Molecular-cellular mechanisms of combined airway hyperresponsiveness in asthma

Background: Excessive airway reaction to combined effect of environmental factors is very common in patients with asthma. The aim of the work was to study granulocytic segment of bronchial inflammation in the correlation with cytokine regulation and lipid peroxidation in patients with airway hyperresponsiveness to cold and osmotic stimuli. Methods: 43 patients with mild asthma with cold and osmotic airway hyperresponsiveness (1st group) were examined. The 2nd group included 11 asthmatics without response to the stimuli. The concentrations of IL-5, IL-12 in the exhaled breath condensate (EBC) and myeloperoxidase (MPO) in the induced sputum (IS) were measured. The number of neutrophils and eosinophils in IS, MPO activity in granulocytes and degree of cytolysis were calculated. The contents of lipid hydroperoxides (LHP) and MPO in the blood were measured. Results: In the 1st group in comparison with the 2nd one there were found high levels of IL-12 (2.94±0.09 vs. 2.53±0.13 pg/mL, р=0.024), IL-5 (3.64±0.37 vs. 2.15±0.14 pg/mL, р=0.0001); the increase of neutrophils in IM (35.4±3.5 vs. 17.2±2.0%, р=0.014); higher granulocytes cytolysis (0.38±0.02 vs. 0.26±0.02, р=0.013), which correlated for neutrophils with the level of IL-12 (r=0.46, р=0.026); there was found out the increase of MPO concentration in IS (199.7±49.0 vs. 81.4+26.2 pixels, р=0.039). The increased level of LHP in the blood serum correlated with the level of MPO in IS (r=0.48, р=0.039) and IL-5 in EBC (r=0.71; р=0.031). Conclusion: Activated pool of neutrophils and stimulated enzyme activity of granulocytes correlate with inflammation and lipid peroxidation which influence the development of osmotic and cold airway hyperresponsiveness.