Longitudinal Modeling of Lung Function Trajectories in Smokers with and without Chronic Obstructive Pulmonary Disease
Longitudinal Modeling of Lung Function Trajectories in Smokers with and without Chronic Obstructive Pulmonary Disease
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DOI：
10.1164/rccm.201707-1405oc
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发表时间：
2018-10-15
影响因子：
24.7
通讯作者：
Estepar, Raul San Jose
中科院分区：
文献类型：
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作者：
Ross, James C.;Castaldi, Peter J.;Estepar, Raul San Jose
基本原理：纵向肺功能轨迹、胸部计算机断层扫描（CT）成像和慢性阻塞性肺疾病（COPD）遗传易感性之间的关系尚未探讨。目的：1）使用数据驱动方法对规范老化研究（NAS）中跨越成年期的纵向数据进行建模，和2）将这些模型应用于COPD基因中人口统计学上相似的受试者（COPD的遗传流行病学）详细的表型特征研究，包括胸部CT。方法：我们对NAS中1,060名受试者的肺功能轨迹进行了建模，中位随访时间为29年。我们将COPD基因中的3,546名非西班牙裔白色男性分配到这些轨迹中进行进一步分析。我们评估了轨迹之间的表型和遗传差异，并跨越年龄strature. Measures和主要结果：我们确定了四个轨迹在NAS的不同水平的最大肺功能和下降速度。在COPDGene中，617名受试者（17%）被分配到最低轨迹，并且具有最大的疾病放射学负担1，283名受试者（36%）被分配到低轨迹，在CT上有肺气肿之前的气道疾病证据; 1，411名受试者（40%）和237名受试者（7%）被分配到其余两个轨迹，并且往往具有保留的肺功能和可忽略的肺气肿。这些轨迹的遗传贡献高达83%（P = 0.02），和成员在较低的肺功能轨迹与更大的COPD，运动能力下降，更大的呼吸困难，更频繁的COPD急性加重的父母的历史。轨迹成员有遗传基础，并与不同的肺结构异常。
Rationale: The relationship between longitudinal lung function trajectories, chest computed tomography (CT) imaging, and genetic predisposition to chronic obstructive pulmonary disease (COPD) has not been explored.Objectives: 1) To model trajectories using a data-driven approach applied to longitudinal data spanning adulthood in the Normative Aging Study (NAS), and 2) to apply these models to demographically similar subjects in the COPDGene (Genetic Epidemiology of COPD) Study with detailed phenotypic characterization including chest CT.Methods: We modeled lung function trajectories in 1,060 subjects in NAS with a median follow-up time of 29 years. We assigned 3,546 non-Hispanic white males in COPDGene to these trajectories for further analysis. We assessed phenotypic and genetic differences between trajectories and across age strata.Measurements and Main Results: We identified four trajectories in NAS with differing levels of maximum lung function and rate of decline. In COPDGene, 617 subjects (17%) were assigned to the lowest trajectory and had the greatest radiologic burden of disease (P < 0.01); 1,283 subjects (36%) were assigned to a low trajectory with evidence of airway disease preceding emphysema on CT; 1,411 subjects (40%) and 237 subjects (7%) were assigned to the remaining two trajectories and tended to have preserved lung function and negligible emphysema. The genetic contribution to these trajectories was as high as 83% (P = 0.02), and membership in lower lung function trajectories was associated with greater parental histories of COPD, decreased exercise capacity, greater dyspnea, and more frequent COPD exacerbations.Conclusions: Data-driven analysis identifies four lung function trajectories. Trajectory membership has a genetic basis and is associated with distinct lung structural abnormalities.