奥马珠单抗治疗“阿司匹林加重性呼吸系统疾病”的阿司匹林过敏及白三烯产量过剩：一个随机对照试验
2020/11/17
摘要：
背景：阿司匹林加重性呼吸系统疾病以及严重的哮喘，非甾体类抗炎药过敏、鼻息肉及白三烯产量过剩为特征。系统性使用糖皮质激素疗法不能完全性抑制终生的阿司匹林过敏。奥马珠单抗对阿司匹林加重性呼吸系统疾病的有效性尚未在随机试验中得到研究。
目的：本研究旨在使用一种随机设计在阿司匹林加重性呼吸疾病患者中评估奥马珠单抗拮抗口服阿司匹林激发试验期间的阿司匹林过敏、白三烯E4产生过量及症状的有效性。
方法：2015年8月至2016年12月期间，我们在Sagamihara国立医院进行一个单中心、双盲、随机、安慰剂对照的交叉试验。根据系统性阿司匹林激发试验被诊断为阿司匹林加重性呼吸系统疾病特应性患者（20-79岁）被随机（1:1）分配到为期3个月的奥马珠单抗治疗组或安慰剂治疗组，随后经历大于18周的洗脱期（交叉设计）。主要终点为阿司匹林口服剂激发实验期间，意向治疗人群的尿白三烯E4浓度的对数水平-时间变化曲线的曲线下面积差值。
检测及主要结果：16名患者完成了本研究，并且被纳入到分析中。奥马珠单抗治疗阶段的“阿司匹林口服剂激发期间的尿白三烯E4浓度的对数水平-时间曲线的曲线下面积”明显比安慰剂治疗阶段更低（（51.1[44.5-59.8] vs80.8[65.4-87.8]）;P＜0.001）。在奥马珠单抗治疗阶段，当阿司匹林累积剂量高达930mg时，16名患者中有10名（62.5%）患者发生口服阿司匹林耐受（P＜0.001）。
结论：奥马珠单抗能抑制口服阿司匹林激发试验期间的尿白三烯E4产生过量及上/下呼吸道症状，进而导致62.5%阿司匹林加重性呼吸系统疾病患者耐受阿司匹林。
Omalizumab for Aspirin Hypersensitivity and Leukotriene Overproduction in Aspirin-exacerbated Respiratory Disease. A Randomized Controlled Trial
Hiroaki Hayashi , Yuma Fukutomi , Chihiro Mitsui , Keiichi Kajiwara, Kentaro Watai , Yosuke Kamide, Yuto Nakamura Yuto Hamada , Yasuhiro Tomita , Kiyoshi Sekiya , Takahiro Tsuburai , Kenji Izuhara , Keiko Wakahara , Naozumi Hashimoto , Yoshinori Hasegawa , Masami Taniguchi
Abstract
Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner.
Objectives: To evaluate omalizumab efficacy against aspirin hypersensitivity, leukotriene E4 overproduction, and symptoms during an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design.
Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20-79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a >18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an oral aspirin challenge.
Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5-59.8]) than in the placebo phase (80.8 [interquartile range, 65.4-87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001).
Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.
背景：阿司匹林加重性呼吸系统疾病以及严重的哮喘，非甾体类抗炎药过敏、鼻息肉及白三烯产量过剩为特征。系统性使用糖皮质激素疗法不能完全性抑制终生的阿司匹林过敏。奥马珠单抗对阿司匹林加重性呼吸系统疾病的有效性尚未在随机试验中得到研究。
目的：本研究旨在使用一种随机设计在阿司匹林加重性呼吸疾病患者中评估奥马珠单抗拮抗口服阿司匹林激发试验期间的阿司匹林过敏、白三烯E4产生过量及症状的有效性。
方法：2015年8月至2016年12月期间，我们在Sagamihara国立医院进行一个单中心、双盲、随机、安慰剂对照的交叉试验。根据系统性阿司匹林激发试验被诊断为阿司匹林加重性呼吸系统疾病特应性患者（20-79岁）被随机（1:1）分配到为期3个月的奥马珠单抗治疗组或安慰剂治疗组，随后经历大于18周的洗脱期（交叉设计）。主要终点为阿司匹林口服剂激发实验期间，意向治疗人群的尿白三烯E4浓度的对数水平-时间变化曲线的曲线下面积差值。
检测及主要结果：16名患者完成了本研究，并且被纳入到分析中。奥马珠单抗治疗阶段的“阿司匹林口服剂激发期间的尿白三烯E4浓度的对数水平-时间曲线的曲线下面积”明显比安慰剂治疗阶段更低（（51.1[44.5-59.8] vs80.8[65.4-87.8]）;P＜0.001）。在奥马珠单抗治疗阶段，当阿司匹林累积剂量高达930mg时，16名患者中有10名（62.5%）患者发生口服阿司匹林耐受（P＜0.001）。
结论：奥马珠单抗能抑制口服阿司匹林激发试验期间的尿白三烯E4产生过量及上/下呼吸道症状，进而导致62.5%阿司匹林加重性呼吸系统疾病患者耐受阿司匹林。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Am J Respir Crit Care Med. 2020 Jun 15;201(12):1488-1498.doi: 10.1164/rccm.201906-1215OC.)
(Am J Respir Crit Care Med. 2020 Jun 15;201(12):1488-1498.doi: 10.1164/rccm.201906-1215OC.)
Omalizumab for Aspirin Hypersensitivity and Leukotriene Overproduction in Aspirin-exacerbated Respiratory Disease. A Randomized Controlled Trial
Hiroaki Hayashi , Yuma Fukutomi , Chihiro Mitsui , Keiichi Kajiwara, Kentaro Watai , Yosuke Kamide, Yuto Nakamura Yuto Hamada , Yasuhiro Tomita , Kiyoshi Sekiya , Takahiro Tsuburai , Kenji Izuhara , Keiko Wakahara , Naozumi Hashimoto , Yoshinori Hasegawa , Masami Taniguchi
Abstract
Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner.
Objectives: To evaluate omalizumab efficacy against aspirin hypersensitivity, leukotriene E4 overproduction, and symptoms during an oral aspirin challenge in patients with aspirin-exacerbated respiratory disease using a randomized design.
Methods: We performed a double-blind, randomized, crossover, placebo-controlled, single-center study at Sagamihara National Hospital between August 2015 and December 2016. Atopic patients (20-79 yr old) with aspirin-exacerbated respiratory disease diagnosed by systemic aspirin challenge were randomized (1:1) to a 3-month treatment with omalizumab or placebo, followed by a >18-week washout period (crossover design). The primary endpoint was the difference in area under logarithm level of urinary leukotriene E4 concentration versus time curve in the intent-to-treat population during an oral aspirin challenge.
Measurements and Main Results: Sixteen patients completed the study and were included in the analysis. The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5-59.8]) than in the placebo phase (80.8 [interquartile range, 65.4-87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001).
Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.
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中重度哮喘中过敏性，嗜酸性粒细胞和2型炎症亚型的重叠
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气候因素和空气质量指数之间的相互作用改善儿童哮喘自我管理
