Aim. To assess the functional status of the small Airways in patients with bronchial asthma associated with obesity, by body plethysmography. Materials and methods. 65 patients with bronchial asthma of mild severity, partially controlled course, including 30 patients with normal body weight and 35 patients with obesity of I degree were examined. Control group-30 healthy volunteers. Examined forced vital capacity (FVC), forced expiratory volume in first second (FEV1) ratio of FEV1 to FVC (FEV1/FVC), maximum volumetric exhalation rate after 25.50 and 75% FVC (MEF75, MEF50, MEF25), average flow velocity in the exhalation interval 25-75% of FVC (MMEF25-75). Method bodyplethysmography was evaluated in bronchial resistance, functional residual capacity (FRC), residual volume of the lungs (RV), total lung capacity (TLC), the percentage of RV/TLC. Results. Patients with bronchial asthma with obesity showed a reduction of indicators of bronchial obstruction: FEV1 of 14% (p=0.02), FEV1/FVC by 14% (p=0.001), MEF75 30% (p=0.001), MEF50 by 35% (p=0.001), MEF25 by 44% (p=0.003), MMEF25-75 by 38% (p=0.001). The increase of bronchial resistance on inhalation in 2 times (p=0.001), on exhalation in 3.3 times (p=0.003) was found, which is typical for generalized bronchial obstruction at the proximal level. An increase in RV by 24% (p=0.03), TLC - by 9% (p=0.03), RV/TLC - by 18% (p=0.03), indicating the presence of "air traps" and dysfunction of the small respiratory tract. Conclusion. In patients with asthma of mild severity associated with obesity, both the central bronchis and the distal lung are affected, which are manifested by generalized bronchial obstruction, the formation of "air traps" and dysfunction of the small respiratory tract.

The aim is to establish interrelations between levels of cytokines and adipokines in blood serum of patients with asthma; to reveal the features of cytokine and adipokine regulation in asthma associated with obesity. Material and Methods -We examined 71 patients with partially controlled mild asthma: 24 normal-weight patients (group 1), 24 overweight patients (group 2), 23 patients with grade I and II obesity (group 3). The control group consisted of 25 healthy volunteers. Blood serum levels of Tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and IL-17A were studied by flow cytometry. The concentrations of leptin and adiponectin were measured by an enzyme immunoassay.Results -Increase levels of TNF-α, IL-6, IL-17A and IL-4 have been found in asthma patients regardless of body weight. At the same time, IL-6 level in the groups 2 and 3 was 1.4 times higher than in group 1. IL-17A level in patients with asthma and obesity was 1.2 times higher than in the groups 1 and 2. The elevation of IL-10 level in 1.8 and 2.3 times in patients of groups 2 аnd 3 in comparison with the group 1, respectively, has been determined. Hyperleptinemia was detected in the groups 2 and 3. A positive correlation between the body mass index and the levels of leptin, IL-4, IL-6, IL-10, IFN-γ and an invert correlation between this index and adiponectin concentration has been established. The interrelations between the levels of leptin, pro-and anti-inflammatory cytokines, depending on the body weight, have been revealed. Conclusion -The production of pro-inflammatory cytokines IL-6 and IL-17A, as well as anti-inflammatory cytokine IL-10 enhances in asthma patients as the body weight increases and the obesity develops. The features of cytokine and adipokine imbalance indicate the prevalence of neutrophilic inflammation in asthma with obesity and demonstrates pathogenetic link between obesity and asthma.

Chronic obstructive pulmonary disease (COPD) is considered a heterogeneous disorder exhibiting different phenotypes. Chronic systemic inflammation is an important link in the COPD pathogenesis. The studies of immune response in the context of clinical and functional phenotypes seems relevant. Objective of our work was to study the features of immune response in clinical and functional phenotypes of COPD.Eighty-three COPD patients of different severity grade and 22 apparently healthy volunteers were examined. After determining the COPD phenotype by clinical and functional signs, the patients were divided in two groups, i.e., 38 subjects with bronchitis, and 45 patients with emphysematous phenotype. Clinical, functional and laboratory research was carried out in standard mode. Static lung volumes and respiratory capacities were investigated, i.e., functional residual capacity, residual lung volume, total lung capacity, bronchial resistance on inspiration and expiration to assess phenotype of the disease. Subpopulations of Th1 and Th17 lymphocytes were determined by the level of blood serum cytokines, tumor necrosis factor (TNFá), interleukins (IL) IL-4, IL-10, IL-17A, IFNã).Different features of immune response were revealed in bronchitic and emphysematous phenotypes of the COPD patients. Activation of inflammatory process with differentiation of naive T lymphocytes along the Th1-dependent pathway was found in 68% of cases with bronchitis and 16% of patients with emphysematous phenotypes. As compared with control group, the patients showed a statistically significant increase in the level of TNFá, IFNã, along with decrease in IL-4. Development of immune response by the Th17 type was found in 32% of cases with bronchitis, and 84% of cases with emphysematous phenotypes. Its emergence was associated with increased IL-17A and IL-10 levels, and a decrease in IFNã/IL-17A compared to the control. Differentiation of T helper cells towards Th1 pathway of immune response has been shown to predominate in bronchitic phenotype and at early stages of the disease. The Th17 type of immune response prevailed with increasing severity of the disorder. In emphysematous phenotype of COPD, the Th17-pathway of immune response develops at early stages of the disease. Some relationships are revealed between the systemic inflammation indexes and functional parameters of external respiration. An inverse relationship between TNFá and the OOL/OEL ratio in Th1 type of immune response has been shown. A direct correlation was found between the level of IL-17A and the parameters of external respiration function (FEV1, FEV1/FVC), as well as between IFNã/IL-17A and functional residual capacity in Th17 type of immune response.The type of immune response is associated with severity of the disease, as well with clinical and functional phenotype of COPD. Progression of the disease, broncho-obstructive disorders and hyperinflation are associated with increased levels of cytokines that provide cell polarization along the Th17 pathway. Determination of COPD phenotype and the type of immune response already at an early stage of the disease will enable prediction of its course and justify the choice of phenotype-oriented therapy.

Combination of bronchial asthma (BA) and obesity is a difficult-to-control phenotype. Studies of inflammatory process with respect to severity of the disease are important for understanding the potential influence of obesity on the BA clinical course. The objective of this study was to determine cytokine profile in patients with mild BA combined with obesity. The study involved fifty-three patients with partially controlled mild BA. The patients were recruited as volunteers and signed an informed consent. The first observation group consisted of 27 asthma patients with normal body weight, the second observation group consisted of 26 patients with BA combined with obesity. A control group included 25 healthy volunteers. All the patients underwent clinical and laboratory examination in accordance with clinical standards for BA and obesity. The levels of TNFα, IL-2, IL-4, IL-6, IL-10 were evaluated in blood serum by means of flow cytometry. The ratios of proand anti-inflammatory cytokines (TNFα/IL-4, TNFα/IL-10, IL-6/IL-4, IL-6/IL-10) were calculated. Asthma patients with obesity (the 2nd group) had elevated levels of IL-2 over control group and group 1, by 38% and 44% respectively(p < 0.05). The concentration of proinflammatory cytokines TNFα and IL-6 was significanty increased in the both patient groups. Mean TNFα level was increased 2.5 times (p < 0.05), and IL-6 levels were increased by 30% (p < 0.05) in the 1st group as compared to the controls. TNFα and IL-6 concentrations showed a 3-fold increase over control values (p < 0.05) in the 2nd group. The level of antiinflammatory cytokine IL-4 was increased in patients with BA, independently of body mass. It should be noted that the concentration of this cytokine in obese patients was higher by 29% than in patients with normal body weight. IL-10 levels in patients from the 2nd group were reduced more than 2 times than in the 1st group. The patients of the 1st group showed a decrease in the IL-6/IL-10 index, in comparison with control parameters, thus indicative of an imbalance due to the elevation of the anti-inflammatory IL-10 cytokine. Among BA patients with obesity (group 2) the TNFα/IL-10 and IL-6/IL-10 indexes were higher than those of the control group (2.3- and 5.5-fold, respectively) and the group 1 (2.6- and 2.5-fold, respectively). Dynamics of these indexes confirms the systemic nature of inflammation and a predominance of non-atopic  inflammation in asthma patients with obesity. Thus, features of the cytokine profile in BA with obesity consist of a significant increase in pro-inflammatory IL-2, IL-6, TNFα cytokines, and a relative decrease in anti-inflammatory IL- 10 cytokine. The development of BA with obesity, even in mild-severity BA, is accompanied by development of a cytokine disbalance, which is typical for a mixed-type inflammation, with a prevalence of neutrophil inflammation.

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