Molecular cellular reactions of the respiratory tract to cold stimulus in non-allergic bronchial asthma

Abstract

Introduction. Macrophages, matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-α) make a significant contribution to the pathophysiological mechanisms of development and course of bronchial asthma.Aim. To evaluate the role of macrophages and MMP-9 regulated by TNF-α signaling in the formation of airway response of non-allergic bronchial asthma patients to cold air hyperventilation.Materials and methods. Spirometric indices of forced expiratory flow, cellular composition of sputum, MMP-9 and TNF-α content in exhaled breath condensate (EBC) were measured in 66 patients with asthma before and after bronchoprovocation test with isocapnic hyperventilation with cold (-20°C) air (IHCA) were evaluated.Results. Two groups of patients with presence (group 1) or absence (group 2) of cold airway hyperresponsiveness were formed. High macrophage and neutrophil counts and a significant decrease in the number of epithelial cells in sputum were recorded after the IHCA. Concentrations of TNF-α and MMP-9 in EBC after IHCA decreased to a greater extent in patients of group 2. The content of epitheliocytes in sputum was correlated with FEF50 (r=-0.49, p=0.03), FEF75 (r=-0.45, p=0.047) and MEF25-75 (r=-0.47, p=0.038), and their content after IHCA test with ΔMEF25-75 (Rs=0.31; p=0.018). We found a correlation between baseline MMP-9 content in EBC and ΔMEF25-75 (Rs=-0.59; p=0.042), as well as between MMP-9 level after IHCA and severity of bronchospasm (ΔMEF25-75) in response to IHCA test (Rs=-0.67; p=0.023).Conclusion. In patients with cold airway hyperresponsiveness, uncontrolled course of asthma and more significant bronchial patency disorders are associated with productive-proliferative inflammation involving macrophages, MMP-9 and TNF-α, which contributes to bronchial remodeling.