THE CHANGE OF GOBLET CELLS IN RESPONSE TO COLD BRONCHIAL CHALLENGE IN PATIENTS WITH BRONCHIAL ASTHMA WITH COLD AIRWAY HYPERRESPONSIVENESS

Abstract

Destruction of bronchial epithelium in patients with bronchial asthma (BA) is at the bottom of the mechanism of epithelial dysfunction, mucociliary insufficiency and bronchial remodeling. The aim of the work is to assess the character of changes that happen in the structural organization of cell elements and secretory activity of bronchial goblet epithelium in response to cold bronchial challenge in BA patients with cold airway hyperresponsiveness (CAHR). 28 patients with mild BA took part in the research. In the first day of the research the collection of the induced sputum was done, then the next day there was conducted a standard 3-minute test of isocapnic hyperventilation with cold (-20ºC) air (IHCA), after that the collection of sputum was done again. In cytograms of the sputum the percentage, the degree of destruction and cytolysis intensity of cell elements was determined; the contents of glycoproteins in goblet epithelial cells (GS) was studied. The first group included 14 patients with CAHR, the group of comparison (the 2nd group) included 14 patients with BA who did not have airway response to IHCA (ΔFEV1=-19.9±1.6 and -2.8±1.3%, respectively, p=0.00001). After IHCA in cytograms of the sputum of the patients with CAHR there was an increase of the number of neutrophils in relation to the basic one (from 39.9±2.8 till 54.0±2.3%, respectively, p=0.0004), the decrease of the number of macrophages (from 45.3±3.4 till 31.4±2.6%, p=0.005) without the changes of the number of eosinophils (10.0±2.2 and 10.4±1.6%, p=0.14) against intensified cytolysis (2.4±0.16 and 3.1±0.16%, p=0.0007). There was a decrease of the number of GC in relation to the initial one (from 0.22±0.02 till 0.16±0.02%; p=0.037) without significant changes of the number of epithelial cells (1.6±0.54 and 1.5±1.20%; p=0.97). The total index of destruction of GC was 0.45±0.02 and 0.51±0.02 (p=0.045); the index of cytolysis intensiveness of GC was 0.20±0.04 and 0.20±0.02 (p=0.27). A high number of GC that had a normal structure (0 and 1 class of destruction) as well as an increase of the number of cells in relation to initial values of the number of cells of II class against the absence of changes of III and IV classes of destruction were quite noticeable. Under cytochemical reaction the number of alcian blue stained GC actively synthesizing and secreting glycoproteins in response to IHCA increased in relation to the basic value (from 59.8±3.3 till 70.8±4.0%, p=0.0002, respectively). There was found a close correlation between the intensified production of GC glycoproteins in response to bronchial challenge and intensification of bronchial response (∆FEV1) to IHCA (r=-0.37; p=0.029). Thus, in the patients with BA and CAHR a short-term cold air exposure leads to the increase of the number of neutrophils and the decrease of the number of GC under intensive production of glycoproteins in them.