Pneumonia and Related Conditions in Critically Ill Patients-Insights from Basic and Experimental Studies.

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia's development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia.

Genetic dissection of host immune response in pneumonia development and progression.

The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls). Experimental data were included in a series of 11 meta-analyses and eight subset analyses related to pneumonia susceptibility and outcome.

Clinical associations of host genetic variations in the genes of cytokines in critically ill patients.

Host genetic variations may influence a changing profile of biochemical markers and outcome in patients with trauma/injury. The objective of this study was to assess clinical associations of single nucleotide polymorphisms (SNPs) in the genes of cytokines in critically ill patients. A total of 430 patients were genotyped for SNPs in the genes of pro- (IL1B, IL6, IL8) and anti-inflammatory (IL4, IL10, IL13) cytokines.

Genetic susceptibility to nosocomial pneumonia, acute respiratory distress syndrome and poor outcome in patients at risk of critical illness.

Genetic susceptibility may partially explain the clinical variability observed during the course of similar infections. To establish the contribution of genetic host factors in the susceptibility to critical illness, we genotyped 750 subjects (419 at high risk of critical illness) for 14 single nucleotide polymorphisms (SNPs) in the xenobiotics detoxification/oxidative stress and vascular homeostasis metabolic pathways. In the group of nosocomial pneumonia (NP; 268 patients) the risk of acute respiratory distress syndrome (ARDS) is significantly higher for the carriers of CYP1A1 rs2606345 T/T genotypes and AhR rs2066853 G/A-A/A genotypes.

CYP1A1, GCLC, AGT, AGTR1 gene-gene interactions in community-acquired pneumonia pulmonary complications.

This study was conducted to establish the possible contribution of functional gene polymorphisms in detoxification/oxidative stress and vascular remodeling pathways to community-acquired pneumonia (CAP) susceptibility in the case-control study (350 CAP patients, 432 control subjects) and to predisposition to the development of CAP complications in the prospective study. All subjects were genotyped for 16 polymorphic variants in the 14 genes of xenobiotics detoxification CYP1A1, AhR, GSTM1, GSTT1, ABCB1, redox-status SOD2, CAT, GCLC, and vascular homeostasis ACE, AGT, AGTR1, NOS3, MTHFR, VEGFα. Risk of pulmonary complications (PC) in the single locus analysis was associated with CYP1A1, GCLC and AGTR1 genes.

Functional polymorphisms in the CYP1A1, ACE, and IL-6 genes contribute to susceptibility to community-acquired and nosocomial pneumonia.

Objectives: To establish the contribution of genetic host factors to the risk of community-acquired pneumonia (CAP) and nosocomial pneumonia (NP) in the population of the Russian Federation.

Methods: A total of 796 subjects (CAP: 334 patients, 134 controls; NP: 216 critically ill patients with NP, 105 critically ill patients without NP) were included in two case-control studies. We analyzed 13 polymorphisms in 11 genes (IL-6, TNF-α, MBL2, CCR5, NOS3, CYP1A1 (three sites), GSTM1, GSTT1, ABCB1, ACE, and MTHFR) using a tetra-primer allele-specific PCR method.

Host genetic risk factors for community-acquired pneumonia.

This study was conducted to establish the contribution of genetic host factors in the susceptibility to community acquired pneumonia (CAP) in the Russian population. Patients with CAP (n=334), volunteers without a previous history of CAP, constantly exposed to infectious agents, control A group (n=141) and a second control group B consisted of healthy persons (n=314) were included in the study. All subjects were genotyped for 13 polymorphic variants in the genes of xenobiotics detoxification CYP1A1 (rs2606345, rs4646903, and rs1048943), GSTM1 (Ins/del), GSTT1 (Ins/del), ABCB1 rs1045642); immune and inflammation response IL-6 (rs1800795), TNF-a (rs1800629), MBL2 (rs7096206), CCR5 (rs333), NOS3 (rs1799983), angiotensin-converting enzyme ACE (rs4340), and occlusive vascular disease/hyperhomocysteinemia MTHFR (rs1801133).