Rogério Pezato

Role of imbalance of eicosanoid pathways and staphylococcal superantigens in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a multifactorial disease of the upper airways with a high prevalence (approximately 11%) in the general population. Different immune and inflammatory mechanisms are involved in its pathogenesis. Alterations in the arachidonic acid pathway (leading to an imbalanced production of eicosanoids) have been linked to the pathophysiology of different diseases especially nasal polyposis, asthma, and aspirin‐exacerbated respiratory disease. Furthermore, viral and bacterial infections have been identified as important factors amplifying the pro‐inflammatory reactions in these pathologies. This review summarizes the impact of an imbalance in the eicosanoid pathway and the effect of Staphylococcus aureus enterotoxins on the regulation of the pro‐inflammatory network in CRS and their translation into disease severity.

The expression of dendritic cell subsets in severe chronic rhinosinusitis with nasal polyps is altered.

BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized as a Th2-driven disease. Activated dendritic cells (DCs) are the main T-cell activators; their role in the chronic inflammatory process of nasal polyposis is still unclear. METHODS The regulation of DC subsets was analyzed in nasal polyp tissue from CRSwNP patients and compared to inferior turbinate tissue from healthy subjects. Tissue localization and expression of both plasmacytoid and myeloid DCs were assayed by means of immunohistochemistry and flow cytometry. Plasmacytoid DCs were also assayed by PCR, and tissue homogenates were assayed for various inflammatory markers. RESULTS The number of plasmacytoid (pDCs) and myeloid (mDCs) dendritic cells was significantly increased in nasal polyp tissue when compared to non-inflamed nasal mucosa. The number of pDCs, but not mDCs, was down-regulated in more severe cases (nasal polyps with asthma) and varied with the cytokine milieu. The amount of pDCs was significantly decreased in IL5+IFNγ - nasal polyp tissue compared to tissues with high IFNγ levels (IL5+IFNγ+). Furthermore, levels of indoleamine 2,3-dioxygenase were increased in nasal polyp compared to inferior turbinate tissue and correlated negatively with the number of pDCs. CONCLUSIONS There is an altered balance of pDC and mDC numbers in nasal polyp tissue. pDCs seem to be more susceptible to an inflammatory cytokine milieu and may play a crucial role in disease severity.

Convergence of two major pathophysiologic mechanisms in nasal polyposis: immune response to Staphylococcus aureus and airway remodeling

This review is addressed two pathophysiologic mechanisms implicated in the pathogenesis of nasal polyposis: the unique remodeling process found in nasal polyp tissue and the immune response of patients with nasal polyposis to Staphylococcus aureus.These two theories converge to the same direction in different aspects, including decreased extracellular matrix production, impaired T regulation and favoring of a Th2 immune response.In patients with nasal polyposis, an exaggerated immune response to Staphylococcus aureus may aggravate the airway remodeling process.

Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF-β1 as compared with healthy nasal mucosa

ObjectiveTo evaluate TGF-β1 expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).MethodsCross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-β1 visualization. Then, the percentage of TGF-β1 expression in stroma and epithelium was objectively quantified using UT Morph software.ResultsA lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05).ConclusionThe lower percentage of TGF-β1 expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.

Why do we not find polyps in the lungs? Bronchial mucosa as a model in the treatment of polyposis.

The link between lower and upper airways has been reported since the beginning of 1800 s. They share the same pseudostratified ciliated columnar epithelium lining and the concept of one airway, one disease is quite well widespread. Nasal polyposis and asthma share basically the same inflammatory process: predominant infiltration of eosinophils, mucus cell hyperplasia, edema, thickened basal membrane, polarization for Th2 cell immune response, similar pro-inflammatory mediators are increased, for example cysteinyl leukotrienes. If the lower and upper airways share a lot of common epithelial structural features so why is the edema in the nasal mucosa able to increase so much the size of the mucosa to the point of developing polyps? The article tries to underline some differences between the nasal and the bronchial mucosa that could be implicated in this aberrant change from normal mucosa to polyps. This paper creates the concept that there are no polyps with the features of nasal polyposis disease in the lower airway and through it is developed the hypothesis of the nasal polyps origin could partially lie on the difference between the upper and lower airway histology.

Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease.

BACKGROUND Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD. METHODS Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges. RESULTS AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-β1 and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal). CONCLUSIONS AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.

Immunoregulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in the Nasal Polyp Microenvironment

Nasal polyposis is a severe, chronic inflammatory condition of the paranasal sinuses and is frequently associated with asthma and aspirin sensitivity. Mesenchymal stem cells exhibit a potent immunosuppressive effect in several inflammatory conditions, and their role in nasal polyposis remains little explored. Hence, we investigated whether bone marrow-derived mesenchymal stem cells could modulate cell phenotype in the nasal polyp milieu. After coculture with mesenchymal stem cells, the frequency of these inflammatory cells was found to decrease. Furthermore, mesenchymal stem cells promoted strong inhibition of CD4+ and CD8+ T cell proliferation, increased the frequency of CD4+CD25+Foxp3 T cells, and changed the global cytokine profile from an inflammatory to an anti-inflammatory response. We believe that mesenchymal stem cells may be a very useful adjunct for investigation of the inflammatory process in nasal polyposis, contributing to better understanding of the inflammatory course of this condition.

Why we should avoid using inferior turbinate tissue as control to Nasal Polyposis studies

Abstract Conclusion: The authors are aware that inferior turbinate mucosa presents different properties from middle turbinate mucosa and any data generated using inferior turbinate as control in Nasal Polyposis (NP) should be analysed very carefully. Objective: This study aims to compare the mechanical properties of inferior turbinate mucosa vs middle turbinate mucosa. Materials and methods: The interstitial hydrostatic pressure behaviour was compared during a saline solution infusion between healthy nasal mucosa from inferior turbinate with middle turbinate (four patients). Results: A significant difference, p = 0.02, was found in the response of interstitial hydrostatic pressure during the saline injection when the inferior turbinate vs middle turbinate was compared.

Acute impact of continuous positive airway pressure on nasal patency: Acute impact of CPAP on nasal patency

Continuous airflow in the upper airway can cause discomfort, leading to nasopharyngeal complaints. The aim of the present study is to evaluate the acute effects of continuous positive upper‐airway pressure on nasal patency in awake normal subjects.

Deviated nose correction by using the spreader graft in the convex side

UNLABELLED A deviated nose is the result of a set of anatomical abnormalities, and for this reason there are many methods for correcting such defects. Therefore we should not use only one single method in all cases of nasal deformities. AIM In this prospective study we propose a new method using a spreader graft on the convex side of the deviated nose. METHODS We performed rhinoplasty in six patients by inserting a spreader graft in the convex side of the deviated nose and followed them for two years. RESULTS All six patients presented an improvement in the external appearance of their noses. CONCLUSIONS This study showed that in some particular cases, the spreader graft technique can be used successfully to correct deviated noses.