Genetic markers for the prognosis of pulmonary hypertension development in purulent-destructive lung diseases

BACKGROUND: Purulent destructive lung diseases (PDLD) include such lung and pleural diseases as pleural empyema with and without fistula, lung abscess with and without sequestration, gangrenous abscess. Lethality of critically ill patients with PDLD remains high due to the development of life-threatening complications. Early stratification of patients for risk of this complications can be useful for choosing a personalized treatment strategy for patients PDLD. Genetic variability of the AQP4 gene, which expression on the surface of lung cells and the immune system can have pathogenetic significance for the development of pulmonary diseases and their complications, is a source of early markers for the prognosis of PDLD. The contribution of AQP4 to the development of pulmonary hypertension has not been previously studied. AIM: To determine the contribution of polymorphic variants of the AQP4 gene to the development of pulmonary hypertension in patients with PDLD and cellular markers of the immune system amount that are pathogenetically significant for its development. METHODS: The study included patients of the Clinical Hospital (18-87 years old) with PDLD that developed after community-acquired pneumonia. The main outcome of the study was pulmonary hypertension development. The method for determining pulmonary hypertension involves the use of echocardiography. The values ​​of SPPA (systolic pressure of the pulmonary artery) ≥ 36 mm Hg and TRJV (tricuspid regurgitant jet velocity) ≥ 2.9 m / s indicate the presence of pulmonary hypertension in the patient. RESULTS: The minor allele AQP4 rs1058427 T presence in patients with PDLD was significantly associated with the development of pulmonary hypertension and an increased number of monocytes in the blood. The presence of minor genotypes AQP4 rs1058427 GT or TT in patients with PDLD indicates a high risk of developing pulmonary hypertension (P=0.000097, TMF, odds ratio=4.19, 95% CI: 2.0–8.7 relative risk=2.16, 95% CI: 1.5-3.1, n=188). After separate analysis of subgroups of patients who had COVID-19 and not had COVID-19, statistical significance of the association remained only for patients carrying the T allele who not had COVID-19. CONCLUSION: The presence of the minor allele of AQP4 rs1058427 in patients with PDLD (GT or TT genotypes) determines an increased risk of developing pulmonary hypertension and increased levels of monocytes in the blood.