重症哮喘患者的辣椒素敏感性增加与临床结果恶化相关
2021/01/13
摘要
原理：辣椒素咳嗽反射敏感性(Capsaicin cough reflex sensitivity，C-CS)与哮喘控制不佳有关，而与重症哮喘的关联尚不清楚。
目标：本研究旨在确定C-CS对重症哮喘的临床影响。
方法：该研究前瞻性纳入了2016年11月至2019年10月之间的157例哮喘患者(包括根据GINA 2015指南在步骤4/5中的122例重症哮喘患者)。进行了辣椒素咳嗽试验，肺功能测定和生物标志物评估。辣椒素诱导至少五声咳嗽所需的浓度(定义为C5)被用作C-CS的指标。还评估了哮喘控制测试(ACT)和合并症。ERS / ATS指南将生物标志物与重症哮喘的4种临床特征相关联[控制不良(ACT <20，n = 58)，频繁发作(≥2/年，n = 28)，入院(≥1/年， n = 17)，并评估了气流受限 (%FEV1 <80，n = 30)。
结果：C-CS升高与哮喘控制不佳，频繁发作和入院有关，特别是在非特应性患者中(n = 54)。同时，C-CS与气流受限无关。多元回归分析表明，升高的C-CS（C5≤2.44µM）是哮喘控制不佳和频繁急性发作的重大风险。在一般因素与合并症方面，吸烟，糖尿病和慢性鼻-鼻窦炎与重症哮喘的临床特征相关(所有p <0.05)。
结论：C-CS升高是重症哮喘的危险因素。本研究提示气道神经元功能障碍与非2型重症哮喘的病理生理学相关。
Increased Capsaicin Sensitivity in Severe Asthmatics Associated with Worse Clinical Outcome
Kanemitsu Y, Fukumitsu K, Kurokawa R, Takeda N, Suzuki M, Yap J, Nishiyama H, Tajiri T, Fukuda S, Uemura T, Ohkubo H, Maeno K, Ito K, Oguri T, Takemura M, Niimi A.
Am J Respir Crit Care Med. 2020 May 1; 201 (9): 1068-1077.
ABSTRACT
Rationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, while its association with severe asthma remains unknown. Objectives: To determine the clinical impact of C-CS on severe asthma.
Methods: We prospectively enrolled 157 asthmatic patients (including 122 severe asthma patients who were in step 4/5 according to the GINA 2015 guideline) between November 2016 and October 2019. Capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin (defined as C5) was adopted as an index of C-CS. Asthma control test (ACT) and comorbidities were also evaluated. Associations of biomarkers with 4 clinical features of severe asthma made by the ERS/ATS guideline [poor control (ACT <20, n = 58), frequent exacerbations (≥2 /year, n = 28), admissions (≥1 /year, n = 17), and airflow limitation (%FEV1 <80, n = 30)] were assessed.
Measurements and Main Results: Heightened C-CS was associated with poor asthma control, frequent exacerbations and admissions, particularly in non-atopic patients (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (C5 ≤2.44 µM) was a significant risk for poor asthma control, and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking, 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.
原理：辣椒素咳嗽反射敏感性(Capsaicin cough reflex sensitivity，C-CS)与哮喘控制不佳有关，而与重症哮喘的关联尚不清楚。
目标：本研究旨在确定C-CS对重症哮喘的临床影响。
方法：该研究前瞻性纳入了2016年11月至2019年10月之间的157例哮喘患者(包括根据GINA 2015指南在步骤4/5中的122例重症哮喘患者)。进行了辣椒素咳嗽试验，肺功能测定和生物标志物评估。辣椒素诱导至少五声咳嗽所需的浓度(定义为C5)被用作C-CS的指标。还评估了哮喘控制测试(ACT)和合并症。ERS / ATS指南将生物标志物与重症哮喘的4种临床特征相关联[控制不良(ACT <20，n = 58)，频繁发作(≥2/年，n = 28)，入院(≥1/年， n = 17)，并评估了气流受限 (%FEV1 <80，n = 30)。
结果：C-CS升高与哮喘控制不佳，频繁发作和入院有关，特别是在非特应性患者中(n = 54)。同时，C-CS与气流受限无关。多元回归分析表明，升高的C-CS（C5≤2.44µM）是哮喘控制不佳和频繁急性发作的重大风险。在一般因素与合并症方面，吸烟，糖尿病和慢性鼻-鼻窦炎与重症哮喘的临床特征相关(所有p <0.05)。
结论：C-CS升高是重症哮喘的危险因素。本研究提示气道神经元功能障碍与非2型重症哮喘的病理生理学相关。
(张红萍1 张欣1 王刚2 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（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 Severe Asthmatics Associated with Worse Clinical Outcome
Kanemitsu Y, Fukumitsu K, Kurokawa R, Takeda N, Suzuki M, Yap J, Nishiyama H, Tajiri T, Fukuda S, Uemura T, Ohkubo H, Maeno K, Ito K, Oguri T, Takemura M, Niimi A.
Am J Respir Crit Care Med. 2020 May 1; 201 (9): 1068-1077.
ABSTRACT
Rationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, while its association with severe asthma remains unknown. Objectives: To determine the clinical impact of C-CS on severe asthma.
Methods: We prospectively enrolled 157 asthmatic patients (including 122 severe asthma patients who were in step 4/5 according to the GINA 2015 guideline) between November 2016 and October 2019. Capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin (defined as C5) was adopted as an index of C-CS. Asthma control test (ACT) and comorbidities were also evaluated. Associations of biomarkers with 4 clinical features of severe asthma made by the ERS/ATS guideline [poor control (ACT <20, n = 58), frequent exacerbations (≥2 /year, n = 28), admissions (≥1 /year, n = 17), and airflow limitation (%FEV1 <80, n = 30)] were assessed.
Measurements and Main Results: Heightened C-CS was associated with poor asthma control, frequent exacerbations and admissions, particularly in non-atopic patients (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (C5 ≤2.44 µM) was a significant risk for poor asthma control, and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking, 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.
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