Severe polypous rhinosinusitis associated with non-allergic bronchial asthma

Introduction. Chronic rhinosinusitis with nasal polyp (CRSwNP) and bronchial asthma (BA) are heterogeneous infl ammatory diseases of the respiratory tract. Despite the fact that BA and CRSwNP are currently considered as separate diseases, they often coexist in one patient and may infl uence each other. Due to the insuffi cient effi cacy of current therapy of severe BA (especially comorbid with CRSwNP), the urgent task is to search for new approaches of treatment of these diseases, which is impossible without a detailed understanding of the molecular and cellular mechanisms of their pathogenesis. The aim of the study was to investigate the course characteristics of CRSwNP in patients with severe asthma. Material and methods. 96 participants were enrolled into 4 groups of 24 in each: group I – patients with hypertrophic rhinitis without BA and atopy (comparison group), group II – patients with CRSwNP, group III – patients with CRSwNP comorbid with allergic BA, group IV – patients with CRSwNP comorbid with non-allergic BA. ELISA was used to determine the concentration of cytokines in supernatants of peripheral blood mononuclear cells (PBMCs) and polyp tissue homogenates. The degree of polyp tissue infi ltration with pro-infl ammatory cells was assessed by histological analysis. Quantitative PCR was used to evaluate the levels of cytokine gene expression in PBM and polyp tissues. The epithelial cells of the polyps were obtained by fl ow sorting. Results. Non-allergic asthma comorbid with CRSwNP is more severe and uncontrolled. CRSwNP is accompanied primarily by local rather than systemic infl ammation. Non-allergic BA leads to more aggressive and recurrent course of CRSwNP, and the polyp tissues characterized by a pronounced infl ammation with eosinophils and neutrophils. Allergic BA comorbid with CRSwNP is associated with suppression of Th1and activation of Th2-immune response, as well as with increased expression of the IL25 and TSLP genes in epithelial cells of polyps. At the same time, non-allergic BA comorbid with CRSwNP was characterized by activation of the Th17-immune response and high expression of IL25, TSLP, IL33 and IL37. Conclusion. BA and CRSwNP are heterogeneous diseases encompassing multiple phenotypes, which arise through distinct molecular mechanisms. Our study revealed the interplay between CRSwNP and BA. Particularly, non-allergic bronchial asthma , primarily, emerges as a factor contributing to a more aggressive course of CRSwNP.