دورية أكاديمية
Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomized controlled trial
| العنوان: | Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomized controlled trial |
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| المؤلفون: | Farne, H, Glanville, N, Johnson, N, Kebadze, T, Aniscenko, J, Regis, E, Zhu, J, Trujillo-Torralbo, M-B, Kon, OM, Mallia, P, Prevost, A, Edwards, M, Johnston, S, Singanayagam, A, Jackson, D |
| المساهمون: | Medical Research Council, Innovate UK |
| المصدر: | 959 ; 950 |
| بيانات النشر: | BMJ Publishing Group |
| سنة النشر: | 2021 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Respiratory System, asthma, viral infection, ADD-ON THERAPY, PROSTAGLANDIN D-2, ALLERGEN CHALLENGE, DOUBLE-BLIND, BI 671800, EFFICACY, EXACERBATIONS, INFLAMMATION, PATHWAY, CELLS, 1103 Clinical Sciences |
| الوصف: | Background and aims The CRTH2 antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesized that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses. Methods Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomized to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 three weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post-infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection. Results Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant- and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), P=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo- but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events, or drug-related withdrawals. Conclusion Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0040-6376 |
| العلاقة: | Thorax; http://hdl.handle.net/10044/1/92518Test; MR/M025330/1 |
| DOI: | 10.1136/thoraxjnl-2021-217429 |
| الإتاحة: | https://doi.org/10.1136/thoraxjnl-2021-217429Test http://hdl.handle.net/10044/1/92518Test |
| حقوق: | © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0Test/ This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0Test/. ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.AF829714 |
| قاعدة البيانات: | BASE |
| تدمد: | 00406376 |
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| DOI: | 10.1136/thoraxjnl-2021-217429 |