Curtis Jeffrey L, Bateman Lori A, Murray Susan, Couper David J, Labaki Wassim W, Freeman Christine M, Arnold Kelly B, Christenson Stephanie A, Alexis Neil E, Kesimer Mehmet, Boucher Richard C, Kaner Robert J, Barjaktarevic Igor, Cooper Christopher B, Hoffman Eric A, Barr R Graham, Bleecker Eugene R, Bowler Russell P, Comellas Alejandro, Dransfield Mark T, Freedman Michael B, Hansel Nadia N, Krishnan Jerry A, Marchetti Nathaniel, Meyers Deborah A, Ohar Jill, O'Neal Wanda K, Ortega Victor E, Paine Iii Robert, Peters Stephen P, Smith Benjamin M, Wedzicha Jadwiga A, Wells J Michael, Woodruff Prescott G, Han MeiLan K, Martinez Fernando J
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States.
Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, United States.
Chronic Obstr Pulm Dis. 2024 Sep 27;11(5):444-459. doi: 10.15326/jcopdf.2023.0490.
The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition.
Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression.
METHODS/DISCUSSION: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture.
SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.
导致一些接触烟草的个体罹患早期慢性阻塞性肺疾病（COPD）的生物学机制尚不清楚。这一知识空白阻碍了针对这种常见疾病的疾病修饰药物的研发。
因此，在美国国立心肺血液研究所的支持下，我们启动了慢性阻塞性肺疾病亚组和中间结局指标研究（SPIROMICS）早期COPD进展研究（SOURCE），这是一项针对有吸烟史、因而有早期COPD风险或已患早期COPD的较年轻个体的多中心观察性队列研究。我们的总体目标是确定那些将在生命早期罹患COPD的个体，对其进行全面表征，并通过将他们与未患COPD的个体进行对比，明确疾病进展的机制。
方法/讨论：SOURCE利用已建立的SPIROMICS临床网络。其目标是招募649名年龄在30 - 55岁之间、所有种族/族裔、吸烟史≥10包年、处于慢性阻塞性肺疾病全球倡议组织（GOLD）0 - 2组或存在比率受损肺量计结果保留情况的参与者；以及另外40名从不吸烟的对照者。参与者接受基线和3年随访，每次随访均包括高分辨率计算机断层扫描、呼吸振荡测定法和肺量测定法（支气管扩张剂给药前后）、呼出气冷凝物（仅基线时），以及广泛的生物样本采集，包括诱导痰。每6个月通过随访电话记录症状、临时医疗保健利用情况和病情加重情况。一项涉及100名参与者（包括所有从不吸烟者）的嵌入式支气管镜亚研究将允许采集下呼吸道样本，用于基因、表观遗传、基因组、免疫学、微生物组、粘蛋白分析以及基底细胞培养。
SOURCE应能为有吸烟史的较年轻个体的肺部疾病自然史及其生物学基础提供新的见解。
