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      Differential expression of innate immunity genes in chronic rhinosinusitis

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          Abstract

          Background:

          Prior research has identified several components of the innate immune system that may play a significant role in chronic rhinosinusitis (CRS), but the role of innate immunity in patients with CRS is poorly understood. The objective of this study was to determine differential expression of innate immunity genes in the mucosa of patients with CRS with nasal polyposis (CRSwNP) and CRS without nasal polyposis (CRSsNP) when compared with controls.

          Methods:

          Control patients (n = 9) and patients with CRS (n = 36) who failed medical management were prospectively enrolled. Ethmoid mucosa samples were harvested during surgery and quantitative real-time polymerase chain reaction was used to determine levels of mRNA expression of Toll-like receptor (TLR) 2 and TLR9 and interleukin-22 receptor (IL-22R). The average change in crossover threshold and fold change were calculated and differences between controls, CRSwNP, and CRSsNP were compared. Statistical analysis was performed using the Kruskall–Wallis and adjusted Mann–Whitney U tests.

          Results:

          Patients with CRSwNP (n = 16) and CRSsNP (n = 20) showed lower mean expression of TLR2 (p < 0.05) compared with controls. Patients with CRSsNP showed significantly higher mean expression of IL-22R (p < 0.05) than controls.

          Conclusion:

          The sinonasal innate immune system may have a significant role in the development of CRS. We found differential expression of innate immune mediators between patients with and without nasal polyposis. These results provide further evidence of disruption of innate immunity at the mucosal level in CRS and highlight differences between polyp- and non–polyp-forming CRS phenotypes at the molecular level. In addition to our knowledge, this is the first report of altered IL-22R expression in CRSsNP patients. This study was a part of the clinical trial NCT01332136 registered in www.clinicaltrials.gov .

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          Most cited references21

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          Differentiation of chronic sinus diseases by measurement of inflammatory mediators.

          Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases. Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic fibrosis patients (CF-NP), eight CRS subjects without polyps, and nine control patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and tissue homogenates were assayed for eotaxin, interleukin (IL)-1beta, IL-2sRalpha, IL-5, interferon (IFN)-gamma, IL-8, transforming growth factor (TGF)-beta1, tumor necrosis factor-alpha, and MPO by enzyme-linked immunosorbent assay or UNICAP system. Nasal polyp and CF-NP showed increased numbers and activation of T cells, while only NP displayed an increase in plasma cells. Nasal polyp had significantly higher levels of eosinophilic markers [eosinophils, eotaxin, and eosinophil cationic protein (ECP)] compared with CRS, controls and CF-NP. Chronic rhinosinusitis was characterized by a Th1 polarization with high levels of IFN-gamma and TGF-beta, while NP showed a Th2 polarization with high IL-5 and immunoglobulin (Ig) E concentrations. Nasal polyp and CF-NP were discriminated by edema from CRS and controls, with CF-NP displaying a very prominent neutrophilic inflammation. Based on cellular and mediator profiles, we suggest that CRS, NP, and CF-NP are distinct disease entities within the group of chronic sinus diseases.
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            Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease.

            Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by the accumulation of inflammatory cells; however, an eosinophil predominance is seen in white (Belgian), but not Asian (south Chinese), patients with polyps. We sought to investigate the association of inflammatory cell predominance with regulatory T-cell and T-effector cell patterns. Nasal mucosal tissue was obtained from 26 consecutive Belgian patients with CRSwNP and 21 Belgian control subjects and 29 south Chinese patients with CRSwNP and 29 south Chinese control subjects, who all underwent phenotyping, including nasal endoscopy and computed tomographic scanning. Tissues were investigated for granulocytes and their products and T-effector/regulatory T cells and related cytokines. Both CRSwNP groups were comparable in terms of symptoms, computed tomographic scan results, and nasal endoscopy results, but asthma comorbidity was significantly higher in white patients. Tissue from white patients with CRSwNP was characterized by eosinophilic inflammation (eosinophil cationic protein/myeloperoxidase ratio > 2), whereas samples from Asian patients were biased toward neutrophilic inflammation (eosinophil cationic protein/myeloperoxidase ratio = 0.25). Both CRSwNP groups demonstrated significant upregulation of the T-cell activation marker soluble IL-2 receptor alpha and significant downregulation of Foxp3 expression and TGF-beta1 protein content versus their respective control groups. However, whereas white patients displayed a significant increase in T(H)2 cytokine and related marker levels versus control subjects and versus Asian patients, the latter showed a T(H)1/T(H)17 cell pattern versus control tissue. Nasal polyps (CRSwNP) from white and Asian patients are both characterized by T-cell activation and impaired regulatory T-cell function; however, T-effector cells in the samples from white patients were T(H)2-biased, whereas samples from their Asian counterparts demonstrated a T(H)1/T(H)17 polarization.
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              Clinical practice guideline: adult sinusitis.

              This guideline provides evidence-based recommendations on managing sinusitis, defined as symptomatic inflammation of the paranasal sinuses. Sinusitis affects 1 in 7 adults in the United States, resulting in about 31 million individuals diagnosed each year. Since sinusitis almost always involves the nasal cavity, the term rhinosinusitis is preferred. The guideline target patient is aged 18 years or older with uncomplicated rhinosinusitis, evaluated in any setting in which an adult with rhinosinusitis would be identified, monitored, or managed. This guideline is intended for all clinicians who are likely to diagnose and manage adults with sinusitis. The primary purpose of this guideline is to improve diagnostic accuracy for adult rhinosinusitis, reduce inappropriate antibiotic use, reduce inappropriate use of radiographic imaging, and promote appropriate use of ancillary tests that include nasal endoscopy, computed tomography, and testing for allergy and immune function. In creating this guideline the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of allergy, emergency medicine, family medicine, health insurance, immunology, infectious disease, internal medicine, medical informatics, nursing, otolaryngology-head and neck surgery, pulmonology, and radiology. The panel made strong recommendations that 1) clinicians should distinguish presumed acute bacterial rhinosinusitis (ABRS) from acute rhinosinusitis caused by viral upper respiratory infections and noninfectious conditions, and a clinician should diagnose ABRS when (a) symptoms or signs of acute rhinosinusitis are present 10 days or more beyond the onset of upper respiratory symptoms, or (b) symptoms or signs of acute rhinosinusitis worsen within 10 days after an initial improvement (double worsening), and 2) the management of ABRS should include an assessment of pain, with analgesic treatment based on the severity of pain. The panel made a recommendation against radiographic imaging for patients who meet diagnostic criteria for acute rhinosinusitis, unless a complication or alternative diagnosis is suspected. The panel made recommendations that 1) if a decision is made to treat ABRS with an antibiotic agent, the clinician should prescribe amoxicillin as first-line therapy for most adults, 2) if the patient worsens or fails to improve with the initial management option by 7 days, the clinician should reassess the patient to confirm ABRS, exclude other causes of illness, and detect complications, 3) clinicians should distinguish chronic rhinosinusitis (CRS) and recurrent acute rhinosinusitis from isolated episodes of ABRS and other causes of sinonasal symptoms, 4) clinicians should assess the patient with CRS or recurrent acute rhinosinusitis for factors that modify management, such as allergic rhinitis, cystic fibrosis, immunocompromised state, ciliary dyskinesia, and anatomic variation, 5) the clinician should corroborate a diagnosis and/or investigate for underlying causes of CRS and recurrent acute rhinosinusitis, 6) the clinician should obtain computed tomography of the paranasal sinuses in diagnosing or evaluating a patient with CRS or recurrent acute rhinosinusitis, and 7) clinicians should educate/counsel patients with CRS or recurrent acute rhinosinusitis regarding control measures. The panel offered as options that 1) clinicians may prescribe symptomatic relief in managing viral rhinosinusitis, 2) clinicians may prescribe symptomatic relief in managing ABRS, 3) observation without use of antibiotics is an option for selected adults with uncomplicated ABRS who have mild illness (mild pain and temperature <38.3 degrees C or 101 degrees F) and assurance of follow-up, 4) the clinician may obtain nasal endoscopy in diagnosing or evaluating a patient with CRS or recurrent acute rhinosinusitis, and 5) the clinician may obtain testing for allergy and immune function in evaluating a patient with CRS or recurrent acute rhinosinusitis. This clinical practice guideline is not intended as a sole source of guidance for managing adults with rhinosinusitis. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.
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                Author and article information

                Journal
                Am J Rhinol Allergy
                Am J Rhinol Allergy
                rhinol
                American Journal of Rhinology & Allergy
                OceanSide Publications, Inc. (Providence, RIUSA )
                1945-8924
                1945-8932
                Sep-Oct 2014
                : 28
                : 5
                : 374-377
                Affiliations
                [1]From the 1Department of Otolaryngology–Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon,
                [2] 2Department of Otolaryngology–Head and Neck Surgery, University of Utah, Salt Lake City, Utah, and
                [3] 3Oregon Hearing Research Center, Department of Otolaryngology–Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon
                Author notes
                Address correspondence to Nathan B. Sautter, M.D., Oregon Health and Science University, Department of Otolaryngology–Head and Neck Surgery, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239 E-mail address: sauttern@ 123456ohsu.edu
                Article
                AJRA502-13
                10.2500/ajra.2014.28.4082
                4151703
                25198021
                6ad6a8c4-9a6b-4346-8552-e3fc9775d751
                Copyright © 2014, OceanSide Publications, Inc., U.S.A.

                This publication is provided under the terms of the Creative Commons Public License ("CCPL" or "License"), in attribution 3.0 unported, further described at http://creativecommons.org/license/by/3.0/legalcode. The work is protected by copyright and/or other applicable law. Any use of the work other then as authorized under this license or copyright law is prohibited

                History
                Categories
                Articles

                Immunology
                chronic rhinosinusitis,chronic rhinosinusitis with nasal polyposis,il-22r,innate immunity,tlr2,tlr9,toll-like receptors

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