Bronchial granulocytes in the development of epithelial destruction and oxidative lipid modification in patients with bronchial asthma with cold and osmotic airway hyperresponsiveness

Abstract

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.