UNCLASSIFIED SPIROMETRIC ABNORMALITIES: RADIOLOGY, EPIDEMIOLOGY, AND GENETICS

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）包括肺气肿和小气道疾病。COPD通常根据FEV 1/FVC比值的降低来定义，COPD的严重程度由FEV 1的降低水平确定。然而，大量FEV 1降低的受试者的FEV 1/FVC正常，这是一种未分类的肺量测定模式。该组可能有多种病因，包括众所周知的限制性过程（例如，间质性肺病、肥胖）和不符合经典肺功能定义的COPD。我们假设一部分未分类的肺功能测定受试者患有COPD，可以根据放射学和遗传学研究确定。COPD基因研究中未分类肺功能测定的参与者将接受胸部CT扫描，使用定量分析评估肺气肿和气道疾病。将评估肺气肿和气道疾病与性别、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SNP进行基因分型，基于人群的遗传关联分析将确定这些SNP是否也影响未分类肺量计组中的肺量计和CT表型。最后，将对CT、生理学和流行病学数据进行聚类分析，使用这些聚类进行遗传关联分析将确定是否可以识别未分类肺量计组的COPD子集。具有未分类肺量测定模式的受试者代表了大量研究不足的人群，其中可能包括大量不符合COPD经典肺量测定标准的COPD受试者。我们将应用最先进的成像和遗传学方法来识别未分类的COPD肺功能测定受试者的子集。 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。慢性阻塞性肺病通常是根据一种称为肺量测定的呼吸测试来定义的，该测试测量在用力呼气（FVC）期间可以吹出的空气量以及在该呼气的第一秒（FEV 1）期间吹出的空气量。COPD受试者的FEV 1/FVC比值降低，COPD的严重程度由FEV 1的降低水平确定。然而，大量FEV 1降低的受试者具有正常的FEV 1/FVC（未分类的肺量测定模式），并且该组中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，间质性肺病、肥胖）和不符合经典肺量测定定义的COPD。我们将使用胸部CT扫描和遗传学研究来识别患有肺气肿和/或小气道疾病的未分类肺功能测定受试者的子集，以便这些个体可以得到更有效的治疗。

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.