Hernandez Paul, Bossé Yohan, Bush Pam, Chapman Kenneth R, Maltais François, Penz Erika D, Walker Brandie L, Lal Avtar, Marciniuk Darcy D
Division of Respirology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval, Quebec City, PQ, Canada; Department of Molecular Medicine, Université Laval, Quebec City, Québec, Canada.
Chest. 2025 Apr;167(4):1044-1063. doi: 10.1016/j.chest.2024.08.037. Epub 2025 Jan 27.
Alpha-1-antitrypsin (A1AT) deficiency is a common hereditary disorder associated with increased risk of developing chronic obstructive pulmonary disease (COPD). Many individuals with severe A1AT deficiency go undiagnosed, or are diagnosed late, and fail to benefit from disease-specific counseling and modifying care. Since the 2012 Canadian Thoracic Society (CTS) A1AT deficiency clinical practice guideline, new approaches to optimal diagnosis using modern genetic testing and studies of A1AT augmentation therapy have been published. We performed a systematic review and meta-analysis, which along with expert clinical input, informed recommendations. We conditionally recommend testing for A1AT deficiency in all individuals with COPD at the time of diagnosis, individuals with adult-onset asthma with persistent airway obstruction, and individuals with unexplained bronchiectasis. We suggest genetic testing with DNA sequencing of SERPINA1 gene as the initial test for individuals with high clinical suspicion for A1AT deficiency, and initial measurement of serum A1AT levels in individuals with moderate clinical suspicion of A1AT deficiency, followed by genetic testing with DNA sequencing of SERPINA1 gene if A1AT level is <23 μmol/L (<1.2 g/L). Following identification of an abnormal gene for A1AT in individuals, whether heterozygote or homozygote, we suggest first-degree relatives be provided genetic counseling and offered testing for A1AT deficiency. The panel conditionally recommends A1AT augmentation therapy to patients who do not smoke or who formerly smoked with COPD (forced expiratory volume in 1 s [FEV] < 80% predicted; associated with emphysema), with documented deficiency genotypes and severely reduced A1AT level (< 11 μmol/L or < 0.57 g/L) in addition to receiving optimal pharmacological and nonpharmacological therapies for COPD.
α-1抗胰蛋白酶（A1AT）缺乏症是一种常见的遗传性疾病，与患慢性阻塞性肺疾病（COPD）的风险增加相关。许多严重A1AT缺乏症患者未被诊断出来，或者诊断较晚，无法从针对该疾病的咨询和调整治疗中获益。自2012年加拿大胸科学会（CTS）A1AT缺乏症临床实践指南发布以来，已发表了使用现代基因检测进行最佳诊断的新方法以及A1AT增强疗法的研究。我们进行了一项系统评价和荟萃分析，并结合专家临床意见得出了相关建议。我们有条件地建议在所有COPD诊断时的患者、患有持续性气道阻塞的成年起病哮喘患者以及不明原因支气管扩张患者中检测A1AT缺乏症。对于临床高度怀疑A1AT缺乏症的患者，我们建议以SERPINA1基因的DNA测序进行基因检测作为初始检测；对于临床中度怀疑A1AT缺乏症的患者，首先检测血清A1AT水平，若A1AT水平<23μmol/L（<1.2g/L），则随后进行SERPINA1基因的DNA测序基因检测。在个体中鉴定出A1AT异常基因后，无论其为杂合子还是纯合子，我们建议为其一级亲属提供遗传咨询并进行A1AT缺乏症检测。该专家组有条件地建议，对于不吸烟或既往吸烟的COPD患者（1秒用力呼气容积[FEV]<预测值的80%；与肺气肿相关），除接受针对COPD的最佳药物和非药物治疗外，若有记录的缺乏症基因型且A1AT水平严重降低（<11μmol/L或<0.57g/L），则给予A1AT增强疗法。
