重症支气管哮喘患者辣椒素敏感性与临床预后相关
2020/07/13
摘要
理由：辣椒素咳嗽反射敏感性（C-CS）与哮喘控制不佳相关，但是其与重症哮喘的关系尚不清楚。
目的：确定C-CS对重症哮喘患者的临床作用。
方法：我们自2016年11月至2019年10月共纳入了157例哮喘患者（其中包括122例符合GINA指南第4或5级的重症哮喘患者）。进行辣椒素咳嗽试验同时，进行肺功能测定及生物标志物评估。以诱导至少五次咳嗽所需的辣椒素浓度作为C-CS指标。同时评估ACT评分及合并症。评估ERS/ATS指南中重症哮喘四种临床特征（哮喘控制不佳[ACT评分<20； n = 58]，急性发作次数[≥2/ yr； n = 28]，住院次数[≥1/ yr； n = 17]及气流阻塞[FEV1pred<80％； n = 30]）与生物标志物的相关性。
测量及主要结果：C-CS增高与哮喘控制不佳、频繁发作和住院相关，尤其在无过敏反应的患者中（n = 54）。 同时C-CS与气流阻塞无相关性。多元回归分析显示，C-CS升高（至少引起五次咳嗽的辣椒素浓度≤2.44μM）是哮喘控制不佳及频繁发作的显著风险因素。在一般因素及合并症方面，吸烟情况、糖尿病和慢性鼻炎-鼻窦炎与重症哮喘的临床特征具有相关性（所有P <0.05）。
结论：C-CS升高是重症哮喘的危险因素。本研究表明气道神经功能障碍与非Th2型重症哮喘病理生理学具有相关性。
Increased Capsaicin Sensitivity in Patients With Severe Asthma Is Associated With Worse Clinical Outcome
Yoshihiro Kanemitsu , Kensuke Fukumitsu , Ryota Kurokawa , Norihisa Takeda , Motohiko Suzuki , Jennifer Yap , Hirono Nishiyama , Tomoko Tajiri , Satoshi Fukuda , Takehiro Uemura , Hirotsugu Ohkubo , Ken Maeno , Yutaka Ito , Tetsuya Oguri , Masaya Takemura , Akio Niimi
Abstract
Rationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, although its association with severe asthma remains unknown.
Objectives: To determine the clinical impact of C-CS on severe asthma.
Methods: We prospectively enrolled 157 patients with asthma (including 122 patients with severe asthma who were in step 4 or 5 according to the Global Initiative for Asthma 2015 guidelines) between November 2016 and October 2019. A capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin was adopted as an index of C-CS. An Asthma Control Test and comorbidities were also evaluated. Associations of biomarkers with four clinical features of severe asthma made by the European Respiratory Society/American Thoracic Society guidelines (poor control [Asthma Control Test < 20; n = 58], frequent exacerbations [≥2/yr; n = 28], admissions [≥1/yr; n = 17], and airflow limitation [FEV1% predicted < 80%; n = 30]) were assessed.
Measurements and Main Results: Heightened C-CS was associated with poor asthma control, frequent exacerbations, and admissions, particularly in patients without atopy (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (at least five coughs by capsaicin ≤ 2.44 μM) was a significant risk for poor asthma control and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking status, diabetes mellitus, and chronic rhinosinusitis were associated with clinical features of severe asthma (all P < 0.05).
Conclusions: Heightened C-CS is a risk factor for severe asthma. The present study suggests the association of airway neuronal dysfunction with the pathophysiology of non-type 2 severe asthma.
理由：辣椒素咳嗽反射敏感性（C-CS）与哮喘控制不佳相关，但是其与重症哮喘的关系尚不清楚。
目的：确定C-CS对重症哮喘患者的临床作用。
方法：我们自2016年11月至2019年10月共纳入了157例哮喘患者（其中包括122例符合GINA指南第4或5级的重症哮喘患者）。进行辣椒素咳嗽试验同时，进行肺功能测定及生物标志物评估。以诱导至少五次咳嗽所需的辣椒素浓度作为C-CS指标。同时评估ACT评分及合并症。评估ERS/ATS指南中重症哮喘四种临床特征（哮喘控制不佳[ACT评分<20； n = 58]，急性发作次数[≥2/ yr； n = 28]，住院次数[≥1/ yr； n = 17]及气流阻塞[FEV1pred<80％； n = 30]）与生物标志物的相关性。
测量及主要结果：C-CS增高与哮喘控制不佳、频繁发作和住院相关，尤其在无过敏反应的患者中（n = 54）。 同时C-CS与气流阻塞无相关性。多元回归分析显示，C-CS升高（至少引起五次咳嗽的辣椒素浓度≤2.44μM）是哮喘控制不佳及频繁发作的显著风险因素。在一般因素及合并症方面，吸烟情况、糖尿病和慢性鼻炎-鼻窦炎与重症哮喘的临床特征具有相关性（所有P <0.05）。
结论：C-CS升高是重症哮喘的危险因素。本研究表明气道神经功能障碍与非Th2型重症哮喘病理生理学具有相关性。
（中日友好医院呼吸与危重症医学科 张鑫 翻译 林江涛 审校）
（Am J Respir Crit Care Med. 2020 May 1;201(9):1068-1077.）
（Am J Respir Crit Care Med. 2020 May 1;201(9):1068-1077.）
Increased Capsaicin Sensitivity in Patients With Severe Asthma Is Associated With Worse Clinical Outcome
Yoshihiro Kanemitsu , Kensuke Fukumitsu , Ryota Kurokawa , Norihisa Takeda , Motohiko Suzuki , Jennifer Yap , Hirono Nishiyama , Tomoko Tajiri , Satoshi Fukuda , Takehiro Uemura , Hirotsugu Ohkubo , Ken Maeno , Yutaka Ito , Tetsuya Oguri , Masaya Takemura , Akio Niimi
Abstract
Rationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, although its association with severe asthma remains unknown.
Objectives: To determine the clinical impact of C-CS on severe asthma.
Methods: We prospectively enrolled 157 patients with asthma (including 122 patients with severe asthma who were in step 4 or 5 according to the Global Initiative for Asthma 2015 guidelines) between November 2016 and October 2019. A capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin was adopted as an index of C-CS. An Asthma Control Test and comorbidities were also evaluated. Associations of biomarkers with four clinical features of severe asthma made by the European Respiratory Society/American Thoracic Society guidelines (poor control [Asthma Control Test < 20; n = 58], frequent exacerbations [≥2/yr; n = 28], admissions [≥1/yr; n = 17], and airflow limitation [FEV1% predicted < 80%; n = 30]) were assessed.
Measurements and Main Results: Heightened C-CS was associated with poor asthma control, frequent exacerbations, and admissions, particularly in patients without atopy (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (at least five coughs by capsaicin ≤ 2.44 μM) was a significant risk for poor asthma control and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking status, diabetes mellitus, and chronic rhinosinusitis were associated with clinical features of severe asthma (all P < 0.05).
Conclusions: Heightened C-CS is a risk factor for severe asthma. The present study suggests the association of airway neuronal dysfunction with the pathophysiology of non-type 2 severe asthma.
上一篇：
控制良好的哮喘降级治疗期间作为哮喘发作预测因子的2型气道炎症生物标志物：长效β受体激动剂降级研究（LASST）
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基于人群的病例发现以确诊未诊断为哮喘或COPD的患者
