Stockley Robert A
Lung Investigation Unit, University Hospitals, Birmingham National Health Service Foundation Trust, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
Chronic Obstr Pulm Dis. 2020 Jul;7(3):163-171. doi: 10.15326/jcopdf.7.3.2019.0151.
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.
α-1抗胰蛋白酶缺乏症（AATD）传统上与早发性全小叶型肺气肿的发生有关，这种肺气肿被认为反映了中性粒细胞弹性蛋白酶引起的直接间质损伤。由于这种酶对α-1抗胰蛋白酶（AAT）的不可逆抑制高度敏感，静脉补充疗法的合理性一直未受到质疑，观察性研究和正式临床试验均支持其疗效。然而，有证据表明，尽管补充AAT可调节肺气肿的进展，但只能减缓其进程。这就引发了一个问题，即我们长期以来对缺乏AAT的个体易患肺气肿原因的看法是否正确。我们对该疾病的理解中有几个方面可能受益于对传统观念的彻底摒弃。本综述探讨了这些概念以及可能对肺气肿进展至关重要的替代途径。
