Phenotypic and molecular-genetic features of asthma-COPD overlap syndrome (ACOS)

Background: ACOS is one of asthma (BA) phenotypes which is little studied that requires a comprehensive investigations. Objective: To evaluate ACOS risk factors, phenotypes & to determine the expression of glucocorticoid receptor (GR) isoforms α,β and their role in ACOS. Methods: The study involved 89 people aged 63,4±10,73 years: 22 with BA, 21-COPD, 26-ACOS in exacerbation and 20 healthy volunteers. The level of mRNA GRα/β was measured by real-time PCR. Results: Cluster analysis indicated 2 ACOS phenotypes: 1) old patients with low smoking index (SI), less bronchial obstruction (BO) and bronchospasm (BS), but better prognosis (iBODE); 2) the middle-aged patients with high SI, heavy BO & BS, worse prognosis. In both clusters GRα & GRβ activity was lower than in controls (p We found correlations of developing ACOS in BA patients with smoking (r=0,531,p=0,009), age (r=0,363,p=0,013), sputum neutrophilia (r=0,482,p=0,003) and sputum eosinophilia (r=0,294,p=0,041). Smoking in women with BA increased the risk of more rapid formation of ACOS compared to men (OR=2,200,95%CI=1,152-4,203). The levels of GRα and GRβ in controls were higher than in patients with BA, COPD, ACOS(p≤0,001). Activity of GRβ in BA [0,421 (0,149;1,235)] was higher than in COPD [0,189 (0,071;0,250)] (p=0,042). We have shown a correlation of the expression of GRα with FEF75 (r=0,454,p=0,030); GRβ–with mMRC (r=0,559,p=0,013), sputum neutrophils (r=-0,500,p=0,018); GRα/GRβ ratio–with administration of antibiotics (r=0,402,p=0,046) in ACOS. Conclusion: Our data indicates risk factors for ACOS, heterogeneity of this group & clinical association of the GRα,β activity with the level of BO, disease severity and type of inflammation.