Validation of serum biomarker signatures predictive of incident COPD

描述（由申请人提供）：慢性阻塞性肺疾病（COPD）是一种慢性气道炎症性疾病，具有重要的全身表现，占其发病率和死亡率的很大一部分。系统性生物标志物的识别，可以预测这种疾病的发病可能会提供重要的见解，其分子机制，并具有重要的意义，预防。然而，迄今为止，COPD的生物标志物的研究受到一次仅使用几种标志物和数据的横截面性质的限制，这已经排除了与COPD发病率暂时相关的生物标志物的任何全面和结论性的解决方案。根据NHLBI资助的HL 095021，我们最近测量了在图森气道阻塞性疾病流行病学研究（TESAOD）的招募调查（1972年）中收集的794份血清样本中的108种分析物，在整个24年随访期内，现已获得有关肺功能和呼吸健康的广泛表型信息。这些分析物代表了参与多种潜在COPD途径的分子，采用基于微珠的多分析物特征方法进行测量，该方法可以优化大型流行病学生物库的利用。在本申请中，我们建议1）验证TESAOD中确定的血清生物标志物特征，以预测瑞士成人空气污染和肺部疾病研究（SAPALDIA）独立队列中的COPD发病率; 2）确定整合血清浓度初始水平和时间变化的信息是否会增加上述生物标志物预测COPD风险的能力。这将导致迄今为止最全面的COPD前瞻性血清生物标志物研究，并将导致确定与COPD发病率最终相关的生物标志物和分子途径。它还将为CADET第二阶段提供基础，在此期间，我们将寻求确定这些靶点和途径影响COPD风险的分子机制的长期目标，并评估其在COPD一级至三级预防中的潜在临床应用。相关性（参见说明）：慢性阻塞性肺疾病（COPD）是一种常见的疾病，具有很大的发病率和死亡率的负担。这项研究将导致与COPD发展相关的分子的鉴定，反过来，可能导致这种疾病的一级至三级预防的潜在临床应用。

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.