Pathophysiological relation between the systemic inflammation and the state of small airways in mild asthma with obesity

The aim of present study was to establish the relationship between the level of blood serum cytokines and indexes of pulmonary function as well as to identify the markers of evolving dysfunction of small airways in obese patients with partially controlled mild bronchial asthma. We have examined 53 patients with mild asthma of partially controlled clinical course complicated with obesity (I-II degree). The control group consisted of 25 healthy volunteers. All participants underwent spirometry, bodyplethysmography. Tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), interleukins (IL) IL2, IL-4, IL-6, IL-10, IL-17A were determined in blood serum. In the patients with partially controlled mild asthma, an increase in IL-17A by 55.8%, and IL-4 by 44.9% was detected, regardless of body mass. According to the results of cluster analysis, two sub-groups were discerned, depending on the state of the small airways and the levels of pro- and anti-inflammatory cytokines. The dysfunction of small airways was shown to be accompanied by hypercytokinemia being more common in bronchial asthma with predominant Th1-and Th17-immune responses. We have revealed an association between IL-17A, IL-6 levels and functional indices reflecting the state of the small airways, as well as correlation between IFNγ and the indices of bronchial obstruction. The features of pulmonary function were found to be dependent on the cytokine status in mild asthma with obesity. Two immuno-functional variants were identified, differing in activity of systemic inflammation, type of immune response, and functional state of the small airways. The revealed relationships allow us to consider IL-17A, IL-6 and IFNγ as markers of small airways dysfunction in mild asthma of partially controlled clinical course associated with obesity

The role of fatty acids and lipid inflammatory mediators in the development of small airway dysfunction in asthma complicated with obesity

Background. Small airway involvement is important in determining the phenotypes of bronchial asthma. Establishing the mechanisms of dysfunction of small airways will make it possible to predict the course and control bronchial asthma.The aim. To study the relationship between the modification of the composition of fatty acids, lipid inflammatory mediators (eicosanoids, plasmalogens) and the functional state of small airways and to identify lipid biomarkers for the development of small airway dysfunction in bronchial asthma associated with obesity.Materials and methods. The study included 85 patients with mild, partially controlled asthma. Of these, 39 patients with normal body weight (Group 1) and 46 patients with grade 1–2 obesity (Group 2). The control group consisted of 30 healthy volunteers. The function of the small airways was assessed according to spirometry and body plethysmography. The composition of fatty acids and plasmalogens in blood plasma was assessed by gas chromatography-mass spectrometry. In the blood serum, the content of thromboxane B2 and leukotriene B4 was determined. Statistical processing was performed using the Statistica 6.1 program (StatSoft Inc., USA). Relationships between pairs of traits were examined using the Spearman correlation test (r). Differences were considered statistically significant at p < 0.05.Results. In the combined course of asthma and obesity, dysfunction of the small airways develops against the background of generalized bronchial obstruction. A violation of lipid metabolism was revealed, manifested by an increase in the levels of saturated, monoenoic, n-6 polyunsaturated fatty acids against the background of a deficiency of n-3 polyunsaturated fatty acids and phospholipids with an alkenyl bond – plasmalogens. It has been shown that bronchial asthma, aggravated by obesity, occurs against the background of increased synthesis of inflammatory lipid mediators – eicosanoids (thromboxane B2 and leukotriene B4). Evaluation of the correlation relationships between the studied lipids and the function of small airways revealed a high degree of relationship between their participants.Conclusion. An important pathogenetic link in the formation of small airway dysfunction in bronchial asthma aggravated by obesity is a violation of fatty acid metabolism and plasmalogen synthesis, an increase in the formation of inflammatory lipid mediators

FEATURES OF CYTOKINE PROFILE IN PATIENTS WITH BRONCHIAL ASTHMA COMBINED WITH OBESITY

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