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Background Periostin is a recently discovered biomarker for eosinophilic inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed chronic inflammatory airway disease. Medical treatments aim to relieve symptoms and maintain clinical control by interfering with the inflammatory cascade. The effect on nasal and serum periostin levels is however yet unknown. We aimed to evaluate the effect of omalizumab, mepolizumab, methylprednisolone and doxycycline on nasal and systemic periostin expression. Methods This study is based on 3 previously published trials. Nasal and systemic periostin were assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14), methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15). There was a control group for each treatment scheme. Doxycycline (200 mg on the first day, followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were administered during 20 days; mepolizumab was injected at baseline and at 4 weeks. Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet. Results Methylprednisolone and omalizumab significantly reduced serum periostin levels at 4 and 8 weeks, respectively, after the start of the treatment. The effect of methylprednisolone was transient. Nasal periostin levels decreased significantly after 8 weeks of treatment with mepolizumab. The periostin expression is in accordance with the previously reported effect on the eosinophilic inflammation and clinical outcome. Conclusion All treatment options distinctly influence periostin expression, reflecting the interference with the local or systemic eosinophilic inflammatory cascade.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease associated with lymphoid aggregates and local IgE production related to Staphylococcus aureus enterotoxins. T-follicular helper cells and their effector cytokine interleukin (IL)-21 play an important role in germinal center proliferation. Methods: IL-21 was determined on the mRNA level by qPCR in nasal tissue of 3 groups of patients: control (n = 17), chronic rhinosinusitis without nasal polyposis (CRSsNP; n = 23), and CRSwNP (n = 35). The expression of IL-21 by CD4+ T cells was analyzed in tissue at baseline and after 24-h stimulation of tissue fragments with S. aureus enterotoxin B (SEB) using flow cytometry. Finally, human nasal IL-21+CXCR5+CD4+ T cells were isolated and coincubated with human blood naive B cells to investigate their functionality. Results: IL-21 mRNA expression was increased in the CRSwNP group (p < 0.05) compared to the control group, and B-cell lymphoma-6 and B-lymphocyte-induced maturation protein-1 were upregulated in CRSwNP versus CRSsNP. Furthermore, SEB was able to increase IL-21 mRNA expression significantly (p < 0.01) in nasal polyps. Flow cytometry revealed that the source of IL-21 was predominantly CD4+ T cells and that IL-21+CD4+ T cells were significantly increased in polyp tissue and further increased after SEB stimulation. Finally, tissue CXCR5+CD4+ T cells derived from nasal polyp tissue were able to induce maturation of human naive B cells. Conclusions: IL-21- and IL-21-producing CD4+ T cells were increased in CRSwNP. In addition, SEB induced an increase in IL-21 and IL-21+CD4+ T cells, suggesting that S. aureus can modulate the function of Tfh cells in nasal polyps. We speculate that T-follicular helper cells and IL-21 are important in the pathophysiology of CRSwNP.

Type III frontal sinusotomy: surgical technique, indications, outcomes, a multi-university retrospective study of 120 cases. Draf type III is one of the advanced endonasal endoscopic surgeries for the frontal sinus. It was popularised by W. Draf in 1991. The procedure - which is also known as the modified endoscopic Lothrop procedure - aims to create the largest possible anteroposterior and lateral to lateral opening between both frontal sinuses and the nasal cavities. This requires the resection of the medial floor of both frontal sinuses, the intersinus septum and the superior nasal septum. The authors present a retrospective study including a cohort of 120 patients who underwent surgery in six Belgian university ENT departments. Mean follow-up was 24.6 months (range: 5-36 months). This paper describes the surgical procedure and reviews the indications, comorbidities, outcomes and complications of the type III frontal sinusotomy. Some correlations are also established with the data published in the worldwide literature. The authors conclude that the Draf III is a demanding procedure requiring considerable expertise in endoscopic sinus surgery. The procedure is effective with a success rate of 87.5%. Indeed, 12.5% of patients only experienced closure of the neoostium while 20% of all the patients had unchanged or worse symptomatology. The percentage of post-operative complications is 7.5%. All complications were managed successfully

Chronic rhinosinusitis with nasal polyps often represents a chronic severe inflammatory disease of the upper airways. Nasal polyps (chronic rhinosinusitis with nasal polyps) are characterized by a T-helper-2 dominated cytokine pattern including high interleukin-5 while chronic rhinosinusitis without polyps exhibits T-helper-1 biased cytokine releas with high IFN-gamma concentrations. S. aureus derived enterotoxins function as superantigens and in nasal polyps a significant higher colonisation and immune response to enterotoxins has been found. Furthermore, S. aureus derived enterotoxins influence local immunoglobulin synthesis and induce polyclonal immunoglobulin E production, which may contribute to severe inflammation via activation of mast cells. From this new understanding of chronic rhinosinusitis with nasal polyps, new therapeutic approaches emerge such as anti-interleukin-5, anti-immunoglobulin E, and antibiotic treatment. These may enlarge the nonsurgical armentarium. Furthermore more evidence is now available that this model of disease modification by superantigens is also applicable to lower airway diseases like late-onset asthma.

Although the etiology of nasal polyposis is still not revealed, insights in the pathogenesis have largely expanded over the last years. Usually nasal polyps occur in adults, are bilateral and are characterized by a manifest tissue eosinophilia. Deposition of plasma-proteins (albumin), potentially driven by subepithelial eosinophilic inflammation, seems to be an early and key pathogenic factor in the development of nasal polyps. Accumulation and activation of eosinophils is favoured by low TGF-beta1 concentrations and overproduction of IL-5 and eotaxin. In nasal polyps high IgE concentrations are measured. Our findings indicate that this IgE is produced locally. Total IgE and the expression of specific IgE is unrelated to skin prick tests, but correlates with the degree of eosinophilia. In addition, we demonstrated the organisation of secondary lymphoid tissue in nasal polyps and a polyclonal hyper-immunoglobulinemia E, associated with the presence of IgE specific to Staph. aureus enterotoxins (SAE), colonization with Staph. aureus and increased eosinophilic inflammation in a relevant subgroup of NP patients (about 50%). In about half of the nasal polyps we thus find a local immune response against SAE. SAE can hereby act as conventional allergens, triggering T- en B-cells to produce sIgE against SAE. On the other hand, SAE can also act as superantigens and induce polyclonal B-cell activation and hyper-immunoglobulinemia. In addition, the presence of IgE antibodies to SAEs seems to be associated with the severity of asthma and nasal polyposis disease. Nasal and oral corticosteroids are currently the standard treatment for NP. This treatment however, is not always sufficient and oral corticosteroids have several side effects. Often surgery is required, which in turn is not free of complications and recurrencies. Increasing insights in the pathophysiology of NP opens perspectives for new pharmacological treatment options, with eosinophilic inflammation, IgE and Staph. aureus as potential targets.