National Heart and Lung Institute, Imperial College London, London, United Kingdom; General State Hospital for Thoracic Diseases of Athens "Sotiria", Greece.
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Respir Med. 2023 May;211:107222. doi: 10.1016/j.rmed.2023.107222. Epub 2023 Mar 23.
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.
α1-抗胰蛋白酶缺乏症（AATD）是一种遗传疾病，其特征是全腺泡性肺气肿，主要发生在下肺叶，并使患者在更年轻时易患慢性阻塞性肺疾病（COPD），尤其是在伴有吸烟的患者中。α1-抗胰蛋白酶（a1-AT）是一种丝氨酸蛋白酶抑制剂，主要阻断中性粒细胞弹性蛋白酶，并维持肺中的蛋白酶/抗蛋白酶平衡，AATD 是由编码 a1-AT 蛋白的 SERPINA1 基因突变引起的。PiZZ 是与严重 AATD 相关的最常见基因型，导致 a1-AT 循环水平降低。除了其抗蛋白酶功能外，a1-AT 还具有抗炎和抗氧化作用，AATD 导致先天免疫功能缺陷。蛋白酶/抗蛋白酶失衡不仅影响肺实质，还影响小气道，最近的研究表明 AATD 与小气道功能障碍有关。小气道结构的改变和周围通气不均匀可能先于肺气肿形成，为早期疾病的检测提供了独特的机会。本综述的目的是总结小气道疾病在 AATD 相关肺部疾病中的作用的现有证据。
