Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomised controlled trial.
Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomised controlled trial.
复制标题
作者：
在一项2期研究中，在辅助性T细胞2型（CRTH 2）拮抗剂timapiprant上表达的化学引诱物受体同源分子改善了肺功能和哮喘控制，有证据表明急性发作减少。我们的目的是评估是否替马匹纶减弱或预防实验性鼻病毒（RV）感染引起的哮喘急性发作。我们进一步假设，替马匹纶将抑制RV诱导的2型炎症，从而改善抗病毒免疫应答。特应性哮喘患者部分控制维持吸入糖皮质激素被随机分配到timapiprant（n=22）或安慰剂（n=22）和挑战与RV-A16 3周后。主要终点是感染后14天内的累积下呼吸道症状评分。在RV-A16感染前和感染期间，对上呼吸道症状、肺功能测定、气道高反应性、呼出气一氧化氮、上呼吸道和下呼吸道样本中的RV-A16病毒载量和可溶性介质以及支气管活检中的CRTH 2染色进行了额外评估。6例受试者中止研究，8例未感染;在16例替马匹纶治疗和14例安慰剂治疗的成功感染受试者中评估了结局。治疗组之间的临床加重严重程度（包括第0-14天的累积下呼吸道症状评分）无差异（差异3.0（95% CI-29.0至17.0），p=0.78）、病毒载量、抗病毒免疫应答或RV-A16诱导的气道炎症（支气管活检除外），其中在安慰剂治疗组而不是替马匹纶治疗组中，在RV-A16感染期间CRTH 2染色增加。Timapiprant具有良好的安全性，没有死亡、严重不良事件或药物相关的停药。在部分控制的哮喘患者中，替马匹纶治疗对RV-A16感染引起的临床病理变化影响不大。
The chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (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 hypothesised that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses. Atopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomised to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 3 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. Six subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant-treated 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-treated but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events or drug-related withdrawals. Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.
登录
查看更多内容
影响因子：
3.2
作者：
Del Vecchio AM;Branigan PJ;Barnathan ES;Flavin SK;Silkoff PE;Turner RB
通讯作者：
Turner RB
影响因子：
4.6
作者：
Mutalithas K;Guillen C;Day C;Brightling CE;Pavord ID;Wardlaw AJ
通讯作者：
Wardlaw AJ
影响因子：
3.2
作者：
Hall, Ian P.;Fowler, Andrew V.;Sutherland, E. Rand
通讯作者：
Sutherland, E. Rand
DOI：
10.1084/jem.193.2.255
发表时间：
2001-01-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hirai H;Tanaka K;Yoshie O;Ogawa K;Kenmotsu K;Takamori Y;Ichimasa M;Sugamura K;Nakamura M;Takano S;Nagata K
通讯作者：
Nagata K
影响因子：
14.2
作者：
Fajt, Merritt L.;Gelhaus, Stacy L.;Freeman, Bruce;Uvalle, Crystal E.;Trudeau, John B.;Holguin, Fernando;Wenzel, Sally E.
通讯作者：
Wenzel, Sally E.