Association of plasma netrin-1 level with inflammatory balance and comorbidities in patients with acute exacerbation of COPD Introduction: Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow restriction and systemic inflammation. Netrin-1 is a protein mainly produced in the central nervous system and has proven anti-inflammatory activity. The aim of this study was to determine netrin-1 level and its relationship with comorbidities in patients with acute exacerbation of COPD. Materials and Methods: The study included 232 patients aged over 40 years who were divided into 3 groups: Group 1: ex-smokers (≥ 20 pack-years) with COPD hospitalized for COPD exacerbation (n= 142), Group 2: current-smokers (≥ 20 pack-years) without COPD (n= 30), Group 3: a control group comprising healthy non-smokers (n= 60). Plasma netrin-1 levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit. Results: There were significant differences in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, C-reactive protein (CRP), and plasma netrin-1 levels between patients with acute exacerbation of COPD and current smokers without COPD, healthy controls (p= 0.001 for all). Netrin-1 levels at discharge were lower in COPD patients with diabetes mellitus (DM) compared to nondiabetic COPD patients (p= 0.01). Weak correlation was observed between netrin-1 level at admission and FEV1, FVC, partial pressure of oxygen, and CRP levels (r= 0.394, p= 0.01; r= -0.366, p= 0.01; r= -0.19, p= 0.05; r= 0.306, p= 0.01). Netrin-1 level at admission was also moderately correlated with smoking history (pack-years) (r= 0.579, p= 0.01). Conclusion: Netrin-1 was elevated in acute exacerbation of COPD and may be an important element in inflammatory balance. Patients with both COPD and DM were found to have lower netrin-1 levels at discharge after resolution of the acute exacerbation.