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Journal Article
Research Support, Non-U.S. Gov't
Review
Small airways disease in patients with alpha-1 antitrypsin deficiency.
Respiratory Medicine 2023 May
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder, characterized by panacinar emphysema mainly in the lower lobes, and predisposes to chronic obstructive pulmonary disease (COPD) at a younger age, especially in patients with concomitant cigarette smoking. Alpha-1 antitrypsin (a1-AT) is a serine protease inhibitor that mainly blocks neutrophil elastase and maintains protease/antiprotease balance in the lung and AATD is caused by mutations in the SERPINA1 gene that encodes a1-AT protein. PiZZ is the most common genotype associated with severe AATD, leading to reduced circulating levels of a1-AT. Besides its antiprotease function, a1-AT has anti-inflammatory and antioxidative effects and AATD results in defective innate immunity. Protease/antiprotease imbalance affects not only the lung parenchyma but also the small airways and recent studies have shown that AATD is associated with small airway dysfunction. Alterations in small airways structure with peripheral ventilation inhomogeneities may precede emphysema formation, providing a unique opportunity to detect early disease. The aim of the present review is to summarize the current evidence for the contribution of small airways disease in AATD-associated lung disease.
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