Demeo Dawn L, Sandhaus Robert A, Barker Alan F, Brantly Mark L, Eden Edward, McElvaney N Gerard, Rennard Stephen, Burchard Esteban, Stocks James M, Stoller James K, Strange Charlie, Turino Gerard M, Campbell Edward J, Silverman Edwin K
Channing Laboratory, 181 Longwood Avenue, Boston, Massachusetts 02115, USA.
Thorax. 2007 Sep;62(9):806-13. doi: 10.1136/thx.2006.075846. Epub 2007 Mar 27.
Severe alpha(1)-antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency.
The AAT Genetic Modifier Study is a multicentre family-based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33-80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV(1)) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV(1) <50% predicted).
In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV(1 )percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV(1) values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non-index cases (p<0.01). Men had lower pre- and post-bronchodilator FEV(1) percentage predicted than women (p<0.0001); the lowest FEV(1) values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non-index groups were examined separately, with men representing the majority of non-index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non-index men but not women.
In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment.
严重的α1抗胰蛋白酶（AAT）缺乏症是一种常染色体隐性遗传病，与慢性阻塞性肺疾病（COPD）风险增加但存在个体差异相关。开展了一项研究，以评估慢性支气管炎、肺炎、哮喘和性别对严重AAT缺乏症个体发生COPD的影响。
AAT基因修饰研究是一项基于家庭的多中心队列研究，旨在研究AAT缺乏症中COPD的遗传和流行病学决定因素。分析纳入了378名（年龄范围33 - 80岁）被确认为SERPINA1 Z突变纯合子的个体。感兴趣的主要结局包括一个定量结局，即1秒用力呼气容积（FEV1）预测百分比，以及一个定性结局，即严重气流受限（FEV1 <预测值的50%）。
在对整个队列的多变量分析中，吸烟、性别、哮喘、慢性支气管炎和肺炎是预测FEV1预测百分比降低和严重气流受限的危险因素（p<0.01）。与非索引病例相比，索引病例的FEV1值更低、吸烟史更长，且16岁前成人哮喘、肺炎和哮喘的报告更多（p<0.01）。男性支气管扩张剂使用前后的FEV1预测百分比低于女性（p<0.0001）；在报告有儿童哮喘病史的男性中观察到最低的FEV1值（26.9%）。当分别检查索引组和非索引组时，男性更严重阻塞的这一趋势仍然存在，在有气流受限的非索引个体中男性占大多数（71%）。在非索引男性而非女性的多变量分析中，慢性支气管炎（比值比3.8，可信区间1.8至12.0）和医生报告的哮喘（比值比4.2，可信区间1.4至13.1）是严重气流受限的预测因素。
在严重AAT缺乏症个体中，除吸烟外，性别、哮喘、慢性支气管炎和肺炎是严重COPD的危险因素。这些结果表明，在严重缺乏AAT的受试者中，男性、有慢性支气管炎症状和/或既往有哮喘或肺炎诊断的个体可能受益于更密切的监测和可能更早的治疗。
