Relationship Between the Functional Activity of Granulocyte Peroxidase and Oxidative Lipid Modification in Asthma Patients with Cold Airway Hyperresponsiveness

Background. Granulocyte myeloperoxidase (MPO) play an important role in the link between the oxidative stress and inflammation that maintain airway hyperresponsiveness. We aimed to assess the relationship between the level of myeloperoxidase activity of granulocytes, the accumulation of oxidatively modified lipids in the bronchi, and cold airway hyperresponsiveness in patients with different inflammation phenotypes of asthma. Methods. 116 patients with asthma (mean age 43.20.8 years; ACT 13.20.27 points; FEV 1 86.61.0%) underwent testing of lung function (FEV 1 ,%), airway response (FEV 1 ) to 3-minute isocapnic hyperventilation with cold (-20C) air (IHCA). The cellular composition (%) of induced sputum (IS) and myeloperoxidase (MPO) activity were studied. The concentration of the products of lipid peroxidation in the expired breath condensate was studied using the ultraviolet absorption spectra of lipid extracts using Unico 2804 spectrophotometer. The concentration of diene conjugates was estimated in units of optical density at 233 nm (E233), conjugated trienes (ketodienes) at 278 nm (E278), and the absorption of unoxidized lipids at 206 nm (E206). The lipid oxidation indexes was calculated as the ratio of absorption E233/206 and E278/206. Results. The patients were divided into two groups depending on the number of neutrophils in the IS (less or over 40%): group 1 included 52 people (neutrophils 23.20.84%, eosinophils 21.21.4%), group 2 -64 people (neutrophils 54.11.4%, eosinophils 14.31.4%). Patients had no differences in FEV 1 and the frequency of cold airway hyperresponsiveness. In patients of group 2, the increase in the number of neutrophils correlated with a more pronounced airway reaction (FEV 1 ) to the IHCA (r=-0.18, p=0.047), and with an increase in the MPO in IS (r=0.47; p=0.0001). A higher concentration of MPO in group 2 (135.912.1 vs. 81.73.6, p=0.00001) showed an intensification of the synthesis and activation of the enzyme excretion into the extracellular space. The level of diene conjugates E233 in group 2 compared with group 1 was significantly higher (0.100.03 vs. 0.040.006, p=0.013), as was E233/206 (0.370.06 vs 0.190.03, p=0.028). A close relationship was found between E278/206 and airway response (MEF 25-75 ) to the IHCA (r=0.39; p=0.017). Conclusion. In patients with uncontrolled asthma, an increase in the number of neutrophils in sputum leads to an increase in the peroxidase activity of granulocytes, associated with the activation of lipid peroxidation and an increase in the response of the respiratory passages to exposure to cold.