UNCLASSIFIED SPIROMETRIC ABNORMALITIES: RADIOLOGY, EPIDEMIOLOGY, AND GENETICS

描述(申请人提供)：慢性阻塞性肺疾病(COPD)包括肺气肿和小气道疾病。COPD的定义通常基于FEV1/FVC比值的降低，COPD的严重程度由FEV1的降低程度决定。然而，大量FEV1降低的受试者FEV1/FVC正常，这是一种未分类的肺活量模式。这一组可能有多种病因，包括众所周知的限制性过程(如间质性肺疾病、肥胖)和不符合经典肺活量测定定义的COPD。我们假设一部分未分类的肺活量测定受试者患有慢性阻塞性肺疾病，这可以通过放射学和遗传学研究来确定。COPD基因研究的参与者将接受胸部CT扫描，并使用定量分析对肺气肿和呼吸道疾病进行评估。将评估肺气肿和呼吸道疾病与性别、种族和体重指数之间的流行病学关系。将对全基因组关联研究中与COPD显著相关的一组SNPs进行基因分型，基于人群的遗传关联分析将确定这些SNPs是否也影响未分类的肺活量测定组的肺活量和CT表型。最后，将对CT、生理和流行病学数据进行聚类分析，使用这些聚类的遗传关联分析将确定是否可以识别未分类的肺活量计量组的COPD子集。有未分类的肺活量模式的受试者代表了一个庞大且研究不足的人群，其中可能包括大量患有COPD的受试者，这些受试者不符合COPD的经典肺活量标准。我们将应用最先进的成像和遗传学方法来确定患有COPD的未分类肺活量测定受试者的子集。 公共卫生相关性：慢性阻塞性肺疾病(COPD)包括肺气肿和小气道疾病。COPD的定义通常基于一种名为肺活量测定的呼吸测试，该测试测量在用力呼气(FVC)期间可以吹出的空气量，以及在呼气第一秒(FEV1)期间吹出的空气量。COPD受试者的FEV1/FVC比值降低，COPD的严重程度由FEV1降低的程度决定。然而，大量FEV1降低的受试者具有正常的FEV1/FVC(未分类的肺活量模式)，这一组的呼吸问题可能有多种原因，包括众所周知的限制性过程(例如间质性肺疾病、肥胖)和不符合经典肺活量测定定义的COPD。我们将使用胸部CT扫描和基因研究来确定患有肺气肿和/或小气道疾病的未分类肺活量测定受试者的子集，以便这些个体能够得到更有效的治疗。

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) includes both emphysema and small airway disease. COPD has typically been defined based on a reduction in the FEV1/FVC ratio, with the severity of COPD determined by the level of reduction in the FEV1. However, a large number of subjects with reduced FEV1 have a normal FEV1/FVC, which is an unclassified spirometric pattern. There are likely multiple etiologies in this group including well-known restrictive processes (e.g. interstitial lung disease, obesity) and COPD which does not meet classic spirometric definitions. We hypothesize that a subset of unclassified spirometry subjects have COPD which can be determined based on radiologic and genetic studies. Participants in the COPDGene Study with unclassified spirometry will undergo chest CT scans, which will be assessed for emphysema and airway disease using quantitative analysis. Epidemiological relationships between emphysema and airway disease with gender, race, and body mass index will be assessed. Genotyping of a panel of SNPs that have been significantly associated with COPD in genome-wide association studies will be performed, and population-based genetic association analysis will determine whether these SNPs also influence spirometric and CT phenotypes in the unclassified spirometry group. Finally, cluster analysis of the CT, physiological, and epidemiological data will be performed, and genetic association analysis using these clusters will determine whether a COPD subset of the unclassified spirometry group can be identified. Subjects with an unclassified spirometric pattern represent a large and understudied population, which likely includes a substantial number of subjects with COPD that do not meet classic spirometric criteria for COPD. We will apply state-of-the-art imaging and genetic methods to identify a subset of unclassified spirometry subjects with COPD. PUBLIC HEALTH RELEVANCE: Chronic obstructive pulmonary disease (COPD) includes both emphysema and small airway disease. COPD is usually defined based on a breathing test called spirometry, which measures the amount of air that can be blown out during a forced expiration (FVC) and the amount of air blown out during the first second of that expiration (FEV1). COPD subjects have a reduced FEV1/FVC ratio, with the severity of COPD determined by the level of reduction in the FEV1. However, a large number of subjects with reduced FEV1 have a normal FEV1/FVC (unclassified spirometric pattern), and there are likely multiple causes for the breathing problems in this group including well-known restrictive processes (e.g. interstitial lung disease, obesity) and COPD which does not meet classic spirometric definitions. We will use chest CT scans and genetic studies to identify the subset of unclassified spirometry subjects that have emphysema and/or small airway disease, so that those individuals can be treated more effectively.