Pathogenetic molecular mechanisms of chronic rhinosinusitis with nasal polyps associated with asthma
The combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype with dysregulation of pro- and anti-inflammatory cytokines as one of the leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1<sup>st</sup> was healthy control (Normal); the 2<sup>nd</sup> had allergic BA associated with CRSwNP; the 3<sup>rd</sup> had nonallergic BA associated with CRSwNP; the 4<sup>th</sup> had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORg transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dysregulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.