The prevalence of COPD is high; in VISN1, 9% of outpatient Veterans had the ICD-9 diagnosis of COPD in FY 2013. COPD is characterized by acute exacerbations (AEs), periods of worsening that require treatment with antibiotics and corticosteroids. AEs result in further disability, negative effects on health-related quality of life, a more rapid decline in forced expiratory volume in one second (FEV1), and higher mortality. PA is a lifestyle behavior that clearly impacts AE risk. Persons with the highest levels of PA have the lowest risk of AEs, independent of lung function. However, the biological mechanisms of how PA affects risk for AEs remain to be elucidated. There is a clinical need for novel biomarkers to identify patients at high risk for AEs and an urgent need for novel treatment strategies to decrease risk for AEs. Premature cellular aging, triggered by multiple mechanisms including telomere shortening, plays a key role in the pathogenesis of COPD. Telomeres are repetitive DNA caps located at the ends of chromosomes that protect DNA against degradation. Telomere repeats are lost with each replicative cycle until a critical length is reached, at which point cell death occurs. Accumulatio of senescent cells that release inflammatory cytokines may directly impair lung-repair capabilities, contributing to decline in lung function. Thus, telomere shortening and the resulting premature cellular senescence may play an important role in increasing risk for AEs. Lifestyle factors are determinants of telomere length, with longer telomeres associated with greater PA. In COPD, the relationships between PA, telomere length, and risk of AEs are unknown. We propose to examine these relationships in 3 cohorts of adults with COPD (total=575 persons). (1) 169 persons at VA Boston have PA directly measured with an accelerometer along with stored buffy coat white cells and data on AEs during a follow-up of 16 months. (2) 302 persons at VA Puget Sound have directly measured PA, stored buffy coat white cells, and information on AEs over 24 months. (3) We have directly measured PA and stored blood samples for 104 additional unique persons after using an internet-mediated walking intervention.
Aim 1 : Determine the cross-sectional relationship between PA and telomere length in 575 persons.
Aim 2 : Explore the relationship between telomere length and risk of AEs in 575 persons with COPD.
Aim 3 : Explore the relationship between change in PA and change in telomere length in 104 persons with COPD after using a PA walking intervention. This study has direct clinical relevance as it will provide preliminary information about a molecular biomarker, telomere length, that may lead to the identification of (1) persons at high risk for COPD AEs and (2) novel targets for pharmacological therapies to decrease risk of AEs. By linking PA and AEs with changes at the molecular level, our results in this pilot grant will provide insight into a personalized approach to Rehabilitation Medicine in patients with COPD.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the Unites States. We propose novel translational research to examine the relationship between physical activity and telomere length and if telomere length is associated with risk of acute exacerbations. This study has direct clinical relevance as it will provide preliminary information about a molecular biomarker, telomere length, that may lead to the identification of (1) persons at high risk for COPD acute exacerbations and (2) novel targets for pharmacological therapies to decrease risk of acute exacerbations.
