Thymic stromal lymphopoietin (TSLP), an epithelial upstream cytokine, initiates production of type 2 cytokines with eosinophilia and possibly airway hyperresponsiveness (AHR) in asthma. This study aimed to determine whether tezepelumab (a human monoclonal antibody targeting TSLP) decreases AHR and airway inflammation in patients with symptomatic asthma on maintenance treatment with inhaled corticosteroids.

In this double-blind, placebo-controlled randomised trial (UPSTREAM), adult patients with asthma and AHR to mannitol received either 700 mg tezepelumab or placebo intravenously at 4-week intervals for 12 weeks. AHR to mannitol was assessed and bronchoscopy was performed at baseline and after 12 weeks. The primary outcome was the change in AHR from baseline to week 12 and secondary outcomes were changes in airway inflammation.

40 patients were randomised to receive either tezepelumab (n=20) or placebo (n=20). The mean change in provoking dose of mannitol causing a 15% reduction in forced expiratory volume in 1 s (PD₁₅) with tezepelumab was 1.9 (95% CI 1.2–2.5) versus 1.0 (95% CI 0.3–1.6) doubling doses with placebo (p=0.06). Nine (45%) tezepelumab and three (16%) placebo patients had a negative PD₁₅ test at week 12 (p=0.04). Airway tissue and bronchoalveolar lavage (BAL) eosinophil levels decreased by 74% (95% CI –53– –86%) and 75% (95% CI –53– –86%), respectively, with tezepelumab compared with an increase of 28% (95% CI –39–270%) and a decrease of 7% (95% CI –49–72%), respectively, with placebo (p=0.004 and p=0.01).

Inhibiting TSLP signalling with tezepelumab reduced the proportion of patients with AHR and decreased eosinophilic inflammation in BAL and airway tissue.

胸腺基质淋巴细胞生成素 (TSLP) 是一种上皮上游细胞因子，可启动 2 型细胞因子的产生，伴有嗜酸性粒细胞增多和哮喘中可能的气道高反应性 (AHR)。本研究旨在确定 tezepelumab（一种针对 TSLP 的人单克隆抗体）是否能降低使用吸入性皮质类固醇维持治疗的症状性哮喘患者的 AHR 和气道炎症。

在这项双盲、安慰剂对照随机试验 (UPSTREAM) 中，患有哮喘和 AHR 甘露醇的成年患者接受 700 mg tezepelumab 或安慰剂静脉注射，间隔 4 周，持续 12 周。评估了甘露醇的 AHR，并在基线和 12 周后进行了支气管镜检查。主要结果是 AHR 从基线到第 12 周的变化，次要结果是气道炎症的变化。

40 名患者被随机分配接受 tezepelumab (n=20) 或安慰剂 (n=20)。使用 tezepelumab导致 1 秒内用力呼气量减少 15% (PD ₁₅ ) 的甘露醇激发剂量的平均变化为 1.9 (95% CI 1.2–2.5) ，而安慰剂加倍剂量为 1.0 (95% CI 0.3–1.6) (p=0.06)。9 名 (45%) tezepelumab 和 3 名 (16%) 安慰剂患者在第 12 周时 PD ₁₅测试为阴性 (p=0.04)。与 tezepelumab 相比，气道组织和支气管肺泡灌洗 (BAL) 嗜酸性粒细胞水平分别降低了 74% (95% CI –53– –86%) 和 75% (95% CI –53– –86%)，而增加了 28 % (95% CI –39–270%) 和减少 7% (95% CI –49–72%)，分别与安慰剂 (p=0.004 和 p=0.01)。

用 tezepelumab 抑制 TSLP 信号传导可降低 AHR 患者的比例，并减少 BAL 和气道组织中的嗜酸性粒细胞炎症。