Alpha-1 Antitrypsin Deficiency: Have We Got the Right Proteinase?

Authors: Stockley, R. A.

Publication: Chronic Obstr Pulm Dis; 7,3: May 2020

Affiliations: Lung Investigation Unit, University Hospitals, Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.

Abstract: Alpha-1 antitrypsin deficiency (AATD) has traditionally been associated with the development of early onset panlobular emphysema thought to reflect the direct interstitial damage caused by neutrophil elastase. Since this enzyme is highly sensitive to irreversible inhibition by alpha-1 antitrypsin (AAT), the logic of intravenous augmentation therapy has remained unquestioned and efficacy is supported by both observational studies and formal clinical trials. However, evidence suggests that although AAT augmentation modulates the progression of emphysema, it only slows it down. This raises the issue of whether our long-held beliefs of the cause of the susceptibility to develop emphysema in deficient individuals are correct. There are several aspects of our understanding of the disease that might benefit from a radical departure from traditional thought. This review addresses these concepts and alternative pathways that may be central to progression of emphysema.