chapter  9
Pages 18

Alpha-1-antitrypsin deficiency was reported in an Alaskan girl who died 800 years ago1 and may have accounted for the premature death of Frederic Chopin in 1849.2,3 It was first described as a clinical entity in 1963 by Laurell and Eriksson who noted an absence of the alpha-1 band on serum protein electrophoresis.4 The major function of alpha-1-antitrypsin is to protect the tissues against the enzyme neutrophil elastase.5,6 Its role in protecting the lungs against proteolytic attack is underscored by the association of plasma deficiency with early-onset panlobular emphysema.7 This association of alpha-1-antitrypsin deficiency with early-onset emphysema gave rise to the protease/antiprotease hypothesis of lung disease. In health there is a balance between proteases and antiproteases but when proteases are in excess then tissue destruction will ensue. The protease/antiprotease hypothesis was developed over 35 years ago but still remains central to our understanding of the pathogenesis of lung disease. It has evolved to include a variety of proteases and their inhibitors (Table 9.1) and has been implicated in other lung diseases such as cystic fibrosis,8

and chronic lung infection.11,12 In this chapter I will review the proteases that contribute to the lung damage in emphysema and then focus on the deficiency of alpha1-antitrypsin which is associated with obstructive lung disease.