Chronic Obstructive Pulmonary Disease (COPD) is a chronic airway inflammatory disease with important systemic manifestations that account for a substantial part of its morbidity and mortality. COPD is currently the fourth leading cause of death in the US and the projected third leading cause of death worldwide by 2020. The identification of systemic biomarkers that can predict inception and progression of this disease may provide important insights into its molecular mechanisms and have critical implications for prevention. Yet, to date, most 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 conclusive resolution of whether these biomarkers are causally linked to COPD or they are simply a consequence of the disease. To overcome these limitations, in this application we propose to use a large prospective population-based cohort that was initiated in 1972 (Tucson Epidemiological Study of Airway Obstructive Disease - TESAOD) and provides detailed respiratory phenotypic information and an extensive collection of serum samples that were collected over the 35-year follow-up period from several thousand participants. In this cohort, we propose to test a large panel of 133 candidate biomarkers variably involved in inflammation, innate immunity, proteolysis, detoxification and oxidative stress, adaptive immune responses to microorganisms, and auto- immune responses. These biomarkers will be tested against incidence and progression of COPD phenotypes (Aim 1) as well as COPD-related and all-cause mortality risk (Aim 2). In addition panels of biomarkers associated with airflow limitation will be compared between subjects with and without asthma (Aim 3). This project will result in the most comprehensive prospective biomarker study of COPD to date.

Public Health Relevance

Chronic Obstructive Pulmonary Disease (COPD) is currently the fourth leading cause of death in the US and the projected third leading cause of death worldwide by 2020. The identification of systemic biomarkers that can predict onset and progression of this disease may have critical implications for prevention. This project aims to overcome some of the existing limitations of biomarker studies of COPD by measuring a large panel of biomarkers in serum samples that were collected over 35 years of follow-up in a large epidemiological cohort. These biomarkers will be then tested to determine if they can predict risk of developing COPD and dying of it.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL095021-03
Application #
8021003
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Croxton, Thomas
Project Start
2009-02-01
Project End
2014-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
3
Fiscal Year
2011
Total Cost
$378,750
Indirect Cost
Name
University of Arizona
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Vasquez, Monica M; Sherrill, Duane L; LeVan, Tricia D et al. (2018) Persistent light to moderate alcohol intake and lung function: A longitudinal study. Alcohol 67:65-71
Vasquez, Monica M; Zhou, Muhan; Hu, Chengcheng et al. (2018) Reply to Bush: Low Lung Function in Young Adult Life Is Associated with Early Mortality. Am J Respir Crit Care Med 197:539
Zhai, Jing; Stern, Debra A; Sherrill, Duane L et al. (2018) Trajectories and Early Determinants of Circulating CC16 from Birth to Age 32 Years. Am J Respir Crit Care Med 198:267-270
Chen, Yin; Vasquez, Monica M; Zhu, Lingxiang et al. (2017) Effects of Retinoids on Augmentation of Club Cell Secretory Protein. Am J Respir Crit Care Med 196:928-931
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
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
Parthasarathy, Sairam; Vasquez, Monica M; Halonen, Marilyn et al. (2015) Persistent insomnia is associated with mortality risk. Am J Med 128:268-75.e2
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
Pugmire, Juliana; Vasquez, Monica M; Zhou, Muhan et al. (2014) Exposure to parental smoking in childhood is associated with persistence of respiratory symptoms into young adult life. J Allergy Clin Immunol 134:962-965.e4

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