Systemic inflammatory markers as predictors of longitudinal outcomes in COPD : Results from the Bergen COPD Cohort Study

Background: Chronic obstructive pulmonary disease (COPD) is major cause of morbidity and mortality worldwide. The prevalence is increasing worldwide, as a result of an increase in cigarette smoking the last decades. The main symptom of COPD is chronic and progressive dyspnea, often accompanied with cough and increased amounts of phlegm. A significant share of the patients suffers episodes with exacerbation of the disease, which may negatively impact quality of life, disease burden and survival. COPD pathophysiology is complex and consists of different disease mechanisms. Inflammation is a central component of COPD, and increased number of immune cells and cytokines are found both in the airways and in the systemic circulation. The COPD pathophysiology is incompletely understood, and there is comprehensive research on inflammatory biomarkers in order to improve diagnosis, identify patients with increased risk of adverse outcome, and to find targets for medical treatment. Aims: 1-Identify diagnostic biomarkers of stable COPD and acute exacerbation of COPD. 2 -Identify inflammatory biomarkers as predictors for longitudinal outcome using longitudinal data: a. as predictors for future exacerbations b. as predictors for change in lung function c. as predictors for mortality and cause of death d. as predictors for lung cancer Methods: The Bergen COPD cohort study (BCCS) included 433 COPD patients and 325 controls between 2006 and 2009. The COPD patients were aged between 40-76, all were former or current smokers. The COPD diagnosis was based on a clinical evaluation combined with an obstructive post-bronchodilator spirometry. Of the 433 COPD patients, 356 patients living in the vicinity of Haukeland University Hospital were also included in the Bergen COPD Exacerbation Study (BCES). All patients and controls went through an extensive examination at inclusion including medical history, physical examination, lung function testing, bioelectrical impedance measurements, HRCT, blood sampling, and microbiological testing. The patients and a selection of the controls were followed up during study visits each 6 months for 3 years, repeating lung function tests and blood sampling each 6 months, bioelectrical impedance each 12 months. In addition, patients were followed up to 9 years regarding mortality and cause of death as well as lung cancer development. Acute exacerbations of COPD (AECOPD) were registered both at each 6-month visit, in addition the patients in the BCES