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 #
5R01HL095021-05
Application #
8431380
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Gan, Weiniu
Project Start
2009-02-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
5
Fiscal Year
2013
Total Cost
$356,964
Indirect Cost
$121,344
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; 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
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
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
Guerra, Stefano; Stern, Debra A; Zhou, Muhan et al. (2013) Combined effects of parental and active smoking on early lung function deficits: a prospective study from birth to age 26 years. Thorax 68:1021-8
Kurzius-Spencer, Margaret; Guerra, Stefano; Sherrill, Duane L et al. (2012) Familial aggregation of allergen-specific sensitization and asthma. Pediatr Allergy Immunol 23:21-7

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