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}
}
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 -
