噻托溴铵可通过调节咳嗽反射敏感性治疗哮喘顽固性咳嗽：一项随机、平行、开放标签试验
2023/07/21
摘要
背景：本研究团队在之前一项非对照研究中曾报道，噻托溴铵可通过调节辣椒素咳嗽反射敏感性（C-CRS）来缓解吸入糖皮质激素和长效β2受体激动剂（ICS/LABA）难治性哮喘患者的慢性咳嗽。
目的：本研究旨在通过一项随机、平行、开放标签试验确定噻托溴铵对哮喘顽固性咳嗽的镇咳作用。
方法：本研究共纳入58名患有ICS/LABA难治性慢性咳嗽的哮喘患者，并以2:1的比例随机加入噻托溴铵5μg（39名患者）或茶碱400 mg（19名患者），持续4周。患者接受相关检查，包括辣椒素咳嗽激发试验和主观测量，如咳嗽严重程度视觉模拟量表（VAS）。本研究采用C5，即诱发至少5次咳嗽的最低辣椒素浓度，作为C-CRS的指标。本研究通过术后分析确定噻托溴铵应答者的预测因素，结果发现咳嗽严重程度VAS至少改善了15毫米。
结果：本研究共有52名患者（噻托溴铵：38名；茶碱：14名）完成了研究。噻托溴铵和茶碱均能显著改善咳嗽严重程度VAS和咳嗽特异性生活质量。噻托溴铵（而不是茶碱）可显著增加C5，而两组的肺功能均未改变。此外，噻托溴铵组咳嗽严重程度VAS的变化与C5值的变化相关。术后分析显示，在添加噻托溴铵之前，C-CRS升高（C5≤1.22µM）是噻托溴胺应答者的独立预测因素。
结论：噻托溴铵可以通过调节C-CRS来缓解ICS/LBA难治性哮喘的慢性咳嗽。C-CRS升高可预测噻托溴铵对哮喘顽固性咳嗽的反应性。
Tiotropium for refractory cough in asthma via cough reflex sensitivity: A randomized, parallel, open-label trial
Fukumitsu K, Kanemitsu Y, Kurokawa R, Takeda N, Tajiri T, Nishiyama H, Ito K, Inoue Y, Yamamoto S, Mori Y, Fukuda S, Uemura T, Ohkubo H, Maeno K, Ito Y, Oguri T, Takemura M, Niimi A.
Abstract
BACKGROUND:We previously reported in an uncontrolled study that tiotropium alleviated chronic cough in asthma refractory to inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) by modulating capsaicin cough reflex sensitivity (C-CRS).
OBJECTIVE:We sought to determine the antitussive effects of tiotropium for refractory cough in asthma in a randomized, parallel, open-label trial.
METHODS:A total of 58 patients with asthma having chronic cough refractory to ICS/LABA were randomized in a 2:1 ratio to add tiotropium 5 μg (39 patients) or theophylline 400 mg (19 patients) for 4 weeks. Patients underwent workups, including capsaicin cough challenge test and subjective measures such as cough severity visual analog scales (VAS). We adopted C5, the lowest capsaicin concentration to induce at least 5 coughs, as an index of C-CRS. We also performed a posthoc analysis to identify factors predicting tiotropium responders, who found an improvement of at least 15 mm in cough severity VAS.
RESULTS:A total of 52 patients (tiotropium, 38; theophylline, 14) completed the study. Both tiotropium and theophylline significantly improved cough severity VAS and cough-specific quality of life. Tiotropium, but not theophylline, significantly increased C5, whereas pulmonary function did not change in either group. In addition, changes in cough severity VAS correlated with changes in C5 values in the tiotropium group. A posthoc analysis revealed that heightened C-CRS (C5 ≤1.22 µM) before the addition of tiotropium was an independent predictor for tiotropium responders.
CONCLUSIONS:Tiotropium may alleviate chronic cough in asthma refractory to ICS/LABA by modulating C-CRS. Heightened C-CRS may predict responsiveness to tiotropium for refractory cough in asthma.
背景：本研究团队在之前一项非对照研究中曾报道，噻托溴铵可通过调节辣椒素咳嗽反射敏感性（C-CRS）来缓解吸入糖皮质激素和长效β2受体激动剂（ICS/LABA）难治性哮喘患者的慢性咳嗽。
目的：本研究旨在通过一项随机、平行、开放标签试验确定噻托溴铵对哮喘顽固性咳嗽的镇咳作用。
方法：本研究共纳入58名患有ICS/LABA难治性慢性咳嗽的哮喘患者，并以2:1的比例随机加入噻托溴铵5μg（39名患者）或茶碱400 mg（19名患者），持续4周。患者接受相关检查，包括辣椒素咳嗽激发试验和主观测量，如咳嗽严重程度视觉模拟量表（VAS）。本研究采用C5，即诱发至少5次咳嗽的最低辣椒素浓度，作为C-CRS的指标。本研究通过术后分析确定噻托溴铵应答者的预测因素，结果发现咳嗽严重程度VAS至少改善了15毫米。
结果：本研究共有52名患者（噻托溴铵：38名；茶碱：14名）完成了研究。噻托溴铵和茶碱均能显著改善咳嗽严重程度VAS和咳嗽特异性生活质量。噻托溴铵（而不是茶碱）可显著增加C5，而两组的肺功能均未改变。此外，噻托溴铵组咳嗽严重程度VAS的变化与C5值的变化相关。术后分析显示，在添加噻托溴铵之前，C-CRS升高（C5≤1.22µM）是噻托溴胺应答者的独立预测因素。
结论：噻托溴铵可以通过调节C-CRS来缓解ICS/LBA难治性哮喘的慢性咳嗽。C-CRS升高可预测噻托溴铵对哮喘顽固性咳嗽的反应性。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Ann Allergy Asthma Immunol. 2023 Jul;131(1):59-68.e3. doi: 10.1016/j.anai.2023.03.032.)
(Ann Allergy Asthma Immunol. 2023 Jul;131(1):59-68.e3. doi: 10.1016/j.anai.2023.03.032.)
Tiotropium for refractory cough in asthma via cough reflex sensitivity: A randomized, parallel, open-label trial
Fukumitsu K, Kanemitsu Y, Kurokawa R, Takeda N, Tajiri T, Nishiyama H, Ito K, Inoue Y, Yamamoto S, Mori Y, Fukuda S, Uemura T, Ohkubo H, Maeno K, Ito Y, Oguri T, Takemura M, Niimi A.
Abstract
BACKGROUND:We previously reported in an uncontrolled study that tiotropium alleviated chronic cough in asthma refractory to inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) by modulating capsaicin cough reflex sensitivity (C-CRS).
OBJECTIVE:We sought to determine the antitussive effects of tiotropium for refractory cough in asthma in a randomized, parallel, open-label trial.
METHODS:A total of 58 patients with asthma having chronic cough refractory to ICS/LABA were randomized in a 2:1 ratio to add tiotropium 5 μg (39 patients) or theophylline 400 mg (19 patients) for 4 weeks. Patients underwent workups, including capsaicin cough challenge test and subjective measures such as cough severity visual analog scales (VAS). We adopted C5, the lowest capsaicin concentration to induce at least 5 coughs, as an index of C-CRS. We also performed a posthoc analysis to identify factors predicting tiotropium responders, who found an improvement of at least 15 mm in cough severity VAS.
RESULTS:A total of 52 patients (tiotropium, 38; theophylline, 14) completed the study. Both tiotropium and theophylline significantly improved cough severity VAS and cough-specific quality of life. Tiotropium, but not theophylline, significantly increased C5, whereas pulmonary function did not change in either group. In addition, changes in cough severity VAS correlated with changes in C5 values in the tiotropium group. A posthoc analysis revealed that heightened C-CRS (C5 ≤1.22 µM) before the addition of tiotropium was an independent predictor for tiotropium responders.
CONCLUSIONS:Tiotropium may alleviate chronic cough in asthma refractory to ICS/LABA by modulating C-CRS. Heightened C-CRS may predict responsiveness to tiotropium for refractory cough in asthma.
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