EVALUATION OF CYTOKINE-MEDIATED MECHANISMS INVOLVED IN DEVELOPMENT OF RESPIRATORY MUSCLE DYSFUNCTION IN THE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Respiratory muscle (RM) strength was studied in 85 men with exacerbations of chronic obstructive pulmonary disease (COPD). The strength indicators of expiratory (MEP) and inspiratory pressure (MIP, SNIP) in oral cavity were registered by means of the MicroRPM device (CareFusion, UK), as well as intranasal pressure levels by SNIP test. The measured MEP, MIP и SNIP values were compared to the proper indices. Serum concentrations of cytokines (IL-4, IL-6, IL-10, IL-17A, IL-21, TNFα, IFNγ and TGF-β) were determined. The results of the study were processed by means of canonical analysis and by clustering methods. Expiratory RM dysfunction was recorded in mild COPD, expiratory-inspiratory RM dysfunction was recorded in moderate COPD and the diaphragm dysfunction was recorded in severe COPD. Three groups of patients with different combinations of RM strength indicators and immune parameters were identified by means of cluster analysis. The cytokine profile in the first cluster was characterized by maximal concentrations of IL-17A, IL-21, TNFα and TGF-β, whereas RM strength indexes showed minimal values. In the second cluster, a decrease of RM strength indicators by 25-40% against control was associated with a sharp rise of IL-6, along with moderate increase of IL-21 and TGF-βconcentrations. In the third cluster, maximal levels of IL-6, IL-10 and IFNγwere registered, along with low levels of IL-17A, IL-21 and TGF-β concentrations, whereas MEP, MIP и SNIP values did not sufficiently differ from their levels in second cluster. The results of canonical and correlation analysis indicated to interconnections between either certain cytokines, or their pool with the RM strength indicators, dyspnea severity and functional state of COPD patients, thus suggesting involvement of cytokine-mediated mechanisms in pathogenesis of the respiratory muscle dysfunction.