The Differences in the Levels of Oxidative Status Marker and Soluble CD95 in Patients with Moderate to Severe COPD during an Exacerbation and a Stable Period.

Studying the features of changes in markers of oxidative stress (OS) and inflammation indicators in COPD patients depending on the degree of bronchial obstruction is one of the priority directions for improving the prognosis and monitoring of the course of this pathology. We conducted a comparative investigation of changes in markers of OS and apoptosis at the systemic and local levels in patients with moderate to severe COPD during exacerbation and stable phase. 105 patients with COPD aged 46-67 and 21 healthy nonsmoking volunteers comparable in age were examined. COPD patients were divided into four groups: moderate COPD (GOLDII) during the exacerbation (GOLDIIex, n = 25) and in the stable phase (GOLDIIst, n = 27), severe COPD (GOLDIII) during the exacerbation (GOLDIIIex, n = 29), and in the stable phase (GOLDIIIst, n = 24). We studied the levels of such lipid peroxidation (LPO) products as diene conjugates (DC) and Schiff bases (SB) and parameters of induced chemiluminescence (Imax, total light sum-S, Imax/S) in blood serum, as well as sCD95 concentration in blood and exhaled breath condensate (EBC). The relationship between the values of the OS system indicators with sCD95, as well as with the parameters of lung function, was investigated. Multidirectional changes in OS indicator levels in COPD patients depending on the severity of obstructive airway disorders have been established. The maximum values of DC (0.26 ± 0.046 RU), Imax (0.265 ± 0.19 RLU), and Imax/S (0.13 ± 0.05) were typical for patients with moderate COPD, while the highest SB level (5.7 ± 2.3 RU) was observed in severe COPD during an exacerbation. The exacerbation of the disease was characterized by an increase in DC concentration in both GOLDIIex (0.26 ± 0.046 RU) and GOLDIIIex (0.209 ± 0.02 RU) compared to the stable moderate and severe COPD (0.202 ± 0.028 RU and 0.19 ± 0.03 RU, respectively, p < 0.05). The established decrease in high values of DC, Imax, Imax/S, and sCD95 and an increase in SB concentration in GOLD III can serve as quantitative indicators of the prognosis of the severity of the disease. The serum concentration of sCD95 in GOLDIIex (366.4 ± 70.5 U/ml) and GOLDIIst (361.4 ± 72.8 U/ml) did not differ from the control group (393.7 ± 80.9 U/ml, p > 0.05). In patients with FEV1 < 49% during the exacerbation and stable phase, the serum levels of Imax/S (0.058 ± 0.01 and 0.062 ± 0.01) and sCD95 (318.2 ± 66.3 U/ml and 321.4 ± 42.5 U/ml) were lower than the values of healthy volunteers (0.08 ± 0.01 and 393.7 ± 80.9 U/ml, respectively, p < 0.05). A positive correlation between sCD95 concentration and airway obstruction degree in all examined COPD patients was established. The revealed numerous associations between sCD95 and OS marker levels in GOLDIII indicate a relationship between systemic radical stress and apoptosis processes both in the respiratory tract and the whole body under conditions of severe inflammation. The established correlations between the values of DC, Imax, and sCD95 in the blood serum and the lung function parameters in all studied patients allow us to consider these indicators as additional prognostic indicators of disease intensification. Our work results help clarify the participation and detail of FRO and apoptosis processes in developing pathophysiological features in moderate to severe COPD in different periods and, accordingly, improve the efficiency of diagnosis and treatment of the disease.

The State of the Nitric Oxide Cycle in Respiratory Tract Diseases.

This review describes the unique links of the functioning of the nitric oxide cycle in the respiratory tract in normal and pathological conditions. The concept of a nitric oxide cycle has been expanded to include the NO-synthase and NO-synthase-independent component of its synthesis and the accompanying redox cascades in varying degrees of reversible reactions. The role of non-NO-synthase cycle components has been shown. Detailed characteristics of substrates for the synthesis of nitric oxide (NO) in the human body, which can be nitrogen oxides, nitrite and nitrate anions, and organic nitrates, as well as nitrates and nitrites of food products, are given. The importance of the human microbiota in the nitric oxide cycle has been shown. The role of significant components of nitrite and nitrate reductase systems in the nitric oxide cycle and the mechanisms of their activation and deactivation (participation of enzymes, cofactors, homeostatic indicators, etc.) under various conditions have been determined. Consideration of these factors allows for a detailed understanding of the mechanisms underlying pathological conditions of the respiratory system and the targeting of therapeutic agents. The complexity of the NO cycle with multidirectional cascades could be best understood using dynamic modeling.

Relationship of Serum Levels of IL-17, IL-18, TNF-α, and Lung Function Parameters in Patients with COPD, Asthma-COPD Overlap, and Bronchial Asthma.

Determination of markers of systemic inflammation is one of the important directions in the study of pathogenesis and improvement of diagnosis of chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and bronchial asthma (BA). The aim of our work was a comparative study of the features of changes in serum levels of IL-17, IL-18, and TNF-α in patients with COPD, ACO, and BA with various severity of the disease, as well as evaluation of the relationship between the level of these cytokines and lung ventilation function. A total of 147 patients with COPD (n = 58), ACO (n = 57), and BA (n = 32) during a stable period have been examined in this study. The control group included 21 healthy nonsmokers with similar sex-age indicators. Serum levels of IL-17, IL-18, and TNF-α were determined by ELISA. The concentrations of these cytokines in the circulation in the studied patients with COPD, ACO, and BA were higher than those in healthy nonsmokers (p ≤ 0.001). IL-17 and IL-18 levels in the blood serum were comparable in all examined patients. The mean TNF-α concentrations in the circulation in COPD and ACO were significantly higher than those in BA (p < 0.001). In patients with COPD, the levels of IL-17 and TNF-α increased progressively against the background of a decrease in numerous spirometric indicators, which allows us to consider these cytokines as systemic biomarkers of disease severity. In BA, the inverse correlations between the level of IL-17 and FEV1/FVC (%) and FEV1 have been found. In patients with ACO, the increase in IL-18 levels was associated with a decrease in FEV1 and TNF-α with FEV1/FVC (%). These findings indicate that IL-17, IL-18, and TNF-α can participate in the mechanisms of systemic inflammation and the genesis of disorders of airway obstruction in COPD, AСO, and BA. An increase in the levels of IL-17 and TNF-α may be associated with impaired bronchial patency in COPD and BA. The established associations of the IL-18 concentration in the blood serum and FEV1 only in patients with ACO allow using the level of IL-18 as a potential marker of the degree of impaired airway obstruction in this disease.

Features of Oxidative and Nitrosative Metabolism in Lung Diseases.

Respiratory diseases are accompanied by intensification of free radical processes at different levels of the biological body organization. Simultaneous stress and suppression of various parts of antioxidant protection lead to the development of oxidative stress (OS) and nitrosative stress (NS). The basic mechanisms of initiation and development of the OS and NS in pulmonary pathology are considered. The antioxidant defense system of the respiratory tract is characterized. The results of the NS and OS marker study in various respiratory diseases are presented. It is shown that NS and OS are multilevel complex-regulated processes, existing and developing in inseparable connection with a number of physiological and pathophysiological processes. The study of NS and OS mechanisms contributes to the improvement of the quality of diagnosis and the development of therapeutic agents that act on different pathogenetic stages of the disease.

Soluble HLA-I and HLA-II Molecules Are Potential Prognostic Markers of Progression of Systemic and Local Inflammation in Patients with COPD.

Soluble molecules of the major histocompatibility complex play an important role in the development of various immune-mediated diseases. However, there is not much information on the participation of these proteins in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of our work was to determine the content of soluble molecules of the major histocompatibility complex of classes I and II (sHLA-I and sHLA-II) in the exhaled breath condensate (EBC) and in the blood serum in patients with moderate to severe COPD during the exacerbation and stable phase. We investigated 105 patients (male) with COPD aged 46-67 and 21 healthy nonsmoking volunteers (male) comparable in age. The content of sHLA-I and sHLA-II molecules was studied using ELISA. We found an increase in the level of sHLA-I and sHLA-II molecules in EBC, as well as an enhancement in the serum content of sHLA-II in all the examined COPD patients compared to healthy nonsmoking volunteers. The revealed negative correlation between the serum concentration of sHLA-II and values of FEV1 and FEV1/FVC in all examined patients with COPD gives a possibility to consider the content of these proteins as an additional systemic marker of disease severity. The maximum endobronchial and serum concentrations of sHLA-I and sHLA-II were detected in patients with severe COPD during the exacerbation. The negative associations between the content of these molecules in EBC and serum and the parameters of lung function in patients with severe COPD were established. These findings suggest a pathogenetic role of sHLA-I and sHLA-II molecules in the mechanisms of the development and progression of local and systemic inflammation in COPD.

Relationship of the Content of Systemic and Endobronchial Soluble Molecules of CD25, CD38, CD8, and HLA-I-CD8 and Lung Function Parameters in COPD Patients.

The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD) is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease. We investigated 91 patients with COPD and 21 healthy nonsmokers. The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC) in moderate-to-severe COPD patients during exacerbation and stable phase were studied. An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected. The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD. The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease.