Pharmacogenetic and clinicopathological markers of BA-COPD (overlap syndrome)

Background: Treatment of patients with overlap remains a difficult clinical challenge and poorly understood problem. Objective: To assess the pharmaco-genetic and pathophysiological features of overlap. Methods: The study involved 67 patients aged 63 ± 10 years: 21 - with bronchial asthma (BA), 21 – with COPD and 25 with Overlap with high severity of symptoms. For genotyping by MDR1 gene (multidrug resistance gene) PCR RLFP method was used. Results: The Overlap group consisted of equal number of male and female patients, unlike groups of BA (24% and 76%) and COPD (76% and 24%) (χ2=11.554, p=0.009). Patients with Overlap compared to BA and COPD showed a greater degree of sputum eosinophilia : Me (25% to 75%) = 19.5 (14.5, 28), 16 (15. 18), 14 (9.5; 16.5), respectively (χ2=9.179, p=0.01 ) and neutrophilia : 47 (32.8, 50), 32 (25, 40), 42 (30; 57.8); (χ2=7.256, p=0.027); bronchial obstruction was more severe: FEV1 (%) M±m = 51±19, 77±16, 60±27 (χ2=20.055, p=0.001) and bronchospasm was observed in a greater number of patients (ΔFEV1≥12%): in 79%, 80% and 36% cases respectively (χ2=7.189, p=0.027). There were more smoking patients in overlap group than in BA and less than in COPD: 54%, 32%, 94%, respectively (χ2=14.709, p=0.001). Patients with overlap received higher doses of inhaled corticosteroids than patients with BA and COPD: 1183±562, 1034±683, 998±850 (mkg/d). The occurrence of CC 3435 MDR1 genotype in overlap syndrome was lower than in BA and COPD (9%, 24%, 14 % respectively). Conclusions: The Overlap phenotype has differences from BA and COPD on clinical, pathogenetic and genetic markers.