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.
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.
|Vasquez, Monica M; Hu, Chengcheng; Roe, Denise J et al. (2016) Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application. BMC Med Res Methodol 16:154|
|Guerra, Stefano; Vasquez, Monica M; Spangenberg, Amber et al. (2016) Club cell secretory protein in serum and bronchoalveolar lavage of patients with asthma. J Allergy Clin Immunol 138:932-934.e1|
|Huang, Shuang; Vasquez, Monica M; Halonen, Marilyn et al. (2015) Asthma, airflow limitation and mortality risk in the general population. Eur Respir J 45:338-46|
|Parthasarathy, Sairam; Vasquez, Monica M; Halonen, Marilyn et al. (2015) Persistent insomnia is associated with mortality risk. Am J Med 128:268-75.e2|
|Guerra, Stefano; Halonen, Marilyn; Vasquez, Monica M et al. (2015) Relation between circulating CC16 concentrations, lung function, and development of chronic obstructive pulmonary disease across the lifespan: a prospective study. Lancet Respir Med 3:613-20|
|Guerra, Stefano; Vasquez, Monica M; Spangenberg, Amber et al. (2013) Serum concentrations of club cell secretory protein (Clara) and cancer mortality in adults: a population-based, prospective cohort study. Lancet Respir Med 1:779-85|
|Guerra, Stefano; Halonen, Marilyn; Sherrill, Duane L et al. (2013) The relation of circulating YKL-40 to levels and decline of lung function in adult life. Respir Med 107:1923-30|