Genetic predisposition partially accounts for the clinical variability of the course of an infectious process. A total of 750 people, including 419 (81.1%) male patients aged 42.9±0.9 years, admitted to the clinics of the V. A. Negovsky Research Institute of General Reanimatology (Moscow, Russia), were genotyped to establish the influence of genetic factors on their susceptibility to critical conditions. Materials and methods. Tetra-primer allele-specific polymerase chain reaction was used to investigate single-nucleotide polymorphisms (SNP) in the xenobiotic detoxification and oxidative stress genes (CYP1A1 (three sites), AhR, ABCB1, SOD2, GCLC and CAT) and in the vascular homeostasis genes (ACE, AGT, AGTR1, NOS3, VEGFα and MTHFR). Results. A total of 268 nosocomial pneumonia (NP) cases were registered in a patient group. Individual SNP analysis has shown that among the patients with NP the risk of acute respiratory distress syndrome (ARDS) is associated with the carriage of the following genotypes: CYP1A1 rs2606345-Т/Т (p=0.0027, OR=2.38; 95% CI: 1.35—4.17) and AhRrs2066853-G/A-A/A (p=0.0012, OR=2.94; 95% CI: 1.54—5.60). The frequency of the C allele of the AGTR1 gene (re5186) was much higher among the survivors (in the NP group). The assessment of a multiplicative genetic model of genes that had demonstrated the highest single-locus effects because of a ARDS risk, as well as in-hospital mortality, could establish the complex genotype including a combination of risky alleles of the detoxi- fication and vascular homeostasis genes (CYP1A1 rs2606345-T — AhR rs2066853-A and ACE rs4340-D — AGT rs699-C — AGTR1 rs5186-C), which was associated with the increased risk of both NP and ARDS, as well as with the likelihood of a fatal outcome. Conclusion. An understanding of the risk factors of NP and ARDS will aid in predicting the outcome of the underlying disease and in developing possible preventive measures.
The problem of predicting the development and outcomes of acute respiratory distress syndrome (ARDS) remains to be solved. Objective: to estimate the informative value of the plasma levels of surfactant protein A (SP2A) as a prognostic biomarker for the development and outcome of ARDS in patients with severe pyoseptic complications in critical conditions. Subjects and methods. This investigation was conducted at the Research Institute of General Reanimatology (RIGR), Russian Academy of Medical Sciences, in 2010—2012. It enrolled 80 patients (including 25 analyzed ones) in accordance with the inclusion and exclusion criteria, as well as 30 apparently healthy donors. ARDS and its stages were diagnosed using the RIGR criteria. Plasma SP2A levels were determined by enzyme immunoassay using a Human Surfactant Protein A ELISA, RD191139200R kit (BioVendor, USA). The findings were statistically analyzed using a Statistica 7.0 package.Sensitivity and specificity of SP2A testing were determined by ROC analysis. The difference between groups at pResults. In patients with ARDS plasma SP2A level was higher than in those without ARDS within the whole study independing on a day of testing. There were no significant dif2 ferences between plasma SP2A levels in the patients with Stages 1 and 2 ARDS. On day 1, the plasma SP2A content of 24.5 ng/ml had a sensitivity of 60.0% and a specificity of 85.7% in predicting the development of ARDS on days 4—5 of intensive care unit admission (the area under the curve 0.74; 95% confidence interval, 0.527—0.872; p=0.0031). On study day 1, the SP2A level of 38.8 ng/ml had a sensitivity of 65.0% and a specificity of 80.0% in predicting a fatal outcome in patients with ARDS (the area under curve 0.74; 95% confidence interval, 0.577—0.866; p=0.0026). Conclusion. On a day when a severe pyoseptic complication was diagnosed, the SP2A level of 24.5 ng/ml served as a sensitive and specific prognostic biomarker for the development of ARDS on days 4—5 of an intensive care unit stay. Within the first 24 hours (on the day when ARDS was diagnosed), the plasma SP2A content of 38.8 ng/ml was a sensitive and specific prognostic biomarker for death prediction in ARDS. Key words: acute respiratory distress syndrome, surfactant protein A, biomarker, prediction, outcomes.