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A Journal on Diseases of the Respiratory System
Official Journal of the Italian Society of Thoracic Endoscopy
Indexed/Abstracted in: EMBASE, Scopus, Emerging Sources Citation Index
Minerva Pneumologica 2013 December;52(4):137-47
Alpha-1 antitrypsin and the pathogenesis of emphysema
Robinson J., Tuder R., Hunt J.
Division of Pulmonary Sciences and Critical Care Medicine Department of Medicine University of Colorado, Aurora, CO, USA
Alpha-1 antitrypsin (AAT) is the most plentiful circulating serine proteinase inhibitor (serpin) and an acute phase reactant in times of stress and infection. In 1963, the association between alpha-1 anti-trypsin deficiency (AATD) and emphysema was first described by Eriksson and Laurell; an observation forming the foundation of the protease:antiprotease imbalance theory in the pathogenesis of emphysema. It is now appreciated that the development of emphysema involves a variety of additional mechanisms including oxidative damage, infection, inflammation, autoimmunity, proteostasis, apoptosis, and senescence. Several of these processes are a part of the lung maintenance program; aimed at preserving lung tissue and function despite constant environmental bombardment by the likes of tobacco smoke, pollutants, and/or infections. Recent work has broadened our understanding of AAT and suggests additional functions beyond the maintenance of protease:antiprotease balance, including modulating infections, inflammation, auto-immunity, and apoptosis. In this review we begin with a discussion of the pathobiology of emphysema and the clinical aspects of AATD as it pertains to emphysema. We then examine the multiple roles AAT may play in the lung maintenance program; highlighting alternative mechanisms by which AATD may contribute to emphysema. We finish by examining the current paradigm for treatment of AATD, and suggest future avenues of research guided by the multiplicity of functions ascribed to AAT.