Cellular inflammation and the profile of bronchial cytokines in patients with bronchial asthma with cold airway hyperresponsiveness

Aim. To study the relationship between the structure of the inflammatory-cell pattern and the profile of respiratory cytokines with the nature of their changes in response to acute cold exposure in asthma.

Materials and methods. 42 patients with a diagnosis of persistent mild-to-moderate asthma were observed. All patients were treated with inhaled glucocorticosteroids. The comprehensive study included the assessment of asthma control, lung function before and after a 3-minute test of isocapnic hyperventilation with cold (-20°C) air (IHCA), the analysis of induced and spontaneously produced sputum with determination of cytosis, cell composition and concentration of IL-1b, IL-8, TNFα, IL-13, IL-18, IL-5, IL-10 initially and after the IHCA test.

Results. According to the results of the response to the IHCA, the patients were divided into two groups: the 1^st group (n=20) was with no reaction to IHCA, the 2^nd group (n=22) with cold airway hyperresponsiveness (CAHR) (AFEVj =-4.2±1.2 and -15.3±1.7%, respectively, p=0.001). The patients were comparable in terms of asthma control (ACT 19.6±1.4 and 19.1±1.3 points, respectively, p>0.05) and lung function (FEVt 94.1±3.1 and 101.2±3.9% pred., respectively, p>0.05). When analyzing sputum cytograms, the patients of both groups were characterized by a mixed pattern of bronchial inflammation with a large pool of eosinophils (4.65±1.49 and 7.0±2.0%, respectively, p>0.05) and neutrophils (57.0±2.18 and 52.2±2.96%, respectively, p>0.05). In response to the IHCA, an increase in cytosis was observed in the 2^nd group (by 0.04±0.21 and 0.94±0.23 cells/mcL, respectively, р<0.01), and the number of bronchial epithelial cells decreased in both groups (by 2.94±1.27 and 2.76±1.44%, respectively, p>0.05). In patients of the 2^nd group, a close relationship was found between the baseline content of sputum epithelial cells and FEVj/FVC (r=-0.57; p=0.009); MEF25-75 (r=-0.47; p=0.048), as well as between the number of macrophages and neutrophils (r=-0.86; p=0.000001), which indicated the dominant role of neutrophils in the implementation of CAHR. Under the influence of the cold trigger, a significant increase in TNFα levels, IL-1b and IL-8 concentrations were registered in group 2 in comparison to the 1^st group. In the general group of patients, a close correlation was found between the level of asthma control (ACT) and changes in the IL-1b concentration after the IHCA (r=-0.34; p=0.043), as well as between the initial concentration of TNFa in the sputum of patients and the severity of the bronchoconstrictor reaction to inhaled cold air (r=0.35; p=0.036).

Conclusion. It is suggested that the neutrophil pool of the bronchi of patients with CAHR is a critical factor in the development of an imbalance in the system of Th2 and Th1 types of cytokines regulating broncho-spasm. Bronchial epithelial cells were considered as an additional factor for stimulating the Th1 profile of cytokines. The decrease in the number of these cells is caused by destruction mediating the release of proinflammatory mediators from the cells.

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