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Objective To evaluate the inflammatory pattern and the interferon (IFN)-γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1. The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r = −0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.

Free radical damage to the respiratory tract in patients with asthma leads to the destruction of the bronchial parenchyma and the generation of signaling molecules of inflammation by parenchymal cells. Objective: to study the role of the structural and functional status of granulocytes in the development of epithelial destruction and oxidative lipid modification in the bronchi of asthma patients with airway hyperresponsiveness to cold and hyperosmolar stimuli. Material and methods. In 48 asthma patients, the level of asthma control was assessed according to the Asthma Control Test (ACT) questionnaire; lung function; bronchial response to 3-minute isocapnic hyperventilation with cold (- 20 °C) air (IHCA) and with ultrasonic inhalation of hypertonic (4.5 %) NaCl solution (IHS). The cellular composition and the degree of cellular destruction in induced sputum (IS) were measured. Reaction products for enzymes from the group of heme-containing peroxidases (myeloperoxidase in neutrophils, peroxidase in eosinophils) with the calculation of the average cytochemical coefficient were studied. The content of lipid peroxidation products in according to ultraviolet absorption spectra of lipid extracts in exhaled breath condensate (EBC) was assessed. Results. Patients of group 1 (n=15) with airway hyperresponsiveness to IHCA and IHS in relation to group 2 (n=33) with a negative reaction had lower ACT (14.7±1.4 vs. 18.4±0.8 points, p=0.017). In sputum, the number of neutrophils in groups 1 and 2 was 41.8±6.4 vs. 33.6±3.4 %, eosinophils – 23.5±3.5 vs. 14.9±2.6 %; average cytochemical coefficient of peroxidase 117.5±12.5 vs. 88.8±8.9 pixels (p=0.07), cell destruction index (CDI) of bronchial epithelium 0.56±0.04 vs. 0.39±0.02 r.u. (p =0.0002). The content of diene conjugates (E233) in EBC in group 1 was higher than in group 2 (0.07±0.008 vs. 0.05±0.005 optical units, p˂0.05). A correlation was found between peroxidase level and CDI, the number of totally destroyed cells (IV class of cell destruction), between the number of neutrophils in IS and E233, as well as the ratio of E233 to E206 (non-oxidized lipids) in EBC. Conclusion. In asthma patients with airway hyperresponsiveness to cold and hyperosmolar stimuli, changes in the structure of the epithelium and the structural and functional profile of granulocytes are associated with the activation of the peroxidase function of granulocytes and are interrelated with lipid peroxidation.