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      Using magnetic resonance imaging to quantify the inflammatory response following allergen challenge in allergic rhinitis

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          Abstract

          Current rhinometric and flow assessments measure nasal patency and are often poorly correlated with rhinitis symptoms. To evaluate magnetic resonance imaging (MRI) as a new method to measure inflammatory changes in nasal and sinus mucosa following nasal allergen challenge. A pilot study ( n = 6) determined the optimal technical settings for MRI to measure inflammatory change which were then adopted for the main study. This study was a single blind, placebo‐controlled, three‐way crossover trial in 14 subjects with seasonal allergic rhinitis. Effects of cetirizine, cetirizine and pseudoephedrine (Cet+PE), or placebo on total nasal symptom scores (TNSS), peak nasal inspiratory flow (PNIF), nasal nitric oxide (nNO), acoustic rhinometry, and MRI end points following nasal intranasal allergen challenge were measured. There were significant changes in all parameters after allergen challenge ( P < 0.01), except for nNO. MRI end points were less variable and more consistent than PNIF and acoustic rhinometry in detecting changes after allergen challenge. Total nasal airspace volume was the most sensitive and reproducible MRI measurement, with a mean reduction from −5.37 cm 3 (95%CI −7.35, −3.38; P < 0.001), which was maximal 60 min after allergen challenge. A change of one in TNSS corresponded to a change in MRI volume of −0.57 cm 3. There was an improvement in all parameters (except nNO) in subjects taking Cet+PE compared with placebo, however this did not achieve significance probably because of the small study size (overall analysis P > 0.07; comparison of active versus placebo P > 0.09). MRI provides novel insights into the anatomical inflammatory changes post allergen challenge and provides a new method for assessment of nasal patency and objective measurement of inflammatory responses.

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          Most cited references36

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          Optimisation of grass pollen nasal allergen challenge for assessment of clinical and immunological outcomes.

          Nasal allergen challenge can be used to assess the clinical and immunological aspects of rhinitis due to inhalant allergens. We aimed to develop a reproducible technique for grass pollen nasal allergen challenge and to study biomarkers within nasal secretions. 20 Grass pollen allergic individuals underwent nasal challenges with purified Timothy grass allergen. An initial dose-titration challenge was used to determine dose-response characteristics. Subsequently, volunteers underwent 3 further challenges using individualised threshold doses. Symptom scores, visual analogue scores, and peak nasal inspiratory flow (PNIF) were recorded at baseline and up to 6h after challenge. Nasal secretions were collected at each time point using synthetic filter papers or absorptive polyurethane sponges and analysed for IL-4, -5, -10, -13, IFN-γ, Tryptase and Eosinophil Cationic Protein (ECP). Challenges gave reproducible symptom scores and decreased PNIF. Tryptase levels in nasal fluid peaked at 5 min after challenge and returned to baseline levels at 1h. ECP, IL-5, IL-13 and IL-4 levels were increased from 2-3 h and showed progressive increases to 5-6 h. Sponges proved the superior nasal fluid sampling technique. We have developed a reproducible nasal allergen challenge technique. This may be used as a surrogate clinical endpoint in trials assessing the efficacy of treatments for allergic rhinitis. Tryptase in local nasal secretions is a potential biomarker of the early phase response; ECP and the Th2 cytokines IL-5, -13 and -4 markers of late phase allergic responses. Our model allows correlation between clinical responses and local biomarkers following nasal allergen challenge. Copyright © 2012 Elsevier B.V. All rights reserved.
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            Nitric oxide in upper airways inflammatory diseases.

            In the human respiratory tract, the main production sites of exhaled nitric oxide (NO) are the nose and paranasal sinuses. In the upper airways, NO has been suggested to be involved at different levels with regulatory, protective, defensive or deleterious effects. Therefore, we review some aspects of the origin, metabolism, and functions of NO in the upper airways, together with the role of NO in some upper airways inflammatory diseases. Furthermore, we discuss the recent improvements in nasal NO measurements, which may be useful to better characterize the involvement of the NO produced by nose and paranasal sinuses in upper airways inflammatory diseases such as allergic rhinitis, nasal polyposis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis.
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              Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

              Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.
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                Author and article information

                Journal
                Immun Inflamm Dis
                Immun Inflamm Dis
                10.1002/(ISSN)2050-4527
                IID3
                Immunity, Inflammation and Disease
                John Wiley and Sons Inc. (Hoboken )
                2050-4527
                17 September 2015
                December 2015
                : 3
                : 4 ( doiID: 10.1002/iid3.2015.3.issue-4 )
                : 445-454
                Affiliations
                [ 1 ] Respiratory Clinical Trials LtdLondon W1G 8HUUK
                [ 2 ] Royal National ThroatNose and Ear Hospital London WC1X 8DAUK
                [ 3 ] National Heart and Lung InstituteImperial College London SW3 6LYUK
                Author notes
                [*] [* ] Correspondence

                Dr. Brian Leaker, Respiratory Clinical Trials Ltd, 18‐22 Queen Anne Street, London W1G 8HU, UK. Tel: +44‐0‐207‐034 ‐3301; Fax: +44‐0‐207‐034‐3362; E‐mail: brian.leaker@ 123456qasmc.com

                Article
                IID386
                10.1002/iid3.86
                4693719
                e16f6bbb-5850-46d7-8f0a-12d8ed0203fe
                © 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

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

                History
                : 29 May 2015
                : 18 August 2015
                : 02 September 2015
                Page count
                Pages: 10
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                iid386
                December 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.2 mode:remove_FC converted:22.12.2015

                acoustic rhinometry,allergic rhinitis,mri,nasal allergen challenge

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