Validation of serum biomarker signatures predictive of incident COPD

描述(申请人提供)：慢性阻塞性肺疾病(COPD)是一种慢性炎症性疾病，具有重要的全身表现，是其发病率和死亡率的重要组成部分。识别可以预测该病发病的系统生物标记物可能会为其分子机制提供重要的见解，并对预防具有重要意义。然而，到目前为止，对COPD生物标记物的研究一直受到一次仅使用几个标记物以及数据横断面性质的限制，这排除了对与COPD发病时间相关的生物标记物的任何全面和决定性的解决。在NHLBI资助的HL095021下，我们最近测量了在图森呼吸道阻塞性疾病流行病学研究(TESAOD)的登记调查(1972)中收集的794个血清样本中的108个分析物，现在可以在其24年的随访期内获得有关肺功能和呼吸健康的广泛表型信息。这些分析物代表了多个潜在的COPD途径中涉及的分子，用基于珠子的多分析物图谱方法进行了测量，该方法允许优化大型流行病学生物信息库的利用。在这项应用中，我们建议1)在瑞士成人空气污染与肺部疾病研究(SAPALDIA)的独立队列中，验证在TESAOD中被确定为预测COPD发病率的血清生物标志物特征；以及2)确定整合血清初始水平和血清浓度时间变化的信息是否提高了上述生物标志物预测COPD风险的能力。这将导致迄今为止对COPD进行最全面的前瞻性血清生物标记物研究，并将导致最终确定与COPD发病率有关的生物标记物和分子途径。它还将为学员阶段II提供基础，在此期间，我们将寻求长期目标，以确定这些靶点和途径影响COPD风险的分子机制，并评估它们在COPD一级到三级预防中的潜在临床应用。相关性(见说明)：慢性阻塞性肺疾病(COPD)是一种常见疾病，具有很大的发病率和死亡率负担。这项研究将导致识别与COPD发展相关的分子，进而可能导致潜在的临床应用，在这种疾病的一级到三级预防中。

DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is a chronic ainway infiammatory disease with important systemic manifestations that account for a substantial part of its morbidity and mortality. The identification of systemic biomarkers that can predict inception of this disease may provide important insights into its molecular mechanisms and have critical implications for prevention. Yet, to date studies of biomarkers of COPD have been limited by the use of only a few markers at a time and by the cross-sectional nature of the data, which has precluded any comprehensive and conclusive resolution of biomarkers temporally linked to incidence of COPD. Under NHLBI-funded HL095021, we have recently measured a large panel of 108 analytes in 794 serum samples that were collected at the enrollment survey (1972) of the Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD), for which extensive phenotypic information on lung function and respiratory health is now available throughout its 24-year follow-up period. These analytes, which represent molecules involved in multiple potential COPD pathways, were measured with a bead-based multi analyte profile approach, which allows optimization of utilization of large epidemiological bio-repositories. In this application, we propose 1) to validate serum biomarker signatures that were identified in TESAOD as predictive of incidence of COPD in the independent cohort of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA); and 2) to determine whether Integrating information on both initial levels and temporal changes in serum concentrations increases the ability of the above biomarkers to predict risk of COPD. This will result in the most comprehensive prospective serum biomarker study of COPD to date and will lead to the identification of biomarkers and molecular pathways conclusively linked to incidence of COPD. It will also provide the foundations for CADET Stage II, during which we will seek the long-term goals of determining the molecular mechanisms through which these targets and pathways affect COPD risk and to evaluate their potential clinical applications in primary to tertiary prevention of COPD. RELEVANCE (See instructions): Chronic Obstructive Pulmonary Disease (COPD) is a common disease that carries a substantial burden of morbidity and mortality. This study will lead to the identification of molecules linked to the development of COPD and, in turn, may lead to potential clinical applications in primary to tertiary prevention of this disease.