Gamma-Glutamyltransferase and C-Reactive Protein in Stable Chronic Obstructive Pulmonary Disease

Systemic inflammation and oxidative stress are the most important features of chronic obstructive pulmonary disease (COPD). The presence of oxidative stress in the airways of smokers, the largest population of COPD patients, is a consequence of direct inhalation of cigarette smoke and increased inflammation-related production of reactive oxygen species. On the other hand, oxidative stress appears to be the key component of many processes associated with chronic inflammation. We intend to examine whether serum C-reactive protein (CRP) concentration and gamma-glutamyltransferase (GGT) activity might be used as auxiliary markers in monitoring level of oxidative stress and inflammation in clinically stable COPD. We also investigated influence of cigarette smoking on these two systemic parameters. Catalytic activity of GGT and concentration of CRP were determined in sera of COPD patients (N=109) and in healthy controls (N=51) by using standard spectrophotometric method and immunoturbidimetric method, respectively. Concentration of CRP and activity of GGT were increased in COPD patients, as compared to healthy controls (p<0.05). We found a significant positive correlation between those two parameters in COPD patients (r=0.202, p=0.0371). Our results showed no difference in GGT activity (p=0.606) or CRP concentration (p=0.573) between groups of patients when subdivided according to the severity of the disease. Smoking did not have a significant impact on CRP and GGT values in COPD patients and healthy controls. We showed an increase of serum CRP and GGT values in COPD patients, and we suggest that serum GGT activity might also represent an inflammation/oxidative stress marker. It seems that COPD patients present higher serum CRP and GGT values than healthy subjects independently from their smoking habits

Plasma Brain-Derived Neurotrophic Factor (BDNF) Concentration and BDNF/TrkB Gene Polymorphisms in Croatian Adults with Asthma

Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B (TrkB) receptor might contribute to normal lung functioning and immune responses ; however, their role in asthma remains unclear. Plasma BDNF concentrations, as well as BDNF and NTRK2 (TrkB gene) polymorphisms, were investigated in 120 asthma patients and 120 healthy individuals using enzyme-linked immunosorbent assay and polymerase chain reaction, respectively. The genotype and allele frequencies of BDNF Val66Met (rs6265) and NTRK2 rs1439050 polymorphisms did not differ between healthy individuals and asthma patients, nor between patients grouped according to severity or different asthma phenotypes. Although plasma BDNF concentrations were higher among healthy subjects carrying the BDNF Val66Met GG genotype compared to the A allele carriers, such differences were not detected in asthma patients, suggesting the influences of other factors. Plasma BDNF concentration was not affected by NTRK2 rs1439050 polymorphism. Asthma patients had higher plasma BDNF concentrations than control subjects ; however, no differences were found between patients subdivided according to asthma severity, or Type-2, allergic, and eosinophilic asthma. Higher plasma BDNF levels were observed in asthma patients with aspirin sensitivity and aspirin-exacerbated respiratory disease. These results suggest that plasma BDNF may serve as a potential peripheral biomarker for asthma, particularly asthma with aspirin sensitivity

TLR5 Variants Are Associated with the Risk for COPD and NSCLC Development, Better Overall Survival of the NSCLC Patients and Increased Chemosensitivity in the H1299 Cell Line

Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive. We performed case&ndash;control genetic association and functional studies on the importance of TLR5 in COPD and LC development, comparing Caucasian COPD/LC patients (n = 974) and healthy donors (n = 1283). Association analysis of three single nucleotide polymorphisms (SNPs) (rs725084, rs2072493_N592S, and rs5744174_F616L) indicated the minor allele of rs2072493_N592S to be associated with increased risk for COPD (OR = 4.41, p &lt; 0.0001) and NSCLC (OR = 5.17, p &lt; 0.0001) development and non-small cell LC risk in the presence of COPD (OR = 1.75, p = 0.0031). The presence of minor alleles (rs5744174 and rs725084) in a co-dominant model was associated with overall survival in squamous cell LC patients. Functional analysis indicated that overexpression of the rs2072493_N592S allele affected the activation of NF-&kappa;B and AP-1, which could be attributed to impaired phosphorylation of p38 and ERK. Overexpression of TLR5N592S was associated with increased chemosensitivity in the H1299 cell line. Finally, genome-wide transcriptomic analysis on WI-38 and H1299 cells overexpressing TLR5WT or TLR5N592S, respectively, indicated the existence of different transcription profiles affecting several cellular pathways potentially associated with a dysregulated immune response. Our results suggest that TLR5 could be recognized as a potential biomarker for COPD and LC development with functional relevance