Types of immune response in patients with asthma and airway hyperresponsiveness to cold and hypoosmolar stimuli

The pathogenesis of asthma may involve allergic inflammation of the "low Th2" subtype, which differs from the "high Th2" subtype by the dominant profile of intercellular signaling molecules. Aim. To study the types of immune response in patients with asthma and airway hyperresponsiveness to cold and osmotic stimuli by analyzing the levels of interleukins (IL)-17A, IL-17F, IL-22, IL-6, IL-4, IL-13, interferon (IFN)-γ, and patterns of bronchial inflammation. Materials and methods. Sixty-five patients with mild persistent asthma were examined. Induced sputum collection, blood sampling for biochemical studies, spirometry, bronchial provocation tests with isocapnic hyperventilation of cold (-20 °C) air (IHCA), and ultrasonic inhalation of distilled water (UIDW) were performed. The cellular composition of sputum (in percentages) was analyzed, and cytokine profiles in peripheral blood serum (IL-17A, IL-17F, IL-22, IL-6, IL-4, IL-13, IFN-γ, in pg/mL) were determined. Results. Group 1 (n=18) included patients with bronchial hyperresponsiveness to the IHCA; Group 2 (n=18) comprised patients with airway hyperresponsiveness to the UIDW; Group 3 (n=29) consisted of non-responders to the triggers. Patients in Groups 1 and 2 had lower baseline bronchial patency indicators. In the sputum of patients in Group 1, higher numbers of neutrophils and proportions of desquamated epithelial cells were recorded, with a correlation observed between the cell content and the airway response to the IHCA. These patients exhibited higher serum concentrations of IL-17A, IL-22, IL-6, IL-4, and IFN-γ. Correlation analysis showed an association between IL-17A levels and airway response to the IHCA: ΔFEV_1IHCA (Rs=-0.33; p=0.049); ΔMEF_50IHCA (Rs=-0.50; p=0.030); between IL-17F levels and ΔFEF_25-75IHCA (Rs=-0.38; p=0.037); ΔMEF_50IHCA (Rs=-0.40; p=0.029). IL-17A levels correlated with IL-17F levels (Rs=0.53; p=0.022), and IL-4 concentrations correlated with IFN-γ levels (Rs=0.53; p=0.0004). Conclusion. Patients with asthma and cold airway hyperresponsiveness are characterized by more pronounced impairments in airway patency, increased neutrophil counts in sputum, and elevated serum levels of IL-17A, IL-22, IL-6, IFN-γ, and IL-4. The immune response in these patients is associated with Th2/Th17 and/or Th1/Th17 types, whereas in individuals with osmotic airway hyperresponsiveness, it is more associated with the Th2 type of inflammation.

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