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      Association of Specific Immunoglobulin E to Staphylococcal Enterotoxin with Airway Hyperresponsiveness in Asthma Patients

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          Abstract

          Background

          Specific immunoglobulin E (IgE) sensitization to staphylococcal enterotoxin (SE) has been recently considered to be related to allergic disease, including asthma. Despite studies on specific IgE (sIgE) to SE and its relationship to asthma diagnosis and severity, the association of sIgE to SE with airway hyperresponsiveness (AHR) remains unclear.

          Methods

          We enrolled 81 asthma patients admitted to the Severance Hospital in Korea from March 1, 2013, to February 28, 2015 and retrospectively reviewed the electronic medical records of the enrolled subjects. The serum levels of sIgE to SE (A/B) of all subjects was measured using the ImmunoCAP 250 (Phadia) system with SE-sIgE positive defined as >0.10 kU/mL.

          Results

          The SE-sIgE level was not significantly correlated with asthma severity (forced expiratory volume in 1 second [FEV 1], FEV 1/forced vital capacity, sputum eosinophils, and serum eosinophils), whereas the SE-sIgE level in patients with positive AHR (mean±standard error of the mean, 0.606±0.273 kU/mL) was significantly higher than that in patients with negative AHR (0.062±0.015 kU/mL, p=0.034). In regression analysis, SE sensitization (sIgE to SE ≥0.010 kU/mL) was a significant risk factor for AHR, after adjustment for age, sex, FEV 1, and sputum eosinophils (odds ratio, 7.090; 95% confidence interval, 1.180–42.600; p=0.032). Prevalence of SE sensitization was higher in patients with allergic rhinitis and non-atopic asthma patients, as compared to patients without allergic rhinitis and atopic asthma patients, respectively, but without statistical significance.

          Conclusion

          SE sensitization is significantly associated with AHR.

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          Most cited references20

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          Role of staphylococcal superantigens in upper airway disease.

          Chronic rhinosinusitis with nasal polyps often represents a chronic severe inflammatory disease of the upper airways and may serve as a model for lower airway diseases such as late-onset intrinsic asthma. Enterotoxins derived from Staphylococcus aureus have been implicated in the pathophysiology of nasal polyps as disease-modifying factors; recent findings using therapeutic proof-of-concept approaches support this hypothesis. Nasal polyps (chronic rhinosinusitis with nasal polyps) are characterized by a T-helper-2 dominated cytokine pattern that includes interleukin-5 and formation of immunoglobulin E. This is in contrast to chronic rhinosinusitis without polyps, which exhibits T-helper-1 biased cytokine release. It is now evident that the cytokine environment is decisive regarding the impact of S. aureus derived enterotoxins, which function as superantigens. S. aureus enterotoxin B further shifts the cytokine pattern in nasal polyps toward T-helper-2 cytokines (increases greater than twofold for interleukin-2, interleukin-4 and interleukin-5), but it disfavours the T-regulatory cytokines interleukin-10 and transforming growth factor-beta1. 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.
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            Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma.

            The role of IgE in patients with severe asthma is not fully understood. We sought to investigate whether IgE to Staphylococcus aureus enterotoxins might be relevant to disease severity in adult asthmatic patients. Specific IgE antibody concentrations in serum against enterotoxins, grass pollen (GP), and house dust mite allergens and total IgE levels were measured in adult cohorts of 69 control subjects, 152 patients with nonsevere asthma, and 166 patients with severe asthma. Severe asthma was defined as inadequately controlled disease despite high-dose inhaled corticosteroids plus at least 2 other controller therapies, including oral steroids. Enterotoxin IgE positivity was significantly greater in patients with severe asthma (59.6%) than in healthy control subjects (13%, P< .001). Twenty-one percent of patients with severe asthma with enterotoxin IgE were considered nonatopic. Logistic regression analyses demonstrated significantly increased risks for enterotoxin IgE-positive subjects to have any asthma (OR, 7.25; 95% CI, 2.7-19.1) or severe asthma (OR, 11.09; 95% CI, 4.1-29.6) versus enterotoxin IgE-negative subjects. The presence of GP or house dust mite IgE antibodies was not associated with either significantly increased risk for asthma or severity. Oral steroid use and hospitalizations were significantly increased in patients with enterotoxin IgE and nonatopic asthma. GP IgE was associated with a higher FEV(1) percent predicted value, and enterotoxin IgE was associated with a lower FEV(1) percent predicted value. Staphylococcal enterotoxin IgE antibodies, but not IgE against inhalant allergens, are risk factors for asthma severity. We hypothesize that the presence of enterotoxin IgE in serum indicates the involvement of staphylococcal superantigens in the pathophysiology of patients with severe asthma. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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              The revised 2014 GINA strategy report: opportunities for change.

              This document reviews a major revision of the Global Initiative for Asthma (GINA) Strategy for Asthma Management and Prevention that was published in 2014. The report aimed not only to update evidence-based recommendations for asthma diagnosis and management but also to innovate through a new format and layout to make its recommendations more clinically relevant and easier to implement.
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                Author and article information

                Journal
                Tuberc Respir Dis (Seoul)
                Tuberc Respir Dis (Seoul)
                TRD
                Tuberculosis and Respiratory Diseases
                The Korean Academy of Tuberculosis and Respiratory Diseases
                1738-3536
                2005-6184
                October 2016
                05 October 2016
                : 79
                : 4
                : 295-301
                Affiliations
                [1 ]Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                [2 ]Department of Internal Medicine, Kunkuk University School of Medicine, Seoul, Korea.
                [3 ]Division of Allergy and Immunology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                Author notes
                Address for correspondence: Hye Jung Park, M.D., Ph.D. Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea. Phone: 82-2-2019-4375, Fax: 82-2-3463-3882, craft7820@ 123456yuhs.ac
                Article
                10.4046/trd.2016.79.4.295
                5077734
                27790282
                c077d8da-a914-4f49-87dd-116648270f2f
                Copyright©2016. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

                It is identical to the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/)

                History
                : 20 April 2016
                : 23 June 2016
                : 09 August 2016
                Categories
                Original Article

                Respiratory medicine
                immunoglobulin e,staphylococcus,enterotoxins,asthma
                Respiratory medicine
                immunoglobulin e, staphylococcus, enterotoxins, asthma

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