Imperial College London
Alternate

DrMichaelEdwards

Faculty of Medicine, National Heart & Lung Institute

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 5291michael.edwards

 
 
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Location

 

346Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Farne:2022:10.1136/thoraxjnl-2021-217429,
author = {Farne, H and Glanville, N and Johnson, N and Kebadze, T and Aniscenko, J and Regis, E and Zhu, J and Trujillo-Torralbo, M-B and Kon, OM and Mallia, P and Prevost, A and Edwards, M and Johnston, S and Singanayagam, A and Jackson, D},
doi = {10.1136/thoraxjnl-2021-217429},
journal = {Thorax},
pages = {950--959},
title = {Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomized controlled trial},
url = {http://dx.doi.org/10.1136/thoraxjnl-2021-217429},
volume = {77},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background and aimsThe 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.MethodsAtopic 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.ResultsSix 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.ConclusionTimapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.
AU  - Farne,H
AU  - Glanville,N
AU  - Johnson,N
AU  - Kebadze,T
AU  - Aniscenko,J
AU  - Regis,E
AU  - Zhu,J
AU  - Trujillo-Torralbo,M-B
AU  - Kon,OM
AU  - Mallia,P
AU  - Prevost,A
AU  - Edwards,M
AU  - Johnston,S
AU  - Singanayagam,A
AU  - Jackson,D
DO  - 10.1136/thoraxjnl-2021-217429
EP  - 959
PY  - 2022///
SN  - 0040-6376
SP  - 950
TI  - Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomized controlled trial
T2  - Thorax
UR  - http://dx.doi.org/10.1136/thoraxjnl-2021-217429
UR  - https://thorax.bmj.com/content/early/2021/10/28/thoraxjnl-2021-217429
UR  - http://hdl.handle.net/10044/1/92518
VL  - 77
ER  -
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