Alpha₁-proteinase inhibitor (A₁-PI) deficiency is a chronic, hereditary condition characterized by a damaged copy of one or both of the Alpha-1 antitrypsin genes. An estimated 25 million people nationwide are heterozygotes for Alpha-1.

Low blood levels of A₁-PI are most commonly associated with progressive, severe pulmonary disease, such as emphysema, that becomes apparent by the third or fourth decade of life.² A₁-PI is understood to be the primary antiprotease in the lower respiratory tract, where it inhibits neutrophil elastase (NE). Normal healthy individuals produce sufficient A₁-PI to control the NE produced by activated neutrophils and are thus able to prevent inappropriate proteolysis of lung tissue by NE. Conditions that increase neutrophil accumulation and activation in the lung, such as respiratory infection and smoking, will in turn increase levels of NE. However, individuals who are severely deficient in endogenous A₁-PI are unable to maintain an appropriate antiprotease defense and are thereby subject to more rapid proteolysis of the alveolar walls leading to chronic lung disease.²