Molecular Markers in Occupational Chronic Obstructive Pulmonary Disease Comorbid with Heart Failure

Abstract

Background.Comorbid heart failure (HF) is common in chronic obstructive pulmonary disease (COPD). Comorbid condition features are studied well in COPD due to tobacco smoke. There is a lack of data about mechanisms, clinical and functional specificity of occupational COPD and HF comorbidity. As occupational COPD and HF share common symptoms and sometimes lung function disorders, there is an unmet need in new markers of HF in occupational COPD.Aims to establish molecular markers associated with occupational COPD with HF comorbidity.Methods.Subjects with occupational COPD were enrolled in a single-center prospective cohort observational study. Comparison group COPD due to tobacco smoke. Then groups were stratified according to HF so the following subgroups were compared: occupational COPD with HF (n=63), occupational COPD without HF (n=52), COPD due to tobacco smoke with HF (n=41), COPD due to tobacco smoke without HF (n=74). Control group healthy people (n=115). Groups were matched by demographics, duration of COPD and HF. CODP was diagnosed according to GOLD 20112020 criteria, HF according to Russian Federal clinical guidelines. Occupational etiological factors were silica dust, organic solvents, metal fumes. Clinical and functional characteristics of CODP and HF were obtained. Serum levels of pulmonary and activation-regulated chemokine (PARC/CCL-18), protein S100, troponin, N terminal pro brain natriuretic peptide (NT-pro-BNP), von Willebrand factor, C-reactive protein were measured by enzyme linked immunosorbent assay, fibrinogen were measured by Clauss method, lactate dehydrogenase, creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase were measured by standard biochemical method. Data are presented as median and interquartile range. Linear regression were used to explore relationships.Results.The molecular specificity of occupational COPD comorbid with HF were the largest increase in serum concentration of PARC-CCL18, NT-pro-BNP, protein S100, troponin, von Willebrand factor and fibrinogen. This factors were associated with length of service. For PARC-CCL18 В=1.1; for NT-pro-BNP В=0.9; for protein S100 В=1.3; for troponin В=0.8, for von Willebrand factor В=1.5 and for fibrinogen В=1.1. Molecular factors also were related to phenotype characteristics of COPD and HF. In multiply regression model the best predictors of comorbidity of CODP and HF were PARC-CCL18 (В=1.1; р=0.002), NT-pro-BNP (В=1.5; р=0.001), protein S100 (В=1.2; р=0.002), troponin (В=0.9; р=0.003). The model was adjusted for gender, age, duration of CODP and HF, FEV1.Conclusions.Occupational CODP comorbid with heart failure is the distinct phenotype. The perspective molecular markers of this phenotype are serum levels of PARC-CCL18, NT-pro-BNP, protein S100, troponin.