled intratracheally into experimental animals [2]. An important component of chronic obstructive pulmonary disease, notably emphysema, is the loss of elastic recoil due to loss of elastin, and an abnormal repair leading to abnormal elastic tissue structure, suggesting that increased elastinolytic proteinases are responsible. The evidence to support this hypothesis is substantial, although it is highly unlikely that a single protease is responsible.
