Beiko Tatsiana, Janech Michael G, Alekseyenko Alexander V, Atkinson Carl, Coxson Harvey O, Barth Jeremy L, Stephenson Sarah E, Wilson Carole L, Schnapp Lynn M, Barker Alan, Brantly Mark, Sandhaus Robert A, Silverman Edwin K, Stoller James K, Trapnell Bruce, Charlie Strange
Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston.
Division of Nephrology, Medical University of South Carolina, Charleston.
Chronic Obstr Pulm Dis. 2017 Jul 15;4(3):204-216. doi: 10.15326/jcopdf.4.3.2016.0180.
Computed tomography (CT) lung density is an accepted biomarker for emphysema in alpha-1 antitrypsin deficiency (AATD), although concerns for radiation exposure limit its longitudinal use. Serum proteins associated with emphysema, particularly in early disease, may provide additional pathogenic insights. We investigated whether distinct proteomic signatures characterize the presence and progression of emphysema in individuals with severe AATD and normal forced expiratory volume in 1 second (FEV). itative lung CT nasking emphysema progression in AATD (QUANTUM-1) is a multicenter, prospective 3-year study of 49 adults with severe AATD and FEV post-bronchodilator values (Post-BD) ≥ 80% predicted. All participants received chest CT, serial spirometry, and contributed to the serum biobank. Volumetric imaging display and analysis (VIDA) software defined the baseline 15 percentile density (PD15) which was indexed to CT-derived total lung capacity (TLC). We measured 317 proteins using a multiplexed immunoassay (Myriad Discovery MAP panel) in 31 individuals with a complete dataset. We analyzed associations between initial PD15/TLC, PD15/TLC annual decline, body mass index (BMI), and protein levels using Pearson's product moment correlation. C-reactive protein (CRP), adipocyte fatty acid-binding protein (AFBP), leptin, and tissue plasminogen activator (tPA) were found to be associated with baseline emphysema and all but leptin were associated with emphysema progression after adjustments were made for age and sex. All 4 proteins were associated with BMI after further adjustment for multiple comparisons was made. The relationship between these proteins and BMI, and further validation of these findings in replicative cohorts require additional studies.
计算机断层扫描（CT）肺密度是α-1抗胰蛋白酶缺乏症（AATD）中肺气肿的公认生物标志物，尽管对辐射暴露的担忧限制了其纵向应用。与肺气肿相关的血清蛋白，尤其是在疾病早期，可能提供额外的致病见解。我们研究了在1秒用力呼气量（FEV）正常的严重AATD个体中，不同的蛋白质组学特征是否可表征肺气肿的存在和进展。AATD中定量肺CT评估肺气肿进展（QUANTUM-1）是一项多中心、前瞻性3年研究，纳入了49名严重AATD且支气管扩张剂后FEV值（支气管扩张剂后）≥预测值80%的成年人。所有参与者均接受胸部CT、系列肺功能测定，并为血清生物样本库提供样本。容积成像显示和分析（VIDA）软件定义了基线第15百分位数密度（PD15），该密度以CT衍生的肺总量（TLC）为指标。我们使用多重免疫测定法（Myriad Discovery MAP检测板）在31名拥有完整数据集的个体中测量了317种蛋白质。我们使用Pearson积矩相关性分析了初始PD15/TLC、PD15/TLC年下降率、体重指数（BMI）和蛋白质水平之间的关联。发现C反应蛋白（CRP）、脂肪细胞脂肪酸结合蛋白（AFBP）、瘦素和组织纤溶酶原激活剂（tPA）与基线肺气肿相关，除瘦素外，在对年龄和性别进行调整后，其余均与肺气肿进展相关。在对多重比较进行进一步调整后，所有这4种蛋白质均与BMI相关。这些蛋白质与BMI之间的关系，以及在复制队列中对这些发现的进一步验证需要更多研究。
