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，具有重要的全身性表现，占其发病率和死亡率的很大一部分。系统生物标记物的识别可以预测该疾病的开始，可能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，迄今为止，COPD生物标志物的研究受到一次仅使用少数标志物和数据的横断面性质的限制，这排除了任何与COPD发病率相关的生物标志物的全面和结束性解决方案。在nhlbi资助的HL095021下，我们最近测量了在图森气道阻塞性疾病流行病学研究（TESAOD）的入组调查（1972年）中收集的794份血清样本中的108种分析物，在24年的随访期间，现在可以获得关于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，采用基于头部的多分析物谱方法进行测量，从而优化了大型流行病学生物库的利用。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中发现的血清生物标志物特征作为COPD发病率的预测指标；2)确定整合血清浓度的初始水平和时间变化信息是否能提高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，并将导致与COPD发病率最终相关的生物标志物和分子途径的鉴定。它还将为CADET II期提供基础，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）是一种常见病，具有很高的发病率和死亡率。这项研究将导致鉴定与COPD发展相关的分子，反过来，可能导致该疾病的一级到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.