Background and aims 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. Methods 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. Results 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. Conclusion Timapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma. Data are available upon reasonable request. Anonymised data are available on reasonable request from the corresponding author, Professor Sebastian Johnston.

中文翻译：

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CRTH2 拮抗作用对哮喘实验性鼻病毒感染反应的影响：一项随机对照试验

背景和目的 在 2 型辅助性 T 细胞 (CRTH2) 拮抗剂 timapirant 上表达的化学引诱物受体同源分子在一项 2 期研究中改善了肺功能和哮喘控制，有证据表明加重减少。我们的目的是评估 timapirant 是否减轻或预防了由实验性鼻病毒 (RV) 感染引起的哮喘恶化。我们进一步假设 timapirant 会抑制 RV 诱导的 2 型炎症，从而改善抗病毒免疫反应。方法 部分控制哮喘并维持吸入皮质类固醇的特应性患者被随机分配至 timapirant (n=22) 或安慰剂 (n=22)，并在 3 周后接受 RV-A16 激发。主要终点是感染后 14 天内的累积下呼吸道症状评分。上呼吸道症状，肺活量测定，在 RV-A16 感染之前和期间，还评估了气道高反应性、呼出的一氧化氮、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 CRTH2 染色。结果6名受试者中止研究，8名未感染；结果在 16 名接受 timapirant 治疗和 14 名接受安慰剂治疗且成功感染的受试者中进行了评估。临床恶化严重程度在治疗组之间没有差异，包括第 0-14 天的累积下呼吸道症状评分（差异 3.0（95% CI -29.0 至 17.0），p=0.78）、病毒载量、抗病毒免疫反应或 RV-A16 -诱导的气道炎症，而不是在支气管活检中，其中 CRTH2 染色在 RV-A16 感染期间在安慰剂治疗组而非 timapirant 治疗组中增加。Timapiprant 具有良好的安全性，没有死亡、严重不良事件或与药物相关的退出。结论 替马匹兰治疗对RV-A16感染引起部分控制的哮喘患者的临床病理变化影响不大。可根据合理要求提供数据。匿名数据可应相应作者 Sebastian Johnston 教授的合理要求提供。