Role of neutrophils and bronchial epithelium in loss of control of bronchial asthma and formation of respiratory tract response to cold stimulus

Introduction. Neutrophils and bronchial epithelium are actively involved in the generation of oxidative stress and the progression of airway inflammation in patients with asthma.
Aim. To study the role of neutrophils and bronchial epithelium as factors contributing to the loss of control over asthma and the formation of the airway response to a cold stimulus.
Materials and methods. A total of 146 patients with a diagnosis of persistent asthma were examined. A survey was conducted on the Asthma Control Test (ACT) questionnaire; a study of the lung function by spirometry with subsequent collection of induced sputum; the next day, a 3-minute isocapnic hyperventilation by cold (-20ºC) air (IHCA) was performed, followed by collection of spontaneously produced sputum. In the sputum, cytosis, cellular composition, and glycoprotein concentration in the goblet-like epithelium were assessed. Group 1 (n=89) included persons with uncontrolled (ACT˂20 points), group 2 (n=57) – with controlled (ACT>20 points) asthma.
Results. Patients of group 1 in comparison with group 2 had a higher increase in FEV₁ to the inhalation of a short-acting β₂ -agonist ‒ 11.0 (5.4; 21.65) vs. 7.55 (4.11; 13.8)%, respectively (p=0.042) and a more pronounced reaction to the IHCA test ‒ -11.0 (-17.6; -2.5) vs. -6.0 (-12.0; - 2.0)% (p=0.031). In patients of group 1, after the IHCA test, an increase in the number of neutrophils was observed from 45.98±2.17 to 52.0±1.78% (p=0.0013) and an increase in the concentration of glycoproteins in mucocytes from 37.9±3.8 to 45.6±4.2% (p=0.002) against the background of a tendency towards an increase in the concentration of goblet cells and a decrease in the number of intact bronchial epithelial cells (from 4.8±0.32 to 3.9±0.30%; p=0.017). Correlation analysis showed the relationship between the level of goblet cell glycoproteins and the initial concentration of neutrophils in sputum (r=-0.49; p=0.039), as well as between the severity of the reaction of the distal bronchi (ΔMEF₅₀) to a cold stimulus and the concentration of neutrophils in sputum after IHCA (r=0.36; p=0.01).
Conclusion. The signs of stimulation of the neutrophilic segment of granulocytes and structural rearrangement of the bronchial epithelium in the sputum of patients with uncontrolled asthma after acute cold exposure were determined. Structural changes in the pool of neutrophils and epithelial parenchyma of the bronchi, indicating an escalation of pro-inflammatory activity, may underlie the emergence and maintenance of the airway response to a cold stimulus and loss of asthma control.

bronchial asthma, cold airway hyperresponsiveness, neutrophils, cytokines, bronchial epithelium, uncontrolled asthma

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