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      Aspirin Sensitivity and Chronic Rhinosinusitis with Polyps: A Fatal Combination

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          Abstract

          Aspirin-exacerbated respiratory disease (AERD) refers to aspirin sensitivity, chronic rhinosinusitis (CRS), nasal polyposis, asthma, eosinophil inflammation in the upper and lower airways, urticaria, angioedema, and anaphylaxis following the ingestion of NSAIDs. Epidemiologic and pathophysiological links between these diseases are established. The precise pathogenesis remains less defined, even though there is some progress in the understanding of several molecular mechanisms. Nevertheless, these combinations of diseases in patients classified by AERD constitute a fatal combination and may be difficult to treat with standard medical and surgical interventions. This paper reviews in brief the epidemiology, clinical features, diagnosis, molecular pathogenesis, and specific therapies of patients classified by AERD and postulates future attempts to gain new insights into this disease.

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          Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.

          Philippe Gevaert, Nicholas van Bruaene, Tom Cattaert … (2011)
          Approximately 85% of nasal polyps (NPs) in white subjects are characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic differentiation and survival. We sought to investigate the therapeutic potential of inhibiting IL-5 with a humanized mAb as treatment for severe nasal polyposis. Thirty patients with severe nasal polyposis (grade 3 or 4 or recurrent after surgery) refractory to corticosteroid therapy were randomized in a double-blind fashion to receive either 2 single intravenous injections (28 days apart) of 750 mg of mepolizumab (n = 20) or placebo (n = 10). Change from baseline in NP score was assessed monthly until 1 month after the last dose (week 8). Computed tomographic scans were also performed at week 8. Twelve of 20 patients receiving mepolizumab had a significantly improved NP score and computed tomographic scan score compared with 1 of 10 patients receiving placebo at week 8 versus baseline. Mepolizumab achieved a statistically significant reduction in NP size for at least 1 month after dosing in 12 of 20 patients. IL-5 inhibition is a potential novel therapeutic approach in patients with severe eosinophilic nasal polyposis. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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            Total and specific IgE in nasal polyps is related to local eosinophilic inflammation.

            G Holtappels, Robrecht van der Wel, P Gevaert … (2001)
            Nasal polyps (NPs) are characterized by eosinophilic inflammation and often coexist with asthma. However, the role of atopy and IgE in NP pathogenesis is unclear. We sought to determine whether there is an association between total and specific IgE to a variety of allergens in polyp and nonpolyp tissue and markers of eosinophilic inflammation or skin test results. Homogenates were prepared from nasal tissue of 20 patients with NPs and 20 patients without NPs and analyzed for concentrations of IL-5, IL-4, eotaxin, leukotriene (LT) C4/D4/E4, sCD23, and histamine (ELISA). Eosinophil cationic protein (ECP), tryptase, and total and specific IgE for inhalant allergens and Staphylococcus aureus enterotoxins were measured (ImmunoCAP). The concentrations of total IgE, IL-5, eotaxin, ECP, LTC4/D4/E4, and sCD23 were significantly higher in NP tissue compared with nonpolyp tissue. Total IgE was significantly correlated to IL-5, ECP, LTC4/D4/E4, and sCD23 and to the number of eosinophils in NPs. On the basis of the presence of specific IgE antibodies in tissue, 3 NP groups were defined. NP group 1 demonstrated no measurable specific IgE, and NP group 2 selected specific IgE. The third group demonstrated a multiclonal specific IgE, including IgE to S aureus enterotoxins, a high total IgE level, and a high prevalence of asthma. These studies suggest that there is an association between increased levels of total IgE, specific IgE, and eosinophilic inflammation in NPs, which may be of relevance in the pathophysiology of nasal polyposis. Similarly, the presence of specific IgE to staphylococcal enterotoxins A and B also points to a possible role of bacterial superantigens.
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              Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.

              Paul van Helden, Heinz Stammberger, Jan Tavernier … (2006)
              Chronic rhinosinusitis with nasal polyps is characterized by an eosinophilic inflammation and high IL-5 levels. Antagonizing the effect of IL-5 is a potential new treatment strategy in patients with nasal polyps. In a double-blind, placebo-controlled, randomized, 2-center safety and pharmacokinetic study, 24 subjects with bilateral nasal polyps were randomized to receive a single intravenous infusion of reslizumab, a humanized anti-human IL-5 mAb, at 3 mg/kg or 1 mg/kg or placebo. We evaluated the safety and pharmacokinetics of reslizumab, and biologic activity was assessed by means of endoscopic evaluation of polyp size, symptoms, peripheral eosinophil counts, peripheral and local IL-5 levels, eotaxin levels, and eosinophil cationic protein levels. We demonstrated that a single injection of reslizumab up to 3 mg/kg is safe and well tolerated. Blood eosinophil numbers and concentrations of eosinophil cationic protein were reduced up to 8 weeks after treatment in serum and nasal secretions. Individual nasal polyp scores improved only in half of the treated patients for 4 weeks. Responders had increased IL-5 concentrations in nasal secretions at baseline compared with nonresponders, and logistic regression analysis revealed that increased nasal IL-5 levels (>40 pg/mL) predict the response to anti-IL-5 treatment. A single injection of anti-IL-5 reduces the size of nasal polyps for 4 weeks in half of the patients, and nasal IL-5 levels predict the response to anti-IL-5 treatment. Intravenous administration of a humanized anti-human IL-5 mAb is safe and reduces the size of nasal polyps in half of the patients.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Allergy (Cairo)
                Journal ID (iso-abbrev): J Allergy (Cairo)
                Journal ID (publisher-id): JA
                Title: Journal of Allergy
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 1687-9783
                ISSN (Electronic): 1687-9791
                Publication date (Print): 2012
                Publication date (Electronic): 14 August 2012
                Volume: 2012
                Electronic Location Identifier: 817910
                Affiliations
                1Departments of Otorhinolaryngology, Head and Neck Surgery, and Plastic Surgery, Asklepios Medical School, Lohmuehlenstraß 5, 20099 Hamburg, Germany
                2Allergy and Intolerance Laboratory, Medical Clinic III, Friedrich-Alexander-University Erlangen-Nuremberg, Glückstraße 4a, 91054 Erlangen, Germany
                Author notes

                Academic Editor: Luis M. Teran

                Article
                DOI: 10.1155/2012/817910
                PMC ID: 3425836
                PubMed ID: 22927869
                SO-VID: 8958f5c3-57a1-47f9-ab20-f5ee917e03a5
                Copyright © Copyright © 2012 Hendrik Graefe et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 28 February 2012
                Date revision received : 16 May 2012
                Date accepted : 13 June 2012
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Immunology
                Data availability:
                ScienceOpen disciplines: Immunology

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