Chronic obstructive pulmonary disease. Aspects of smoking, biomarkers and cardiovascular disease

Author: Morten Kraen; Malmö Klinisk Fysiologi; []

Keywords: ;

Abstract: Chronic obstructive pulmonary disease (COPD) is a common and preventable disease characterized by airflow obstruction and emphysema development. COPD often coexist with cardiovascular disease (CVD) and both diseases have common risk factors i.e. age and smoking and shared features i.e. chronic inflammation. Smoking is of particular interest as it substantially increases the risk of developing COPD and CVD and is known to elicit systemic inflammatory responses. COPD (and CVD as well) often go unnoticed for years in the preclinical or early stage of disease so arguably, early disease detection is of great importantance and vital to improve prognosis. Plasma biomarkers of inflammation could be instrumental in this task and in recent years many new biomarkers have been described, but very few make it into clinical use.This thesis deals with COPD and its comorbidity (CVD) and their common risk factor smoking, with focus on the role of new and established biomarkers of COPD and atherosclerosis.All papers in this thesis are cross sectional studies based on the ROLLS study population. ROLLS was an invitational study including 450 subjects on the basis of self-reported smoking habits and pulmonary symptoms. All participants underwent a one day study protocol consisting of transthoracic echocardiography, lung function tests, carotid ultrasound examination, resting blood pressure measurement, blood sample analysis and a questionnaire.In paper I the aim was to study the impact of smoking status on echocardiographic variables of cardiac function in a population without clinically evident cardiopulmonary disease. Here, no convincing effect of current or prior smoking on echocardiographic variables of systolic and diastolic function could be detected, even if smokers had significantly higher cardiac index due to a slightly increased heart rate. In paper II the aim was to examine whether brain natriuretic peptide (BNP), an established marker of cardiac dysfunction, could be used as a biomarker of COPD in a population with normal cardiac function. The results showed no significant differences in BNP levels between subjects with COPD and controls. Thus, the clinical value of BNP in this setting is limited. Paper III evaluated matrix metalloproteinases (MMP´s) as biomarkers of COPD and atherosclerosis and the impact of smoking. The results showed that MMP´s are influenced by smoking status and that MMP-1 and MMP-12 are independent predictors of concomitant COPD and carotid plaque even when adjusting for traditional risk factors.In paper IV the aim was to explore whether a novel inflammatory biomarker, fibroblast growth factor 23 (FGF23), was influenced by COPD status and impaired pulmonary function. The findings showed that FGF23 was associated with the presence of COPD even after adjusting for traditional risk factors, and that FGF23 was associated with impaired pulmonary function and gas exchange.In conclusion, this thesis evaluated the impact of smoking on cardiac function and MMP´s and explored the current (BNP) and future (MMP and FGF23) value of biomarkers in COPD and CVD