The authors consider the role of genetic studies in modern medicine. The high death rates due to critical conditions (sepsis, multiple organ dysfunction, acute respiratory distress syndrome, nosocomial infections) initiate a search for prognostic models. The paper presents the results of the investigations made at the V.A. Negovsky Research Institute of General Reanimatology jointly with the V. N. Vavilov Institute of General Genetics. The panel of genetic markers, which is associated with the increased risk of both community-associated and nosocomial pneumonia (combinations of polymorphic variants in the xenobiotic detoxification gene (CYP1A1), cytokines (IL-6), and renin-angiotensin-converting enzyme (ACE), has been revealed. Genetic factors are essential in determining a response to drugs; 20—95% of the individual variability in the efficiency of their metabolism has been ascertained to result from genetic variability. An associative study has revealed differences in the efficiency of antibacterial therapy in terms of the GSTP1 and ABCB1 genes. Thus, it can be said that the possibilities of molecular genetic methods open prospects for developing the new area in reanimatology — critical care genetics. Identification of groups at increased risk for life-threatening conditions is particularly important in preventing their development and detecting their early markers for the timely determination of the required volume of specialized medical care. Key words: multifactorial diseases, gene polymorphism, xenobiotic detoxification genes, community-associated pneumonia, nosocomial pneumonia.

The study included 243 patients with acute community-acquired pneumonia and 173 healthy subjects. The following candidate loci were used to investigate genetic variability: 3 sites of CYP1A1, GSTM1, GSTT1, GSTP1, ACE gene of the rennin-angiotensin system, chemokine receptor gene CCR5. Enhanced predisposition to pneumonia was shown to be characteristic of homozygotes in deletion at the ACE locus (OR = 1.8; p = 0.013), carriers of normal alleles of the GSTM1 locus (OR = 1.7; p = 0.010), and homozygotes in allele 606T of the CYP1A1 gene (OR = 1.6; p = 0.020).

Objective: to reveal the clinical and morphological features of acute community-acquired and nosocomial pneumonia (NP). Materials and methods. The results of treatment were retrospectively assessed and those of autoptic studies were analyzed in 43 dead patients with pneumonia. There were two groups: 1) 13 subjects with community-acquired pneumonia; 2) 30 subjects with NP. Results. A clinicomorphological study revealed different stages of acute respiratory distress syndrome (ARDS) in both groups. The probability of its development increases if microbial associations are identified as an etiological factor. In community-acquired pneumonia, ARDS was detected in 6 of the 13 cases in which 5 (83.3%) cases were in the presence of progressive pulmonary inflammation. In Group 2, ARDS was recorded in 21 of the 30 cases and it followed the occurrence of pneumonic infiltration. On days 2 and 3 of ARDS, there were hyaline membranes and a preponderance of interstitial edema. Five days later, inflammatory changes were prevalent, severe alveolar edema (subtotal and total) and multiple hemorrhages were noted, and the number of hyaline membranes increased. Conclusion: The analysis has indicated that ARDS, including acute pulmonary lesion, as the first stage of respiratory distress syndrome in patients with pneumonia of varying genesis is more frequently detectable than traditionally thought. Acute respiratory failure in 27 (62.8%) of the 43 patients was caused by different stages of ARDS, which alone or in combination with other complications was as a cause of death. Key words: acute community-acquired pneumonia, nosocomial pneumonia, respiratory distress syndrome.

The review of the literature considers the etiology and pathogenesis of acute lung injury (ALI) in pneumonias. The development of ALI in pneumonias is largely determined by the properties of microorganisms and by the features of the macroor-ganism. The pathogenic properties of microorganisms lead to a damage to the air-blood barrier and to an impairment of the local protective mechanism in the lung. Alveolar damage, a systemic inflammatory reaction, and extracardiac pulmonary edema provoke ALI in pneumonias. The authors show it difficult to make a differential diagnosis and important to detect the early signs of ALI in pneumonias of various genesis. Transpulmonary thermodilution and identification of the markers of alveolar epithelial damage are promising methods. Key words: acute lung injury, pneumonia, sepsis, cytokines, transpul-monary thermodilution.

Objective: to define the diagnostic and prognostic value of the serum levels of proinflammatory cytokines in patients with pneumonia of various genesis. Materials and methods. Enzyme immunoassay was used to investigate proinflammatory cytokines (tumors necrosis factor-a (TNF-a), interleukin(IL)-1a, IL-1/3, IL-6) in the venous blood serum of patients with primary (n=4) and secondary (n=20) pneumonia. Results. Critically patients with pneumonia of various genesis were observed to have statistically significantly higher venous blood TNF-a and IL-6 levels. Primary and secondary pneumonias are characterized by statistically significant differences in the levels of TNF-a and IL-6 within the first 24 hours on day 3 of the patients’ stay in an intensive care unit. In the study group, two subgroups of patients with heterodirectionally and statistically significant changes in the content of all the test cytokines within 1 to 3 days were identified. With a poor outcome of the disease, there was a statistically significant increase in IL-1/8 within the first 24 hours and in TNF-a and IL-6 on day 3. Conclusion. Measurement of proinflammatory cytokines in critically ill patients with pneumonia is of diagnostic and predictive value. Key words: pneumonia, cytokines.

Objective: to study the efficiency of respiratory, non-respiratory, and pharmacological treatments in patients with acute respiratory distress syndrome (ARDS) induced by direct (aspiration pneumonitis, bilateral pneumonia, or lung contusion) and indirect (abdominal sepsis, polytrauma, or hemorrhagic shock) damaging factors. Subjects and methods. The results of treatment were retrospectively analyzed in 185 patients (122 men and 63 women whose age varied 18 to 69 years) with ARDS resulting from aspiration pneumonitis, bilateral pneumonia, or lung contusion (84 patients, including 53 men and 31 women) or from abdominal sepsis, polytrauma, or hemorrhagic shock (101 patients, including 69 men and 32 women). The efficiency of a lung opening maneuver, mechanical ventilation in the prone position, Surfactant BL, perftoran, and their combination use in ARDS developing due to direct and indirect damaging factors was studied. Results. The study treatment modalities were ascertained to show varying clinical efficiency in patients with ARDS caused by direct and indirect damaging factors. Conclusion. The findings made it possible to substantiate the necessity of setting off ARDS induced by direct and indirect damaging factors, to develop and propose new approaches to the differentiated treatment of different forms of ARDS. Key words: acute respiratory distress syndrome, direct damaging factors, indirect damaging factors, thoracopul-monary compliance, lung extravascular fluid, respiratory support, mechanical ventilation, positive end-expiratory pressure, lung opening maneuver, prone position, perftoran, surfactant.