Fatigue, physical performance, and systemic inflammation in patients with chronic obstructive pulmonary disease

Thesis (Ph.D.)--University of Washington, 2016-06

Patients with chronic obstructive pulmonary disease (COPD) often experience multiple symptoms, which are highly interrelated. Symptom burden in COPD affects physical and mental health negatively. Fatigue is the second most prevalent symptom after dyspnea in COPD. It is increasingly recognized as a key symptom and clinical indicator of functional limitation among COPD patients. Although the underlying mechanism of fatigue is still unknown, recent studies suggests that inflammation may play a role in development of fatigue. The aim of this dissertation study was to examine influencing factors and impacts of fatigue for patients with COPD. It was part of a longitudinal observational study of COPD patients to examine the biological causes and functional consequences of depression. In the first paper, we examined interrelationships among dyspnea, anxiety, depressive symptoms, and fatigue as contributing factors of physical performance in COPD. We found that dyspnea was the strongest predictor of impaired physical performance. Greater anxiety was associated with enhanced physical performance. Dyspnea was associated with anxiety, and depression, and fatigue, and anxiety and depression were associated with fatigue. These findings showed that multiple symptoms are interrelated to each other. Furthermore, symptoms experienced by COPD patients have impacts on physical performance. Longitudinal studies are needed to confirm the directionality of these relationships. The second study was performed to explore the association between systemic inflammation and fatigue over one year in patients with COPD. Four inflammatory markers were included C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, and tumor necrosis factor - a. IL-8 and CRP were associated with fatigue after adjusting for potential confounders when using baseline data. However, the longitudinal data analyses did not show any associations between systemic inflammation and fatigue. It indicates systemic inflammation may play a role in the development of fatigue in COPD. The CRP may serve as a potential biomarker of fatigue in COPD. Depressive symptoms are closely associated with fatigue among COPD patients. Further studies are needed to confirm the role of inflammatory biomarkers in the development of fatigue. Findings of this dissertation study can be used to develop an exercise intervention to improve symptom burden for the COPD population.