Antitrypsin deficiency: still more to learn about the lung after 60 years

Abstract

The past 60 years have seen multiple publications related to lung disease in α1-antitrypsin deficiency largely reflecting the pathophysiology, biochemical effect and outcomes of augmentation therapy. However, the complexity of disease phenotype and the impact of the natural history presents problems of patient management, study design and hence interpretation of outcome. Although many national and some international registries exist, the lack of consistent in-depth assessment and importantly, the impact of augmentation therapy likely influences our perception of the true natural history. Development of new therapeutic strategies, and even assessment of the role and efficacy of augmentation, remain a challenge as powering such studies for conventional COPD outcomes is impractical due to relative rarity of the genetic condition and the presence of clinical phenotypic variation. The current review approaches these issues, discusses the nature and complexity of assessing patient variability, and provides guidance on further studies required to address them.